Toxicological features of maleilated polyflavonoids from Pinus radiata (D. Don.) as potential functional additives for biomaterials design.

PubMed

García, Danny E; Medina, Paulina A; Zúñiga, Valentina I

2017-11-01

Polyflavonoids from Pinus radiata (D. Don.) are an abundant natural oligomers highly desirable as renewable chemicals. However, structural modification of polyflavonoids is a viable strategy in order to use such polyphenols as macrobuilding-blocks for biomaterial design. Polyflavonoids were esterified with three five-member cyclic anhydrides (maleic, itaconic, and citraconic) at 20 °C during 24 h in order to diversify physicochemical-, and biological-properties for agricultural, and food-packaging applications. In addition, the influence of the chemical modification, as well as the chemical structure of the grafting on toxicological features was evaluated. Structural features of derivatives were analyzed by spectroscopy (FT-IR and 1 H-NMR), and the degree of substitution was calculated. Toxicological profile was assessed by using three target species in a wide range of concentration (0.01-100 mgL - 1 ). Effect of polyflavonoids on the growth rate (Selenastrum capricornutum), mortality (Daphnia magna), and germination and radicle length (Lactuca sativa) was determined. Chemical modification affects the toxicological profile on the derivatives in a high extent. Results described remarkable differences in function of the target specie. The bioassays indicate differences of the polyflavonoids toxicological profile associated to the chemical structure of the grafting. Results allowed conclude that polyflavonoids from pine bark show slight toxic properties. Copyright © 2017 Elsevier Ltd. All rights reserved.

Solid State Chemistry of Clathrate Phases: Crystal Structure, Chemical Bonding and Preparation Routes

NASA Astrophysics Data System (ADS)

Baitinger, Michael; Böhme, Bodo; Ormeci, Alim; Grin, Yuri

Clathrates represent a family of inorganic materials called cage compounds. The key feature of their crystal structures is a three-dimensional (host) framework bearing large cavities (cages) with 20-28 vertices. These polyhedral cages bear—as a rule—guest species. Depending on the formal charge of the framework, clathrates are grouped in anionic, cationic and neutral. While the bonding in the framework is of (polar) covalent nature, the guest-host interaction can be ionic, covalent or even van-der Waals, depending on the chemical composition of the clathrates. The chemical composition and structural features of the cationic clathrates can be described by the enhanced Zintl concept, whereas the composition of the anionic clathrates deviates often from the Zintl counts, indicating additional atomic interactions in comparison with the ionic-covalent Zintl model. These interactions can be visualized and studied by applying modern quantum chemical approaches such as electron localizability.

A general representation scheme for crystalline solids based on Voronoi-tessellation real feature values and atomic property data

PubMed Central

Jalem, Randy; Nakayama, Masanobu; Noda, Yusuke; Le, Tam; Takeuchi, Ichiro; Tateyama, Yoshitaka; Yamazaki, Hisatsugu

2018-01-01

Abstract Increasing attention has been paid to materials informatics approaches that promise efficient and fast discovery and optimization of functional inorganic materials. Technical breakthrough is urgently requested to advance this field and efforts have been made in the development of materials descriptors to encode or represent characteristics of crystalline solids, such as chemical composition, crystal structure, electronic structure, etc. We propose a general representation scheme for crystalline solids that lifts restrictions on atom ordering, cell periodicity, and system cell size based on structural descriptors of directly binned Voronoi-tessellation real feature values and atomic/chemical descriptors based on the electronegativity of elements in the crystal. Comparison was made vs. radial distribution function (RDF) feature vector, in terms of predictive accuracy on density functional theory (DFT) material properties: cohesive energy (CE), density (d), electronic band gap (BG), and decomposition energy (Ed). It was confirmed that the proposed feature vector from Voronoi real value binning generally outperforms the RDF-based one for the prediction of aforementioned properties. Together with electronegativity-based features, Voronoi-tessellation features from a given crystal structure that are derived from second-nearest neighbor information contribute significantly towards prediction. PMID:29707064

A general representation scheme for crystalline solids based on Voronoi-tessellation real feature values and atomic property data.

PubMed

Jalem, Randy; Nakayama, Masanobu; Noda, Yusuke; Le, Tam; Takeuchi, Ichiro; Tateyama, Yoshitaka; Yamazaki, Hisatsugu

2018-01-01

Increasing attention has been paid to materials informatics approaches that promise efficient and fast discovery and optimization of functional inorganic materials. Technical breakthrough is urgently requested to advance this field and efforts have been made in the development of materials descriptors to encode or represent characteristics of crystalline solids, such as chemical composition, crystal structure, electronic structure, etc. We propose a general representation scheme for crystalline solids that lifts restrictions on atom ordering, cell periodicity, and system cell size based on structural descriptors of directly binned Voronoi-tessellation real feature values and atomic/chemical descriptors based on the electronegativity of elements in the crystal. Comparison was made vs. radial distribution function (RDF) feature vector, in terms of predictive accuracy on density functional theory (DFT) material properties: cohesive energy (CE), density ( d ), electronic band gap (BG), and decomposition energy (Ed). It was confirmed that the proposed feature vector from Voronoi real value binning generally outperforms the RDF-based one for the prediction of aforementioned properties. Together with electronegativity-based features, Voronoi-tessellation features from a given crystal structure that are derived from second-nearest neighbor information contribute significantly towards prediction.

Chemicals used in the rubber industry. An overview.

PubMed

Fishbein, L

1983-01-01

Hundreds of chemicals illustrative of many structural and use categories are employed in the rubber industry. The present overview has centered on the structural features of a number of compounds representative of several select use categories, eg, vulcanizing agents, accelerators, antioxidants, antiozonants, and blowing agents, with focus on the nature of their impurities, their chemical degradation, and by-products, as well as on those chemicals that can be converted to N-nitrosamines.

Weighted Feature Significance: A Simple, Interpretable Model of Compound Toxicity Based on the Statistical Enrichment of Structural Features

PubMed Central

Huang, Ruili; Southall, Noel; Xia, Menghang; Cho, Ming-Hsuang; Jadhav, Ajit; Nguyen, Dac-Trung; Inglese, James; Tice, Raymond R.; Austin, Christopher P.

2009-01-01

In support of the U.S. Tox21 program, we have developed a simple and chemically intuitive model we call weighted feature significance (WFS) to predict the toxicological activity of compounds, based on the statistical enrichment of structural features in toxic compounds. We trained and tested the model on the following: (1) data from quantitative high–throughput screening cytotoxicity and caspase activation assays conducted at the National Institutes of Health Chemical Genomics Center, (2) data from Salmonella typhimurium reverse mutagenicity assays conducted by the U.S. National Toxicology Program, and (3) hepatotoxicity data published in the Registry of Toxic Effects of Chemical Substances. Enrichments of structural features in toxic compounds are evaluated for their statistical significance and compiled into a simple additive model of toxicity and then used to score new compounds for potential toxicity. The predictive power of the model for cytotoxicity was validated using an independent set of compounds from the U.S. Environmental Protection Agency tested also at the National Institutes of Health Chemical Genomics Center. We compared the performance of our WFS approach with classical classification methods such as Naive Bayesian clustering and support vector machines. In most test cases, WFS showed similar or slightly better predictive power, especially in the prediction of hepatotoxic compounds, where WFS appeared to have the best performance among the three methods. The new algorithm has the important advantages of simplicity, power, interpretability, and ease of implementation. PMID:19805409

Special Features of Structure Formation in Pipes from Medium-Carbon Low-Alloy Steel 32G2F Under Heat Treatment

NASA Astrophysics Data System (ADS)

Stepanov, A. I.; Belikov, S. V.; Musikhin, S. A.; Burmasov, S. P.; Popov, A. A.

2017-03-01

Special features of formation of structure and properties of seamless pipes from medium-carbon low-alloy steel for oil and gas applications are considered and associated with chemical inhomogeneity of the metal of the pipes.

Automated Inference of Chemical Discriminants of Biological Activity.

PubMed

Raschka, Sebastian; Scott, Anne M; Huertas, Mar; Li, Weiming; Kuhn, Leslie A

2018-01-01

Ligand-based virtual screening has become a standard technique for the efficient discovery of bioactive small molecules. Following assays to determine the activity of compounds selected by virtual screening, or other approaches in which dozens to thousands of molecules have been tested, machine learning techniques make it straightforward to discover the patterns of chemical groups that correlate with the desired biological activity. Defining the chemical features that generate activity can be used to guide the selection of molecules for subsequent rounds of screening and assaying, as well as help design new, more active molecules for organic synthesis.The quantitative structure-activity relationship machine learning protocols we describe here, using decision trees, random forests, and sequential feature selection, take as input the chemical structure of a single, known active small molecule (e.g., an inhibitor, agonist, or substrate) for comparison with the structure of each tested molecule. Knowledge of the atomic structure of the protein target and its interactions with the active compound are not required. These protocols can be modified and applied to any data set that consists of a series of measured structural, chemical, or other features for each tested molecule, along with the experimentally measured value of the response variable you would like to predict or optimize for your project, for instance, inhibitory activity in a biological assay or ΔG binding . To illustrate the use of different machine learning algorithms, we step through the analysis of a dataset of inhibitor candidates from virtual screening that were tested recently for their ability to inhibit GPCR-mediated signaling in a vertebrate.

Postmortem Biochemistry of Meat and Fish.

ERIC Educational Resources Information Center

Hultin, Herbert O.

1984-01-01

Discusses structural and chemical features of muscle tissue. Emphasizes chemical and physical changes which occur during processing and storage and how these changes affect the eating quality of meat and fish. (JN)

Structure-based classification and ontology in chemistry

PubMed Central

2012-01-01

Background Recent years have seen an explosion in the availability of data in the chemistry domain. With this information explosion, however, retrieving relevant results from the available information, and organising those results, become even harder problems. Computational processing is essential to filter and organise the available resources so as to better facilitate the work of scientists. Ontologies encode expert domain knowledge in a hierarchically organised machine-processable format. One such ontology for the chemical domain is ChEBI. ChEBI provides a classification of chemicals based on their structural features and a role or activity-based classification. An example of a structure-based class is 'pentacyclic compound' (compounds containing five-ring structures), while an example of a role-based class is 'analgesic', since many different chemicals can act as analgesics without sharing structural features. Structure-based classification in chemistry exploits elegant regularities and symmetries in the underlying chemical domain. As yet, there has been neither a systematic analysis of the types of structural classification in use in chemistry nor a comparison to the capabilities of available technologies. Results We analyze the different categories of structural classes in chemistry, presenting a list of patterns for features found in class definitions. We compare these patterns of class definition to tools which allow for automation of hierarchy construction within cheminformatics and within logic-based ontology technology, going into detail in the latter case with respect to the expressive capabilities of the Web Ontology Language and recent extensions for modelling structured objects. Finally we discuss the relationships and interactions between cheminformatics approaches and logic-based approaches. Conclusion Systems that perform intelligent reasoning tasks on chemistry data require a diverse set of underlying computational utilities including algorithmic, statistical and logic-based tools. For the task of automatic structure-based classification of chemical entities, essential to managing the vast swathes of chemical data being brought online, systems which are capable of hybrid reasoning combining several different approaches are crucial. We provide a thorough review of the available tools and methodologies, and identify areas of open research. PMID:22480202

Bioprospecting for Exopolysaccharides from Deep-Sea Hydrothermal Vent Bacteria: Relationship between Bacterial Diversity and Chemical Diversity

PubMed Central

Delbarre-Ladrat, Christine; Leyva Salas, Marcia; Zykwinska, Agata; Colliec-Jouault, Sylvia

2017-01-01

Many bacteria biosynthesize structurally diverse exopolysaccharides (EPS) and excrete them into their surrounding environment. The EPS functional features have found many applications in industries such as cosmetics and pharmaceutics. In particular, some EPS produced by marine bacteria are composed of uronic acids, neutral sugars, and N-acetylhexosamines, and may also bear some functional sulfate groups. This suggests that they can share common structural features with glycosaminoglycans (GAG) like the two EPS (HE800 and GY785) originating from the deep sea. In an attempt to discover new EPS that may be promising candidates as GAG-mimetics, fifty-one marine bacterial strains originating from deep-sea hydrothermal vents were screened. The analysis of the EPS chemical structure in relation to bacterial species showed that Vibrio, Alteromonas, and Pseudoalteromonas strains were the main producers. Moreover, they produced EPS with distinct structural features, which might be useful for targeting marine bacteria that could possibly produce structurally GAG-mimetic EPS. PMID:28930185

Elemental Analysis of Beryllium Samples Using a Microzond-EGP-10 Unit

NASA Astrophysics Data System (ADS)

Buzoverya, M. E.; Karpov, I. A.; Gorodnov, A. A.; Shishpor, I. V.; Kireycheva, V. I.

2017-12-01

Results concerning the structural and elemental analysis of beryllium samples obtained via different technologies using a Microzond-EGP-10 unit with the help of the PIXE and RBS methods are presented. As a result, the overall chemical composition and the nature of inclusions were determined. The mapping method made it possible to reveal the structural features of beryllium samples: to select the grains of the main substance having different size and chemical composition, to visualize the interfaces between the regions of different composition, and to describe the features of the distribution of impurities in the samples.

Chemically Patterned Inverse Opal Created by a Selective Photolysis Modification Process.

PubMed

Tian, Tian; Gao, Ning; Gu, Chen; Li, Jian; Wang, Hui; Lan, Yue; Yin, Xianpeng; Li, Guangtao

2015-09-02

Anisotropic photonic crystal materials have long been pursued for their broad applications. A novel method for creating chemically patterned inverse opals is proposed here. The patterning technique is based on selective photolysis of a photolabile polymer together with postmodification on released amine groups. The patterning method allows regioselective modification within an inverse opal structure, taking advantage of selective chemical reaction. Moreover, combined with the unique signal self-reporting feature of the photonic crystal, the fabricated structure is capable of various applications, including gradient photonic bandgap and dynamic chemical patterns. The proposed method provides the ability to extend the structural and chemical complexity of the photonic crystal, as well as its potential applications.

Graph wavelet alignment kernels for drug virtual screening.

PubMed

Smalter, Aaron; Huan, Jun; Lushington, Gerald

2009-06-01

In this paper, we introduce a novel statistical modeling technique for target property prediction, with applications to virtual screening and drug design. In our method, we use graphs to model chemical structures and apply a wavelet analysis of graphs to summarize features capturing graph local topology. We design a novel graph kernel function to utilize the topology features to build predictive models for chemicals via Support Vector Machine classifier. We call the new graph kernel a graph wavelet-alignment kernel. We have evaluated the efficacy of the wavelet-alignment kernel using a set of chemical structure-activity prediction benchmarks. Our results indicate that the use of the kernel function yields performance profiles comparable to, and sometimes exceeding that of the existing state-of-the-art chemical classification approaches. In addition, our results also show that the use of wavelet functions significantly decreases the computational costs for graph kernel computation with more than ten fold speedup.

Complex, multi-scale small intestinal topography replicated in cellular growth substrates fabricated via chemical vapor deposition of Parylene C.

PubMed

Koppes, Abigail N; Kamath, Megha; Pfluger, Courtney A; Burkey, Daniel D; Dokmeci, Mehmet; Wang, Lin; Carrier, Rebecca L

2016-08-22

Native small intestine possesses distinct multi-scale structures (e.g., crypts, villi) not included in traditional 2D intestinal culture models for drug delivery and regenerative medicine. The known impact of structure on cell function motivates exploration of the influence of intestinal topography on the phenotype of cultured epithelial cells, but the irregular, macro- to submicron-scale features of native intestine are challenging to precisely replicate in cellular growth substrates. Herein, we utilized chemical vapor deposition of Parylene C on decellularized porcine small intestine to create polymeric intestinal replicas containing biomimetic irregular, multi-scale structures. These replicas were used as molds for polydimethylsiloxane (PDMS) growth substrates with macro to submicron intestinal topographical features. Resultant PDMS replicas exhibit multiscale resolution including macro- to micro-scale folds, crypt and villus structures, and submicron-scale features of the underlying basement membrane. After 10 d of human epithelial colorectal cell culture on PDMS substrates, the inclusion of biomimetic topographical features enhanced alkaline phosphatase expression 2.3-fold compared to flat controls, suggesting biomimetic topography is important in induced epithelial differentiation. This work presents a facile, inexpensive method for precisely replicating complex hierarchal features of native tissue, towards a new model for regenerative medicine and drug delivery for intestinal disorders and diseases.

Creating and Using a Consumer Chemical Molecular Graphics Database: The "Molecule of the Day" - A Great Way To Begin Your Lecture

NASA Astrophysics Data System (ADS)

Scharberg, Maureen A.; Cox, Oran E.; Barelli, Carl A.

1997-07-01

"The Molecule of the Day" consumer chemical database has been created to allow introductory chemistry students to explore molecular structures of chemicals in household products, and to provide opportunities in molecular modeling for undergraduate chemistry students. Before class begins, an overhead transparency is displayed which shows a three-dimensional molecular structure of a household chemical, and lists relevant features and uses of this chemical. Within answers to questionnaires, students have commented that this molecular graphics database has helped them to visually connect the microscopic structure of a molecule with its physical and chemical properties, as well as its uses in consumer products. It is anticipated that this database will be incorporated into a navigational software package such as Netscape.

Computational and Statistical Analyses of Amino Acid Usage and Physico-Chemical Properties of the Twelve Late Embryogenesis Abundant Protein Classes

PubMed Central

Jaspard, Emmanuel; Macherel, David; Hunault, Gilles

2012-01-01

Late Embryogenesis Abundant Proteins (LEAPs) are ubiquitous proteins expected to play major roles in desiccation tolerance. Little is known about their structure - function relationships because of the scarcity of 3-D structures for LEAPs. The previous building of LEAPdb, a database dedicated to LEAPs from plants and other organisms, led to the classification of 710 LEAPs into 12 non-overlapping classes with distinct properties. Using this resource, numerous physico-chemical properties of LEAPs and amino acid usage by LEAPs have been computed and statistically analyzed, revealing distinctive features for each class. This unprecedented analysis allowed a rigorous characterization of the 12 LEAP classes, which differed also in multiple structural and physico-chemical features. Although most LEAPs can be predicted as intrinsically disordered proteins, the analysis indicates that LEAP class 7 (PF03168) and probably LEAP class 11 (PF04927) are natively folded proteins. This study thus provides a detailed description of the structural properties of this protein family opening the path toward further LEAP structure - function analysis. Finally, since each LEAP class can be clearly characterized by a unique set of physico-chemical properties, this will allow development of software to predict proteins as LEAPs. PMID:22615859

Predictive analysis of the influence of the chemical composition and pre-processing regimen on structural properties of steel alloys using machine learning techniques

NASA Astrophysics Data System (ADS)

Krishnamurthy, Narayanan; Maddali, Siddharth; Romanov, Vyacheslav; Hawk, Jeffrey

We present some structural properties of multi-component steel alloys as predicted by a random forest machine-learning model. These non-parametric models are trained on high-dimensional data sets defined by features such as chemical composition, pre-processing temperatures and environmental influences, the latter of which are based upon standardized testing procedures for tensile, creep and rupture properties as defined by the American Society of Testing and Materials (ASTM). We quantify the goodness of fit of these models as well as the inferred relative importance of each of these features, all with a conveniently defined metric and scale. The models are tested with synthetic data points, generated subject to the appropriate mathematical constraints for the various features. By this we highlight possible trends in the increase or degradation of the structural properties with perturbations in the features of importance. This work is presented as part of the Data Science Initiative at the National Energy Technology Laboratory, directed specifically towards the computational design of steel alloys.

Identification of Chemical Features Linked to Thyroperoxidase ...

EPA Pesticide Factsheets

Disruption of maternal serum thyroid hormone (TH) adversely affects fetal neurodevelopment. Therefore, assay development within the US EPA ToxCast program is ongoing to enable screening for chemicals that may disrupt TH, in support of the Endocrine Disruption Screening Program (EDSP21). The AUR-TPO assay was recently developed to screen >1,000 ToxCast chemicals for potential thyroperoxidase (TPO) inhibition activity. TPO is critical for TH synthesis and is a known target of thyroid-disrupting chemicals. The bioactivity results from the AUR-TPO assay were used to identify chemical substructures associated with in vitro TPO inhibition. Substructure profiles were generated for each chemical in the ToxCast test set using the publicly-available ToxPrint 2.0 chemotypes. Chemotypes enriched among the putative TPO inhibitors were identified using a cumulative hypergeometric probability (p < 0.01). Of the total 729 chemotypes evaluated, 31 were overrepresented among TPO inhibitors. Examination of those 31 chemotypes revealed four basic pharmacophores that accounted for 70% of the ToxCast chemicals active in the AUR-TPO assay: aromatic alcohols, aromatic amines, thiocarbonyls and phosphothioates. Chemico-structural analysis of AUR-TPO screening results enabled the identification of chemical features that likely drive TPO inhibition in the AUR-TPO assay. This highlights the potential to identify thyroid-disrupting chemicals in silico using structural alerts identified by

Chemical name extraction based on automatic training data generation and rich feature set.

PubMed

Yan, Su; Spangler, W Scott; Chen, Ying

2013-01-01

The automation of extracting chemical names from text has significant value to biomedical and life science research. A major barrier in this task is the difficulty of getting a sizable and good quality data to train a reliable entity extraction model. Another difficulty is the selection of informative features of chemical names, since comprehensive domain knowledge on chemistry nomenclature is required. Leveraging random text generation techniques, we explore the idea of automatically creating training sets for the task of chemical name extraction. Assuming the availability of an incomplete list of chemical names, called a dictionary, we are able to generate well-controlled, random, yet realistic chemical-like training documents. We statistically analyze the construction of chemical names based on the incomplete dictionary, and propose a series of new features, without relying on any domain knowledge. Compared to state-of-the-art models learned from manually labeled data and domain knowledge, our solution shows better or comparable results in annotating real-world data with less human effort. Moreover, we report an interesting observation about the language for chemical names. That is, both the structural and semantic components of chemical names follow a Zipfian distribution, which resembles many natural languages.

Chemical Dynamics of nano-Aluminum and Iodine Based Oxidizers

NASA Astrophysics Data System (ADS)

Little, Brian; Ridge, Claron; Overdeep, Kyle; Slizewski, Dylan; Lindsay, Michael

2017-06-01

As observed in previous studies of nanoenergetic powder composites, micro/nano-structural features such as particle morphology and/or reactant spatial distance are expected to strongly influence properties that govern the combustion behavior of energetic materials (EM). In this study, highly reactive composites containing crystalline iodine (V) oxide or iodate salts with nano-sized aluminum (nAl) were blended by two different processing techniques and then collected as a powder for characterization. Physiochemical techniques such as thermal gravimetric analysis, calorimetry, X-ray diffraction, electron microscopy, high speed photography, pressure profile analysis, temperature programmed reactions, and spectroscopy were employed to characterize these EM with emphasis on correlating the chemical reactivity with inherent structural features and variations in stoichiometry. This work is a continuation of efforts to probe the chemical dynamics of nAl-iodine based composites.

gWEGA: GPU-accelerated WEGA for molecular superposition and shape comparison.

PubMed

Yan, Xin; Li, Jiabo; Gu, Qiong; Xu, Jun

2014-06-05

Virtual screening of a large chemical library for drug lead identification requires searching/superimposing a large number of three-dimensional (3D) chemical structures. This article reports a graphic processing unit (GPU)-accelerated weighted Gaussian algorithm (gWEGA) that expedites shape or shape-feature similarity score-based virtual screening. With 86 GPU nodes (each node has one GPU card), gWEGA can screen 110 million conformations derived from an entire ZINC drug-like database with diverse antidiabetic agents as query structures within 2 s (i.e., screening more than 55 million conformations per second). The rapid screening speed was accomplished through the massive parallelization on multiple GPU nodes and rapid prescreening of 3D structures (based on their shape descriptors and pharmacophore feature compositions). Copyright © 2014 Wiley Periodicals, Inc.

Predominant information quality scheme for the essential amino acids: an information-theoretical analysis.

PubMed

Esquivel, Rodolfo O; Molina-Espíritu, Moyocoyani; López-Rosa, Sheila; Soriano-Correa, Catalina; Barrientos-Salcedo, Carolina; Kohout, Miroslav; Dehesa, Jesús S

2015-08-24

In this work we undertake a pioneer information-theoretical analysis of 18 selected amino acids extracted from a natural protein, bacteriorhodopsin (1C3W). The conformational structures of each amino acid are analyzed by use of various quantum chemistry methodologies at high levels of theory: HF, M062X and CISD(Full). The Shannon entropy, Fisher information and disequilibrium are determined to grasp the spatial spreading features of delocalizability, order and uniformity of the optimized structures. These three entropic measures uniquely characterize all amino acids through a predominant information-theoretic quality scheme (PIQS), which gathers all chemical families by means of three major spreading features: delocalization, narrowness and uniformity. This scheme recognizes four major chemical families: aliphatic (delocalized), aromatic (delocalized), electro-attractive (narrowed) and tiny (uniform). All chemical families recognized by the existing energy-based classifications are embraced by this entropic scheme. Finally, novel chemical patterns are shown in the information planes associated with the PIQS entropic measures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Atmospheric pressure chemical ionization studies of non-polar isomeric hydrocarbons using ion mobility spectrometry and mass spectrometry with different ionization techniques

NASA Technical Reports Server (NTRS)

Borsdorf, H.; Nazarov, E. G.; Eiceman, G. A.

2002-01-01

The ionization pathways were determined for sets of isomeric non-polar hydrocarbons (structural isomers, cis/trans isomers) using ion mobility spectrometry and mass spectrometry with different techniques of atmospheric pressure chemical ionization to assess the influence of structural features on ion formation. Depending on the structural features, different ions were observed using mass spectrometry. Unsaturated hydrocarbons formed mostly [M - 1]+ and [(M - 1)2H]+ ions while mainly [M - 3]+ and [(M - 3)H2O]+ ions were found for saturated cis/trans isomers using photoionization and 63Ni ionization. These ionization methods and corona discharge ionization were used for ion mobility measurements of these compounds. Different ions were detected for compounds with different structural features. 63Ni ionization and photoionization provide comparable ions for every set of isomers. The product ions formed can be clearly attributed to the structures identified. However, differences in relative abundance of product ions were found. Although corona discharge ionization permits the most sensitive detection of non-polar hydrocarbons, the spectra detected are complex and differ from those obtained with 63Ni ionization and photoionization. c. 2002 American Society for Mass Spectrometry.

Profiling of the Tox21 Chemical Collection for Mitochondrial ...

EPA Pesticide Factsheets

Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding how different environmental chemicals and drug-like molecules impact mitochondrial function represents an initial step in predicting exposure-related toxic effects and defining a possible role for such compounds in the onset of various diseases. OBJECTIVES: To identify individual chemicals and general structural features associated with the disruption of mitochondrial membrane potential (MMP). METHODS: We used a multiplexed quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 10,000 compound library (~8300 unique chemicals) at 15 concentrations in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. RESULTS: In the primary screening, approximately 11% of the compounds (913 unique compounds) decreased the MMP after 1 h of treatment without affecting cell viability. Additionally, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay) ≤ 3, p<0.05]. Over 11% of the structural clusters that constitute the Tox21 library (76 of 651 clusters) were significantly enriched for compounds that decreased the MMP. CONCLUSIONS: Our multiplexed qHTS approach

An “ADME Module” in the Adverse Outcome Pathway ...

EPA Pesticide Factsheets

The Adverse Outcome Pathway (AOP) framework has generated intense interest for its utility to organize knowledge on the toxicity mechanisms, starting from a molecular initiating event (MIE) to an adverse outcome across various levels of biological organization. While the AOP framework is designed to be chemical agnostic, it is widely recognized that considering chemicals’ absorption, distribution, metabolism, and excretion (ADME) behaviors is critical in applying the AOP framework in chemical-specific risk assessment. Currently, information being generated as part of the Organisation for Economic Co-operation and Development (OECD) AOP Development Programme is being consolidated into an AOP Knowledgebase (http://aopwiki.org). To enhance the use of this Knowledgebase in risk assessment, an ADME Module has been developed to contain the ADME information needed to connect MIEs and other key events in an AOP for specific chemicals. The conceptual structure of this module characterizes the potential of a chemical to reach the target MIE based on either its structure-based features or relative rates of ADME. The key features of this module include (1) a framework for connecting biology-based AOP to biochemical-based ADME and chemical/human activity-based exposure pathways; (2) links to qualitative tools (e.g., structure-based cheminformatic model) that screen for chemicals that could potentially reach the target MIE; (3) links to quantitative tools (e.g., dose-r

Application of Functional Use Predictions to Aid in Structure ...

EPA Pesticide Factsheets

Humans are potentially exposed to thousands of anthropogenic chemicals in commerce. Recent work has shown that the bulk of this exposure may occur in near-field indoor environments (e.g., home, school, work, etc.). Advances in suspect screening analyses (SSA) now allow an improved understanding of the chemicals present in these environments. However, due to the nature of suspect screening techniques, investigators are often left with chemical formula predictions, with the possibility of many chemical structures matching to each formula. Here, newly developed quantitative structure-use relationship (QSUR) models are used to identify potential exposure sources for candidate structures. Previously, a suspect screening workflow was introduced and applied to house dust samples collected from the U.S. Department of Housing and Urban Development’s American Healthy Homes Survey (AHHS) [Rager, et al., Env. Int. 88 (2016)]. This workflow utilized the US EPA’s Distributed Structure-Searchable Toxicity (DSSTox) Database to link identified molecular features to molecular formulas, and ultimately chemical structures. Multiple QSUR models were applied to support the evaluation of candidate structures. These QSURs predict the likelihood of a chemical having a functional use commonly associated with consumer products having near-field use. For 3,228 structures identified as possible chemicals in AHHS house dust samples, we were able to obtain the required descriptors to appl

Discrimination Enhancement with Transient Feature Analysis of a Graphene Chemical Sensor.

PubMed

Nallon, Eric C; Schnee, Vincent P; Bright, Collin J; Polcha, Michael P; Li, Qiliang

2016-01-19

A graphene chemical sensor is subjected to a set of structurally and chemically similar hydrocarbon compounds consisting of toluene, o-xylene, p-xylene, and mesitylene. The fractional change in resistance of the sensor upon exposure to these compounds exhibits a similar response magnitude among compounds, whereas large variation is observed within repetitions for each compound, causing a response overlap. Therefore, traditional features depending on maximum response change will cause confusion during further discrimination and classification analysis. More robust features that are less sensitive to concentration, sampling, and drift variability would provide higher quality information. In this work, we have explored the advantage of using transient-based exponential fitting coefficients to enhance the discrimination of similar compounds. The advantages of such feature analysis to discriminate each compound is evaluated using principle component analysis (PCA). In addition, machine learning-based classification algorithms were used to compare the prediction accuracies when using fitting coefficients as features. The additional features greatly enhanced the discrimination between compounds while performing PCA and also improved the prediction accuracy by 34% when using linear discrimination analysis.

EPAs DSSTox Chemical Database: A Resource for the Non-Targeted Testing Community (EPA NTA workshop)

EPA Science Inventory

EPA’s DSSTox database project, which includes coverage of the ToxCast and Tox21 high-throughput testing inventories, provides high-quality chemical-structure files for inventories of toxicological and environmental relevance. A feature of the DSSTox project, which differentiates ...

Identification of the chemical constituents of Chinese medicine Yi-Xin-Shu capsule by molecular feature orientated precursor ion selection and tandem mass spectrometry structure elucidation.

PubMed

Wang, Hong-ping; Chen, Chang; Liu, Yan; Yang, Hong-Jun; Wu, Hong-Wei; Xiao, Hong-Bin

2015-11-01

The incomplete identification of the chemical components of traditional Chinese medicinal formula has been one of the bottlenecks in the modernization of traditional Chinese medicine. Tandem mass spectrometry has been widely used for the identification of chemical substances. Current automatic tandem mass spectrometry acquisition, where precursor ions were selected according to their signal intensity, encounters a drawback in chemical substances identification when samples contain many overlapping signals. Compounds in minor or trace amounts could not be identified because most tandem mass spectrometry information was lost. Herein, a molecular feature orientated precursor ion selection and tandem mass spectrometry structure elucidation method for complex Chinese medicine chemical constituent analysis was developed. The precursor ions were selected according to their two-dimensional characteristics of retention times and mass-to-charge ratio ranges from herbal compounds, so that all precursor ions from herbal compounds were included and more minor chemical constituents in Chinese medicine were identified. Compared to the conventional automatic tandem mass spectrometry setups, the approach is novel and can overcome the drawback for chemical substances identification. As an example, 276 compounds from the Chinese Medicine of Yi-Xin-Shu capsule were identified. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

EFFECTS OF CYTOSOLIC CONVERSION OF ESTRONE TO ESTRADIOL ON RAINBOW TROUT ER BINDING AFFINITY

EPA Science Inventory

Relative binding affinity (RBA) for estrone (E1) to the rainbow trout (Oncorhynchus mykiss) estrogen receptor (rtER) was measured as part of a larger effort to determine chemical structural features predictive of chemical estrogenicity in fish. Estrone RBA was found to vary consi...

Rapid experimental measurements of physicochemical properties to inform models and testing.

PubMed

Nicolas, Chantel I; Mansouri, Kamel; Phillips, Katherine A; Grulke, Christopher M; Richard, Ann M; Williams, Antony J; Rabinowitz, James; Isaacs, Kristin K; Yau, Alice; Wambaugh, John F

2018-05-02

The structures and physicochemical properties of chemicals are important for determining their potential toxicological effects, toxicokinetics, and route(s) of exposure. These data are needed to prioritize the risk for thousands of environmental chemicals, but experimental values are often lacking. In an attempt to efficiently fill data gaps in physicochemical property information, we generated new data for 200 structurally diverse compounds, which were rigorously selected from the USEPA ToxCast chemical library, and whose structures are available within the Distributed Structure-Searchable Toxicity Database (DSSTox). This pilot study evaluated rapid experimental methods to determine five physicochemical properties, including the log of the octanol:water partition coefficient (known as log(K ow ) or logP), vapor pressure, water solubility, Henry's law constant, and the acid dissociation constant (pKa). For most compounds, experiments were successful for at least one property; log(K ow ) yielded the largest return (176 values). It was determined that 77 ToxPrint structural features were enriched in chemicals with at least one measurement failure, indicating which features may have played a role in rapid method failures. To gauge consistency with traditional measurement methods, the new measurements were compared with previous measurements (where available). Since quantitative structure-activity/property relationship (QSAR/QSPR) models are used to fill gaps in physicochemical property information, 5 suites of QSPRs were evaluated for their predictive ability and chemical coverage or applicability domain of new experimental measurements. The ability to have accurate measurements of these properties will facilitate better exposure predictions in two ways: 1) direct input of these experimental measurements into exposure models; and 2) construction of QSPRs with a wider applicability domain, as their predicted physicochemical values can be used to parameterize exposure models in the absence of experimental data. Published by Elsevier B.V.

Features of Crystallization of Rapidly Quenched Ni45Ti32Hf18Cu5 and Ni25Ti32Hf18Cu25 Alloys from Melt with High-Temperature Shape Memory Effect

NASA Astrophysics Data System (ADS)

Pushin, A. V.; Pushin, V. G.; Kuntsevich, T. E.; Kuranova, N. N.; Makarov, V. V.; Uksusnikov, A. N.; Kourov, N. I.

2017-12-01

A comparative study of the structure and the chemical and phase composition of Ni45Ti32Hf18Cu5 and Ni25Ti32Hf18Cu25 amorphous alloys obtained by fast-quenching of melt stream by spinning has been carried out by transmission and scanning electron microscopy and X-ray diffraction. The critical temperatures of their devitrification were determined by the data of temperatures measurements of electrical resistance. The features of the formation of ultrafine structure and the phase transformation at the vitrification depending on the regimes of heat treatment and chemical composition of alloy have been established.

Structure-Based Design of Highly Selective Inhibitors of the CREB Binding Protein Bromodomain.

PubMed

Denny, R Aldrin; Flick, Andrew C; Coe, Jotham; Langille, Jonathan; Basak, Arindrajit; Liu, Shenping; Stock, Ingrid; Sahasrabudhe, Parag; Bonin, Paul; Hay, Duncan A; Brennan, Paul E; Pletcher, Mathew; Jones, Lyn H; Chekler, Eugene L Piatnitski

2017-07-13

Chemical probes are required for preclinical target validation to interrogate novel biological targets and pathways. Selective inhibitors of the CREB binding protein (CREBBP)/EP300 bromodomains are required to facilitate the elucidation of biology associated with these important epigenetic targets. Medicinal chemistry optimization that paid particular attention to physiochemical properties delivered chemical probes with desirable potency, selectivity, and permeability attributes. An important feature of the optimization process was the successful application of rational structure-based drug design to address bromodomain selectivity issues (particularly against the structurally related BRD4 protein).

Visualizing chemical functionality in plant cell walls

DOE PAGES

Zeng, Yining; Himmel, Michael E.; Ding, Shi-You

2017-11-30

Understanding plant cell wall cross-linking chemistry and polymeric architecture is key to the efficient utilization of biomass in all prospects from rational genetic modification to downstream chemical and biological conversion to produce fuels and value chemicals. In fact, the bulk properties of cell wall recalcitrance are collectively determined by its chemical features over a wide range of length scales from tissue, cellular to polymeric architectures. Microscopic visualization of cell walls from the nanometer to the micrometer scale offers an in situ approach to study their chemical functionality considering its spatial and chemical complexity, particularly the capabilities of characterizing biomass non-destructivelymore » and in real-time during conversion processes. Microscopic characterization has revealed heterogeneity in the distribution of chemical features, which would otherwise be hidden in bulk analysis. Key microscopic features include cell wall type, wall layering, and wall composition - especially cellulose and lignin distributions. Microscopic tools, such as atomic force microscopy, stimulated Raman scattering microscopy, and fluorescence microscopy, have been applied to investigations of cell wall structure and chemistry from the native wall to wall treated by thermal chemical pretreatment and enzymatic hydrolysis. While advancing our current understanding of plant cell wall recalcitrance and deconstruction, microscopic tools with improved spatial resolution will steadily enhance our fundamental understanding of cell wall function.« less

Visualizing chemical functionality in plant cell walls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeng, Yining; Himmel, Michael E.; Ding, Shi-You

Understanding plant cell wall cross-linking chemistry and polymeric architecture is key to the efficient utilization of biomass in all prospects from rational genetic modification to downstream chemical and biological conversion to produce fuels and value chemicals. In fact, the bulk properties of cell wall recalcitrance are collectively determined by its chemical features over a wide range of length scales from tissue, cellular to polymeric architectures. Microscopic visualization of cell walls from the nanometer to the micrometer scale offers an in situ approach to study their chemical functionality considering its spatial and chemical complexity, particularly the capabilities of characterizing biomass non-destructivelymore » and in real-time during conversion processes. Microscopic characterization has revealed heterogeneity in the distribution of chemical features, which would otherwise be hidden in bulk analysis. Key microscopic features include cell wall type, wall layering, and wall composition - especially cellulose and lignin distributions. Microscopic tools, such as atomic force microscopy, stimulated Raman scattering microscopy, and fluorescence microscopy, have been applied to investigations of cell wall structure and chemistry from the native wall to wall treated by thermal chemical pretreatment and enzymatic hydrolysis. While advancing our current understanding of plant cell wall recalcitrance and deconstruction, microscopic tools with improved spatial resolution will steadily enhance our fundamental understanding of cell wall function.« less

Visualizing chemical functionality in plant cell walls.

PubMed

Zeng, Yining; Himmel, Michael E; Ding, Shi-You

2017-01-01

Understanding plant cell wall cross-linking chemistry and polymeric architecture is key to the efficient utilization of biomass in all prospects from rational genetic modification to downstream chemical and biological conversion to produce fuels and value chemicals. In fact, the bulk properties of cell wall recalcitrance are collectively determined by its chemical features over a wide range of length scales from tissue, cellular to polymeric architectures. Microscopic visualization of cell walls from the nanometer to the micrometer scale offers an in situ approach to study their chemical functionality considering its spatial and chemical complexity, particularly the capabilities of characterizing biomass non-destructively and in real-time during conversion processes. Microscopic characterization has revealed heterogeneity in the distribution of chemical features, which would otherwise be hidden in bulk analysis. Key microscopic features include cell wall type, wall layering, and wall composition-especially cellulose and lignin distributions. Microscopic tools, such as atomic force microscopy, stimulated Raman scattering microscopy, and fluorescence microscopy, have been applied to investigations of cell wall structure and chemistry from the native wall to wall treated by thermal chemical pretreatment and enzymatic hydrolysis. While advancing our current understanding of plant cell wall recalcitrance and deconstruction, microscopic tools with improved spatial resolution will steadily enhance our fundamental understanding of cell wall function.

Chemical features of Ganoderma polysaccharides with antioxidant, antitumor and antimicrobial activities.

PubMed

Ferreira, Isabel C F R; Heleno, Sandrina A; Reis, Filipa S; Stojkovic, Dejan; Queiroz, Maria João R P; Vasconcelos, M Helena; Sokovic, Marina

2015-06-01

Ganoderma genus comprises one of the most commonly studied species worldwide, Ganoderma lucidum. However, other Ganoderma species have been also reported as important sources of bioactive compounds. Polysaccharides are important contributors to the medicinal properties reported for Ganoderma species, as demonstrated by the numerous publications, including reviews, on this matter. Yet, what are the chemical features of Ganoderma polysaccharides that have bioactivity? In the present manuscript, the chemical features of Ganoderma polysaccharides with reported antioxidant, antitumor and antimicrobial activities (the most studied worldwide) are analyzed in detail. The composition of sugars (homo- versus hetero-glucans and other polysaccharides), type of glycosidic linkages, branching patterns, and linkage to proteins are discussed. Methods for extraction, isolation and identification are evaluated and, finally, the bioactivity of polysaccharidic extracts and purified compounds are discussed. The integration of data allows deduction of structure-activity relationships and gives clues to the chemical aspects involved in Ganoderma bioactivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Scanning probe microscopy in mineralogical studies: about origin of the observed roughness of natural silica-rich glasses

NASA Astrophysics Data System (ADS)

Golubev, Ye A.; Isaenko, S. I.

2017-10-01

We have studied different mineralogical objects: natural glasses of impact (tektites, impactites) and volcanic (obsidians) origin, using atomic force microscopy, X-ray microanalysis, infrared and Raman spectroscopy. The spectroscopy showed the difference in the structure and chemical composition of the glasses of different origin. The analysis of the dependence of nanoscale heterogeneity of the glasses, revealed by the atomic force microscopy, on their structural and chemical features was carried out.

First principles pseudopotential calculation of electron energy loss near edge structures of lattice imperfections.

PubMed

Mizoguchi, Teruyasu; Matsunaga, Katsuyuki; Tochigi, Eita; Ikuhara, Yuichi

2012-01-01

Theoretical calculations of electron energy loss near edge structures (ELNES) of lattice imperfections, particularly a Ni(111)/ZrO₂(111) heterointerface and an Al₂O₃ stacking fault on the {1100} plane, are performed using a first principles pseudopotential method. The present calculation can qualitatively reproduce spectral features as well as chemical shifts in experiment by employing a special pseudopotential designed for the excited atom with a core-hole. From the calculation, spectral changes observed in O-K ELNES from a Ni/ZrO₂ interface can be attributable to interfacial oxygen-Ni interactions. In the O-K ELNES of Al₂O₃ stacking faults, theoretical calculation suggests that the spectral feature reflects coordination environment and chemical bonding. Powerful combinations of ELNES with a pseudopotential method used to investigate the atomic and electronic structures of lattice imperfections are demonstrated. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pressure-decoupled magnetic and structural transitions of the parent compound of iron-based 122 superconductors BaFe2As2

PubMed Central

Wu, J. J.; Lin, Jung-Fu; Wang, X. C.; Liu, Q. Q.; Zhu, J. L.; Xiao, Y. M.; Chow, P.; Jin, Changqing

2013-01-01

The recent discovery of iron ferropnictide superconductors has received intensive concern in connection with magnetically involved superconductors. Prominent features of ferropnictide superconductors are becoming apparent: the parent compounds exhibit an antiferromagnetic ordered spin density wave (SDW) state, the magnetic-phase transition is always accompanied by a crystal structural transition, and superconductivity can be induced by suppressing the SDW phase via either chemical doping or applied external pressure to the parent state. These features generated considerable interest in the interplay between magnetism and structure in chemically doped samples, showing crystal structure transitions always precede or coincide with magnetic transition. Pressure-tuned transition, on the other hand, would be more straightforward to superconducting mechanism studies because there are no disorder effects caused by chemical doping; however, remarkably little is known about the interplay in the parent compounds under controlled pressure due to the experimental challenge of in situ measuring both of magnetic and crystal structure evolution at high pressure and low temperatures. Here we show from combined synchrotron Mössbauer and X-ray diffraction at high pressures that the magnetic ordering surprisingly precedes the structural transition at high pressures in the parent compound BaFe2As2, in sharp contrast to the chemical-doping case. The results can be well understood in terms of the spin fluctuations in the emerging nematic phase before the long-range magnetic order that sheds light on understanding how the parent compound evolves from a SDW state to a superconducting phase, a key scientific inquiry of iron-based superconductors. PMID:24101468

Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential

PubMed Central

Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Witt, Kristine L.; Richard, Ann; Tice, Raymond R.; Simeonov, Anton; Austin, Christopher P.

2014-01-01

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases. Objectives: We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP). Methods: We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (~ 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. Results: Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay ≤ 3; p < 0.05]. More than 11% of the structural clusters that constitute the Tox21 library (76 of 651 clusters) were significantly enriched for compounds that decreased the MMP. Conclusions: Our multiplexed qHTS approach allowed us to generate a robust and reliable data set to evaluate the ability of thousands of drugs and environmental compounds to decrease MMP. The use of structure-based clustering analysis allowed us to identify molecular features that are likely responsible for the observed activity. Citation: Attene-Ramos MS, Huang R, Michael S, Witt KL, Richard A, Tice RR, Simeonov A, Austin CP, Xia M. 2015. Profiling of the Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential. Environ Health Perspect 123:49–56; http://dx.doi.org/10.1289/ehp.1408642 PMID:25302578

ADMET Evaluation in Drug Discovery. 18. Reliable Prediction of Chemical-Induced Urinary Tract Toxicity by Boosting Machine Learning Approaches.

PubMed

Lei, Tailong; Sun, Huiyong; Kang, Yu; Zhu, Feng; Liu, Hui; Zhou, Wenfang; Wang, Zhe; Li, Dan; Li, Youyong; Hou, Tingjun

2017-11-06

Xenobiotic chemicals and their metabolites are mainly excreted out of our bodies by the urinary tract through the urine. Chemical-induced urinary tract toxicity is one of the main reasons that cause failure during drug development, and it is a common adverse event for medications, natural supplements, and environmental chemicals. Despite its importance, there are only a few in silico models for assessing urinary tract toxicity for a large number of compounds with diverse chemical structures. Here, we developed a series of qualitative and quantitative structure-activity relationship (QSAR) models for predicting urinary tract toxicity. In our study, the recursive feature elimination method incorporated with random forests (RFE-RF) was used for dimension reduction, and then eight machine learning approaches were used for QSAR modeling, i.e., relevance vector machine (RVM), support vector machine (SVM), regularized random forest (RRF), C5.0 trees, eXtreme gradient boosting (XGBoost), AdaBoost.M1, SVM boosting (SVMBoost), and RVM boosting (RVMBoost). For building classification models, the synthetic minority oversampling technique was used to handle the imbalance data set problem. Among all the machine learning approaches, SVMBoost based on the RBF kernel achieves both the best quantitative (q ext 2 = 0.845) and qualitative predictions for the test set (MCC of 0.787, AUC of 0.893, sensitivity of 89.6%, specificity of 94.1%, and global accuracy of 90.8%). The application domains were then analyzed, and all of the tested chemicals fall within the application domain coverage. We also examined the structure features of the chemicals with large prediction errors. In brief, both the regression and classification models developed by the SVMBoost approach have reliable prediction capability for assessing chemical-induced urinary tract toxicity.

Non a Priori Automatic Discovery of 3D Chemical Patterns: Application to Mutagenicity.

PubMed

Rabatel, Julien; Fannes, Thomas; Lepailleur, Alban; Le Goff, Jérémie; Crémilleux, Bruno; Ramon, Jan; Bureau, Ronan; Cuissart, Bertrand

2017-10-01

This article introduces a new type of structural fragment called a geometrical pattern. Such geometrical patterns are defined as molecular graphs that include a labelling of atoms together with constraints on interatomic distances. The discovery of geometrical patterns in a chemical dataset relies on the induction of multiple decision trees combined in random forests. Each computational step corresponds to a refinement of a preceding set of constraints, extending a previous geometrical pattern. This paper focuses on the mutagenicity of chemicals via the definition of structural alerts in relation with these geometrical patterns. It follows an experimental assessment of the main geometrical patterns to show how they can efficiently originate the definition of a chemical feature related to a chemical function or a chemical property. Geometrical patterns have provided a valuable and innovative approach to bring new pieces of information for discovering and assessing structural characteristics in relation to a particular biological phenotype. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Importance of asparagine on the conformational stability and chemical reactivity of selected anti-inflammatory peptides

NASA Astrophysics Data System (ADS)

Soriano-Correa, Catalina; Barrientos-Salcedo, Carolina; Campos-Fernández, Linda; Alvarado-Salazar, Andres; Esquivel, Rodolfo O.

2015-08-01

Inflammatory response events are initiated by a complex series of molecular reactions that generate chemical intermediaries. The structure and properties of peptides and proteins are determined by the charge distribution of their side chains, which play an essential role in its electronic structure and physicochemical properties, hence on its biological functionality. The aim of this study was to analyze the effect of changing one central amino acid, such as substituting asparagine for aspartic acid, from Cys-Asn-Ser in aqueous solution, by assessing the conformational stability, physicochemical properties, chemical reactivity and their relationship with anti-inflammatory activity; employing quantum-chemical descriptors at the M06-2X/6-311+G(d,p) level. Our results suggest that asparagine plays a more critical role than aspartic acid in the structural stability, physicochemical features, and chemical reactivity of these tripeptides. Substituent groups in the side chain cause significant changes on the conformational stability and chemical reactivity, and consequently on their anti-inflammatory activity.

Electron-Poor Polar Intermetallics: Complex Structures, Novel Clusters, and Intriguing Bonding with Pronounced Electron Delocalization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Qisheng; Miller, Gordon J.

Intermetallic compounds represent an extensive pool of candidates for energy related applications stemming from magnetic, electric, optic, caloric, and catalytic properties. The discovery of novel intermetallic compounds can enhance understanding of the chemical principles that govern structural stability and chemical bonding as well as finding new applications. Valence electron-poor polar intermetallics with valence electron concentrations (VECs) between 2.0 and 3.0 e –/atom show a plethora of unprecedented and fascinating structural motifs and bonding features. Furthermore, establishing simple structure-bonding-property relationships is especially challenging for this compound class because commonly accepted valence electron counting rules are inappropriate.

Electron-Poor Polar Intermetallics: Complex Structures, Novel Clusters, and Intriguing Bonding with Pronounced Electron Delocalization

DOE PAGES

Lin, Qisheng; Miller, Gordon J.

2017-12-18

Intermetallic compounds represent an extensive pool of candidates for energy related applications stemming from magnetic, electric, optic, caloric, and catalytic properties. The discovery of novel intermetallic compounds can enhance understanding of the chemical principles that govern structural stability and chemical bonding as well as finding new applications. Valence electron-poor polar intermetallics with valence electron concentrations (VECs) between 2.0 and 3.0 e –/atom show a plethora of unprecedented and fascinating structural motifs and bonding features. Furthermore, establishing simple structure-bonding-property relationships is especially challenging for this compound class because commonly accepted valence electron counting rules are inappropriate.

Cytotoxic triterpenoid saponins from Aesculus glabra Willd.

PubMed

Yuan, Wei; Wang, Ping; Deng, Guangrui; Li, Shiyou

2012-03-01

Twenty-four acylated polyhydroxyoleanene saponins were isolated from the seeds of Aesculus glabra. Sixteen of them, namely aesculiosides G1-G16 (1-16), were determined as compounds by spectroscopic and chemical analysis. The structural features of all 24 saponins are: (1) arabinofuranosyl units affixed to C-3 of the glucuronopyranosyl unit in the trisaccharide chain; (2) no 24-OH substitution; (3) C-2 sugar moiety substitution of the 3-O-glucuronopyranosyl unit is either glucopyranosyl or galactopyranosyl. The features of these isolated saponin structures provide more evidence for chemical taxonomy within the genus Aesculus. The cytotoxicity of the aesculiosides (1-16) were tested against A549 and PC-3 cancer cell lines with GI₅₀ from 5.4 to >25 μM. Copyright © 2011 Elsevier Ltd. All rights reserved.

Parkinson’s disease and pesticides: a toxicological perspective

PubMed Central

Hatcher, Jaime M.; Pennell, Kurt D.; Miller, Gary W.

2017-01-01

Environmental factors have been shown to contribute to the incidence of Parkinson’s disease (PD). Pesticides, which represent one of the primary classes of environmental agents associated with PD, share the common feature of being intentionally released into the environment to control or eliminate pests. Pesticides consist of multiple classes and subclasses of insecticides, herbicides, rodenticides, fungicides, fumigants and others and exhibit a vast array of chemically diverse structures. In this review we examine the evidence regarding the ability of each of the major pesticide subclasses to increase the incidence of PD. We propose that, from a toxicological perspective, it would be beneficial to identify specific subclasses, common structural features and the propensity for widespread human exposure when considering the potential role in PD, rather than using the overly broad term of ‘pesticides’ to describe this diverse group of chemicals. Furthermore, these chemicals and their environmentally relevant combinations should be evaluated for their ability to promote or accelerate PD and not merely for being singular causative agents. PMID:18453001

Fabrication and Characterization of Woodpile Structures for Direct Laser Acceleration

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuinness, C.; Colby, E.; England, R.J.

2010-08-26

An eight and nine layer three dimensional photonic crystal with a defect designed specifically for accelerator applications has been fabricated. The structures were fabricated using a combination of nanofabrication techniques, including low pressure chemical vapor deposition, optical lithography, and chemical mechanical polishing. Limits imposed by the optical lithography set the minimum feature size to 400 nm, corresponding to a structure with a bandgap centered at 4.26 {micro}m. Reflection spectroscopy reveal a peak in reflectivity about the predicted region, and good agreement with simulation is shown. The eight and nine layer structures will be aligned and bonded together to form themore » complete seventeen layer woodpile accelerator structure.« less

Exposomics research using suspect screening and non ...

EPA Pesticide Factsheets

High-resolution mass spectrometry (HRMS) is used for suspect screening (SSA) and non-targeted analysis (NTA) in an attempt to characterize xenobiotic chemicals in various samples broadly and efficiently. These important techniques aid characterization of the exposome, the totality of human exposures, and provide critical information on thousands of chemicals in commerce for which exposure data are lacking. The Environmental Protection Agency (EPA) SSA and NTA capabilities consist of analytical instrumentation [liquid chromatography (LC) with time of flight (TOF) and quadrupole-TOF (Q-TOF) HRMS], workflows (feature extraction, formula generation, structure prediction, spectral matching, chemical confirmation), and tools (databases; models for predicting retention time, functional use, media occurrence, and media concentration; and schemes for ranking features and chemicals). Suspect screening (SSA) and non-targeted analysis (NTA) are used to characterize xenobiotic chemicals in various samples and aid characterization of the exposome, the totality of human exposures, and provide critical information on thousands of chemicals in commerce for which exposure data are lacking.

Chemical, Physical, and Biological Factors Shape Littoral Invertebrate Community Structure in Coal-Mining End-Pit Lakes

NASA Astrophysics Data System (ADS)

Luek, Andreas; Rasmussen, Joseph B.

2017-04-01

Aquatic invertebrates form the base of the consumer food web in lakes. In coal-mining end-pit lakes, invertebrates are exposed to an environment with potentially challenging physical and chemical features. We hypothesized that the physical and chemical features of end-pit lakes reduce critical littoral habitat and thus reduce invertebrate diversity, thereby limiting the potential for these lakes to be naturalized. We used a multivariate approach using principle component analysis and redundancy analysis to study relationships between invertebrate community structure, habitat features, and water quality in five end-pit lakes and five natural lakes in the Rocky Mountain foothills of west-central Alberta, Canada. Results show a significantly different invertebrate community structure was present in end-pit lakes as compared with reference lakes in the same region, which could be accounted for by water hardness, conductivity, slope of the littoral zone, and phosphorus concentrations. Habitat diversity in end-pit lakes was also limited, cover provided by macrophytes was scarce, and basin slopes were significantly steeper in pit lakes. Although water chemistry is currently the strongest influencing factor on the invertebrate community, physical challenges of habitat homogeneity and steep slopes in the littoral zones were identified as major drivers of invertebrate community structure. The addition of floating wetlands to the littoral zone of existing pit lakes can add habitat complexity without the need for large-scale alterations to basing morphology, while impermeable capping of waste-rock and the inclusion of littoral habitat in the planning process of new pit lakes can improve the success of integrating new pit lakes into the landscape.

Chemical, Physical, and Biological Factors Shape Littoral Invertebrate Community Structure in Coal-Mining End-Pit Lakes.

PubMed

Luek, Andreas; Rasmussen, Joseph B

2017-04-01

Aquatic invertebrates form the base of the consumer food web in lakes. In coal-mining end-pit lakes, invertebrates are exposed to an environment with potentially challenging physical and chemical features. We hypothesized that the physical and chemical features of end-pit lakes reduce critical littoral habitat and thus reduce invertebrate diversity, thereby limiting the potential for these lakes to be naturalized. We used a multivariate approach using principle component analysis and redundancy analysis to study relationships between invertebrate community structure, habitat features, and water quality in five end-pit lakes and five natural lakes in the Rocky Mountain foothills of west-central Alberta, Canada. Results show a significantly different invertebrate community structure was present in end-pit lakes as compared with reference lakes in the same region, which could be accounted for by water hardness, conductivity, slope of the littoral zone, and phosphorus concentrations. Habitat diversity in end-pit lakes was also limited, cover provided by macrophytes was scarce, and basin slopes were significantly steeper in pit lakes. Although water chemistry is currently the strongest influencing factor on the invertebrate community, physical challenges of habitat homogeneity and steep slopes in the littoral zones were identified as major drivers of invertebrate community structure. The addition of floating wetlands to the littoral zone of existing pit lakes can add habitat complexity without the need for large-scale alterations to basing morphology, while impermeable capping of waste-rock and the inclusion of littoral habitat in the planning process of new pit lakes can improve the success of integrating new pit lakes into the landscape.

Chemically Active, Porous 3D-Printed Thermoplastic Composites.

PubMed

Evans, Kent A; Kennedy, Zachary C; Arey, Bruce W; Christ, Josef F; Schaef, Herbert T; Nune, Satish K; Erikson, Rebecca L

2018-05-02

Metal-organic frameworks (MOFs) exhibit exceptional properties and are widely investigated because of their structural and functional versatility relevant to catalysis, separations, and sensing applications. However, their commercial or large-scale application is often limited by their powder forms which make integration into devices challenging. Here, we report the production of MOF-thermoplastic polymer composites in well-defined and customizable forms and with complex internal structural features accessed via a standard three-dimensional (3D) printer. MOFs (zeolitic imidazolate framework; ZIF-8) were incorporated homogeneously into both poly(lactic acid) (PLA) and thermoplastic polyurethane (TPU) matrices at high loadings (up to 50% by mass), extruded into filaments, and utilized for on-demand access to 3D structures by fused deposition modeling. Printed, rigid PLA/MOF composites display a large surface area (SA avg = 531 m 2 g -1 ) and hierarchical pore features, whereas flexible TPU/MOF composites achieve a high surface area (SA avg = 706 m 2 g -1 ) by employing a simple method developed to expose obstructed micropores postprinting. Critically, embedded particles in the plastic matrices retain their ability to participate in chemical interactions characteristic of the parent framework. The fabrication strategies were extended to other MOFs and illustrate the potential of 3D printing to create unique porous and high surface area chemically active structures.

Determination of absolute configuration of natural products: theoretical calculation of electronic circular dichroism as a tool

USDA-ARS?s Scientific Manuscript database

Determination of absolute configuration (AC) is one of the most challenging features in the structure elucidation of chiral natural products, especially those with complex structures. With revolutionary advancements in the area of quantum chemical calculations of chiroptical spectroscopy over the pa...

Classification of chemical substances, reactions, and interactions: The effect of expertise

NASA Astrophysics Data System (ADS)

Stains, Marilyne Nicole Olivia

2007-12-01

This project explored the strategies that undergraduate and graduate chemistry students engaged in when solving classification tasks involving microscopic (particulate) representations of chemical substances and microscopic and symbolic representations of different chemical reactions. We were specifically interested in characterizing the basic features to which students pay attention while classifying, identifying the patterns of reasoning that they follow, and comparing the performance of students with different levels of preparation in the discipline. In general, our results suggest that advanced levels of expertise in chemical classification do not necessarily evolve in a linear and continuous way with academic training. Novice students had a tendency to reduce the cognitive demand of the task and rely on common-sense reasoning; they had difficulties differentiating concepts (conceptual undifferentiation) and based their classification decisions on only one variable (reduction). These ways of thinking lead them to consider extraneous features, pay more attention to explicit or surface features than implicit features and to overlook important and relevant features. However, unfamiliar levels of representations (microscopic level) seemed to trigger deeper and more meaningful thinking processes. On the other hand, expert students classified entities using a specific set of rules that they applied throughout the classification tasks. They considered a larger variety of implicit features and the unfamiliarity with the microscopic level of representation did not affect their reasoning processes. Consequently, novices created numerous small groups, few of them being chemically meaningful, while experts created few but large chemically meaningful groups. Novices also had difficulties correctly classifying entities in chemically meaningful groups. Finally, expert chemists in our study used classification schemes that are not necessarily traditionally taught in classroom chemistry (e.g. the structure of substances is more relevant to them than their composition when classifying substances as compounds or elements). This result suggests that practice in the field may develop different types of knowledge framework than those usually presented in chemistry textbooks.

Structure-based predictions of 13C-NMR chemical shifts for a series of 2-functionalized 5-(methylsulfonyl)-1-phenyl-1H-indoles derivatives using GA-based MLR method

NASA Astrophysics Data System (ADS)

Ghavami, Raouf; Sadeghi, Faridoon; Rasouli, Zolikha; Djannati, Farhad

2012-12-01

Experimental values for the 13C NMR chemical shifts (ppm, TMS = 0) at 300 K ranging from 96.28 ppm (C4' of indole derivative 17) to 159.93 ppm (C4' of indole derivative 23) relative to deuteride chloroform (CDCl3, 77.0 ppm) or dimethylsulfoxide (DMSO, 39.50 ppm) as internal reference in CDCl3 or DMSO-d6 solutions have been collected from literature for thirty 2-functionalized 5-(methylsulfonyl)-1-phenyl-1H-indole derivatives containing different substituted groups. An effective quantitative structure-property relationship (QSPR) models were built using hybrid method combining genetic algorithm (GA) based on stepwise selection multiple linear regression (SWS-MLR) as feature-selection tools and correlation models between each carbon atom of indole derivative and calculated descriptors. Each compound was depicted by molecular structural descriptors that encode constitutional, topological, geometrical, electrostatic, and quantum chemical features. The accuracy of all developed models were confirmed using different types of internal and external procedures and various statistical tests. Furthermore, the domain of applicability for each model which indicates the area of reliable predictions was defined.

Reaction-diffusion processes at the nano- and microscales

NASA Astrophysics Data System (ADS)

Epstein, Irving R.; Xu, Bing

2016-04-01

The bottom-up fabrication of nano- and microscale structures from primary building blocks (molecules, colloidal particles) has made remarkable progress over the past two decades, but most research has focused on structural aspects, leaving our understanding of the dynamic and spatiotemporal aspects at a relatively primitive stage. In this Review, we draw inspiration from living cells to argue that it is now time to move beyond the generation of structures and explore dynamic processes at the nanoscale. We first introduce nanoscale self-assembly, self-organization and reaction-diffusion processes as essential features of cells. Then, we highlight recent progress towards designing and controlling these fundamental features of life in abiological systems. Specifically, we discuss examples of reaction-diffusion processes that lead to such outcomes as self-assembly, self-organization, unique nanostructures, chemical waves and dynamic order to illustrate their ubiquity within a unifying context of dynamic oscillations and energy dissipation. Finally, we suggest future directions for research on reaction-diffusion processes at the nano- and microscales that we find hold particular promise for a new understanding of science at the nanoscale and the development of new kinds of nanotechnologies for chemical transport, chemical communication and integration with living systems.

The Conformational Stability and Biophysical Properties of the Eukaryotic Thioredoxins of Pisum Sativum Are Not Family-Conserved

PubMed Central

Aguado-Llera, David; Martínez-Gómez, Ana Isabel; Prieto, Jesús; Marenchino, Marco; Traverso, José Angel; Gómez, Javier; Chueca, Ana; Neira, José L.

2011-01-01

Thioredoxins (TRXs) are ubiquitous proteins involved in redox processes. About forty genes encode TRX or TRX-related proteins in plants, grouped in different families according to their subcellular localization. For instance, the h-type TRXs are located in cytoplasm or mitochondria, whereas f-type TRXs have a plastidial origin, although both types of proteins have an eukaryotic origin as opposed to other TRXs. Herein, we study the conformational and the biophysical features of TRXh1, TRXh2 and TRXf from Pisum sativum. The modelled structures of the three proteins show the well-known TRX fold. While sharing similar pH-denaturations features, the chemical and thermal stabilities are different, being PsTRXh1 (Pisum sativum thioredoxin h1) the most stable isoform; moreover, the three proteins follow a three-state denaturation model, during the chemical-denaturations. These differences in the thermal- and chemical-denaturations result from changes, in a broad sense, of the several ASAs (accessible surface areas) of the proteins. Thus, although a strong relationship can be found between the primary amino acid sequence and the structure among TRXs, that between the residue sequence and the conformational stability and biophysical properties is not. We discuss how these differences in the biophysical properties of TRXs determine their unique functions in pea, and we show how residues involved in the biophysical features described (pH-titrations, dimerizations and chemical-denaturations) belong to regions involved in interaction with other proteins. Our results suggest that the sequence demands of protein-protein function are relatively rigid, with different protein-binding pockets (some in common) for each of the three proteins, but the demands of structure and conformational stability per se (as long as there is a maintained core), are less so. PMID:21364950

Direct observation and analysis of york-shell materials using low-voltage high-resolution scanning electron microscopy: Nanometal-particles encapsulated in metal-oxide, carbon, and polymer

NASA Astrophysics Data System (ADS)

Asahina, Shunsuke; Suga, Mitsuo; Takahashi, Hideyuki; Young Jeong, Hu; Galeano, Carolina; Schüth, Ferdi; Terasaki, Osamu

2014-11-01

Nanometal particles show characteristic features in chemical and physical properties depending on their sizes and shapes. For keeping and further enhancing their features, the particles should be protected from coalescence or degradation. One approach is to encapsulate the nanometal particles inside pores with chemically inert or functional materials, such as carbon, polymer, and metal oxides, which contain mesopores to allow permeation of only chemicals not the nanometal particles. Recently developed low-voltage high-resolution scanning electron microscopy was applied to the study of structural, chemical, and electron state of both nanometal particles and encapsulating materials in yolk-shell materials of Au@C, Ru/Pt@C, Au@TiO2, and Pt@Polymer. Progresses in the following categories were shown for the yolk-shell materials: (i) resolution of topographic image contrast by secondary electrons, of atomic-number contrast by back-scattered electrons, and of elemental mapping by X-ray energy dispersive spectroscopy; (ii) sample preparation for observing internal structures; and (iii) X-ray spectroscopy such as soft X-ray emission spectroscopy. Transmission electron microscopy was also used for characterization of Au@C.

Giant surfactants provide a versatile platform for sub-10-nm nanostructure engineering

PubMed Central

Yu, Xinfei; Yue, Kan; Hsieh, I-Fan; Li, Yiwen; Dong, Xue-Hui; Liu, Chang; Xin, Yu; Wang, Hsiao-Fang; Shi, An-Chang; Newkome, George R.; Chen, Er-Qiang; Zhang, Wen-Bin; Cheng, Stephen Z. D.

2013-01-01

The engineering of structures across different length scales is central to the design of novel materials with controlled macroscopic properties. Herein, we introduce a unique class of self-assembling materials, which are built upon shape- and volume-persistent molecular nanoparticles and other structural motifs, such as polymers, and can be viewed as a size-amplified version of the corresponding small-molecule counterparts. Among them, “giant surfactants” with precise molecular structures have been synthesized by “clicking” compact and polar molecular nanoparticles to flexible polymer tails of various composition and architecture at specific sites. Capturing the structural features of small-molecule surfactants but possessing much larger sizes, giant surfactants bridge the gap between small-molecule surfactants and block copolymers and demonstrate a duality of both materials in terms of their self-assembly behaviors. The controlled structural variations of these giant surfactants through precision synthesis further reveal that their self-assemblies are remarkably sensitive to primary chemical structures, leading to highly diverse, thermodynamically stable nanostructures with feature sizes around 10 nm or smaller in the bulk, thin-film, and solution states, as dictated by the collective physical interactions and geometric constraints. The results suggest that this class of materials provides a versatile platform for engineering nanostructures with sub-10-nm feature sizes. These findings are not only scientifically intriguing in understanding the chemical and physical principles of the self-assembly, but also technologically relevant, such as in nanopatterning technology and microelectronics. PMID:23716680

Identifying Chemical Groups for Biomonitoring

PubMed Central

Krowech, Gail; Hoover, Sara; Plummer, Laurel; Sandy, Martha; Zeise, Lauren; Solomon, Gina

2016-01-01

Summary: Regulatory agencies face daunting challenges identifying emerging chemical hazards because of the large number of chemicals in commerce and limited data on exposure and toxicology. Evaluating one chemical at a time is inefficient and can lead to replacement with uncharacterized chemicals or chemicals with structural features already linked to toxicity. The Office of Environmental Health Hazard Assessment (OEHHA) has developed a process for constructing and assessing chemical groups for potential biomonitoring in California. We screen for chemicals with significant exposure potential and propose possible chemical groups, based on structure and function. To support formal consideration of these groups by Biomonitoring California’s Scientific Guidance Panel, we conduct a detailed review of exposure and toxicity data and examine the likelihood of detection in biological samples. To date, 12 chemical groups have been constructed and added to the pool of chemicals that can be selected for Biomonitoring California studies, including p,p´-bisphenols, brominated and chlorinated organic compounds used as flame retardants, non-halogenated aromatic phosphates, and synthetic polycyclic musks. Evaluating chemical groups, rather than individual chemicals, is an efficient way to respond to shifts in chemical use and the emergence of new chemicals. This strategy can enable earlier identification of important chemicals for monitoring and intervention. PMID:27905275

Micro-chemical and micro-structural investigation of archaeological bronze weapons from the Ayanis fortress (lake Van, Eastern Anatolia, Turkey)

NASA Astrophysics Data System (ADS)

Faraldi, F.; Çilingirǒglu, A.; Angelini, E.; Riccucci, C.; De Caro, T.; Batmaz, A.; Mezzi, A.; Caschera, D.; Cortese, B.

2013-12-01

Bronze weapons (VII cen BC) found during the archaeological excavation of the Ayanis fortress (lake Van, eastern Anatolia, Turkey) are investigated in order to determine their chemical composition and metallurgical features as well as to identify the micro-chemical and micro-structural nature of the corrosion products grown during long-term burial. Small fragments were sampled from the artefacts and analysed by means of the combined use of optical microscopy (OM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS). The results show that the bronze artefacts have been manufactured by using alloys with a controlled and refined chemical composition demonstrating the high level metallurgical competence and skill of the Urartian craftsmen and artists. Furthermore, the micro-structural and metallurgical investigations evidence the presence of equiaxed grains in the matrix, indicating that the artefact were produced by repeated cycles of mechanical shaping and thermal annealing treatments to restore the alloy ductility. From the degradation point of view, the results show the structures and the chemical composition of the stratified corrosion layers (i.e. the patina) where the copper or tin depletion phenomenon is commonly observed with the surface enrichment of some elements coming from the burial soil, mainly Cl, which is related to the high concentration of chlorides in the Ayanis soil. The results reveal also that another source of degradation is the inter-granular corrosion phenomenon likely increased by the metallurgical features of the alloys caused by the high temperature manufacturing process that induces crystallisation and segregation phenomena along the grain boundaries.

Applicability of PM3 to transphosphorylation reaction path: Toward designing a minimal ribozyme

NASA Technical Reports Server (NTRS)

Manchester, John I.; Shibata, Masayuki; Setlik, Robert F.; Ornstein, Rick L.; Rein, Robert

1993-01-01

A growing body of evidence shows that RNA can catalyze many of the reactions necessary both for replication of genetic material and the possible transition into the modern protein-based world. However, contemporary ribozymes are too large to have self-assembled from a prebiotic oligonucleotide pool. Still, it is likely that the major features of the earliest ribozymes have been preserved as molecular fossils in the catalytic RNA of today. Therefore, the search for a minimal ribozyme has been aimed at finding the necessary structural features of a modern ribozyme (Beaudry and Joyce, 1990). Both a three-dimensional model and quantum chemical calculations are required to quantitatively determine the effects of structural features of the ribozyme on the reaction it catalyzes. Using this model, quantum chemical calculations must be performed to determine quantitatively the effects of structural features on catalysis. Previous studies of the reaction path have been conducted at the ab initio level, but these methods are limited to small models due to enormous computational requirements. Semiempirical methods have been applied to large systems in the past; however, the accuracy of these methods depends largely on a simple model of the ribozyme-catalyzed reaction, or hydrolysis of phosphoric acid. We find that the results are qualitatively similar to ab initio results using large basis sets. Therefore, PM3 is suitable for studying the reaction path of the ribozyme-catalyzed reaction.

Chemical properties and biological activity of a polysaccharide from Melocactus depressus.

PubMed

da Silva, Bernadete P; Parente, José P

2002-01-01

An arabinogalactan with mean Mr of 6.85 x 10(4), was isolated from the pulps of Melocactus depressus Hook by fractionation on Sephacryl S-300 HR. Chemical and spectroscopic studies indicated that it has a branched arabinogalactan type structure composed of beta-(1-->4) linked D-galactopyranose residues with beta-(1-->3) and beta-(1-->6) branching points. Its structural features include also alpha-(1-->2), alpha-(1-->3) and alpha-(1-->5) linked L-arabinofuranose residues. The polysaccharide demonstrated a phagocytosis stimulating property.

Multiple Routes to Smart Nanostructured Materials from Diatom Microalgae: A Chemical Perspective.

PubMed

Ragni, Roberta; Cicco, Stefania R; Vona, Danilo; Farinola, Gianluca M

2018-05-01

Diatoms are unicellular photosynthetic microalgae, ubiquitously diffused in both marine and freshwater environments, which exist worldwide with more than 100 000 species, each with different morphologies and dimensions, but typically ranging from 10 to 200 µm. A special feature of diatoms is their production of siliceous micro- to nanoporous cell walls, the frustules, whose hierarchical organization of silica layers produces extraordinarily intricate pore patterns. Due to the high surface area, mechanical resistance, unique optical features, and biocompatibility, a number of applications of diatom frustules have been investigated in photonics, sensing, optoelectronics, biomedicine, and energy conversion and storage. Current progress in diatom-based nanotechnology relies primarily on the availability of various strategies to isolate frustules, retaining their morphological features, and modify their chemical composition for applications that are not restricted to those of the bare biosilica produced by diatoms. Chemical or biological methods that decorate, integrate, convert, or mimic diatoms' biosilica shells while preserving their structural features represent powerful tools in developing scalable, low-cost routes to a wide variety of nanostructured smart materials. Here, the different approaches to chemical modification as the basis for the description of applications relating to the different materials thus obtained are presented. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Giant magnetoresistance and anomalous transport in phosphorene-based multilayers with noncollinear magnetization

NASA Astrophysics Data System (ADS)

Zare, Moslem; Majidi, Leyla; Asgari, Reza

2017-03-01

We theoretically investigate the unusual features of the magnetotransport in a monolayer phosphorene ferromagnetic/normal/ferromagnetic (F/N/F) hybrid structure. We find that the charge conductance can feature a minimum at parallel (P) configuration and a maximum near the antiparallel (AP) configuration of magnetization in the F/N/F structure with n -doped F and p -doped N regions and also a finite conductance in the AP configuration with the N region of n -type doping. In particular, the proposed structure exhibits giant magnetoresistance, which can be tuned to unity. This perfect switching is found to show strong robustness with respect to increasing the contact length and tuning the chemical potential of the N region with a gate voltage. We also explore the oscillatory behavior of the charge conductance or magnetoresistance in terms of the size of the N region. We further demonstrate the penetration of the spin-transfer torque into the right F region and show that, unlike graphene structure, the spin-transfer torque is very sensitive to the chemical potential of the N region as well as the exchange field of the F region.

Automated compound classification using a chemical ontology.

PubMed

Bobach, Claudia; Böhme, Timo; Laube, Ulf; Püschel, Anett; Weber, Lutz

2012-12-29

Classification of chemical compounds into compound classes by using structure derived descriptors is a well-established method to aid the evaluation and abstraction of compound properties in chemical compound databases. MeSH and recently ChEBI are examples of chemical ontologies that provide a hierarchical classification of compounds into general compound classes of biological interest based on their structural as well as property or use features. In these ontologies, compounds have been assigned manually to their respective classes. However, with the ever increasing possibilities to extract new compounds from text documents using name-to-structure tools and considering the large number of compounds deposited in databases, automated and comprehensive chemical classification methods are needed to avoid the error prone and time consuming manual classification of compounds. In the present work we implement principles and methods to construct a chemical ontology of classes that shall support the automated, high-quality compound classification in chemical databases or text documents. While SMARTS expressions have already been used to define chemical structure class concepts, in the present work we have extended the expressive power of such class definitions by expanding their structure-based reasoning logic. Thus, to achieve the required precision and granularity of chemical class definitions, sets of SMARTS class definitions are connected by OR and NOT logical operators. In addition, AND logic has been implemented to allow the concomitant use of flexible atom lists and stereochemistry definitions. The resulting chemical ontology is a multi-hierarchical taxonomy of concept nodes connected by directed, transitive relationships. A proposal for a rule based definition of chemical classes has been made that allows to define chemical compound classes more precisely than before. The proposed structure-based reasoning logic allows to translate chemistry expert knowledge into a computer interpretable form, preventing erroneous compound assignments and allowing automatic compound classification. The automated assignment of compounds in databases, compound structure files or text documents to their related ontology classes is possible through the integration with a chemical structure search engine. As an application example, the annotation of chemical structure files with a prototypic ontology is demonstrated.

Automated compound classification using a chemical ontology

PubMed Central

2012-01-01

Background Classification of chemical compounds into compound classes by using structure derived descriptors is a well-established method to aid the evaluation and abstraction of compound properties in chemical compound databases. MeSH and recently ChEBI are examples of chemical ontologies that provide a hierarchical classification of compounds into general compound classes of biological interest based on their structural as well as property or use features. In these ontologies, compounds have been assigned manually to their respective classes. However, with the ever increasing possibilities to extract new compounds from text documents using name-to-structure tools and considering the large number of compounds deposited in databases, automated and comprehensive chemical classification methods are needed to avoid the error prone and time consuming manual classification of compounds. Results In the present work we implement principles and methods to construct a chemical ontology of classes that shall support the automated, high-quality compound classification in chemical databases or text documents. While SMARTS expressions have already been used to define chemical structure class concepts, in the present work we have extended the expressive power of such class definitions by expanding their structure-based reasoning logic. Thus, to achieve the required precision and granularity of chemical class definitions, sets of SMARTS class definitions are connected by OR and NOT logical operators. In addition, AND logic has been implemented to allow the concomitant use of flexible atom lists and stereochemistry definitions. The resulting chemical ontology is a multi-hierarchical taxonomy of concept nodes connected by directed, transitive relationships. Conclusions A proposal for a rule based definition of chemical classes has been made that allows to define chemical compound classes more precisely than before. The proposed structure-based reasoning logic allows to translate chemistry expert knowledge into a computer interpretable form, preventing erroneous compound assignments and allowing automatic compound classification. The automated assignment of compounds in databases, compound structure files or text documents to their related ontology classes is possible through the integration with a chemical structure search engine. As an application example, the annotation of chemical structure files with a prototypic ontology is demonstrated. PMID:23273256

Aggregating Data for Computational Toxicology Applications ...

EPA Pesticide Factsheets

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built usi

Advances in Toxico-Cheminformatics: Supporting a New ...

EPA Pesticide Factsheets

EPA’s National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through the harnessing of legacy toxicity data, creation of data linkages, and generation of new high-throughput screening (HTS) data. The DSSTox project is working to improve public access to quality structure-annotated chemical toxicity information in less summarized forms than traditionally employed in SAR modeling, and in ways that facilitate both data-mining and read-across. Both DSSTox Structure-Files and the dedicated on-line DSSTox Structure-Browser are enabling seamless structure-based searching and linkages to and from previously isolated, chemically indexed public toxicity data resources (e.g., NTP, EPA IRIS, CPDB). Most recently, structure-enabled search capabilities have been extended to chemical exposure-related microarray experiments in the public EBI Array Express database, additionally linking this resource to the NIEHS CEBS toxicogenomics database. The public DSSTox chemical and bioassay inventory has been recently integrated into PubChem, allowing a user to take full advantage of PubChem structure-activity and bioassay clustering features. The DSSTox project is providing cheminformatics support for EPA’s ToxCastTM project, as well as supporting collaborations with the National Toxicology Program (NTP) HTS and the NIH Chemical Genomics Center (NCGC). Phase I of the ToxCastTM project is generating HT

Vessel with filter and method of use

DOEpatents

Morrell, Jonathan S.; Ripley, Edward B.; Cecala, David M.

2008-01-29

Chemical processing apparatuses which incorporate a process vessel, such as a crucible or retort, and which include a gas separation or filtration system. Various embodiments incorporate such features as loose filtration material, semi-rigid filtration material, and structured filtration material. The vessel may include material that is a microwave susceptor. Filtration media may be selected so that if it inadvertently mixes with the chemical process or the reaction products of such process, it would not adversely affect the results of the chemical process.

Development and Application of a Three-Dimensional Finite Element Vapor Intrusion Model

PubMed Central

Pennell, Kelly G.; Bozkurt, Ozgur; Suuberg, Eric M.

2010-01-01

Details of a three-dimensional finite element model of soil vapor intrusion, including the overall modeling process and the stepwise approach, are provided. The model is a quantitative modeling tool that can help guide vapor intrusion characterization efforts. It solves the soil gas continuity equation coupled with the chemical transport equation, allowing for both advective and diffusive transport. Three-dimensional pressure, velocity, and chemical concentration fields are produced from the model. Results from simulations involving common site features, such as impervious surfaces, porous foundation sub-base material, and adjacent structures are summarized herein. The results suggest that site-specific features are important to consider when characterizing vapor intrusion risks. More importantly, the results suggest that soil gas or subslab gas samples taken without proper regard for particular site features may not be suitable for evaluating vapor intrusion risks; rather, careful attention needs to be given to the many factors that affect chemical transport into and around buildings. PMID:19418819

Odor Impression Prediction from Mass Spectra.

PubMed

Nozaki, Yuji; Nakamoto, Takamichi

2016-01-01

The sense of smell arises from the perception of odors from chemicals. However, the relationship between the impression of odor and the numerous physicochemical parameters has yet to be understood owing to its complexity. As such, there is no established general method for predicting the impression of odor of a chemical only from its physicochemical properties. In this study, we designed a novel predictive model based on an artificial neural network with a deep structure for predicting odor impression utilizing the mass spectra of chemicals, and we conducted a series of computational analyses to evaluate its performance. Feature vectors extracted from the original high-dimensional space using two autoencoders equipped with both input and output layers in the model are used to build a mapping function from the feature space of mass spectra to the feature space of sensory data. The results of predictions obtained by the proposed new method have notable accuracy (R≅0.76) in comparison with a conventional method (R≅0.61).

Understanding the Structural Ensembles of a Highly Extended Disordered Protein†

PubMed Central

Daughdrill, Gary W.; Kashtanov, Stepan; Stancik, Amber; Hill, Shannon E.; Helms, Gregory; Muschol, Martin

2013-01-01

Developing a comprehensive description of the equilibrium structural ensembles for intrinsically disordered proteins (IDPs) is essential to understanding their function. The p53 transactivation domain (p53TAD) is an IDP that interacts with multiple protein partners and contains numerous phosphorylation sites. Multiple techniques were used to investigate the equilibrium structural ensemble of p53TAD in its native and chemically unfolded states. The results from these experiments show that the native state of p53TAD has dimensions similar to a classical random coil while the chemically unfolded state is more extended. To investigate the molecular properties responsible for this behavior, a novel algorithm that generates diverse and unbiased structural ensembles of IDPs was developed. This algorithm was used to generate a large pool of plausible p53TAD structures that were reweighted to identify a subset of structures with the best fit to small angle X-ray scattering data. High weight structures in the native state ensemble show features that are localized to protein binding sites and regions with high proline content. The features localized to the protein binding sites are mostly eliminated in the chemically unfolded ensemble; while, the regions with high proline content remain relatively unaffected. Data from NMR experiments support these results, showing that residues from the protein binding sites experience larger environmental changes upon unfolding by urea than regions with high proline content. This behavior is consistent with the urea-induced exposure of nonpolar and aromatic side-chains in the protein binding sites that are partially excluded from solvent in the native state ensemble. PMID:21979461

"Just as the Structural Formula Does": Names, Diagrams, and the Structure of Organic Chemistry at the 1892 Geneva Nomenclature Congress.

PubMed

Hepler-Smith, Evan

2015-02-01

At the Geneva Nomenclature Congress of 1892, some of the foremost organic chemists of the late nineteenth century crafted a novel relationship between chemical substances, chemical diagrams, and chemical names that has shaped practices of chemical representation ever since. During the 1880s, the French chemist Charles Friedel organised the nomenclature reform effort that culminated in the Geneva Congress; in the disorderly nomenclature of German synthetic chemistry, Friedel saw an opportunity to advance French national interests and his own pedagogical goals. Friedel and a group of close colleagues reconceived nomenclature as a unified field, in which all chemical names ought to relate clearly to one another and to the structure of the compounds they represented. The German chemist Adolf von Baeyer went a step farther, arguing for names that precisely and uniquely corresponded to the structural formula of each compound, tailored for use in chemical dictionaries and handbooks. Baeyer's vision prevailed at the Geneva Congress, which consequently codified rules for rigorously mapping structural formulas into names, resulting in names that faithfully represented the features of these diagrams but not always the chemical behaviour of the compounds themselves. This approach ultimately limited both the number of chemical compounds that the Geneva rules were able to encompass and the breadth of their application. However, the relationship between diagram and name established at the Geneva Congress became the foundation not only of subsequent systems of chemical nomenclature but of methods of organising information that have supported the modern chemical sciences.

PSSP-RFE: accurate prediction of protein structural class by recursive feature extraction from PSI-BLAST profile, physical-chemical property and functional annotations.

PubMed

Li, Liqi; Cui, Xiang; Yu, Sanjiu; Zhang, Yuan; Luo, Zhong; Yang, Hua; Zhou, Yue; Zheng, Xiaoqi

2014-01-01

Protein structure prediction is critical to functional annotation of the massively accumulated biological sequences, which prompts an imperative need for the development of high-throughput technologies. As a first and key step in protein structure prediction, protein structural class prediction becomes an increasingly challenging task. Amongst most homological-based approaches, the accuracies of protein structural class prediction are sufficiently high for high similarity datasets, but still far from being satisfactory for low similarity datasets, i.e., below 40% in pairwise sequence similarity. Therefore, we present a novel method for accurate and reliable protein structural class prediction for both high and low similarity datasets. This method is based on Support Vector Machine (SVM) in conjunction with integrated features from position-specific score matrix (PSSM), PROFEAT and Gene Ontology (GO). A feature selection approach, SVM-RFE, is also used to rank the integrated feature vectors through recursively removing the feature with the lowest ranking score. The definitive top features selected by SVM-RFE are input into the SVM engines to predict the structural class of a query protein. To validate our method, jackknife tests were applied to seven widely used benchmark datasets, reaching overall accuracies between 84.61% and 99.79%, which are significantly higher than those achieved by state-of-the-art tools. These results suggest that our method could serve as an accurate and cost-effective alternative to existing methods in protein structural classification, especially for low similarity datasets.

A review of whole cell wall NMR by the direct-dissolution of biomass

DOE PAGES

Foston, Marcus B.; Samuel, Reichel; He, Jian; ...

2016-01-19

To fully realize the potential of lignocellulosic biomass as a renewable resource for the production of fuels, chemicals, and materials, an improved understanding of the chemical and molecular structures within biomass and how those structures are formed during biosynthesis and transformed during (thermochemical and biological) conversion must be developed. This effort will require analytical techniques which are not only in-depth, rapid, and cost-effective, but also leave native cell wall features intact. Whole plant cell wall nuclear magnetic resonance (NMR) analysis facilitates unparalleled structural characterization of lignocellulosic biomass without causing (or with minimal) structural modification. The objective of this review ismore » to summarize research pertaining to solution- or gel-state whole plant cell wall NMR analysis of biomass, demonstrating the capability of NMR to delineate the structural features and transformations of biomass. In particular, this review will focus on the application of a two-dimensional solution-state NMR technique and perdeuterated ionic liquid based organic electrolyte solvents for the direct dissolution and analysis of biomass. Furthermore, we believe this type of analysis will be critical to advancing biofuel research, improving bioprocessing methodology, and enhancing plant bioengineering efforts.« less

A review of whole cell wall NMR by the direct-dissolution of biomass

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foston, Marcus B.; Samuel, Reichel; He, Jian

To fully realize the potential of lignocellulosic biomass as a renewable resource for the production of fuels, chemicals, and materials, an improved understanding of the chemical and molecular structures within biomass and how those structures are formed during biosynthesis and transformed during (thermochemical and biological) conversion must be developed. This effort will require analytical techniques which are not only in-depth, rapid, and cost-effective, but also leave native cell wall features intact. Whole plant cell wall nuclear magnetic resonance (NMR) analysis facilitates unparalleled structural characterization of lignocellulosic biomass without causing (or with minimal) structural modification. The objective of this review ismore » to summarize research pertaining to solution- or gel-state whole plant cell wall NMR analysis of biomass, demonstrating the capability of NMR to delineate the structural features and transformations of biomass. In particular, this review will focus on the application of a two-dimensional solution-state NMR technique and perdeuterated ionic liquid based organic electrolyte solvents for the direct dissolution and analysis of biomass. Furthermore, we believe this type of analysis will be critical to advancing biofuel research, improving bioprocessing methodology, and enhancing plant bioengineering efforts.« less

Reactions of methamidophos with mammalian cholinesterase.

DOT National Transportation Integrated Search

1978-07-01

The lethality of methamidophos, a phosphoramidothioate, to rats (i.p. LD50, 15 mg/kg), is similar to that of such potent organophosphate compounds as parathion and paraoxon. Certain distinctive features of its chemical structure, and reported failure...

A Chemical Understanding of the Band Convergence in Thermoelectric CoSb 3 Skutterudites: Influence of Electron Population, Local Thermal Expansion, and Bonding Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanus, Riley; Guo, Xingyu; Tang, Yinglu

2017-01-13

N-Type skutterudites, such as Yb xCo 4Sb 12, have recently been shown to exhibit high valley degeneracy with possible band convergence, explaining the excellent thermoelectric efficiency of these materials. Using a combined theoretical and experimental approach involving temperature-dependent synchrotron diffraction, molecular orbital diagrams, and computational studies, the chemical nature of critical features in the band structure is highlighted. We identify how n-type doping on the filler site induces structural changes that are observed in both the diffraction data and computational results. Additionally, we show how chemical n-type doping slightly alters the electronic band structure, moving the high-valley degeneracy secondary conductionmore » band closer to the primary conduction band and thus inducing band convergence.« less

New Approach to Synthesis of Powder and Composite Materials by Electron Beam. Part 1. Technological Features of the Process

NASA Astrophysics Data System (ADS)

Rudskoy, A. I.; Kondrat'ev, S. Yu.; Sokolov, Yu. A.

2016-05-01

Possibilities of electron beam synthesis of structural and tool composite materials are considered. It is shown that a novel process involving mathematical modeling of each individual operation makes it possible to create materials with programmable structure and predictable properties from granules of various specified chemical compositions and sizes.

Alternative Life Styles for Extraterrestrial Chemists

NASA Astrophysics Data System (ADS)

Benner, S.

2002-12-01

Life is no more (and no less) than a special type of organic chemistry, one that combines a frequently encountered property of organic molecules (the ability to undergo spontaneous chemical transformation) with an uncommon property (the ability to direct the synthesis of self-copies) in a way that allows new molecular features arising through spontaneous transformation to themselves be copied. Any chemical system having this combination will undergo natural selection, evolving in structure to replicate faster through more efficient use of molecular resources and energy. Axiomatically, life cannot exist in an environment at thermodynamic equilibrium. If it were, by the second law of thermodynamics, no net chemical transformation would be possible. Beyond this constraint, it is difficult to define environmental conditions or chemical structures necessary for life. Water is certainly not required for a chemical system to copy itself; in the laboratory, non-aqueous environments appear to support this behavior better. Chemical transformations that might support energy and chemical metabolisms are known in environments as acidic as the aerosols in the atmosphere of Venus, or as basic as the atmosphere of Jupiter. Laboratory experiments with analogs of the nucleic acids, proteins, sugars, and lipids show that the particular molecular structures found in terrean life need not be universal, even those life in water near neutral pH. Indeed, while both water and biological macromolecules are commonly regarded as essential for terrean-like life, water destroys terrean biological macromolecules. These chemical realities create a complex decision environment as NASA attempts to design instrumentation carried by missions, select places in the solar system to send them, and chose laboratory studies on Earth to provide their scientific support. This talk will review a hierarchy of chemical possibilities and constraints that start with the chemistry of terrean life, and takes steps towards weird life. We shall consider alternative amino acid building blocks for proteins, alternative building blocks for nucleic acids, alternative structural features of genetic and catalytic molecules, alternative nucleophile-electrophile pairs to support metabolism, non-polar reaction modes that might support metabolism, non-terrean pH (< 0, > 14) and solvent environments for life, extreme temperature ranges (especially sub zero Celsius) low temperature ranges, alternative thermodynamic design for metabolic pathways, alternative dimensionalities of genetic and catalytic molecules, and approaches for isolating life other than conventional cell structures. Each of these discussions will combine experimental and theoretical information. The first involves organic chemical synthesis that creates new forms of chemical matter to ask "What if?" and "Why not?" questions. The second draws on a century of literature in physical organic chemistry to formulate general constraints on the structure and transformation of organic matter to provide constraints on possible Darwinian chemistries in the galaxy.

Magnitude differences in agronomic, chemical, nutritional, and structural features among different varieties of forage corn grown on dry land and irrigated land.

PubMed

Xin, Hangshu; Abeysekara, Samen; Zhang, Xuewei; Yu, Peiqiang

2015-03-11

In this study, eight varieties of corn forage grown in semiarid western Canada (including Pioneer P2501, Pioneer P39m26, Pioneer P7443, Hyland HL3085, Hyland HLBaxxos, Hyland HLR219, Hyland HLSR22, and Pickseed Silex BT) were selected to explore the effect of irrigation implementation in comparison with nonirrigation on (1) agronomic characteristics, (2) basic chemical profiles explored by using a near-infrared reflectance (NIR) system, and (3) protein and carbohydrate internal structural parameters revealed by using an attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) system. Also, principal component analysis (PCA) was performed on spectroscopic data for clarification of differences in molecular structural makeup among the varieties. The results showed that irrigation treatment significantly increased (P < 0.05) contents of dry matter (DM) and organic matter (OM) but decreased crude protein (CP) of corn forages. Significant interactions of irrigation treatment and corn variety were observed on most agronomic characteristics (DM yield, T/ha, days to tasseling, days to silking) and crude fiber (CF) and ether extract (EE) contents as well as some spectral data such as cellulosic compounds (CELC) peak intensity, peak ratios of CHO third peak to CELC, α-helix to β-sheet, and CHO third peak to amide I. Additionally, the spectral ratios of chemical functional groups that related to structural and nonstructural carbohydrates and protein polymers in forages did not remain constant over corn varieties cultivated with and without water treatment. Moreover, different cultivars had different growth, structure, and nutrition performances in this study. Although significant differences could be found in peak intensities, PCA results indicated some structural similarities existed between two treated corn forages with the exception of HL3085 and HLBaxxos. In conclusion, irrigation and corn variety had interaction effects on agronomic, chemical, nutritional, and structural features. Further study on the optimum level of irrigation for corn forage cultivation might be helpful in semiarid regions such as western Canada.

Predicting hepatotoxicity using ToxCast in vitro bioactivity and ...

EPA Pesticide Factsheets

Background: The U.S. EPA ToxCastTM program is screening thousands of environmental chemicals for bioactivity using hundreds of high-throughput in vitro assays to build predictive models of toxicity. We represented chemicals based on bioactivity and chemical structure descriptors then used supervised machine learning to predict their hepatotoxic effects.Results: A set of 677 chemicals were represented by 711 in vitro bioactivity descriptors (from ToxCast assays), 4,376 chemical structure descriptors (from QikProp, OpenBabel, PADEL, and PubChem), and three hepatotoxicity categories (from animal studies). Hepatotoxicants were defined by rat liver histopathology observed after chronic chemical testing and grouped into hypertrophy (161), injury (101) and proliferative lesions (99). Classifiers were built using six machine learning algorithms: linear discriminant analysis (LDA), Naïve Bayes (NB), support vector classification (SVM), classification and regression trees (CART), k-nearest neighbors (KNN) and an ensemble of classifiers (ENSMB). Classifiers of hepatotoxicity were built using chemical structure, ToxCast bioactivity, and a hybrid representation. Predictive performance was evaluated using 10-fold cross-validation testing and in-loop, filter-based, feature subset selection. Hybrid classifiers had the best balanced accuracy for predicting hypertrophy (0.78±0.08), injury (0.73±0.10) and proliferative lesions (0.72±0.09). Though chemical and bioactivity class

Integration of QSAR and SAR methods for the mechanistic interpretation of predictive models for carcinogenicity

PubMed Central

Fjodorova, Natalja; Novič, Marjana

2012-01-01

The knowledge-based Toxtree expert system (SAR approach) was integrated with the statistically based counter propagation artificial neural network (CP ANN) model (QSAR approach) to contribute to a better mechanistic understanding of a carcinogenicity model for non-congeneric chemicals using Dragon descriptors and carcinogenic potency for rats as a response. The transparency of the CP ANN algorithm was demonstrated using intrinsic mapping technique specifically Kohonen maps. Chemical structures were represented by Dragon descriptors that express the structural and electronic features of molecules such as their shape and electronic surrounding related to reactivity of molecules. It was illustrated how the descriptors are correlated with particular structural alerts (SAs) for carcinogenicity with recognized mechanistic link to carcinogenic activity. Moreover, the Kohonen mapping technique enables one to examine the separation of carcinogens and non-carcinogens (for rats) within a family of chemicals with a particular SA for carcinogenicity. The mechanistic interpretation of models is important for the evaluation of safety of chemicals. PMID:24688639

On a Molecular Basis, Investigate Association of Molecular Structure with Bioactive Compounds, Anti-Nutritional Factors and Chemical and Nutrient Profiles of Canola Seeds and Co-Products from Canola Processing: Comparison Crusher Plants within Canada and within China as well as between Canada and China.

PubMed

Gomaa, Walaa M S; Mosaad, Gamal M; Yu, Peiqiang

2018-04-21

The objectives of this study were to: (1) Use molecular spectroscopy as a novel technique to quantify protein molecular structures in relation to its chemical profiles and bioenergy values in oil-seeds and co-products from bio-oil processing. (2) Determine and compare: (a) protein molecular structure using Fourier transform infrared (FT/IR-ATR) molecular spectroscopy technique; (b) bioactive compounds, anti-nutritional factors, and chemical composition; and (c) bioenergy values in oil seeds (canola seeds), co-products (meal or pellets) from bio-oil processing plants in Canada in comparison with China. (3) Determine the relationship between protein molecular structural features and nutrient profiles in oil-seeds and co-products from bio-oil processing. Our results showed the possibility to characterize protein molecular structure using FT/IR molecular spectroscopy. Processing induced changes between oil seeds and co-products were found in the chemical, bioenergy profiles and protein molecular structure. However, no strong correlation was found between the chemical and nutrient profiles of oil seeds (canola seeds) and their protein molecular structure. On the other hand, co-products were strongly correlated with protein molecular structure in the chemical profile and bioenergy values. Generally, comparisons of oil seeds (canola seeds) and co-products (meal or pellets) in Canada, in China, and between Canada and China indicated the presence of variations among different crusher plants and bio-oil processing products.

Self-Assembly in Systems Containing Silicone Compounds

NASA Astrophysics Data System (ADS)

Ferreira, Maira Silva; Loh, Watson

2009-01-01

Chemical systems formed by silicone solvents and surfactants have potential applications in a variety of industrial products. In spite of their technological relevance, there are few reports on the scientific literature that focus on characterizing such ternary systems. In this work, we have aimed to develop a general, structural investigation on the phase diagram of one system that typically comprises silicone-based chemicals, by means of the SAXS (small-angle X-ray scattering) technique. Important features such as the presence of diverse aggregation states in the overall system, either on their own or in equilibrium with other structures, have been detected. As a result, optically isotropic chemical systems (direct and/or reversed microemulsions) and liquid crystals with lamellar or hexagonal packing have been identified and characterized.

The ISS National Inventory of Chemical Substances (INSC).

PubMed

Binetti, Roberto; Costamagna, Francesca Marina; Ceccarelli, Federica; D'angiolini, Antonella; Fabri, Alessandra; Riva, Giovanni; Satalia, Susanna; Marcello, Ida

2008-01-01

The INSC (Inventario Nazionale delle Sostanze Chimiche), a factual data bank, produced by Istituto Superiore di Sanità (ISS), consists of an electronic tool on chemical information developed for routine and emergency purposes. Historical background, current status and future perspectives of INSC are discussed. The structure and the feature of INSC are briefly examined. Aspects of information retrieval and the criteria for inclusion of data and priority selection are also considered.

Diterpenes from the Marine Algae of the Genus Dictyota.

PubMed

Chen, Jiayun; Li, Hong; Zhao, Zishuo; Xia, Xue; Li, Bo; Zhang, Jinrong; Yan, Xiaojun

2018-05-11

Species of the brown algae of the genus Dictyota are rich sources of bioactive secondary metabolites with diverse structural features. Excellent progress has been made in the discovery of diterpenes possessing broad chemical defensive activities from this genus. Most of these diterpenes exhibit significant biological activities, such as antiviral, cytotoxic and chemical defensive activities. In the present review, we summarized diterpenes isolated from the brown algae of the genus.

Chemical exchange in biomacromolecules: Past, present, and future

PubMed Central

Palmer, Arthur G.

2014-01-01

The perspective reviews quantitative investigations of chemical exchange phenomena in proteins and other biological macromolecules using NMR spectroscopy, particularly relaxation dispersion methods. The emphasis is on techniques and applications that quantify the populations, interconversion kinetics, and structural features of sparsely populated conformational states in equilibrium with a highly populated ground state. Applications to folding, mol ecular recognition, catalysis, and allostery by proteins and nucleic acids are highlighted. PMID:24656076

Interaction Structures for Narrow-Band Millimeter-Wave Communications TWTs.

DTIC Science & Technology

1981-04-01

comb would be cut from a single piece of copper, probably by a reliable but inexpensive technique such as electroerosion or "chemical milling". All...dimensional. These features would facilitate fabrication by chemical (photo-lithographic) or laser milling as well as by electroerosion with traveling...c, d) has also been implemented since this design should be more robust as well as compatible with electroerosion cutting using a traveling-wire

Internal Domains of Natural Porous Media Revealed: Critical Locations for Transport, Storage, and Chemical Reaction

DOE PAGES

Zachara, John; Brantley, Sue; Chorover, Jon; ...

2016-02-05

Internal pore domains exist within rocks, lithic fragments, subsurface sediments, and soil aggregates. These domains, termed internal domains in porous media (IDPM), represent a subset of a material’s porosity, contain a significant fraction of their porosity as nanopores, dominate the reactive surface area of diverse media types, and are important locations for chemical reactivity and fluid storage. IDPM are key features controlling hydrocarbon release from shales in hydraulic fracture systems, organic matter decomposition in soil, weathering and soil formation, and contaminant behavior in the vadose zone and groundwater. It is traditionally difficult to interrogate, advances in instrumentation and imaging methodsmore » are providing new insights on the physical structures and chemical attributes of IDPM, and their contributions to system behaviors. We discuss analytical methods to characterize IDPM, evaluate information on their size distributions, connectivity, and extended structures; determine whether they exhibit unique chemical reactivity; and assess the potential for their inclusion in reactive transport models. Moreover, ongoing developments in measurement technologies and sensitivity, and computer-assisted interpretation will improve understanding of these critical features in the future. Finally, impactful research opportunities exist to advance understanding of IDPM, and to incorporate their effects in reactive transport models for improved environmental simulation and prediction.« less

Chemical characterization of organic aerosol above a mid-latitude forest reveals a complex mixture of highly-functionalized chemical species and diverse structural features with temporal variability

NASA Astrophysics Data System (ADS)

Gentner, D. R.; Ditto, J.; Barnes, E.; Khare, P.

2017-12-01

Highly-functionalized organic compounds are known to be a major component of the complex mixture of the particle-phase compounds that comprise organic aerosol, yet little is known about the identity of many of these compounds, and their formation pathways and roles in atmospheric processes are poorly understood. We present results from the comprehensive chemical speciation of PM10 organic aerosols collected in July 2016 at the remote mid-latitude forest field site during PROPHET. Samples were analyzed via liquid and gas chromatography coupled with a quadrupole time-of-flight tandem mass spectrometry (MS×MS) following electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). 8 hr samples were collected during day- and night-time sampling periods rather than more typical 24-hour samples. This analysis of the organic aerosol yielded over 12,000 unique compounds for which we have high accuracy molecular masses, formulas, and additional information on structural features using MS×MS. O:C ratios were 0.3 on average, yet the top 10% of compounds ranged 0.7-2.3. 70% and 69% of day- and night-time samples were nitrogen-containing, whereas 26% and 24% contained sulfur, respectively. Within these broader molecular categories, we observed a wide variety of molecular features that reveal a diversity of functional groups and moieties. In this presentation, we present the results of our speciation, temporal variability, connections to air parcel back trajectories and other bulk properties, and potential formation pathways.

Statistical molecular design of balanced compound libraries for QSAR modeling.

PubMed

Linusson, A; Elofsson, M; Andersson, I E; Dahlgren, M K

2010-01-01

A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds' biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.

Simultaneous Speciation, Structure, and Equilibrium Constant Determination in the Ni2+-EDTA-CN- Ternary System via High-Resolution Laboratory X-ray Absorption Fine Structure Spectroscopy and Theoretical Calculations.

PubMed

Bajnóczi, Éva G; Németh, Zoltán; Vankó, György

2017-11-20

Even quite simple chemical systems can involve many components and chemical states, and sometimes it can be very difficult to differentiate them by their hardly separable physical-chemical properties. The Ni II -EDTA-CN - (EDTA = ethylenediaminetetraacetic acid) ternary system is a good example for this problem where, in spite of its fairly simple components and numerous investigations, several molecular combinations can exist, all of them not having been identified unambiguously yet. In order to achieve a detailed understanding of the reaction steps and chemical equilibria, methods are required in which the structural transitions in the different reaction steps can be followed via element-selective complex spectral feature sets. With the help of our recently developed von Hámos type high-resolution laboratory X-ray absorption spectrometer, both the structural variations and stability constants of the forming complexes were determined from the same measurement series, proving that X-ray absorption spectroscopy can be considered as a multifaced, table-top tool in coordination chemistry. Furthermore, with the help of theoretical calculations, independent structural evidence was also given for the formation of the [NiEDTA(CN)] 3- mixed complex.

Principles for identification of High Potency Category Chemicals for which the Dermal Sensitisation Threshold (DST) approach should not be applied.

PubMed

Roberts, David W; Api, Anne Marie; Safford, Robert J; Lalko, Jon F

2015-08-01

An essential step in ensuring the toxicological safety of chemicals used in consumer products is the evaluation of their skin sensitising potential. The sensitising potency, coupled with information on exposure levels, can be used in a Quantitative Risk Assessment (QRA) to determine an acceptable level of a given chemical in a given product. Where consumer skin exposure is low, a risk assessment can be conducted using the Dermal Sensitisation Threshold (DST) approach, avoiding the need to determine potency experimentally. Since skin sensitisation involves chemical reaction with skin proteins, the first step in the DST approach is to assess, on the basis of the chemical structure, whether the chemical is expected to be reactive or not. Our accompanying publication describes the probabilistic derivation of a DST of 64 μg/cm(2) for chemicals assessed as reactive. This would protect against 95% of chemicals assessed as reactive, but the remaining 5% would include chemicals with very high potency. Here we discuss the chemical properties and structural features of high potency sensitisers, and derive an approach whereby they can be identified and consequently excluded from application of the DST. Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical biology on the genome.

PubMed

Balasubramanian, Shankar

2014-08-15

In this article I discuss studies towards understanding the structure and function of DNA in the context of genomes from the perspective of a chemist. The first area I describe concerns the studies that led to the invention and subsequent development of a method for sequencing DNA on a genome scale at high speed and low cost, now known as Solexa/Illumina sequencing. The second theme will feature the four-stranded DNA structure known as a G-quadruplex with a focus on its fundamental properties, its presence in cellular genomic DNA and the prospects for targeting such a structure in cels with small molecules. The final topic for discussion is naturally occurring chemically modified DNA bases with an emphasis on chemistry for decoding (or sequencing) such modifications in genomic DNA. The genome is a fruitful topic to be further elucidated by the creation and application of chemical approaches. Copyright © 2014 Elsevier Ltd. All rights reserved.

Characterization of remote O2-plasma-enhanced CVD SiO2/GaN(0001) structure using photoemission measurements

NASA Astrophysics Data System (ADS)

Truyen, Nguyen Xuan; Ohta, Akio; Makihara, Katsunori; Ikeda, Mitsuhisa; Miyazaki, Seiichi

2018-01-01

The control of chemical composition and bonding features at a SiO2/GaN interface is a key to realizing high-performance GaN power devices. In this study, an ∼5.2-nm-thick SiO2 film has been deposited on an epitaxial GaN(0001) surface by remote O2-plasma-enhanced chemical vapor deposition (O2-RPCVD) using SiH4 and Ar/O2 mixture gases at a substrate temperature of 500 °C. The depth profile of chemical structures and electronic defects of the O2-RPCVD SiO2/GaN structures has been evaluated from a combination of SiO2 thinning examined by X-ray photoelectron spectroscopy (XPS) and the total photoelectron yield spectroscopy (PYS) measurements. As a highlight, we found that O2-RPCVD is effective for fabricating an abrupt SiO2/GaN interface.

Ketide Synthase (KS) Domain Prediction and Analysis of Iterative Type II PKS Gene in Marine Sponge-Associated Actinobacteria Producing Biosurfactants and Antimicrobial Agents

PubMed Central

Selvin, Joseph; Sathiyanarayanan, Ganesan; Lipton, Anuj N.; Al-Dhabi, Naif Abdullah; Valan Arasu, Mariadhas; Kiran, George S.

2016-01-01

The important biological macromolecules, such as lipopeptide and glycolipid biosurfactant producing marine actinobacteria were analyzed and their potential linkage between type II polyketide synthase (PKS) genes was explored. A unique feature of type II PKS genes is their high amino acid (AA) sequence homology and conserved gene organization. These enzymes mediate the biosynthesis of polyketide natural products with enormous structural complexity and chemical nature by combinatorial use of various domains. Therefore, deciphering the order of AA sequence encoded by PKS domains tailored the chemical structure of polyketide analogs still remains a great challenge. The present work deals with an in vitro and in silico analysis of PKS type II genes from five actinobacterial species to correlate KS domain architecture and structural features. Our present analysis reveals the unique protein domain organization of iterative type II PKS and KS domain of marine actinobacteria. The findings of this study would have implications in metabolic pathway reconstruction and design of semi-synthetic genomes to achieve rational design of novel natural products. PMID:26903957

The precursors effects on biomimetic hydroxyapatite ceramic powders.

PubMed

Yoruç, Afife Binnaz Hazar; Aydınoğlu, Aysu

2017-06-01

In this study, effects of the starting material on chemical, physical, and biological properties of biomimetic hydroxyapatite ceramic powders (BHA) were investigated. Characterization and chemical analysis of BHA powders were performed by using XRD, FT-IR, and ICP-AES. Microstructural features such as size and morphology of the resulting BHA powders were characterized by using BET, nano particle sizer, pycnometer, and SEM. Additionally, biological properties of the BHA ceramic powders were also investigated by using water-soluble tetrazolium salts test (WST-1). According to the chemical analysis of BHA ceramic powders, chemical structures of ceramics which are prepared under different conditions and by using different starting materials show differences. Ceramic powders which are produced at 80°C are mainly composed of hydroxyapatite, dental hydroxyapatite (contain Na and Mg elements in addition to Ca), and calcium phosphate sulfide. However, these structures are altered at high temperatures such as 900°C depending on the features of starting materials and form various calcium phosphate ceramics and/or their mixtures such as Na-Mg-hydroxyapatite, hydroxyapatite, Mg-Whitlockit, and chloroapatite. In vitro cytotoxicity studies showed that amorphous ceramics produced at 80°C and ceramics containing chloroapatite structure as main or secondary phases were found to be extremely cytotoxic. Furthermore, cell culture studies showed that highly crystalline pure hydroxyapatite structures were extremely cytotoxic due to their high crystallinity values. Consequently, the current study indicates that the selection of starting materials which can be used in the production of calcium phosphate ceramics is very important. It is possible to produce calcium phosphate ceramics which have sufficient biocompatibility at physiological pH values and by using appropriate starting materials. Copyright © 2017 Elsevier B.V. All rights reserved.

Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins

NASA Astrophysics Data System (ADS)

Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

2016-03-01

The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm- 1 and 1545 cm- 1, respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties.

Chemical cross-linking and native mass spectrometry: A fruitful combination for structural biology

PubMed Central

Sinz, Andrea; Arlt, Christian; Chorev, Dror; Sharon, Michal

2015-01-01

Mass spectrometry (MS) is becoming increasingly popular in the field of structural biology for analyzing protein three-dimensional-structures and for mapping protein–protein interactions. In this review, the specific contributions of chemical crosslinking and native MS are outlined to reveal the structural features of proteins and protein assemblies. Both strategies are illustrated based on the examples of the tetrameric tumor suppressor protein p53 and multisubunit vinculin-Arp2/3 hybrid complexes. We describe the distinct advantages and limitations of each technique and highlight synergistic effects when both techniques are combined. Integrating both methods is especially useful for characterizing large protein assemblies and for capturing transient interactions. We also point out the future directions we foresee for a combination of in vivo crosslinking and native MS for structural investigation of intact protein assemblies. PMID:25970732

Nanomotor dynamics in a chemically oscillating medium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, Bryan, E-mail: bryan.robertson@mail.utoronto.ca; Kapral, Raymond, E-mail: rkapral@chem.utoronto.ca

2015-04-21

Synthetic nanomotors powered by chemical reactions have potential uses as cargo transport vehicles in both in vivo and in vitro applications. In many situations, motors will have to operate in out-of-equilibrium complex chemically reacting media, which supply fuel to the motors and remove the products they produce. Using molecular simulation and mean-field theory, this paper describes some of the new features that arise when a chemically powered nanomotor, operating through a diffusiophoretic mechanism, moves in an environment that supports an oscillatory chemical reaction network. It is shown how oscillations in the concentrations in chemical species in the environment give risemore » to oscillatory motor dynamics. More importantly, since the catalytic reactions on the motor that are responsible for its propulsion couple to the bulk phase reaction network, the motor can change its local environment. This process can give rise to distinctive spatiotemporal structures in reaction-diffusion media that occur as a result of active motor motion. Such locally induced nonequilibrium structure will play an important role in applications that involve motor dynamics in complex chemical media.« less

Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin.

PubMed

Kocsis, Bela; Domokos, J; Szabo, D

2016-05-23

Quinolones are potent antimicrobial agents with a basic chemical structure of bicyclic ring. Fluorine atom at position C-6 and various substitutions on the basic quinolone structure yielded fluoroquinolones, namely norfloxacin, ciprofloxacin, levofloxacin, moxifloxacin and numerous other agents. The target molecules of quinolones and fluoroquinolones are bacterial gyrase and topoisomerase IV enzymes. Broad-spectrum and excellent tissue penetration make fluoroquinolones potent agents but their toxic side effects and increasing number of resistant pathogens set limits on their use. This review focuses on recent advances concerning quinolones and fluoroquinolones, we will be summarising chemical structure, mode of action, pharmacokinetic properties and toxicity. We will be describing fluoroquinolones introduced in clinical trials, namely avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and non-fluorinated nemonoxacin. These agents have been proved to have enhanced antibacterial effect even against ciprofloxacin resistant pathogens, and found to be well tolerated in both oral and parenteral administrations. These features are going to make them potential antimicrobial agents in the future.

Function-Oriented Synthesis: How to Design Simplified Analogues of Antibacterial Nucleoside Natural Products?

PubMed

Ichikawa, Satoshi

2016-06-01

It is important to pursue function-oriented synthesis (FOS), a strategy for the design of less structurally complex targets with comparable or superior activity that can be made in a practical manner, because compared to synthetic drugs, many biologically relevant natural products possess large and complex chemical structures that may restrict chemical modifications in a structure-activity relationship study. In this account, we describe recent efforts to simplify complex nucleoside natural products including caprazamycins. Considering the structure-activity relationship study with several truncated analogues, three types of simplified derivatives, namely, oxazolidine, isoxazolidine, and lactam-fused isoxazolidine-containing uridine derivatives, were designed and efficiently synthesized. These simplified derivatives have exhibited promising antibacterial activities. A significant feature of our studies is the rational and drastic simplification of the molecular architecture of caprazamycins. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug-resistant bacteria. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recent Methods for Purification and Structure Determination of Oligonucleotides.

PubMed

Zhang, Qiulong; Lv, Huanhuan; Wang, Lili; Chen, Man; Li, Fangfei; Liang, Chao; Yu, Yuanyuan; Jiang, Feng; Lu, Aiping; Zhang, Ge

2016-12-18

Aptamers are single-stranded DNA or RNA oligonucleotides that can interact with target molecules through specific three-dimensional structures. The excellent features, such as high specificity and affinity for target proteins, small size, chemical stability, low immunogenicity, facile chemical synthesis, versatility in structural design and engineering, and accessible for site-specific modifications with functional moieties, make aptamers attractive molecules in the fields of clinical diagnostics and biopharmaceutical therapeutics. However, difficulties in purification and structural identification of aptamers remain a major impediment to their broad clinical application. In this mini-review, we present the recently attractive developments regarding the purification and identification of aptamers. We also discuss the advantages, limitations, and prospects for the major methods applied in purifying and identifying aptamers, which could facilitate the application of aptamers.

13C nuclear magnetic resonance data of lanosterol derivatives—Profiling the steric topology of the steroid skeleton via substituent effects on its 13C NMR

NASA Astrophysics Data System (ADS)

Dias, Jerry Ray; Gao, Hongwu

2009-12-01

The 13C NMR spectra of over 24 tetracyclic triterpenoid derivatives have been structurally analyzed. The 13C NMR chemical shifts allow one to probe the steric topology of the rigid steroid skeleton and inductive effects of its substituents. Use of deuterium labeling in chemical shift assignment and B-ring aromatic terpenoids are also featured.

Building Structure Feature-based Models for Predicting Isoform-specific Human Cytochrome P-450 (hCYP 3A4, 2D6 and 2C9) Inhibition Assay Results in ToxCast

EPA Science Inventory

EPA’s ToxCast project is using high-throughput screening (HTS) to profile and prioritize chemicals for further testing. ToxCast Phase I evaluated 309 unique chemicals, the majority pesticide actives, in over 500 HTS assays. These included 3 human cytochrome P450 (hCYP3A4, hCYP2...

Computational identification of structural factors affecting the mutagenic potential of aromatic amines: study design and experimental validation.

PubMed

Slavov, Svetoslav H; Stoyanova-Slavova, Iva; Mattes, William; Beger, Richard D; Brüschweiler, Beat J

2018-07-01

A grid-based, alignment-independent 3D-SDAR (three-dimensional spectral data-activity relationship) approach based on simulated 13 C and 15 N NMR chemical shifts augmented with through-space interatomic distances was used to model the mutagenicity of 554 primary and 419 secondary aromatic amines. A robust modeling strategy supported by extensive validation including randomized training/hold-out test set pairs, validation sets, "blind" external test sets as well as experimental validation was applied to avoid over-parameterization and build Organization for Economic Cooperation and Development (OECD 2004) compliant models. Based on an experimental validation set of 23 chemicals tested in a two-strain Salmonella typhimurium Ames assay, 3D-SDAR was able to achieve performance comparable to 5-strain (Ames) predictions by Lhasa Limited's Derek and Sarah Nexus for the same set. Furthermore, mapping of the most frequently occurring bins on the primary and secondary aromatic amine structures allowed the identification of molecular features that were associated either positively or negatively with mutagenicity. Prominent structural features found to enhance the mutagenic potential included: nitrobenzene moieties, conjugated π-systems, nitrothiophene groups, and aromatic hydroxylamine moieties. 3D-SDAR was also able to capture "true" negative contributions that are particularly difficult to detect through alternative methods. These include sulphonamide, acetamide, and other functional groups, which not only lack contributions to the overall mutagenic potential, but are known to actively lower it, if present in the chemical structures of what otherwise would be potential mutagens.

Phase-space reaction network on a multisaddle energy landscape: HCN isomerization.

PubMed

Li, Chun-Biu; Matsunaga, Yasuhiro; Toda, Mikito; Komatsuzaki, Tamiki

2005-11-08

By using the HCN/CNH isomerization reaction as an illustrative vehicle of chemical reactions on multisaddle energy landscapes, we give explicit visualizations of molecular motions associated with a straight-through reaction tube in the phase space inside which all reactive trajectories pass from one basin to another, with eliminating recrossing trajectories in the configuration space. This visualization provides us with a chemical intuition of how chemical species "walk along" the reaction-rate slope in the multidimensional phase space compared with the intrinsic reaction path in the configuration space. The distinct nonergodic features in the two different HCN and CNH wells can be easily demonstrated by a section of Poincare surface of section in those potential minima, which predicts in a priori the pattern of trajectories residing in the potential well. We elucidate the global phase-space structure which gives rise to the non-Markovian dynamics or the dynamical correlation of sequential multisaddle chemical reactions. The phase-space structure relevant to the controllability of the product state in chemical reactions is also discussed.

Investigation of the impedance modulation of thin films with a chemically-sensitive field-effect transistor

NASA Astrophysics Data System (ADS)

Wiseman, John M.

1988-12-01

This study resulted in the design and fabrication of a Chemically-Sensitive Field-Effect Transistor (CHEMFET) with an interdigitated gate electrode structure. The electrical performance of the CHEMFET, both in the time-domain and frequency domain, was evaluated for detecting changes in the molecular structure and chemical composition in three thin films: an epoxy, copper phthalocyanine (CuPc), and acetylcholinesterase (ACHE). The change in the chemical state of a film was manifested as a change in the electrical impedance of the interdigitated gate electrode structure. For the epoxy, its molecular structure changed as a result of the curing reaction. To induce a change in the chemical state of the CuPc and ACHE films they were exposed to part-per billion concentrations of a challenge gas, either nitrogen dioxide (NO2) or the the organophosphorus compound, diisopropyl methylphosphonate (DIMP). The results clearly show that the CHEMFET can detect chemical and structural changes in an epoxy and CuPc film. The sensitivity of the ACHE film was not unequivocally determined due to long term drift in the ACHE film's electrical properties. The most remarkable result of this effort was the demonstration of a unique selectivity feature in the CHEMFET's frequency dependent response to a challenge gas. The examination of the relative changes in the electrical properties of the CHEMFET at different frequencies showed that the CHEMFET can be used to distinguish between NO2 and Dimp EXPOSURE.

Study of the Chemical Space of Selected Bacteriostatic Sulfonamides from an Information Theory Point of View.

PubMed

López-Rosa, Sheila; Molina-Espíritu, Moyocoyani; Esquivel, Rodolfo O; Soriano-Correa, Catalina; Dehesa, Jésus S

2016-12-05

The relative structural location of a selected group of 27 sulfonamide-like molecules in a chemical space defined by three information theory quantities (Shannon entropy, Fisher information, and disequilibrium) is discussed. This group is composed of 15 active bacteriostatic molecules, 11 theoretically designed ones, and para-aminobenzoic acid. This endeavor allows molecules that share common chemical properties through the molecular backbone, but with significant differences in the identity of the chemical substituents, which might result in bacteriostatic activity, to be structurally classified and characterized. This is performed by quantifying the structural changes on the electron density distribution due to different functional groups and number of electrons. The macroscopic molecular features are described by means of the entropy-like notions of spatial electronic delocalization, order, and uniformity. Hence, an information theory three-dimensional space (IT-3D) emerges that allows molecules with common properties to be gathered. This space witnesses the biological activity of the sulfonamides. Some structural aspects and information theory properties can be associated, as a result of the IT-3D chemical space, with the bacteriostatic activity of these molecules. Most interesting is that the active bacteriostatic molecules are more similar to para-aminobenzoic acid than to the theoretically designed analogues. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

TIPdb: a database of anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan.

PubMed

Lin, Ying-Chi; Wang, Chia-Chi; Chen, Ih-Sheng; Jheng, Jhao-Liang; Li, Jih-Heng; Tung, Chun-Wei

2013-01-01

The unique geographic features of Taiwan are attributed to the rich indigenous and endemic plant species in Taiwan. These plants serve as resourceful bank for biologically active phytochemicals. Given that these plant-derived chemicals are prototypes of potential drugs for diseases, databases connecting the chemical structures and pharmacological activities may facilitate drug development. To enhance the utility of the data, it is desirable to develop a database of chemical compounds and corresponding activities from indigenous plants in Taiwan. A database of anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan was constructed. The database, TIPdb, is composed of a standardized format of published anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan. A browse function was implemented for users to browse the database in a taxonomy-based manner. Search functions can be utilized to filter records of interest by botanical name, part, chemical class, or compound name. The structured and searchable database TIPdb was constructed to serve as a comprehensive and standardized resource for anticancer, antiplatelet, and antituberculosis compounds search. The manually curated chemical structures and activities provide a great opportunity to develop quantitative structure-activity relationship models for the high-throughput screening of potential anticancer, antiplatelet, and antituberculosis drugs.

TIPdb: A Database of Anticancer, Antiplatelet, and Antituberculosis Phytochemicals from Indigenous Plants in Taiwan

PubMed Central

Lin, Ying-Chi; Wang, Chia-Chi; Chen, Ih-Sheng; Jheng, Jhao-Liang; Li, Jih-Heng; Tung, Chun-Wei

2013-01-01

The unique geographic features of Taiwan are attributed to the rich indigenous and endemic plant species in Taiwan. These plants serve as resourceful bank for biologically active phytochemicals. Given that these plant-derived chemicals are prototypes of potential drugs for diseases, databases connecting the chemical structures and pharmacological activities may facilitate drug development. To enhance the utility of the data, it is desirable to develop a database of chemical compounds and corresponding activities from indigenous plants in Taiwan. A database of anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan was constructed. The database, TIPdb, is composed of a standardized format of published anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan. A browse function was implemented for users to browse the database in a taxonomy-based manner. Search functions can be utilized to filter records of interest by botanical name, part, chemical class, or compound name. The structured and searchable database TIPdb was constructed to serve as a comprehensive and standardized resource for anticancer, antiplatelet, and antituberculosis compounds search. The manually curated chemical structures and activities provide a great opportunity to develop quantitative structure-activity relationship models for the high-throughput screening of potential anticancer, antiplatelet, and antituberculosis drugs. PMID:23766708

DMS-MaPseq for genome-wide or targeted RNA structure probing in vivo.

PubMed

Zubradt, Meghan; Gupta, Paromita; Persad, Sitara; Lambowitz, Alan M; Weissman, Jonathan S; Rouskin, Silvi

2017-01-01

Coupling of structure-specific in vivo chemical modification to next-generation sequencing is transforming RNA secondary structure studies in living cells. The dominant strategy for detecting in vivo chemical modifications uses reverse transcriptase truncation products, which introduce biases and necessitate population-average assessments of RNA structure. Here we present dimethyl sulfate (DMS) mutational profiling with sequencing (DMS-MaPseq), which encodes DMS modifications as mismatches using a thermostable group II intron reverse transcriptase. DMS-MaPseq yields a high signal-to-noise ratio, can report multiple structural features per molecule, and allows both genome-wide studies and focused in vivo investigations of even low-abundance RNAs. We apply DMS-MaPseq for the first analysis of RNA structure within an animal tissue and to identify a functional structure involved in noncanonical translation initiation. Additionally, we use DMS-MaPseq to compare the in vivo structure of pre-mRNAs with their mature isoforms. These applications illustrate DMS-MaPseq's capacity to dramatically expand in vivo analysis of RNA structure.

Recent Advances in Characterization of Lignin Polymer by Solution-State Nuclear Magnetic Resonance (NMR) Methodology

PubMed Central

Wen, Jia-Long; Sun, Shao-Long; Xue, Bai-Liang; Sun, Run-Cang

2013-01-01

The demand for efficient utilization of biomass induces a detailed analysis of the fundamental chemical structures of biomass, especially the complex structures of lignin polymers, which have long been recognized for their negative impact on biorefinery. Traditionally, it has been attempted to reveal the complicated and heterogeneous structure of lignin by a series of chemical analyses, such as thioacidolysis (TA), nitrobenzene oxidation (NBO), and derivatization followed by reductive cleavage (DFRC). Recent advances in nuclear magnetic resonance (NMR) technology undoubtedly have made solution-state NMR become the most widely used technique in structural characterization of lignin due to its versatility in illustrating structural features and structural transformations of lignin polymers. As one of the most promising diagnostic tools, NMR provides unambiguous evidence for specific structures as well as quantitative structural information. The recent advances in two-dimensional solution-state NMR techniques for structural analysis of lignin in isolated and whole cell wall states (in situ), as well as their applications are reviewed. PMID:28809313

Polycyclic Aromatic Hydrocarbons and Infrared Astrophysics with Spitzer

NASA Technical Reports Server (NTRS)

Allamandola, L. J.; Hudgins, D. M.

2004-01-01

PAH spectral features are now being used as new probes of the ISM. PAH ionization states reflect the ionization balance of the medium while PAH size and structure reflect the energetic and chemical history of the medium. This paper will focus on recent applications of the NASA Ames PAH IR spectral Database to interpret astronomical observations made by the Spitzer Space telescope and other space based infrared instruments. Examples will be given showing how changes in the spectral characteristics of different objects reveal interstellar PAH characteristics such as structure, size and composition, as well as provide insight into the chemical history and physical nature of the emission zones.

Nonlinear absorption in AlGaAs/GaAs multiple quantum well structures grown by metalorganic chemical vapor deposition

NASA Technical Reports Server (NTRS)

Lee, H. C.; Hariz, A.; Dapkus, P. D.; Kost, A.; Kawase, M.

1987-01-01

This paper reports the study of growth conditions for achieving the sharp exciton resonances and low-intensity saturation of these resonances in AlGaAs-GaAs multiple quantum well structures grown by metalorganic chemical vapor deposition. Low growth temperature is necessary to observe this sharp resonance feature at room temperature. The optimal growth conditions are a tradeoff between the high temperatures required for high quality AlGaAs and low temperatures required for high-purity GaAs. A strong optical saturation of the excitonic absorption has been observed. A saturation density as low as 250 W/sq cm is reported.

Hybrid strategies for nanolithography and chemical patterning

NASA Astrophysics Data System (ADS)

Srinivasan, Charan

Remarkable technological advances in photolithography have extended patterning to the sub-50-nm regime. However, because photolithography is a top-down approach, it faces substantial technological and economic challenges in maintaining the downward scaling trends of feature sizes below 30 nm. Concurrently, fundamental research on chemical self-assembly has enabled the path to access molecular length scales. The key to the success of photolithography is its inherent economies of scale, which justify the large capital investment for its implementation. In this thesis research, top-down and bottom-up approaches have been combined synergistically, and these hybrid strategies have been employed in applications that do not have the economies of scale found in semiconductor chip manufacturing. The specific instances of techniques developed here include molecular-ruler lithography and a series of nanoscale chemical patterning methods. Molecular-ruler lithography utilizes self-assembled multilayered films as a sidewall spacer on initial photolithographically patterned gold features (parent) to place a second-generation feature (daughter) in precise proximity to the parent. The parent-daughter separation, which is on the nanometer length scale, is defined by the thickness of the molecular-ruler resist. Analogous to protocols followed in industry to evaluate lithographic performance, electrical test-pad structures were designed to interrogate the nanostructures patterned by molecular-ruler nanolithography, failure modes creating electrical shorts were mapped to each lithographic step, and subsequent lithographic optimization was performed to pattern nanoscale devices with excellent electrical performance. The optimized lithographic processes were applied to generate nanoscale devices such as nanowires and thin-film transistors (TFTs). Metallic nanowires were patterned by depositing a tertiary generation material in the nanogap and surrounding micron-scale regions, and then chemically removing the parent and daughter structures selectively. This processing was also performed on silicon-on-insulator substrates and the metallic nanowires were used as a hard mask to transfer the pattern to the single crystalline silicon epilayer resulting in a quaternary generation structure of single-crystalline silicon nanowire field-effect transistors. Additionally, the proof of concept for patterning nanoscale pentacene TFTs utilizing molecular-rulers was demonstrated. For applications in sub-100-nm lithography, the limitations on the relative heights of parent and daughter structures were overcome and processes to integrate molecular-ruler nanolithography with existing complementary metal-oxide-semiconductor (CMOS) processing were developed. Pattern transfer to underlying SiO2 substrates has opened a new avenue of opportunities to apply these nanostructures in nanofluidics and in non-traditional lithography such as imprint lithography. Additionally, the molecular-ruler process has been shown to increase the spatial density of features created by high-resolution techniques such as electron-beam lithography. A limitation of photolithography is its inability to pattern chemical functionality on surfaces. To overcome this limitation, two techniques were developed to extend nanolithography beyond semiconductors and apply them to patterning of self-assembled monolayers. First, a novel bilayer resist was devised to protect and to pattern chemical functionality on surfaces by being able to withstand conditions necessary for both chemical self-assembly and photooxidation of the Au-S bond while not disrupting the preexisting SAM. In addition to photolithography, soft-lithographic approaches such as microcontact printing are often used to create chemical patterns. In this work, a technique for the creation of chemical patterns of inserted molecules with dilute coverages (≤10%) was implemented. As part of the research in chemical patterning, a method for characterizing chemical patterns using scanning electron microscopy has been developed. These tools are the standard for metrology in nanolithography, and thus are readily accessible as our advances in chemical patterning are adopted and applied by the lithography community.

Fabrication of elastomeric silk fibers.

PubMed

Bradner, Sarah A; Partlow, Benjamin P; Cebe, Peggy; Omenetto, Fiorenzo G; Kaplan, David L

2017-09-01

Methods to generate fibers from hydrogels, with control over mechanical properties, fiber diameter, and crystallinity, while retaining cytocompatibility and degradability, would expand options for biomaterials. Here, we exploited features of silk fibroin protein for the formation of tunable silk hydrogel fibers. The biological, chemical, and morphological features inherent to silk were combined with elastomeric properties gained through enzymatic crosslinking of the protein. Postprocessing via methanol and autoclaving provided tunable control of fiber features. Mechanical, optical, and chemical analyses demonstrated control of fiber properties by exploiting the physical cross-links, and generating double network hydrogels consisting of chemical and physical cross-links. Structure and chemical analyses revealed crystallinity from 30 to 50%, modulus from 0.5 to 4 MPa, and ultimate strength 1-5 MPa depending on the processing method. Fabrication and postprocessing combined provided fibers with extensibility from 100 to 400% ultimate strain. Fibers strained to 100% exhibited fourth order birefringence, revealing macroscopic orientation driven by chain mobility. The physical cross-links were influenced in part by the drying rate of fabricated materials, where bound water, packing density, and microstructural homogeneity influenced cross-linking efficiency. The ability to generate robust and versatile hydrogel microfibers is desirable for bottom-up assembly of biological tissues and for broader biomaterial applications. © 2017 Wiley Periodicals, Inc.

Chemical property based sequence characterization of PpcA and its homolog proteins PpcB-E: A mathematical approach

PubMed Central

Pal Choudhury, Pabitra

2017-01-01

Periplasmic c7 type cytochrome A (PpcA) protein is determined in Geobacter sulfurreducens along with its other four homologs (PpcB-E). From the crystal structure viewpoint the observation emerges that PpcA protein can bind with Deoxycholate (DXCA), while its other homologs do not. But it is yet to be established with certainty the reason behind this from primary protein sequence information. This study is primarily based on primary protein sequence analysis through the chemical basis of embedded amino acids. Firstly, we look for the chemical group specific score of amino acids. Along with this, we have developed a new methodology for the phylogenetic analysis based on chemical group dissimilarities of amino acids. This new methodology is applied to the cytochrome c7 family members and pinpoint how a particular sequence is differing with others. Secondly, we build a graph theoretic model on using amino acid sequences which is also applied to the cytochrome c7 family members and some unique characteristics and their domains are highlighted. Thirdly, we search for unique patterns as subsequences which are common among the group or specific individual member. In all the cases, we are able to show some distinct features of PpcA that emerges PpcA as an outstanding protein compared to its other homologs, resulting towards its binding with deoxycholate. Similarly, some notable features for the structurally dissimilar protein PpcD compared to the other homologs are also brought out. Further, the five members of cytochrome family being homolog proteins, they must have some common significant features which are also enumerated in this study. PMID:28362850

DemQSAR: predicting human volume of distribution and clearance of drugs

NASA Astrophysics Data System (ADS)

Demir-Kavuk, Ozgur; Bentzien, Jörg; Muegge, Ingo; Knapp, Ernst-Walter

2011-12-01

In silico methods characterizing molecular compounds with respect to pharmacologically relevant properties can accelerate the identification of new drugs and reduce their development costs. Quantitative structure-activity/-property relationship (QSAR/QSPR) correlate structure and physico-chemical properties of molecular compounds with a specific functional activity/property under study. Typically a large number of molecular features are generated for the compounds. In many cases the number of generated features exceeds the number of molecular compounds with known property values that are available for learning. Machine learning methods tend to overfit the training data in such situations, i.e. the method adjusts to very specific features of the training data, which are not characteristic for the considered property. This problem can be alleviated by diminishing the influence of unimportant, redundant or even misleading features. A better strategy is to eliminate such features completely. Ideally, a molecular property can be described by a small number of features that are chemically interpretable. The purpose of the present contribution is to provide a predictive modeling approach, which combines feature generation, feature selection, model building and control of overtraining into a single application called DemQSAR. DemQSAR is used to predict human volume of distribution (VDss) and human clearance (CL). To control overtraining, quadratic and linear regularization terms were employed. A recursive feature selection approach is used to reduce the number of descriptors. The prediction performance is as good as the best predictions reported in the recent literature. The example presented here demonstrates that DemQSAR can generate a model that uses very few features while maintaining high predictive power. A standalone DemQSAR Java application for model building of any user defined property as well as a web interface for the prediction of human VDss and CL is available on the webpage of DemPRED: http://agknapp.chemie.fu-berlin.de/dempred/.

DemQSAR: predicting human volume of distribution and clearance of drugs.

PubMed

Demir-Kavuk, Ozgur; Bentzien, Jörg; Muegge, Ingo; Knapp, Ernst-Walter

2011-12-01

In silico methods characterizing molecular compounds with respect to pharmacologically relevant properties can accelerate the identification of new drugs and reduce their development costs. Quantitative structure-activity/-property relationship (QSAR/QSPR) correlate structure and physico-chemical properties of molecular compounds with a specific functional activity/property under study. Typically a large number of molecular features are generated for the compounds. In many cases the number of generated features exceeds the number of molecular compounds with known property values that are available for learning. Machine learning methods tend to overfit the training data in such situations, i.e. the method adjusts to very specific features of the training data, which are not characteristic for the considered property. This problem can be alleviated by diminishing the influence of unimportant, redundant or even misleading features. A better strategy is to eliminate such features completely. Ideally, a molecular property can be described by a small number of features that are chemically interpretable. The purpose of the present contribution is to provide a predictive modeling approach, which combines feature generation, feature selection, model building and control of overtraining into a single application called DemQSAR. DemQSAR is used to predict human volume of distribution (VD(ss)) and human clearance (CL). To control overtraining, quadratic and linear regularization terms were employed. A recursive feature selection approach is used to reduce the number of descriptors. The prediction performance is as good as the best predictions reported in the recent literature. The example presented here demonstrates that DemQSAR can generate a model that uses very few features while maintaining high predictive power. A standalone DemQSAR Java application for model building of any user defined property as well as a web interface for the prediction of human VD(ss) and CL is available on the webpage of DemPRED: http://agknapp.chemie.fu-berlin.de/dempred/ .

Aggregating Data for Computational Toxicology Applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System

PubMed Central

Judson, Richard S.; Martin, Matthew T.; Egeghy, Peter; Gangwal, Sumit; Reif, David M.; Kothiya, Parth; Wolf, Maritja; Cathey, Tommy; Transue, Thomas; Smith, Doris; Vail, James; Frame, Alicia; Mosher, Shad; Cohen Hubal, Elaine A.; Richard, Ann M.

2012-01-01

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases. PMID:22408426

Aggregating data for computational toxicology applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System.

PubMed

Judson, Richard S; Martin, Matthew T; Egeghy, Peter; Gangwal, Sumit; Reif, David M; Kothiya, Parth; Wolf, Maritja; Cathey, Tommy; Transue, Thomas; Smith, Doris; Vail, James; Frame, Alicia; Mosher, Shad; Cohen Hubal, Elaine A; Richard, Ann M

2012-01-01

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.

Informing the Human Plasma Protein Binding of ...

EPA Pesticide Factsheets

The free fraction of a xenobiotic in plasma (Fub) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data is scarce for environmentally relevant chemicals. The presented work explores the merit of utilizing available pharmaceutical data to predict Fub for environmentally relevant chemicals via machine learning techniques. Quantitative structure-activity relationship (QSAR) models were constructed with k nearest neighbors (kNN), support vector machines (SVM), and random forest (RF) machine learning algorithms from a training set of 1045 pharmaceuticals. The models were then evaluated with independent test sets of pharmaceuticals (200 compounds) and environmentally relevant ToxCast chemicals (406 total, in two groups of 238 and 168 compounds). The selection of a minimal feature set of 10-15 2D molecular descriptors allowed for both informative feature interpretation and practical applicability domain assessment via a bounded box of descriptor ranges and principal component analysis. The diverse pharmaceutical and environmental chemical sets exhibit similarities in terms of chemical space (99-82% overlap), as well as comparable bias and variance in constructed learning curves. All the models exhibit significant predictability with mean absolute errors (MAE) in the range of 0.10-0.18 Fub. The models performed best for highly bound chemicals (MAE 0.07-0.12), neutrals (MAE 0

Chemical sensors based on N-substituted polyaniline derivatives: reactivity and adsorption studies via electronic structure calculations.

PubMed

Mandú, Larissa O; Batagin-Neto, Augusto

2018-06-09

Conjugated organic polymers represent an important class of materials for varied technological applications including in active layers of chemical sensors. In this context, polyaniline (PANI) derivatives are promising candidates, mainly due to their high chemical stability, good processability, versatility of synthesis, polymerization, and doping, as well as relative low cost. In this study, electronic structure calculations were carried out for varied N-substituted PANI derivatives in order to investigate the potential sensory properties of these materials. The opto-electronic properties of nine distinct compounds were evaluated and discussed in terms of the employed substituents. Preliminary reactivity studies were performed in order to identify adsorption centers on the oligomer structures via condensed-to-atoms Fukui indexes (CAFI). Finally, adsorption studies were carried out for selected derivatives considering five distinct gaseous analytes. The influence of the analytes on the oligomer properties were investigated via the evaluation of average binding energies and changes on the structural features, optical absorption spectra, frontier orbitals distribution, and total density of states in relation to the isolated oligomers. The obtained results indicate the derivatives PANI-NO 2 and PANI-C 6 H 5 as promising materials for the development of improved chemical sensors.

Modeling the Biodegradability of Chemical Compounds Using the Online CHEmical Modeling Environment (OCHEM)

PubMed Central

Vorberg, Susann

2013-01-01

Abstract Biodegradability describes the capacity of substances to be mineralized by free‐living bacteria. It is a crucial property in estimating a compound’s long‐term impact on the environment. The ability to reliably predict biodegradability would reduce the need for laborious experimental testing. However, this endpoint is difficult to model due to unavailability or inconsistency of experimental data. Our approach makes use of the Online Chemical Modeling Environment (OCHEM) and its rich supply of machine learning methods and descriptor sets to build classification models for ready biodegradability. These models were analyzed to determine the relationship between characteristic structural properties and biodegradation activity. The distinguishing feature of the developed models is their ability to estimate the accuracy of prediction for each individual compound. The models developed using seven individual descriptor sets were combined in a consensus model, which provided the highest accuracy. The identified overrepresented structural fragments can be used by chemists to improve the biodegradability of new chemical compounds. The consensus model, the datasets used, and the calculated structural fragments are publicly available at http://ochem.eu/article/31660. PMID:27485201

Synthesis of Hollow Sphere and 1D Structural Materials by Sol-Gel Process.

PubMed

Li, Fa-Liang; Zhang, Hai-Jun

2017-08-25

The sol-gel method is a simple and facile wet chemical process for fabricating advanced materials with high homogeneity, high purity, and excellent chemical reactivity at a relatively low temperature. By adjusting the processing parameters, the sol-gel technique can be used to prepare hollow sphere and 1D structural materials that exhibit a wide application in the fields of catalyst, drug or gene carriers, photoactive, sensors and Li-ion batteries. This feature article reviewed the development of the preparation of hollow sphere and 1D structural materials using the sol-gel method. The effects of calcination temperature, soaking time, pH value, surfactant, etc., on the preparation of hollow sphere and 1D structural materials were summarized, and their formation mechanisms were generalized. Finally, possible future research directions of the sol-gel technique were outlined.

Synthesis of Hollow Sphere and 1D Structural Materials by Sol-Gel Process

PubMed Central

Li, Fa-Liang; Zhang, Hai-Jun

2017-01-01

The sol-gel method is a simple and facile wet chemical process for fabricating advanced materials with high homogeneity, high purity, and excellent chemical reactivity at a relatively low temperature. By adjusting the processing parameters, the sol-gel technique can be used to prepare hollow sphere and 1D structural materials that exhibit a wide application in the fields of catalyst, drug or gene carriers, photoactive, sensors and Li-ion batteries. This feature article reviewed the development of the preparation of hollow sphere and 1D structural materials using the sol-gel method. The effects of calcination temperature, soaking time, pH value, surfactant, etc., on the preparation of hollow sphere and 1D structural materials were summarized, and their formation mechanisms were generalized. Finally, possible future research directions of the sol-gel technique were outlined. PMID:28841188

Fungal prion HET-s as a model for structural complexity and self-propagation in prions.

PubMed

Wan, William; Stubbs, Gerald

2014-04-08

The highly ordered and reproducible structure of the fungal prion HET-s makes it an excellent model system for studying the inherent properties of prions, self-propagating infectious proteins that have been implicated in a number of fatal diseases. In particular, the HET-s prion-forming domain readily folds into a relatively complex two-rung β-solenoid amyloid. The faithful self-propagation of this fold involves a diverse array of inter- and intramolecular structural features. These features include a long flexible loop connecting the two rungs, buried polar residues, salt bridges, and asparagine ladders. We have used site-directed mutagenesis and X-ray fiber diffraction to probe the relative importance of these features for the formation of β-solenoid structure, as well as the cumulative effects of multiple mutations. Using fibrillization kinetics and chemical stability assays, we have determined the biophysical effects of our mutations on the assembly and stability of the prion-forming domain. We have found that a diversity of structural features provides a level of redundancy that allows robust folding and stability even in the face of significant sequence alterations and suboptimal environmental conditions. Our findings provide fundamental insights into the structural interactions necessary for self-propagation. Propagation of prion structure seems to require an obligatory level of complexity that may not be reproducible in short peptide models.

LICSS - a chemical spreadsheet in microsoft excel

PubMed Central

2012-01-01

Background Representations of chemical datasets in spreadsheet format are important for ready data assimilation and manipulation. In addition to the normal spreadsheet facilities, chemical spreadsheets need to have visualisable chemical structures and data searchable by chemical as well as textual queries. Many such chemical spreadsheet tools are available, some operating in the familiar Microsoft Excel environment. However, within this group, the performance of Excel is often compromised, particularly in terms of the number of compounds which can usefully be stored on a sheet. Summary LICSS is a lightweight chemical spreadsheet within Microsoft Excel for Windows. LICSS stores structures solely as Smiles strings. Chemical operations are carried out by calling Java code modules which use the CDK, JChemPaint and OPSIN libraries to provide cheminformatics functionality. Compounds in sheets or charts may be visualised (individually or en masse), and sheets may be searched by substructure or similarity. All the molecular descriptors available in CDK may be calculated for compounds (in batch or on-the-fly), and various cheminformatic operations such as fingerprint calculation, Sammon mapping, clustering and R group table creation may be carried out. We detail here the features of LICSS and how they are implemented. We also explain the design criteria, particularly in terms of potential corporate use, which led to this particular implementation. Conclusions LICSS is an Excel-based chemical spreadsheet with a difference: • It can usefully be used on sheets containing hundreds of thousands of compounds; it doesn't compromise the normal performance of Microsoft Excel • It is designed to be installed and run in environments in which users do not have admin privileges; installation involves merely file copying, and sharing of LICSS sheets invokes automatic installation • It is free and extensible LICSS is open source software and we hope sufficient detail is provided here to enable developers to add their own features and share with the community. PMID:22301088

LICSS - a chemical spreadsheet in microsoft excel.

PubMed

Lawson, Kevin R; Lawson, Jonty

2012-02-02

Representations of chemical datasets in spreadsheet format are important for ready data assimilation and manipulation. In addition to the normal spreadsheet facilities, chemical spreadsheets need to have visualisable chemical structures and data searchable by chemical as well as textual queries. Many such chemical spreadsheet tools are available, some operating in the familiar Microsoft Excel environment. However, within this group, the performance of Excel is often compromised, particularly in terms of the number of compounds which can usefully be stored on a sheet. LICSS is a lightweight chemical spreadsheet within Microsoft Excel for Windows. LICSS stores structures solely as Smiles strings. Chemical operations are carried out by calling Java code modules which use the CDK, JChemPaint and OPSIN libraries to provide cheminformatics functionality. Compounds in sheets or charts may be visualised (individually or en masse), and sheets may be searched by substructure or similarity. All the molecular descriptors available in CDK may be calculated for compounds (in batch or on-the-fly), and various cheminformatic operations such as fingerprint calculation, Sammon mapping, clustering and R group table creation may be carried out.We detail here the features of LICSS and how they are implemented. We also explain the design criteria, particularly in terms of potential corporate use, which led to this particular implementation. LICSS is an Excel-based chemical spreadsheet with a difference:• It can usefully be used on sheets containing hundreds of thousands of compounds; it doesn't compromise the normal performance of Microsoft Excel• It is designed to be installed and run in environments in which users do not have admin privileges; installation involves merely file copying, and sharing of LICSS sheets invokes automatic installation• It is free and extensibleLICSS is open source software and we hope sufficient detail is provided here to enable developers to add their own features and share with the community.

[Strategy of molecular design of drugs: the unification of macro-properties and micro-structures of a molecule].

PubMed

Guo, Zong-Ru

2008-03-01

The interaction of a drug with the organism involves both the disposition of a drug by the organism and the action of a drug on the organism. The disposition of various exogenous substances, including drugs, complies with general rules. The underlying physical and chemical changes to different drugs in view of time and space, i. e. pharmacokinetics, share common characteristics, that is the tout ensemble of a molecule and its macroscopic properties convey direct effect on the pharmacokinetic behavior as the tendency and consequence of biological evolution. The action of a drug on the organism, on the other hand, implicates the physico-chemical binding of a drug molecule to the target protein, which induces pharmacological and toxicological effects. The biological reactions, no matter beneficial or adverse, are all specific and individual manifestation of the drug molecule and determined by the interactive binding between definitive atoms or groups of the drug molecule and the macromolecular target in three-dimension. Such critical atoms, groups, or fragments responsible for the interaction reflect the microscopic structures of drug molecules and are called pharmacophore. In this context, a drug molecule is presumed as an assembly of macroscopic property and microscopic structure, with the macroscopic properties determining the absorption, distribution, metabolism and elimination of drugs and the microscopic structure coining pharmacological action. The knowledge of the internal relationship between macroscopy/microscopy and PK/PD conduces to comprehension of drug action and guides molecular drug design, because this conception facilitates the identification of structural features necessary for biological response, and the determination of factors modulating the physico-chemical and pharmacokinetic properties. The factors determining macro-properties include molecular weight, solubility, charge, lipophilicity (partition), and polar surface area, etc., which are destined by molecular scaffolds and/or side chain(s) apart from pharmacophore. The features of micro-structures contributing to specific activity contain hydrogen bonding donor and acceptor, positive and negative charge centers, hydrophobic centers and centers of aromatic rings. Different combinations and spacial arrangements of these features determine the distinct activity presented. The macro-property and micro-structure are integrated into a single molecule, and are inseparable. The macro-property reflects overall contribution of atoms and groups in the micro-structure. On the other hand, structural changes aimed to adjust macroscopic property usually alter the relative position of the microscopic structure. The goal of molecular drug design is to integrate the macroscopic and microscopic factors in optimized manner. In the early stage of molecular design, both macroscopic property and microscopic structure should be considered to make pharmacodynamics, pharmacokinetics, and physico-chemical properties in optimal match. Therefore, it required the existence of structural overlapping among acceptable pharmacokinetics, visible developing potential and specific pharmacodynamics. The larger the scope of overlapping, the higher the possibility to be a drug.

Porous Structure Design of Polymeric Membranes for Gas Separation

DOE PAGES

Zhang, Jinshui; Schott, Jennifer Ann; Mahurin, Shannon Mark; ...

2017-04-04

High-performance polymeric membranes for gas separation are of interest for molecular-level separations in industrial-scale chemical, energy and environmental processes. To overcome the inherent trade-off relationship between permeability and selectivity, the creation of permanent microporosity in polymeric matrices is highly desirable because the porous structures can provide a high fractional free volume to facilitate gas transport through the dense layer. In this feature article, recent developments in the formation of porous polymeric membranes and potential strategies for pore structure design are reviewed.

Structure and chemical characteristics of natural mineral deposit Terbunskaya (Lipetsk region, Russia)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Motyleva, S., E-mail: motyleva-svetlana@mail.ru; Mertvishcheva, M.; Shchuchka, R.

New knowledge about the mineralogical features Terbunsky mineral. Investigated 5 fractions isolated from the incision (2-2,5 m). Terbunskaya deposit belongs to minerals Santonian age. Scanning electron microscopy and energy dispersive analysis of fractions isolated studied in detail. In the coarse fractions found ancient organic remains of algae and micro-organisms that have been sedimented together with the mineral component during geological periods. The share of organic inclusions does not exceed 1.5%. Chemical composition confirms the presence of silicon and carbonate organisms. Advantageously proportion of minerals having a layered structure with a plurality of micro and nano pore size 600 - 80-nm andmore » an average chemical composition (wt%): Na (0,64), Mg (0,54), Al (13.48), Si (27 57), K (2.39) Ca (0.75)« less

Structural characterization and mechanical performance of calcium phosphate scaffolds and natural bones: a comparative study.

PubMed

Fuentes, Elena; Sáenz de Viteri, Virginia; Igartua, Amaya; Martinetti, Roberta; Dolcini, Laura; Barandika, Gotzone

2010-01-01

The knowledge of the mechanical response of bones and their substitutes is pertinent to numerous medical problems. Understanding the effects of mechanical influence on the body is the first step toward developing innovative treatment and rehabilitation concepts for orthopedic disorders. This was a comparative study of 5 synthetic scaffolds based on porous calcium phosphates and natural bones, with regard to their microstructural, chemical, and mechanical characterizations. The structural and chemical characterizations of the scaffolds were examined by means of X-ray diffraction, scanning electron microscopy, and X-ray spectroscopy analysis. The mechanical characterization of bones and bone graft biomaterials was carried out through compression tests using samples with noncomplex geometry. Analysis of the chemical composition, surface features, porosity, and compressive strength indicates that hydroxyapatite-based materials and trabecular bone have similar properties.

Nano-Optics for Chemical and Materials Characterization

NASA Astrophysics Data System (ADS)

Beversluis, Michael; Stranick, Stephan

2007-03-01

Light microscopy can provide non-destructive, real-time, three-dimensional imaging with chemically-specific contrast, but diffraction frequently limits the resolution to roughly 200 nm. Recently, structured illumination techniques have allowed fluorescence imaging to reach 50 nm resolution [1]. Since these fluorescence techniques were developed for use in microbiology, a key challenge is to take the resolution-enhancing features and apply them to contrast mechanisms like vibrational spectroscopy (e.g., Raman and CARS microscopy) that provide morphological and chemically specific imaging.. We are developing a new hybrid technique that combines the resolution enhancement of structured illumination microscopy with scanning techniques that can record hyperspectral images with 100 nm spatial resolution. We will show such superresolving images of semiconductor nanostructures and discuss the advantages and requirements for this technique. Referenence: 1. M. G. L. Gustafsson, P. Natl. Acad. Sci. USA 102, 13081-13086 (2005).

Synthetic and semi-synthetic chondroitin sulfate oligosaccharides, polysaccharides, and glycomimetics.

PubMed

Bedini, Emiliano; Parrilli, Michelangelo

2012-07-15

Chondroitin sulfate (CS) is a sulfated polysaccharide involved in a myriad of biological processes. Due to the variable sulfation pattern of CS polymer chains, the need to study in detail structure-activity relationships regarding CS biomedical features has provoked much interest in obtaining synthetic CS species. This paper reviews two decades of synthetic and semi-synthetic CS oligosaccharides, polysaccharides, and glycomimetics obtained by chemical, chemoenzymatic, enzymatic, and microbiological-chemical strategies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Soil cover of gas-bearing areas

NASA Astrophysics Data System (ADS)

Mozharova, N. V.

2010-08-01

Natural soils with disturbed functioning parameters compared to the background soils with conservative technogenic-pedogenic features were distinguished on vast areas above the artificial underground gas storages in the zones of spreading and predominant impact of hydrocarbon gases. The disturbance of the functioning parameters is related to the increase in the methane concentration, the bacterial oxidation intensity and destruction, and the complex microbiological and physicochemical synthesis of iron oxides. The technogenic-pedogenic features include neoformations of bacteriomorphic microdispersed iron oxides. The impurity components consist of elements typical for biogenic structures. New soil layers, horizons, specific anthropogenically modified soils, and soil-like structures were formed on small areas in the industrial zones of underground gas storages due to the mechanical disturbance, the deposition of drilling sludge, and the chemical contamination. Among the soils, postlithogenic formations were identified—chemotechnosols (soddy-podzolic soils and chernozems), as well as synlithogenic ones: strato-chemotechnosols and stratochemoembryozems. The soil-like bodies included postlithogenic soil-like structures (chemotechnozems) and synlithogenic ones (strato-chemotechnozems). A substantive approach was used for the soil diagnostics. The morphological and magnetic profiles and the physical, chemical, and physicochemical properties of the soils were analyzed. The micromorphological composition of the soil magnetic fraction was used as a magnetic label.

Genetically Encoded Chemical Probes In Cells Reveal the Binding Path of Urocortin-I to CRF Class B GPCR

PubMed Central

Coin, Irene; Katritch, Vsevolod; Sun, Tingting; Xiang, Zheng; Siu, Fai Yiu; Beyermann, Michael; Stevens, Raymond C.; Wang, Lei

2014-01-01

SUMMARY Molecular determinants regulating the activation of class B G-protein coupled receptors (GPCRs) by native peptide agonists are largely unknown. We have investigated here the interaction between the corticotropin releasing factor receptor type 1 (CRF1R) and its native 40-mer peptide ligand Urocortin-I directly in mammalian cells. By incorporating unnatural amino acid photo-chemical and new click-chemical probes into the receptor, 44 inter-molecular spatial constraints have been derived for the ligand-receptor interaction. The data were analyzed in the context of the recently resolved crystal structure of CRF1R transmembrane domain and existing extracellular domain structures, yielding a complete conformational model for the peptide-receptor complex. Structural features of the receptor-ligand complex yield molecular insights on the mechanism of receptor activation. The experimental strategy provides unique information on full-length post-translationally modified GPCRs in the native membrane of the live cell, complementing in vitro biophysical reductionist approaches. PMID:24290358

Predictive Modeling of Chemical Hazard by Integrating Numerical Descriptors of Chemical Structures and Short-term Toxicity Assay Data

PubMed Central

Rusyn, Ivan; Sedykh, Alexander; Guyton, Kathryn Z.; Tropsha, Alexander

2012-01-01

Quantitative structure-activity relationship (QSAR) models are widely used for in silico prediction of in vivo toxicity of drug candidates or environmental chemicals, adding value to candidate selection in drug development or in a search for less hazardous and more sustainable alternatives for chemicals in commerce. The development of traditional QSAR models is enabled by numerical descriptors representing the inherent chemical properties that can be easily defined for any number of molecules; however, traditional QSAR models often have limited predictive power due to the lack of data and complexity of in vivo endpoints. Although it has been indeed difficult to obtain experimentally derived toxicity data on a large number of chemicals in the past, the results of quantitative in vitro screening of thousands of environmental chemicals in hundreds of experimental systems are now available and continue to accumulate. In addition, publicly accessible toxicogenomics data collected on hundreds of chemicals provide another dimension of molecular information that is potentially useful for predictive toxicity modeling. These new characteristics of molecular bioactivity arising from short-term biological assays, i.e., in vitro screening and/or in vivo toxicogenomics data can now be exploited in combination with chemical structural information to generate hybrid QSAR–like quantitative models to predict human toxicity and carcinogenicity. Using several case studies, we illustrate the benefits of a hybrid modeling approach, namely improvements in the accuracy of models, enhanced interpretation of the most predictive features, and expanded applicability domain for wider chemical space coverage. PMID:22387746

Structural-functional diversity of the natural oligopeptides.

PubMed

Zamyatnin, Alexander A

2018-03-01

Natural oligopeptides may regulate nearly all vital processes. To date, the chemical structures of many oligopeptides have been identified from >2000 organisms representing all the biological kingdoms. We have considered a number of mathematical (sequence length), chemical, physical, and biological features of an array of natural oligopeptides on the basis of the oligopeptide EROP-Moscow database (http://erop.inbi.ras.ru, 15,351 entries) data. There is the substantial difference of these substances from polypeptide molecules of proteins according to their physicochemical characteristics. These characteristics may be critical for understanding the molecular mechanisms of the action of oligopeptides that lead to the development of physiological effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

WebChem Viewer: a tool for the easy dissemination of chemical and structural data sets

PubMed Central

2014-01-01

Background Sharing sets of chemical data (e.g., chemical properties, docking scores, etc.) among collaborators with diverse skill sets is a common task in computer-aided drug design and medicinal chemistry. The ability to associate this data with images of the relevant molecular structures greatly facilitates scientific communication. There is a need for a simple, free, open-source program that can automatically export aggregated reports of entire chemical data sets to files viewable on any computer, regardless of the operating system and without requiring the installation of additional software. Results We here present a program called WebChem Viewer that automatically generates these types of highly portable reports. Furthermore, in designing WebChem Viewer we have also created a useful online web application for remotely generating molecular structures from SMILES strings. We encourage the direct use of this online application as well as its incorporation into other software packages. Conclusions With these features, WebChem Viewer enables interdisciplinary collaborations that require the sharing and visualization of small molecule structures and associated sets of heterogeneous chemical data. The program is released under the FreeBSD license and can be downloaded from http://nbcr.ucsd.edu/WebChemViewer. The associated web application (called “Smiley2png 1.0”) can be accessed through freely available web services provided by the National Biomedical Computation Resource at http://nbcr.ucsd.edu. PMID:24886360

Many faces of carbon

NASA Astrophysics Data System (ADS)

Wang, Qian; Zhang, Shunhong; Jena, Puru

2016-12-01

Due to the special electronic configuration, small atomic size, light mass, and flexible bonding features, carbon exhibits many different structural configurations with very different physical and chemical properties. Here we focus our discussion on three recent forms of carbon, namely, metallic carbon, magnetic carbon, and all-pentagon-based carbon. The metallic carbon can be used for metallic interconnects in future electronic circuits, nano devices and microprocessors while the magnetic carbon can have applications in spintronics. All-pentagon-based carbon nano-structure, penta-graphene, not only expands the family of carbon materials with a number of new features, but also provides the materials basis for the 2D packing of pentagons pursued by mathematicians for almost a century.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unal, B.; Jenks, C.J.; Thiel, P.A.

From other work, two preferred sites have been suggested for metals and semimetals adsorbed on the fivefold surfaces of icosahedral, Al-based quasicrystals. Because of their appearance in scanning tunneling microscopy (STM) images, these sites are known as dark stars and white flowers. In this paper, we analyze four bulk structural models in physical space to determine the types, chemical decorations, and densities of the dark star - and, to a lesser extent, the white flower - adsorption sites for the fivefold planes of icosahedral Al-Pd-Mn. We find that the chemical decorations of these sites are heterogeneous, even within a singlemore » model. Both features are also structurally heterogeneous, according to STM measurements, and the structural variation is consistent with the bulk structure models. Finally, from the models, the density of dark stars in the planes correlates with the step height. This may explain previous experimental observations of different properties for different terraces.« less

A spatiotemporally controllable chemical gradient generator via acoustically oscillating sharp-edge structures.

PubMed

Huang, Po-Hsun; Chan, Chung Yu; Li, Peng; Nama, Nitesh; Xie, Yuliang; Wei, Cheng-Hsin; Chen, Yuchao; Ahmed, Daniel; Huang, Tony Jun

2015-11-07

The ability to generate stable, spatiotemporally controllable concentration gradients is critical for resolving the dynamics of cellular response to a chemical microenvironment. Here we demonstrate an acoustofluidic gradient generator based on acoustically oscillating sharp-edge structures, which facilitates in a step-wise fashion the rapid mixing of fluids to generate tunable, dynamic chemical gradients. By controlling the driving voltage of a piezoelectric transducer, we demonstrated that the chemical gradient profiles can be conveniently altered (spatially controllable). By adjusting the actuation time of the piezoelectric transducer, moreover, we generated pulsatile chemical gradients (temporally controllable). With these two characteristics combined, we have developed a spatiotemporally controllable gradient generator. The applicability and biocompatibility of our acoustofluidic gradient generator are validated by demonstrating the migration of human dermal microvascular endothelial cells (HMVEC-d) in response to a generated vascular endothelial growth factor (VEGF) gradient, and by preserving the viability of HMVEC-d cells after long-term exposure to an acoustic field. Our device features advantages such as simple fabrication and operation, compact and biocompatible device, and generation of spatiotemporally tunable gradients.

Linking high resolution mass spectrometry data with exposure ...

EPA Pesticide Factsheets

There is a growing need in the field of exposure science for monitoring methods that rapidly screen environmental media for suspect contaminants. Measurement and analysis platforms, based on high resolution mass spectrometry (HRMS), now exist to meet this need. Here we describe results of a study that links HRMS data with exposure predictions from the U.S. EPA's ExpoCast™ program and in vitro bioassay data from the U.S. interagency Tox21 consortium. Vacuum dust samples were collected from 56 households across the U.S. as part of the American Healthy Homes Survey (AHHS). Sample extracts were analyzed using liquid chromatography time-of-flight mass spectrometry (LC–TOF/MS) with electrospray ionization. On average, approximately 2000 molecular features were identified per sample (based on accurate mass) in negative ion mode, and 3000 in positive ion mode. Exact mass, isotope distribution, and isotope spacing were used to match molecular features with a unique listing of chemical formulas extracted from EPA's Distributed Structure-Searchable Toxicity (DSSTox) database. A total of 978 DSSTox formulas were consistent with the dust LC–TOF/molecular feature data (match score ≥ 90); these formulas mapped to 3228 possible chemicals in the database. Correct assignment of a unique chemical to a given formula required additional validation steps. Each suspect chemical was prioritized for follow-up confirmation using abundance and detection frequency results, along wi

Linking high resolution mass spectrometry data with exposure and toxicity forecasts to advance high-throughput environmental monitoring

EPA Pesticide Factsheets

There is a growing need in the field of exposure science for monitoring methods that rapidly screen environmental media for suspect contaminants. Measurement and analysis platforms, based on high resolution mass spectrometry (HRMS), now exist to meet this need. Here we describe results of a study that links HRMS data with exposure predictions from the U.S. EPA's ExpoCast? program and in vitro bioassay data from the U.S. interagency Tox21 consortium. Vacuum dust samples were collected from 56 households across the U.S. as part of the American Healthy Homes Survey (AHHS). Sample extracts were analyzed using liquid chromatography time-of-flight mass spectrometry (LC??TOF/MS) with electrospray ionization. On average, approximately 2000 molecular features were identified per sample (based on accurate mass) in negative ion mode, and 3000 in positive ion mode. Exact mass, isotope distribution, and isotope spacing were used to match molecular features with a unique listing of chemical formulas extracted from EPA's Distributed Structure-Searchable Toxicity (DSSTox) database. A total of 978 DSSTox formulas were consistent with the dust LC??TOF/molecular feature data (match score ? 90); these formulas mapped to 3228 possible chemicals in the database. Correct assignment of a unique chemical to a given formula required additional validation steps. Each suspect chemical was prioritized for follow-up confirmation using abundance and detection frequency results, along with exp

UV absorption investigation of ferromagnetically filled ultra-thick carbon onions, carriers of the 217.5 nm Interstellar Absorption Feature

NASA Astrophysics Data System (ADS)

Boi, Filippo S.; Zhang, Xiaotian; Ivaturi, Sameera; Liu, Qianyang; Wen, Jiqiu; Wang, Shanling

2017-12-01

Carbon nano-onions (CNOs) are fullerene-like structures which consist of quasi-spherical closed carbon shells. These structures have become a subject of great interest thanks to their characteristic absorption feature of interstellar origin (at 217.5 nm, 4.6 μm-1). An additional extinction peak at 3.8 μm-1 has also been reported and attributed to absorption by graphitic residues between the as-grown CNOs. Here, we report the ultraviolet absorption properties of ultra-thick CNOs filled with FePt3 crystals, which also exhibit two main absorption peaks—features located at 4.58 μm-1 and 3.44 μm-1. The presence of this additional feature is surprising and is attributed to nonmagnetic graphite flakes produced as a by-product in the pyrolysis experiment (as confirmed by magnetic separation methods). Instead, the feature at 4.58 μm-1 is associated with the π-plasmonic resonance of the CNOs structures. The FePt3 filled CNOs were fabricated in situ by an advanced one-step fast process consisting in the direct sublimation and pyrolysis of two molecular precursors, namely, ferrocene and dichloro-cyclooctadiene-platinum in a chemical vapour deposition system. The morphological, structural, and magnetic properties of the as-grown filled CNOs were characterized by a means of scanning and transmission electron microscopy, X-ray diffraction, and magnetometry.

Bioactive natural compounds from the plant endophytic fungi Pestalotiopsis spp.

PubMed

Wang, Kuiwu; Lei, Jinxiu; Wei, Jiguang; Yao, Nan

2012-11-01

The plant-endophytic strains of the fungus Pestalotiopsis (Amphisphaeriaceae) are distributed throughout the world. Previous chemical investigation of members of the genus resulted in the discovery of various bioactive secondary metabolites including chromones, cytosporones, polyketides, terpenoids and coumarins with diverse structural features. The present report reviews the papers, which have appeared in the literature till now, concerning the isolation, structural elucidation, and biological activities of the secondary metabolites from Pestalotiopsis species.

Method to fabricate layered material compositions

DOEpatents

Fleming, James G.; Lin, Shawn-Yu

2004-11-02

A new class of processes suited to the fabrication of layered material compositions is disclosed. Layered material compositions are typically three-dimensional structures which can be decomposed into a stack of structured layers. The best known examples are the photonic lattices. The present invention combines the characteristic features of photolithography and chemical-mechanical polishing to permit the direct and facile fabrication of, e.g., photonic lattices having photonic bandgaps in the 0.1-20.mu. spectral range.

Luminescent Lanthanide MOFs: A Unique Platform for Chemical Sensing

PubMed Central

Zhao, Shu-Na; Wang, Guangbo

2018-01-01

In recent years, lanthanide metal–organic frameworks (LnMOFs) have developed to be an interesting subclass of MOFs. The combination of the characteristic luminescent properties of Ln ions with the intriguing topological structures of MOFs opens up promising possibilities for the design of LnMOF-based chemical sensors. In this review, we present the most recent developments of LnMOFs as chemical sensors by briefly introducing the general luminescence features of LnMOFs, followed by a comprehensive investigation of the applications of LnMOF sensors for cations, anions, small molecules, nitroaromatic explosives, gases, vapors, pH, and temperature, as well as biomolecules. PMID:29642458

Chemical fractionation-enhanced structural characterization of marine dissolved organic matter

NASA Astrophysics Data System (ADS)

Arakawa, N.; Aluwihare, L.

2016-02-01

Describing the molecular fingerprint of dissolved organic matter (DOM) requires sample processing methods and separation techniques that can adequately minimize its complexity. We have employed acid hydrolysis as a way to make the subcomponents of marine solid phase-extracted (PPL) DOM more accessible to analytical techniques. Using a combination of NMR and chemical derivatization or reduction analyzed by comprehensive (GCxGC) gas chromatography, we observed chemical features strikingly similar to terrestrial DOM. In particular, we observed reduced alicylic hydrocarbons believed to be the backbone of previously identified carboxylic rich alicyclic material (CRAM). Additionally, we found carbohydrates, amino acids and small lipids and acids.

Relationship of carbohydrate molecular spectroscopic features in combined feeds to carbohydrate utilization and availability in ruminants

NASA Astrophysics Data System (ADS)

Zhang, Xuewei; Yu, Peiqiang

To date, there is no study on the relationship between carbohydrate (CHO) molecular structures and nutrient availability of combined feeds in ruminants. The objective of this study was to use molecular spectroscopy to reveal the relationship between CHO molecular spectral profiles (in terms of functional groups (biomolecular, biopolymer) spectral peak area and height intensity) and CHO chemical profiles, CHO subfractions, energy values, and CHO rumen degradation kinetics of combined feeds of hulless barley with pure wheat dried distillers grains with solubles (DDGS) at five different combination ratios (hulless barley to pure wheat DDGS: 100:0, 75:25, 50:50, 25:75, 0:100). The molecular spectroscopic parameters assessed included: lignin biopolymer molecular spectra profile (peak area and height, region and baseline: ca. 1539-1504 cm-1); structural carbohydrate (STCHO, peaks area region and baseline: ca. 1485-1186 cm-1) mainly associated with hemi- and cellulosic compounds; cellulosic materials peak area (centered at ca. 1240 cm-1 with region and baseline: ca. 1272-1186 cm-1); total carbohydrate (CHO, peaks area region and baseline: ca. 1186-946 cm-1). The results showed that the functional groups (biomolecular, biopolymer) in the combined feeds are sensitive to the changes of carbohydrate chemical and nutrient profiles. The changes of the CHO molecular spectroscopic features in the combined feeds were highly correlated with CHO chemical profiles, CHO subfractions, in situ CHO rumen degradation kinetics and fermentable organic matter supply. Further study is needed to investigate possibility of using CHO molecular spectral features as a predictor to estimate nutrient availability in combined feeds for animals and quantify their relationship.

DMS-MaPseq for genome-wide or targeted RNA structure probing in vivo

PubMed Central

Zubradt, Meghan; Gupta, Paromita; Persad, Sitara; Lambowitz, Alan M.; Weissman, Jonathan S.; Rouskin, Silvi

2017-01-01

Coupling structure-specific in vivo chemical modification to next-generation sequencing is transforming RNA secondary structural studies in living cells. The dominant strategy for detecting in vivo chemical modifications uses reverse transcriptase truncation products, which introduces biases and necessitates population-average assessments of RNA structure. Here we present dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq), which encodes DMS modifications as mismatches using a thermostable group II intron reverse transcriptase (TGIRT). DMS-MaPseq yields a high signal-to-noise ratio, can report multiple structural features per molecule, and allows both genome-wide studies and focused in vivo investigations of even low abundance RNAs. We apply DMS-MaPseq for the first analysis of RNA structure within an animal tissue and to identify a functional structure involved in non-canonical translation initiation. Additionally, we use DMS-MaPseq to compare the in vivo structure of pre-mRNAs to their mature isoforms. These applications illustrate DMS-MaPseq’s capacity to dramatically expand in vivo analysis of RNA structure. PMID:27819661

Weighted similarity-based clustering of chemical structures and bioactivity data in early drug discovery.

PubMed

Perualila-Tan, Nolen Joy; Shkedy, Ziv; Talloen, Willem; Göhlmann, Hinrich W H; Moerbeke, Marijke Van; Kasim, Adetayo

2016-08-01

The modern process of discovering candidate molecules in early drug discovery phase includes a wide range of approaches to extract vital information from the intersection of biology and chemistry. A typical strategy in compound selection involves compound clustering based on chemical similarity to obtain representative chemically diverse compounds (not incorporating potency information). In this paper, we propose an integrative clustering approach that makes use of both biological (compound efficacy) and chemical (structural features) data sources for the purpose of discovering a subset of compounds with aligned structural and biological properties. The datasets are integrated at the similarity level by assigning complementary weights to produce a weighted similarity matrix, serving as a generic input in any clustering algorithm. This new analysis work flow is semi-supervised method since, after the determination of clusters, a secondary analysis is performed wherein it finds differentially expressed genes associated to the derived integrated cluster(s) to further explain the compound-induced biological effects inside the cell. In this paper, datasets from two drug development oncology projects are used to illustrate the usefulness of the weighted similarity-based clustering approach to integrate multi-source high-dimensional information to aid drug discovery. Compounds that are structurally and biologically similar to the reference compounds are discovered using this proposed integrative approach.

Natural chemical shielding analysis of nuclear magnetic resonance shielding tensors from gauge-including atomic orbital calculations

NASA Astrophysics Data System (ADS)

Bohmann, Jonathan A.; Weinhold, Frank; Farrar, Thomas C.

1997-07-01

Nuclear magnetic shielding tensors computed by the gauge including atomic orbital (GIAO) method in the Hartree-Fock self-consistent-field (HF-SCF) framework are partitioned into magnetic contributions from chemical bonds and lone pairs by means of natural chemical shielding (NCS) analysis, an extension of natural bond orbital (NBO) analysis. NCS analysis complements the description provided by alternative localized orbital methods by directly calculating chemical shieldings due to delocalized features in the electronic structure, such as bond conjugation and hyperconjugation. Examples of NCS tensor decomposition are reported for CH4, CO, and H2CO, for which a graphical mnemonic due to Cornwell is used to illustrate the effect of hyperconjugative delocalization on the carbon shielding.

Using non-invasive molecular spectroscopic techniques to detect unique aspects of protein Amide functional groups and chemical properties of modeled forage from different sourced-origins.

PubMed

Ji, Cuiying; Zhang, Xuewei; Yu, Peiqiang

2016-03-05

The non-invasive molecular spectroscopic technique-FT/IR is capable to detect the molecular structure spectral features that are associated with biological, nutritional and biodegradation functions. However, to date, few researches have been conducted to use these non-invasive molecular spectroscopic techniques to study forage internal protein structures associated with biodegradation and biological functions. The objectives of this study were to detect unique aspects and association of protein Amide functional groups in terms of protein Amide I and II spectral profiles and chemical properties in the alfalfa forage (Medicago sativa L.) from different sourced-origins. In this study, alfalfa hay with two different origins was used as modeled forage for molecular structure and chemical property study. In each forage origin, five to seven sources were analyzed. The molecular spectral profiles were determined using FT/IR non-invasive molecular spectroscopy. The parameters of protein spectral profiles included functional groups of Amide I, Amide II and Amide I to II ratio. The results show that the modeled forage Amide I and Amide II were centered at 1653 cm(-1) and 1545 cm(-1), respectively. The Amide I spectral height and area intensities were from 0.02 to 0.03 and 2.67 to 3.36 AI, respectively. The Amide II spectral height and area intensities were from 0.01 to 0.02 and 0.71 to 0.93 AI, respectively. The Amide I to II spectral peak height and area ratios were from 1.86 to 1.88 and 3.68 to 3.79, respectively. Our results show that the non-invasive molecular spectroscopic techniques are capable to detect forage internal protein structure features which are associated with forage chemical properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Aromatic Rings Commonly Used in Medicinal Chemistry: Force Fields Comparison and Interactions With Water Toward the Design of New Chemical Entities.

PubMed

Polêto, Marcelo D; Rusu, Victor H; Grisci, Bruno I; Dorn, Marcio; Lins, Roberto D; Verli, Hugo

2018-01-01

The identification of lead compounds usually includes a step of chemical diversity generation. Its rationale may be supported by both qualitative (SAR) and quantitative (QSAR) approaches, offering models of the putative ligand-receptor interactions. In both scenarios, our understanding of which interactions functional groups can perform is mostly based on their chemical nature (such as electronegativity, volume, melting point, lipophilicity etc.) instead of their dynamics in aqueous, biological solutions (solvent accessibility, lifetime of hydrogen bonds, solvent structure etc.). As a consequence, it is challenging to predict from 2D structures which functional groups will be able to perform interactions with the target receptor, at which intensity and relative abundance in the biological environment, all of which will contribute to ligand potency and intrinsic activity. With this in mind, the aim of this work is to assess properties of aromatic rings, commonly used for drug design, in aqueous solution through molecular dynamics simulations in order to characterize their chemical features and infer their impact in complexation dynamics. For this, common aromatic and heteroaromatic rings were selected and received new atomic charge set based on the direction and module of the dipole moment from MP2/6-31G * calculations, while other topological terms were taken from GROMOS53A6 force field. Afterwards, liquid physicochemical properties were simulated for a calibration set composed by nearly 40 molecules and compared to their respective experimental data, in order to validate each topology. Based on the reliance of the employed strategy, we expanded the dataset to more than 100 aromatic rings. Properties in aqueous solution such as solvent accessible surface area, H-bonds availability, H-bonds residence time, and water structure around heteroatoms were calculated for each ring, creating a database of potential interactions, shedding light on features of drugs in biological solutions, on the structural basis for bioisosterism and on the enthalpic/entropic costs for ligand-receptor complexation dynamics.

Chemical computing with reaction-diffusion processes.

PubMed

Gorecki, J; Gizynski, K; Guzowski, J; Gorecka, J N; Garstecki, P; Gruenert, G; Dittrich, P

2015-07-28

Chemical reactions are responsible for information processing in living organisms. It is believed that the basic features of biological computing activity are reflected by a reaction-diffusion medium. We illustrate the ideas of chemical information processing considering the Belousov-Zhabotinsky (BZ) reaction and its photosensitive variant. The computational universality of information processing is demonstrated. For different methods of information coding constructions of the simplest signal processing devices are described. The function performed by a particular device is determined by the geometrical structure of oscillatory (or of excitable) and non-excitable regions of the medium. In a living organism, the brain is created as a self-grown structure of interacting nonlinear elements and reaches its functionality as the result of learning. We discuss whether such a strategy can be adopted for generation of chemical information processing devices. Recent studies have shown that lipid-covered droplets containing solution of reagents of BZ reaction can be transported by a flowing oil. Therefore, structures of droplets can be spontaneously formed at specific non-equilibrium conditions, for example forced by flows in a microfluidic reactor. We describe how to introduce information to a droplet structure, track the information flow inside it and optimize medium evolution to achieve the maximum reliability. Applications of droplet structures for classification tasks are discussed. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Relationships between chemical structure, mechanical properties and materials processing in nanopatterned organosilicate fins.

PubMed

Stan, Gheorghe; Gates, Richard S; Hu, Qichi; Kjoller, Kevin; Prater, Craig; Jit Singh, Kanwal; Mays, Ebony; King, Sean W

2017-01-01

The exploitation of nanoscale size effects to create new nanostructured materials necessitates the development of an understanding of relationships between molecular structure, physical properties and material processing at the nanoscale. Numerous metrologies capable of thermal, mechanical, and electrical characterization at the nanoscale have been demonstrated over the past two decades. However, the ability to perform nanoscale molecular/chemical structure characterization has only been recently demonstrated with the advent of atomic-force-microscopy-based infrared spectroscopy (AFM-IR) and related techniques. Therefore, we have combined measurements of chemical structures with AFM-IR and of mechanical properties with contact resonance AFM (CR-AFM) to investigate the fabrication of 20-500 nm wide fin structures in a nanoporous organosilicate material. We show that by combining these two techniques, one can clearly observe variations of chemical structure and mechanical properties that correlate with the fabrication process and the feature size of the organosilicate fins. Specifically, we have observed an inverse correlation between the concentration of terminal organic groups and the stiffness of nanopatterned organosilicate fins. The selective removal of the organic component during etching results in a stiffness increase and reinsertion via chemical silylation results in a stiffness decrease. Examination of this effect as a function of fin width indicates that the loss of terminal organic groups and stiffness increase occur primarily at the exposed surfaces of the fins over a length scale of 10-20 nm. While the observed structure-property relationships are specific to organosilicates, we believe the combined demonstration of AFM-IR with CR-AFM should pave the way for a similar nanoscale characterization of other materials where the understanding of such relationships is essential.

Complex, Dynamic Combination of Physical, Chemical and Nutritional Variables Controls Spatio-Temporal Variation of Sandy Beach Community Structure

PubMed Central

Ortega Cisneros, Kelly; Smit, Albertus J.; Laudien, Jürgen; Schoeman, David S.

2011-01-01

Sandy beach ecological theory states that physical features of the beach control macrobenthic community structure on all but the most dissipative beaches. However, few studies have simultaneously evaluated the relative importance of physical, chemical and biological factors as potential explanatory variables for meso-scale spatio-temporal patterns of intertidal community structure in these systems. Here, we investigate macroinfaunal community structure of a micro-tidal sandy beach that is located on an oligotrophic subtropical coast and is influenced by seasonal estuarine input. We repeatedly sampled biological and environmental variables at a series of beach transects arranged at increasing distances from the estuary mouth. Sampling took place over a period of five months, corresponding with the transition between the dry and wet season. This allowed assessment of biological-physical relationships across chemical and nutritional gradients associated with a range of estuarine inputs. Physical, chemical, and biological response variables, as well as measures of community structure, showed significant spatio-temporal patterns. In general, bivariate relationships between biological and environmental variables were rare and weak. However, multivariate correlation approaches identified a variety of environmental variables (i.e., sampling session, the C∶N ratio of particulate organic matter, dissolved inorganic nutrient concentrations, various size fractions of photopigment concentrations, salinity and, to a lesser extent, beach width and sediment kurtosis) that either alone or combined provided significant explanatory power for spatio-temporal patterns of macroinfaunal community structure. Overall, these results showed that the macrobenthic community on Mtunzini Beach was not structured primarily by physical factors, but instead by a complex and dynamic blend of nutritional, chemical and physical drivers. This emphasises the need to recognise ocean-exposed sandy beaches as functional ecosystems in their own right. PMID:21858213

Complex, dynamic combination of physical, chemical and nutritional variables controls spatio-temporal variation of sandy beach community structure.

PubMed

Ortega Cisneros, Kelly; Smit, Albertus J; Laudien, Jürgen; Schoeman, David S

2011-01-01

Sandy beach ecological theory states that physical features of the beach control macrobenthic community structure on all but the most dissipative beaches. However, few studies have simultaneously evaluated the relative importance of physical, chemical and biological factors as potential explanatory variables for meso-scale spatio-temporal patterns of intertidal community structure in these systems. Here, we investigate macroinfaunal community structure of a micro-tidal sandy beach that is located on an oligotrophic subtropical coast and is influenced by seasonal estuarine input. We repeatedly sampled biological and environmental variables at a series of beach transects arranged at increasing distances from the estuary mouth. Sampling took place over a period of five months, corresponding with the transition between the dry and wet season. This allowed assessment of biological-physical relationships across chemical and nutritional gradients associated with a range of estuarine inputs. Physical, chemical, and biological response variables, as well as measures of community structure, showed significant spatio-temporal patterns. In general, bivariate relationships between biological and environmental variables were rare and weak. However, multivariate correlation approaches identified a variety of environmental variables (i.e., sampling session, the C∶N ratio of particulate organic matter, dissolved inorganic nutrient concentrations, various size fractions of photopigment concentrations, salinity and, to a lesser extent, beach width and sediment kurtosis) that either alone or combined provided significant explanatory power for spatio-temporal patterns of macroinfaunal community structure. Overall, these results showed that the macrobenthic community on Mtunzini Beach was not structured primarily by physical factors, but instead by a complex and dynamic blend of nutritional, chemical and physical drivers. This emphasises the need to recognise ocean-exposed sandy beaches as functional ecosystems in their own right.

Ligand-based and structure-based approaches in identifying ideal pharmacophore against c-Jun N-terminal kinase-3.

PubMed

Kumar, B V S Suneel; Kotla, Rohith; Buddiga, Revanth; Roy, Jyoti; Singh, Sardar Shamshair; Gundla, Rambabu; Ravikumar, Muttineni; Sarma, Jagarlapudi A R P

2011-01-01

Structure and ligand based pharmacophore modeling and docking studies carried out using diversified set of c-Jun N-terminal kinase-3 (JNK3) inhibitors are presented in this paper. Ligand based pharmacophore model (LBPM) was developed for 106 inhibitors of JNK3 using a training set of 21 compounds to reveal structural and chemical features necessary for these molecules to inhibit JNK3. Hypo1 consisted of two hydrogen bond acceptors (HBA), one hydrogen bond donor (HBD), and a hydrophobic (HY) feature with a correlation coefficient (r²) of 0.950. This pharmacophore model was validated using test set containing 85 inhibitors and had a good r² of 0.846. All the molecules were docked using Glide software and interestingly, all the docked conformations showed hydrogen bond interactions with important hinge region amino acids (Gln155 and Met149)and these interactions were compared with Hypo1 features. The results of ligand based pharmacophore model (LBPM)and docking studies are validated each other. The structure based pharmacophore model (SBPM) studies have identified additional features, two hydrogen bond donors and one hydrogen bond acceptor. The combination of these methodologies is useful in designing ideal pharmacophore which provides a powerful tool for the discovery of novel and selective JNK3 inhibitors.

Novel structural features of xylanase A1 from Paenibacillus sp. JDR-2

Treesearch

Franz J. St John; James F. Preston; Edwin Pozharski

2012-01-01

The Gram-positive bacterium Paenibacillus sp. JDR-2 (PbJDR2) has been shown to have novel properties in the utilization of the abundant but chemically complex hemicellulosic sugar glucuronoxylan. Xylanase A1 of PbJDR2 (PbXynA1) has been implicated in an efficient process in which extracellular...

New features of recording equipment based on photothermoplastic medium for earth observation from space

NASA Astrophysics Data System (ADS)

Rotaru, V. K.

2017-11-01

Photothermoplastic medium (PTPM) is a non-silver two-layer, semiconductor-thermoplastic, structure for optical data recording, which is radiative resistant. It allows to record photographic, holographic and other kinds of optical data without any wet chemical development that giving the maximal economic effect for Space and airborn usage.

Periodic and Aperiodic Close Packing: A Spontaneous Hard-Sphere Model.

ERIC Educational Resources Information Center

van de Waal, B. W.

1985-01-01

Shows how to make close-packed models from balloons and table tennis balls to illustrate structural features of clusters and organometallic cluster-compounds (which are of great interest in the study of chemical reactions). These models provide a very inexpensive and tactile illustration of the organization of matter for concrete operational…

Synthetic substances with morphine-like effect

PubMed Central

Braenden, Olav J.; Eddy, Nathan B.; Halbach, H.

1955-01-01

For morphine-, morphinan-, pethidine-, methadone-, and dithienyl-butenylamine groups of analgesic compounds a systematic survey is given of how analgesic activity is quantitatively affected by alteration of the chemical constitution. Features common to the structural formulae of substances with morphine-like analgesic effect are pointed out. ImagesFIG. 1FIG. 1(Contd.) PMID:13284565

Structural evolution and electronic properties of n-type doped hydrogenated amorphous silicon thin films

NASA Astrophysics Data System (ADS)

He, Jian; Li, Wei; Xu, Rui; Qi, Kang-Cheng; Jiang, Ya-Dong

2011-12-01

The relationship between structure and electronic properties of n-type doped hydrogenated amorphous silicon (a-Si:H) thin films was investigated. Samples with different features were prepared by plasma enhanced chemical vapor deposition (PECVD) at various substrate temperatures. Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy were used to evaluate the structural evolution, meanwhile, electronic-spin resonance (ESR) and optical measurement were applied to explore the electronic properties of P-doped a-Si:H thin films. Results reveal that the changes in materials structure affect directly the electronic properties and the doping efficiency of dopant.

A parallel implementation of the Wuchty algorithm with additional experimental filters to more thoroughly explore RNA conformational space.

PubMed

Stone, Jonathan W; Bleckley, Samuel; Lavelle, Sean; Schroeder, Susan J

2015-01-01

We present new modifications to the Wuchty algorithm in order to better define and explore possible conformations for an RNA sequence. The new features, including parallelization, energy-independent lonely pair constraints, context-dependent chemical probing constraints, helix filters, and optional multibranch loops, provide useful tools for exploring the landscape of RNA folding. Chemical probing alone may not necessarily define a single unique structure. The helix filters and optional multibranch loops are global constraints on RNA structure that are an especially useful tool for generating models of encapsidated viral RNA for which cryoelectron microscopy or crystallography data may be available. The computations generate a combinatorially complete set of structures near a free energy minimum and thus provide data on the density and diversity of structures near the bottom of a folding funnel for an RNA sequence. The conformational landscapes for some RNA sequences may resemble a low, wide basin rather than a steep funnel that converges to a single structure.

Crystal-chemical characteristics of nontronites from bottom sediments of Pacific ocean

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palchik, N. A., E-mail: nadezhda@igm.nsc.ru; Moroz, T. N.; Grigorieva, T. N.

A crystal-chemical analysis of the nontronite samples formed in deep-water sediments of the underwater Juan-de-Fuca ridge in the Pacific ocean has been performed using powder X-ray diffraction, IR spectroscopy, and Mössbauer spectroscopy. A comparison with the previously investigated nontronites from different regions of the Sea of Okhotsk showed that the structural features of these formations are due to the difference in the physicochemical parameters of their crystallization. The values of the basal interplanar spacing d{sub 001} (within 11–13 Å) in the samples analyzed are determined by the degree of hydration and cation filling of the interlayer space, while the differencesmore » in the IR spectra are due to isomorphic substitutions in the structure. The character of cation distribution and the nature and concentration of stacking faults in nontronite structures are determined. The differences in the composition, structure, and properties of nontronites of different origin are confirmed by theoretical calculations of their structural parameters.« less

Plasmon mediated inverse Faraday effect in a graphene-dielectric-metal structure.

PubMed

Bychkov, Igor V; Kuzmin, Dmitry A; Tolkachev, Valentine A; Plaksin, Pavel S; Shavrov, Vladimir G

2018-01-01

This Letter shows the features of inverse Faraday effect (IFE) in a graphene-dielectric-metal (GDM) structure. The constants of propagation and attenuation of the surface plasmon-polariton modes are calculated. The effective magnetic field induced by surface plasmon modes in the dielectric due to the IFE is estimated to reach above 1 tesla. The possibility to control the distribution of the magnetic field by chemical potential of graphene is shown. The concept of strain-driven control of the IFE in the structure has been proposed and investigated.

Computational Approaches to Chemical Hazard Assessment

PubMed Central

Luechtefeld, Thomas; Hartung, Thomas

2018-01-01

Summary Computational prediction of toxicity has reached new heights as a result of decades of growth in the magnitude and diversity of biological data. Public packages for statistics and machine learning make model creation faster. New theory in machine learning and cheminformatics enables integration of chemical structure, toxicogenomics, simulated and physical data in the prediction of chemical health hazards, and other toxicological information. Our earlier publications have characterized a toxicological dataset of unprecedented scale resulting from the European REACH legislation (Registration Evaluation Authorisation and Restriction of Chemicals). These publications dove into potential use cases for regulatory data and some models for exploiting this data. This article analyzes the options for the identification and categorization of chemicals, moves on to the derivation of descriptive features for chemicals, discusses different kinds of targets modeled in computational toxicology, and ends with a high-level perspective of the algorithms used to create computational toxicology models. PMID:29101769

In vitro Cytotoxicity and Genotoxicity Analysis of Ten Tannery Chemicals Using SOS/umu Tests and High-content In vitro Micronucleus Tests.

PubMed

Huang, Zehao; Li, Na; Rao, Kaifeng; Liu, Cuiting; Wang, Zijian; Ma, Mei

2018-01-01

More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transformations of dislocation martensite in tempering secondary-hardening steel

NASA Astrophysics Data System (ADS)

Gorynin, I. V.; Rybin, V. V.; Malyshevskii, V. A.; Semicheva, T. G.; Sherokhina, L. G.

1999-09-01

Analysis of the evolution of the fine structure of secondary-hardening steel in tempering makes it possible to understand the nature of processes that cause changes in the strength and ductility. They are connected with the changes that occur in the solid solution, the ensemble of disperse segregations of the carbide phase, and the dislocation structure of martensite. These transformations are interrelated, and their specific features are determined by the chemical composition of the steel.

The surface science of nanocrystals

NASA Astrophysics Data System (ADS)

Boles, Michael A.; Ling, Daishun; Hyeon, Taeghwan; Talapin, Dmitri V.

2016-02-01

All nanomaterials share a common feature of large surface-to-volume ratio, making their surfaces the dominant player in many physical and chemical processes. Surface ligands -- molecules that bind to the surface -- are an essential component of nanomaterial synthesis, processing and application. Understanding the structure and properties of nanoscale interfaces requires an intricate mix of concepts and techniques borrowed from surface science and coordination chemistry. Our Review elaborates these connections and discusses the bonding, electronic structure and chemical transformations at nanomaterial surfaces. We specifically focus on the role of surface ligands in tuning and rationally designing properties of functional nanomaterials. Given their importance for biomedical (imaging, diagnostics and therapeutics) and optoelectronic (light-emitting devices, transistors, solar cells) applications, we end with an assessment of application-targeted surface engineering.

A three-dimensional numerical study on instability of sinusoidal flame induced by multiple shock waves

NASA Astrophysics Data System (ADS)

Chen, Xiao; Dong, Gang; Jiang, Hua

2017-04-01

The instabilities of a three-dimensional sinusoidally premixed flame induced by an incident shock wave with Mach = 1.7 and its reshock waves were studied by using the Navier-Stokes (NS) equations with a single-step chemical reaction and a high resolution, 9th-order weighted essentially non-oscillatory scheme. The computational results were validated by the grid independence test and the experimental results in the literature. The computational results show that after the passage of incident shock wave the flame interface develops in symmetric structure accompanied by large-scale transverse vortex structures. After the interactions by successive reshock waves, the flame interface is gradually destabilized and broken up, and the large-scale vortex structures are gradually transformed into small-scale vortex structures. The small-scale vortices tend to be isotropic later. The results also reveal that the evolution of the flame interface is affected by both mixing process and chemical reaction. In order to identify the relationship between the mixing and the chemical reaction, a dimensionless parameter, η , that is defined as the ratio of mixing time scale to chemical reaction time scale, is introduced. It is found that at each interaction stage the effect of chemical reaction is enhanced with time. The enhanced effect of chemical reaction at the interaction stage by incident shock wave is greater than that at the interaction stages by reshock waves. The result suggests that the parameter η can reasonably character the features of flame interface development induced by the multiple shock waves.

Atoms in Action: Observing Atomic Motion with Dynamic in situ X-ray Diffraction

NASA Astrophysics Data System (ADS)

Cox, Jordan Michael

Metal-organic framework (MOF) materials are rich in both structural diversity and application. These materials are comprised of metal atoms or clusters which are connected in a three-dimensional polymer-like network by bridging organic linker molecules. One of the major attractive features in MOFs is their permanent pore space which can potentially be used to adsorb or exchange foreign molecules from/with the surrounding environment. While MOFs are an active area of scientific interest, MOF materials are still relatively new, only 20 years old. As such, there is still much that needs to be understood about these materials before they can be effectively applied to widespread chemical problems like CO2 sequestration or low-pressure hydrogen fuel storage. One of the most important facets of MOF chemistry to understand in order to rationally design MOF materials with tailor-made properties is the relationship between the structural features in a MOF and the chemical and physical properties of that material. By examining in detail the atomic structure of a MOF with known properties under a variety of conditions, scientists can begin to unravel the guiding principles which govern these relationships. X-ray diffraction remains one of the most effective tools for determining the structure of a crystalline material with atomic resolution, and has been applied to the determination of MOF structures for years. Typically these experiments have been carried out using powder X-ray diffraction, but this technique lacks the high-resolution structural information found in single-crystal methods. Some studies have been reported which use specialized devices, sometimes called Environmental Control Cells, to study single crystalline MOFs under non-ambient chemical conditions in situ . However, these in situ studies are performed under static conditions. Even in cases where the ECC provides continued access to the local chemical environment during diffraction data collections, the environment is left static or data is not collected until after the material has equilibrated to its new environment. First, a unique ECC has been designed and constructed which allows continuous access to the local chemical environment of a single-crystal sample while maintaining ease of use, minimizing size, and which is easily adaptable to a wide variety of gaseous and liquid chemical stimuli. Novel methods have been developed and are herein described for utilizing this ECC and in situ X-ray diffraction methods in a dynamic manner for monitoring the structural responses of single crystals to changes in their local chemical environment. These methods provide the opportunity for the determination of changes in unit cell parameters and even complete crystal structures during adsorption, desorption, and exchange processes in MOF materials. The application of these methods to the determination of the dehydration process of a previously reported cobalt-based MOF have revealed surprising structural and dynamics data. Several new intermediate structures have been determined in this process, including one metastable species and several actively transitioning species during the dehydration process. Applying these methods to the ethanol solvation process in the same material again yielded results which were richer in structural information than the previously reported ex situ structures. A computational study of rotational potential energy surfaces in a family of photochromic MOF linkers revealed the important role rotational stereoisomers can play in maintaining light-activated functionality when these linkers are incorporated into next-generation functional MOF materials. Finally, the application of novel photocrystallography techniques were used in conjunction with spectroscopic methods to determine the nature of the anomalous behavior of a photochromic diarylethene single-crystal.

Internal Domains of Natural Porous Media Revealed: Critical Locations for Transport, Storage, and Chemical Reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zachara, John M.; Brantley, Susan L.; Chorover, Jon D.

2016-03-16

Internal pore domains exist within rocks, lithic fragments, subsurface sediments and soil aggregates. These domains, which we term internal domains in porous media (IDPM), contain a significant fraction of their porosity as nanopores, dominate the reactive surface area of diverse porous media types, and are important locations for chemical reactivity and hydrocarbon storage. Traditionally difficult to interrogate, advances in instrumentation and imaging methods are providing new insights on the physical structures and chemical attributes of IDPM. In this review we: discuss analytical methods to characterize IDPM, evaluate what has been learned about their size distributions, connectivity, and extended structures; determinemore » whether they exhibit unique chemical reactivity; and assess potential for their inclusion in reactive transport models. Three key findings are noteworthy. 1) A combination of methods now allows complete characterization of the porosity spectrum of natural materials and its connectivity; while imaging microscopies are providing three dimensional representations of the interconnected pore network. 2) Chemical reactivity in pores <10 nm is expected to be different from micro and macropores, yet research performed to date is inconclusive on the nature, direction, and magnitude of effect. 3) Existing continuum reactive transport models treat IDPM as a sub-grid feature with average, empirical, scale-dependent parameters; and are not formulated to include detailed information on pore networks. Overall we find that IDPM are key features controlling hydrocarbon release from shales in hydrofracking systems, organic matter stabilization and recalcitrance in soil, weathering and soil formation, and long term inorganic and organic contaminant behavior in the vadose zone and groundwater. We conclude with an assessment of impactful research opportunities to advance understanding of IDPM, and to incorporate their important effects in reactive transport models for improved environmental simulation and prediction.« less

Physico-chemical properties and cytotoxic effects of sugar-based surfactants: Impact of structural variations.

PubMed

Lu, Biao; Vayssade, Muriel; Miao, Yong; Chagnault, Vincent; Grand, Eric; Wadouachi, Anne; Postel, Denis; Drelich, Audrey; Egles, Christophe; Pezron, Isabelle

2016-09-01

Surfactants derived from the biorefinery process can present interesting surface-active properties, low cytotoxicity, high biocompatibility and biodegradability. They are therefore considered as potential sustainable substitutes to currently used petroleum-based surfactants. To better understand and anticipate their performances, structure-property relationships need to be carefully investigated. For this reason, we applied a multidisciplinary approach to systematically explore the effect of subtle structural variations on both physico-chemical properties and biological effects. Four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or maltose head group by an amide linkage, were synthesized and evaluated together along with two commercially available standard surfactants. Physico-chemical properties including solubility, Krafft point, surface-tension lowering and critical micellar concentration (CMC) in water and biological medium were explored. Cytotoxicity evaluation by measuring proliferation index and metabolic activity against dermal fibroblasts showed that all surfactants studied may induce cell death at low concentrations (below their CMC). Results revealed significant differences in both physico-chemical properties and cytotoxic effects depending on molecule structural features, such as the position of the linkage on the sugar head-group, or the orientation of the amide linkage. Furthermore, the cytotoxic response increased with the reduction of surfactant CMC. This study underscores the relevance of a methodical and multidisciplinary approach that enables the consideration of surfactant solution properties when applied to biological materials. Overall, our results will contribute to a better understanding of the concomitant impact of surfactant structure at physico-chemical and biological levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural Distortions under pressure and doping in superconducting BaFe2As2

NASA Astrophysics Data System (ADS)

Kimber, Simon

2010-03-01

The discovery of a new family of high-TC materials, the iron arsenides, has led to a resurgence of interest in superconductivity. Several important traits of these materials are now apparent: for example, layers of iron tetrahedrally coordinated by arsenic are crucial structural ingredients. The structure and properties of chemically substituted samples are known to be intimately linked; however, until recently (1), remarkably little was known about this relationship when high pressure is used to induce superconductivity in undoped compounds. Here we show that the key structural features in BaFe2As2 show the same behaviour under pressure as found in chemically substituted samples. Using experimentally derived structural data, we show that the electronic structure evolves similarly in both cases. Our results show that, in contrast to the cuprates, structural distortions are more important than charge doping in the iron arsenides. This work was performed at the Helmholtz-Zentrum Berlin in collaboration with Ames Laboratory, Goethe-Universit"at Frankfurt, JCNS J"ulich and the Institute Laue-Langevin. (1) S.A.J. Kimber et al, Nature Materials,

Enzymatic Inverse Opal Hydrogel Particles for Biocatalyst.

PubMed

Wang, Huan; Gu, Hongcheng; Chen, Zhuoyue; Shang, Luoran; Zhao, Ze; Gu, Zhongze; Zhao, Yuanjin

2017-04-19

Enzymatic carriers have a demonstrated value for chemical reactions and industrial applications. Here, we present a novel kind of inverse opal hydrogel particles as the enzymatic carriers. The particles were negatively replicated from spherical colloidal crystal templates by using magnetic nanoparticles tagged acrylamide hydrogel. Thus, they were endowed with the features of monodispersity, small volume, complete penetrating structure, and controllable motion, which are all beneficial for improving the efficiency of biocatalysis. In addition, due to the ordered porous nanostructure, the inverse opal hydrogel particles were imparted with unique photonic band gaps (PBGs) and vivid structural colors for encoding varieties of immobilized enzymes and for constructing a multienzymes biocatalysis system. These features of the inverse opal hydrogel particles indicate that they are ideal enzymatic carriers for biocatalysis.

Analysis of active volcanoes from the Earth Observing System

NASA Technical Reports Server (NTRS)

Mouginis-Mark, Peter; Rowland, Scott; Crisp, Joy; Glaze, Lori; Jones, Kenneth; Kahle, Anne; Pieri, David; Zebker, Howard; Krueger, Arlin; Walter, Lou

1991-01-01

The Earth Observing System (EOS) scheduled for launch in 1997 and 1999 is briefly described, and the EOS volcanology investigation objectives are discussed. The volcanology investigation will include long- and short-term monitoring of selected volcanoes, the detection of precursor activity associated with unanticipated eruptions, and a detailed study of on-going eruptions. A variety of instruments on the EOS platforms will enable the study of local- and regional-scale thermal and deformational features of volcanoes, and the chemical and structural features of volcanic eruption plumes and aerosols.

Electronic fingerprints of DNA bases on graphene.

PubMed

Ahmed, Towfiq; Kilina, Svetlana; Das, Tanmoy; Haraldsen, Jason T; Rehr, John J; Balatsky, Alexander V

2012-02-08

We calculate the electronic local density of states (LDOS) of DNA nucleotide bases (A,C,G,T), deposited on graphene. We observe significant base-dependent features in the LDOS in an energy range within a few electronvolts of the Fermi level. These features can serve as electronic fingerprints for the identification of individual bases in scanning tunneling spectroscopy (STS) experiments that perform image and site dependent spectroscopy on biomolecules. Thus the fingerprints of DNA-graphene hybrid structures may provide an alternative route to DNA sequencing using STS. © 2012 American Chemical Society

The Laurencia Paradox: An Endless Source of Chemodiversity.

PubMed

Harizani, Maria; Ioannou, Efstathia; Roussis, Vassilios

Nature, the most prolific source of biological and chemical diversity, has provided mankind with treatments for health problems since ancient times and continues to be the most promising reservoir of bioactive chemicals for the development of modern drugs. In addition to the terrestrial organisms that still remain a promising source of new bioactive metabolites, the marine environment, covering approximately 70% of the Earth's surface and containing a largely unexplored biodiversity, offers an enormous resource for the discovery of novel compounds. According to the MarinLit database, more than 27,000 metabolites from marine macro- and microorganisms have been isolated to date providing material and key structures for the development of new products in the pharmaceutical, food, cosmeceutical, chemical, and agrochemical sectors. Algae, which thrive in the euphotic zone, were among the first marine organisms that were investigated as sources of food, nutritional supplements, soil fertilizers, and bioactive metabolites.Red algae of the genus Laurencia are accepted unanimously as one of the richest sources of new secondary metabolites. Their cosmopolitan distribution, along with the chemical variation influenced to a significant degree by environmental and genetic factors, have resulted in an endless parade of metabolites, often featuring multiple halogenation sites.The present contribution, covering the literature until August 2015, offers a comprehensive view of the chemical wealth and the taxonomic problems currently impeding chemical and biological investigations of the genus Laurencia. Since mollusks feeding on Laurencia are, in many cases, bioaccumulating, and utilize algal metabolites as chemical weaponry against natural enemies, metabolites of postulated dietary origin of sea hares that feed on Laurencia species are also included in the present review. Altogether, 1047 secondary metabolites, often featuring new carbocyclic skeletons, have been included.The chapter addresses: (1) the "Laurencia complex", the botanical description and the growth and population dynamics of the genus, as well as its chemical diversity and ecological relations; (2) the secondary metabolites, which are organized according to their chemical structures and are classified into sesquiterpenes, diterpenes, triterpenes, acetogenins, indoles, aromatic compounds, steroids, and miscellaneous compounds, as well as their sources of isolation which are depicted in tabulated form, and (3) the biological activity organized according to the biological target and the ecological functions of Laurencia metabolites.

Resolving Transition Metal Chemical Space: Feature Selection for Machine Learning and Structure-Property Relationships.

PubMed

Janet, Jon Paul; Kulik, Heather J

2017-11-22

Machine learning (ML) of quantum mechanical properties shows promise for accelerating chemical discovery. For transition metal chemistry where accurate calculations are computationally costly and available training data sets are small, the molecular representation becomes a critical ingredient in ML model predictive accuracy. We introduce a series of revised autocorrelation functions (RACs) that encode relationships of the heuristic atomic properties (e.g., size, connectivity, and electronegativity) on a molecular graph. We alter the starting point, scope, and nature of the quantities evaluated in standard ACs to make these RACs amenable to inorganic chemistry. On an organic molecule set, we first demonstrate superior standard AC performance to other presently available topological descriptors for ML model training, with mean unsigned errors (MUEs) for atomization energies on set-aside test molecules as low as 6 kcal/mol. For inorganic chemistry, our RACs yield 1 kcal/mol ML MUEs on set-aside test molecules in spin-state splitting in comparison to 15-20× higher errors for feature sets that encode whole-molecule structural information. Systematic feature selection methods including univariate filtering, recursive feature elimination, and direct optimization (e.g., random forest and LASSO) are compared. Random-forest- or LASSO-selected subsets 4-5× smaller than the full RAC set produce sub- to 1 kcal/mol spin-splitting MUEs, with good transferability to metal-ligand bond length prediction (0.004-5 Å MUE) and redox potential on a smaller data set (0.2-0.3 eV MUE). Evaluation of feature selection results across property sets reveals the relative importance of local, electronic descriptors (e.g., electronegativity, atomic number) in spin-splitting and distal, steric effects in redox potential and bond lengths.

Detection of topological phase transitions through entropy measurements: The case of germanene

NASA Astrophysics Data System (ADS)

Grassano, D.; Pulci, O.; Shubnyi, V. O.; Sharapov, S. G.; Gusynin, V. P.; Kavokin, A. V.; Varlamov, A. A.

2018-05-01

We propose a characterization tool for studies of the band structure of new materials promising for the observation of topological phase transitions. We show that a specific resonant feature in the entropy per electron dependence on the chemical potential may be considered as a fingerprint of the transition between topological and trivial insulator phases. The entropy per electron in a honeycomb two-dimensional crystal of germanene subjected to the external electric field is obtained from the first-principles calculation of the density of electronic states and the Maxwell relation. We demonstrate that, in agreement with the recent prediction of the analytical model, strong spikes in the entropy per particle dependence on the chemical potential appear at low temperatures. They are observed at the values of the applied bias both below and above the critical value that corresponds to the transition between the topological insulator and trivial insulator phases, whereas the giant resonant feature in the vicinity of the zero chemical potential is strongly suppressed at the topological transition point, in the low-temperature limit. In a wide energy range, the van Hove singularities in the electronic density of states manifest themselves as zeros in the entropy per particle dependence on the chemical potential.

Effects of isopropanol on collagen fibrils in new parchment

PubMed Central

2012-01-01

Background Isopropanol is widely used by conservators to relax the creases and folds of parchment artefacts. At present, little is known of the possible side effects of the chemical on parchments main structural component- collagen. This study uses X-ray Diffraction to investigate the effects of a range of isopropanol concentrations on the dimensions of the nanostructure of the collagen component of new parchment. Results It is found in this study that the packing features of the collagen molecules within the collagen fibril are altered by exposure to isopropanol. The results suggest that this chemical treatment can induce a loss of structural water from the collagen within parchment and thus a rearrangement of intermolecular bonding. This study also finds that the effects of isopropanol treatment are permanent to parchment artefacts and cannot be reversed with rehydration using deionised water. Conclusions This study has shown that isopropanol induces permanent changes to the packing features of collagen within parchment artefacts and has provided scientific evidence that its use to remove creases and folds on parchment artefacts will cause structural change that may contribute to long-term deterioration of parchment artefacts. This work provides valuable information that informs conservation practitioners regarding the use of isopropanol on parchment artefacts. PMID:22462769

General Platform for Systematic Quantitative Evaluation of Small-Molecule Permeability in Bacteria

PubMed Central

2015-01-01

The chemical features that impact small-molecule permeability across bacterial membranes are poorly understood, and the resulting lack of tools to predict permeability presents a major obstacle to the discovery and development of novel antibiotics. Antibacterials are known to have vastly different structural and physicochemical properties compared to nonantiinfective drugs, as illustrated herein by principal component analysis (PCA). To understand how these properties influence bacterial permeability, we have developed a systematic approach to evaluate the penetration of diverse compounds into bacteria with distinct cellular envelopes. Intracellular compound accumulation is quantitated using LC-MS/MS, then PCA and Pearson pairwise correlations are used to identify structural and physicochemical parameters that correlate with accumulation. An initial study using 10 sulfonyladenosines in Escherichia coli, Bacillus subtilis, and Mycobacterium smegmatis has identified nonobvious correlations between chemical structure and permeability that differ among the various bacteria. Effects of cotreatment with efflux pump inhibitors were also investigated. This sets the stage for use of this platform in larger prospective analyses of diverse chemotypes to identify global relationships between chemical structure and bacterial permeability that would enable the development of predictive tools to accelerate antibiotic drug discovery. PMID:25198656

Impact of Tropopause Structures on Deep Convective Transport Observed during MACPEX

NASA Astrophysics Data System (ADS)

Mullendore, G. L.; Bigelbach, B. C.; Christensen, L. E.; Maddox, E.; Pinkney, K.; Wagner, S.

2016-12-01

Deep convection is the most efficient method of transporting boundary layer mass to the upper troposphere and stratosphere (UTLS). The Mid-latitude Airborne Cirrus Properties Experiment (MACPEX) was conducted during April of 2011 over the central U.S. With a focus on cirrus clouds, the campaign flights often sampled large cirrus anvils downstream from deep convection and included an extensive observational suite of chemical measurements on a high altitude aircraft. As double-tropopause structures are a common feature in the central U.S. during the springtime, the MACPEX campaign provides a good opportunity to gather cases of deep convective transport in the context of both single and double tropopause structures. Sampling of chemical plumes well downstream from convection allows for sampling in relatively quiescent conditions and analysis of irreversible transport. The analysis presented includes multiple methods to assess air mass source and possible convective processing, including back trajectories and ratios of chemical concentrations. Although missions were flown downstream of deep convection, recent processing by convection does not seem likely in all cases that high altitude carbon monoxide plumes were observed. Additionally, the impact of single and double tropopause structures on deep convective transport is shown to be strongly dependent on high stability layers.

Chemically Active, Porous 3D-Printed Thermoplastic Composites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evans, Kent A.; Kennedy, Zachary C.; Arey, Bruce W.

Metal-organic frameworks (MOFs) exhibit exceptional properties and are widely investigated because of their structural and functional versatility relevant to catalysis, separations, and sensing applications. However, their commercial or large-scale application is often limited by their powder forms. To address this, we report the production of MOF-thermoplastic polymer composites accessed via a standard 3D printer. MOFs (Zeolitic imidazolate framework; ZIF-8) were successfully incorporated homogeneously into both poly(lactic acid) (PLA) and thermoplastic polyurethane (TPU) matrices, extruded into filaments, and utilized for on-demand access to 3D structures by fused-deposition modeling. Printed rigid PLA-MOF composites displayed good structural integrity, high surface area ((SA)avg =more » 531 m2 g-1) and hierarchical pore features. Flexible TPU-MOF composites (SAavg = 706 m2 g-1) were achieved by employing a sacrificial fluoropolymer readily removed post-printing. Critically, embedded particles in the plastic matrices retain their ability to participate in chemical interactions characteristic of the parent MOF. The fabrication strategies can be extended to other MOFs and illustrate the potential of 3D printing to create unique porous and high surface area chemically-active structures.« less

Viscoelasticity of biofilms and their recalcitrance to mechanical and chemical challenges

PubMed Central

Peterson, Brandon W.; He, Yan; Ren, Yijin; Zerdoum, Aidan; Libera, Matthew R.; Sharma, Prashant K.; van Winkelhoff, Arie-Jan; Neut, Danielle; Stoodley, Paul; van der Mei, Henny C.; Busscher, Henk J.

2015-01-01

We summarize different studies describing mechanisms through which bacteria in a biofilm mode of growth resist mechanical and chemical challenges. Acknowledging previous microscopic work describing voids and channels in biofilms that govern a biofilms response to such challenges, we advocate a more quantitative approach that builds on the relation between structure and composition of materials with their viscoelastic properties. Biofilms possess features of both viscoelastic solids and liquids, like skin or blood, and stress relaxation of biofilms has been found to be a corollary of their structure and composition, including the EPS matrix and bacterial interactions. Review of the literature on viscoelastic properties of biofilms in ancient and modern environments as well as of infectious biofilms reveals that the viscoelastic properties of a biofilm relate with antimicrobial penetration in a biofilm. In addition, also the removal of biofilm from surfaces appears governed by the viscoelasticity of a biofilm. Herewith, it is established that the viscoelasticity of biofilms, as a corollary of structure and composition, performs a role in their protection against mechanical and chemical challenges. Pathways are discussed to make biofilms more susceptible to antimicrobials by intervening with their viscoelasticity, as a quantifiable expression of their structure and composition. PMID:25725015

Bubble Jet agent release cartridge for chemical single cell stimulation.

PubMed

Wangler, N; Welsche, M; Blazek, M; Blessing, M; Vervliet-Scheebaum, M; Reski, R; Müller, C; Reinecke, H; Steigert, J; Roth, G; Zengerle, R; Paust, N

2013-02-01

We present a new method for the distinct specific chemical stimulation of single cells and small cell clusters within their natural environment. By single-drop release of chemical agents with droplets in size of typical cell diameters (d <30 μm) on-demand micro gradients can be generated for the specific manipulation of single cells. A single channel and a double channel agent release cartridge with integrated fluidic structures and integrated agent reservoirs are shown, tested, and compared in this publication. The single channel setup features a fluidic structure fabricated by anisotropic etching of silicon. To allow for simultaneous release of different agents even though maintaining the same device size, the second type comprises a double channel fluidic structure, fabricated by photolithographic patterning of TMMF. Dispensed droplet volumes are V = 15 pl and V = 10 pl for the silicon and the TMMF based setups, respectively. Utilizing the agent release cartridges, the application in biological assays was demonstrated by hormone-stimulated premature bud formation in Physcomitrella patens and the individual staining of one single L 929 cell within a confluent grown cell culture.

Self-assembly of active colloidal molecules with dynamic function

NASA Astrophysics Data System (ADS)

Soto, Rodrigo; Golestanian, Ramin

2015-05-01

Catalytically active colloids maintain nonequilibrium conditions in which they produce and deplete chemicals and hence effectively act as sources and sinks of molecules. While individual colloids that are symmetrically coated do not exhibit any form of dynamical activity, the concentration fields resulting from their chemical activity decay as 1 /r and produce gradients that attract or repel other colloids depending on their surface chemistry and ambient variables. This results in a nonequilibrium analog of ionic systems, but with the remarkable novel feature of action-reaction symmetry breaking. We study solutions of such chemically active colloids in dilute conditions when they join up to form molecules via generalized ionic bonds and discuss how we can achieve structures with time-dependent functionality. In particular, we study a molecule that adopts a spontaneous oscillatory pattern of conformations and another that exhibits a run-and-tumble dynamics similar to bacteria. Our study shows that catalytically active colloids could be used for designing self-assembled structures that possess dynamical functionalities that are determined by their prescribed three-dimensional structures, a strategy that follows the design principle of proteins.

ChemDoodle Web Components: HTML5 toolkit for chemical graphics, interfaces, and informatics.

PubMed

Burger, Melanie C

2015-01-01

ChemDoodle Web Components (abbreviated CWC, iChemLabs, LLC) is a light-weight (~340 KB) JavaScript/HTML5 toolkit for chemical graphics, structure editing, interfaces, and informatics based on the proprietary ChemDoodle desktop software. The library uses and WebGL technologies and other HTML5 features to provide solutions for creating chemistry-related applications for the web on desktop and mobile platforms. CWC can serve a broad range of scientific disciplines including crystallography, materials science, organic and inorganic chemistry, biochemistry and chemical biology. CWC is freely available for in-house use and is open source (GPL v3) for all other uses.Graphical abstractAdd interactive 2D and 3D chemical sketchers, graphics, and spectra to websites and apps with ChemDoodle Web Components.

Determining the Energetics of the Hydrogen Bond through FTIR: A Hands-On Physical Chemistry Lab Experiment

ERIC Educational Resources Information Center

Guerin, Abby C.; Riley, Kristi; Rupnik, Kresimir; Kuroda, Daniel G.

2016-01-01

Hydrogen bonds are very important chemical structures that are responsible for many unique and important properties of solvents, such as the solvation power of water. These distinctive features are directly related to the stabilization energy conferred by hydrogen bonds to the solvent. Thus, the characterization of hydrogen bond energetics has…

The Role of Feature Selection and Statistical Weighting in Predicting In Vivo Toxicity Using In Vitro Assay and QSAR Data (SOT)

EPA Science Inventory

Our study assesses the value of both in vitro assay and quantitative structure activity relationship (QSAR) data in predicting in vivo toxicity using numerous statistical models and approaches to process the data. Our models are built on datasets of (i) 586 chemicals for which bo...

Paleokarst processes in the Eocene limestones of the Pyramids Plateau, Giza, Egypt

NASA Astrophysics Data System (ADS)

El Aref, M. M.; Refai, E.

The Eocene limestones of the Pyramids plateau are characterized by landforms of stepped terraced escarpment and karst ridges with isolated hills. The carbonate country rocks are also dominated by minor surface, surface to subsurface and subsurface solution features associated with karst products. The systematic field observations eludicate the denudation trend of the minor solution features and suggest the origin of the regional landscapes. The lithologic and structural characters of the limestone country rocks comprise the main factors controlling the surface and subsurface karst evolution. The development of the karst features and the associated sediments in the study area provides information on the paleohydrolic, chemical and climatic environments involved in the origin of the karstification.

Adaptive machine and its thermodynamic costs

NASA Astrophysics Data System (ADS)

Allahverdyan, Armen E.; Wang, Q. A.

2013-03-01

We study the minimal thermodynamically consistent model for an adaptive machine that transfers particles from a higher chemical potential reservoir to a lower one. This model describes essentials of the inhomogeneous catalysis. It is supposed to function with the maximal current under uncertain chemical potentials: if they change, the machine tunes its own structure fitting it to the maximal current under new conditions. This adaptation is possible under two limitations: (i) The degree of freedom that controls the machine's structure has to have a stored energy (described via a negative temperature). The origin of this result is traced back to the Le Chatelier principle. (ii) The machine has to malfunction at a constant environment due to structural fluctuations, whose relative magnitude is controlled solely by the stored energy. We argue that several features of the adaptive machine are similar to those of living organisms (energy storage, aging).

Structure elucidation of metabolite x17299 by interpretation of mass spectrometric data.

PubMed

Zhang, Qibo; Ford, Lisa A; Evans, Anne M; Toal, Douglas R

2017-01-01

A major bottleneck in metabolomic studies is metabolite identification from accurate mass spectrometric data. Metabolite x17299 was identified in plasma as an unknown in a metabolomic study using a compound-centric approach where the associated ion features of the compound were used to determine the true molecular mass. The aim of this work is to elucidate the chemical structure of x17299, a new compound by de novo interpretation of mass spectrometric data. An Orbitrap Elite mass spectrometer was used for acquisition of mass spectra up to MS 4 at high resolution. Synthetic standards of N,N,N -trimethyl-l-alanyl-l-proline betaine (l,l-TMAP), a diastereomer, and an enantiomer were chemically prepared. The planar structure of x17299 was successfully proposed by de novo mechanistic interpretation of mass spectrometric data without any laborious purification and nuclear magnetic resonance spectroscopic analysis. The proposed structure was verified by deuterium exchanged mass spectrometric analysis and confirmed by comparison to a synthetic standard. Relative configuration of x17299 was determined by direct chromatographic comparison to a pair of synthetic diastereomers. Absolute configuration was assigned after derivatization of x17299 with a chiral auxiliary group followed by its chromatographic comparison to a pair of synthetic standards. The chemical structure of metabolite x17299 was determined to be l,l-TMAP.

Self-organization in precipitation reactions far from the equilibrium

PubMed Central

Nakouzi, Elias; Steinbock, Oliver

2016-01-01

Far from the thermodynamic equilibrium, many precipitation reactions create complex product structures with fascinating features caused by their unusual origins. Unlike the dissipative patterns in other self-organizing reactions, these features can be permanent, suggesting potential applications in materials science and engineering. We review four distinct classes of precipitation reactions, describe similarities and differences, and discuss related challenges for theoretical studies. These classes are hollow micro- and macrotubes in chemical gardens, polycrystalline silica carbonate aggregates (biomorphs), Liesegang bands, and propagating precipitation-dissolution fronts. In many cases, these systems show intricate structural hierarchies that span from the nanometer scale into the macroscopic world. We summarize recent experimental progress that often involves growth under tightly regulated conditions by means of wet stamping, holographic heating, and controlled electric, magnetic, or pH perturbations. In this research field, progress requires mechanistic insights that cannot be derived from experiments alone. We discuss how mesoscopic aspects of the product structures can be modeled by reaction-transport equations and suggest important targets for future studies that should also include materials features at the nanoscale. PMID:27551688

Bohm's Quantum Potential and the Visualization of Molecular Structure

NASA Technical Reports Server (NTRS)

Levit, Creon; Chancellor, Marisa K. (Technical Monitor)

1997-01-01

David Bohm's ontological interpretation of quantum theory can shed light on otherwise counter-intuitive quantum mechanical phenomena including chemical bonding. In the field of quantum chemistry, Richard Bader has shown that the topology of the Laplacian of the electronic charge density characterizes many features of molecular structure and reactivity. Visual and computational examination suggests that the Laplacian of Bader and the quantum potential of Bohm are morphologically equivalent. It appears that Bohmian mechanics and the quantum potential can make chemistry as clear as they makes physics.

Structure elucidation of the new citharoxazole from the Mediterranean deep-sea sponge Latrunculia (Biannulata) citharistae.

PubMed

Genta-Jouve, Grégory; Francezon, Nellie; Puissant, Alexandre; Auberger, Patrick; Vacelet, Jean; Pérez, Thierry; Fontana, Angelo; Mourabit, Ali Al; Thomas, Olivier P

2011-08-01

Citharoxazole (1), a new batzelline derivative featuring a benzoxazole moiety, was isolated from the Mediterranean deep-sea sponge Latrunculia (Biannulata) citharistae Vacelet, 1969, together with the known batzelline C (2). This is the first chemical study of a Mediterranean Latrunculia species and the benzoxazole moiety is unprecedented for this family of marine natural products. The structure was mainly elucidated by the interpretation of NMR spectra and especially HMBC correlations. Copyright © 2011 John Wiley & Sons, Ltd.

Phase I Metabolic Stability and Electrophilic Reactivity of 2-Phenylaminophenylacetic Acid Derived Compounds.

PubMed

Pang, Yi Yun; Tan, Yee Min; Chan, Eric Chun Yong; Ho, Han Kiat

2016-07-18

Diclofenac and lumiracoxib are two highly analogous 2-phenylaminophenylacetic acid anti-inflammatory drugs exhibiting occasional dose-limiting hepatotoxicities. Prior data indicate that bioactivation and reactive metabolite formation play roles in the observed toxicity, but the exact chemical influence of the substituents remains elusive. In order to elucidate the role of chemical influence on metabolism related toxicity, metabolic stability and electrophilic reactivity were investigated for a series of structurally related analogues and their resulting metabolites. The resulting analogues embody progressive physiochemical changes through varying halogeno- and aliphatic substituents at two positions and were subjected to in vitro human liver microsomal metabolic stability and cell-based GSH depletion assays (to measure electrophilic reactivity). LC-MS/MS analysis of the GSH trapped reactive intermediates derived from the analogues was then used to identify the putative structures of reactive metabolites. We found that chemical modifications of the structural backbone led to noticeable perturbations of metabolic stability, electrophilic reactivity, and structures and composition of reactive metabolites. With the acquired data, the relationships between stability, reactivity, and toxicity were investigated in an attempt to correlate between Phase I metabolism and in vitro toxicity. A positive correlation was identified between reactivity and in vitro toxicity, indicating that electrophilic reactivity can be an indicator for in vitro toxicity. All in all, the effect of substituents on the structures and reactivity of the metabolites, however subtle the changes, should be taken into consideration during future drug design involving similar chemical features.

ClassyFire: automated chemical classification with a comprehensive, computable taxonomy.

PubMed

Djoumbou Feunang, Yannick; Eisner, Roman; Knox, Craig; Chepelev, Leonid; Hastings, Janna; Owen, Gareth; Fahy, Eoin; Steinbeck, Christoph; Subramanian, Shankar; Bolton, Evan; Greiner, Russell; Wishart, David S

2016-01-01

Scientists have long been driven by the desire to describe, organize, classify, and compare objects using taxonomies and/or ontologies. In contrast to biology, geology, and many other scientific disciplines, the world of chemistry still lacks a standardized chemical ontology or taxonomy. Several attempts at chemical classification have been made; but they have mostly been limited to either manual, or semi-automated proof-of-principle applications. This is regrettable as comprehensive chemical classification and description tools could not only improve our understanding of chemistry but also improve the linkage between chemistry and many other fields. For instance, the chemical classification of a compound could help predict its metabolic fate in humans, its druggability or potential hazards associated with it, among others. However, the sheer number (tens of millions of compounds) and complexity of chemical structures is such that any manual classification effort would prove to be near impossible. We have developed a comprehensive, flexible, and computable, purely structure-based chemical taxonomy (ChemOnt), along with a computer program (ClassyFire) that uses only chemical structures and structural features to automatically assign all known chemical compounds to a taxonomy consisting of >4800 different categories. This new chemical taxonomy consists of up to 11 different levels (Kingdom, SuperClass, Class, SubClass, etc.) with each of the categories defined by unambiguous, computable structural rules. Furthermore each category is named using a consensus-based nomenclature and described (in English) based on the characteristic common structural properties of the compounds it contains. The ClassyFire webserver is freely accessible at http://classyfire.wishartlab.com/. Moreover, a Ruby API version is available at https://bitbucket.org/wishartlab/classyfire_api, which provides programmatic access to the ClassyFire server and database. ClassyFire has been used to annotate over 77 million compounds and has already been integrated into other software packages to automatically generate textual descriptions for, and/or infer biological properties of over 100,000 compounds. Additional examples and applications are provided in this paper. ClassyFire, in combination with ChemOnt (ClassyFire's comprehensive chemical taxonomy), now allows chemists and cheminformaticians to perform large-scale, rapid and automated chemical classification. Moreover, a freely accessible API allows easy access to more than 77 million "ClassyFire" classified compounds. The results can be used to help annotate well studied, as well as lesser-known compounds. In addition, these chemical classifications can be used as input for data integration, and many other cheminformatics-related tasks.

Exploiting the Synergy of Powder X-ray Diffraction and Solid-State NMR Spectroscopy in Structure Determination of Organic Molecular Solids

PubMed Central

2013-01-01

We report a strategy for structure determination of organic materials in which complete solid-state nuclear magnetic resonance (NMR) spectral data is utilized within the context of structure determination from powder X-ray diffraction (XRD) data. Following determination of the crystal structure from powder XRD data, first-principles density functional theory-based techniques within the GIPAW approach are exploited to calculate the solid-state NMR data for the structure, followed by careful scrutiny of the agreement with experimental solid-state NMR data. The successful application of this approach is demonstrated by structure determination of the 1:1 cocrystal of indomethacin and nicotinamide. The 1H and 13C chemical shifts calculated for the crystal structure determined from the powder XRD data are in excellent agreement with those measured experimentally, notably including the two-dimensional correlation of 1H and 13C chemical shifts for directly bonded 13C–1H moieties. The key feature of this combined approach is that the quality of the structure determined is assessed both against experimental powder XRD data and against experimental solid-state NMR data, thus providing a very robust validation of the veracity of the structure. PMID:24386493

Exploiting the Synergy of Powder X-ray Diffraction and Solid-State NMR Spectroscopy in Structure Determination of Organic Molecular Solids.

PubMed

Dudenko, Dmytro V; Williams, P Andrew; Hughes, Colan E; Antzutkin, Oleg N; Velaga, Sitaram P; Brown, Steven P; Harris, Kenneth D M

2013-06-13

We report a strategy for structure determination of organic materials in which complete solid-state nuclear magnetic resonance (NMR) spectral data is utilized within the context of structure determination from powder X-ray diffraction (XRD) data. Following determination of the crystal structure from powder XRD data, first-principles density functional theory-based techniques within the GIPAW approach are exploited to calculate the solid-state NMR data for the structure, followed by careful scrutiny of the agreement with experimental solid-state NMR data. The successful application of this approach is demonstrated by structure determination of the 1:1 cocrystal of indomethacin and nicotinamide. The 1 H and 13 C chemical shifts calculated for the crystal structure determined from the powder XRD data are in excellent agreement with those measured experimentally, notably including the two-dimensional correlation of 1 H and 13 C chemical shifts for directly bonded 13 C- 1 H moieties. The key feature of this combined approach is that the quality of the structure determined is assessed both against experimental powder XRD data and against experimental solid-state NMR data, thus providing a very robust validation of the veracity of the structure.

Automated building of organometallic complexes from 3D fragments.

PubMed

Foscato, Marco; Venkatraman, Vishwesh; Occhipinti, Giovanni; Alsberg, Bjørn K; Jensen, Vidar R

2014-07-28

A method for the automated construction of three-dimensional (3D) molecular models of organometallic species in design studies is described. Molecular structure fragments derived from crystallographic structures and accurate molecular-level calculations are used as 3D building blocks in the construction of multiple molecular models of analogous compounds. The method allows for precise control of stereochemistry and geometrical features that may otherwise be very challenging, or even impossible, to achieve with commonly available generators of 3D chemical structures. The new method was tested in the construction of three sets of active or metastable organometallic species of catalytic reactions in the homogeneous phase. The performance of the method was compared with those of commonly available methods for automated generation of 3D models, demonstrating higher accuracy of the prepared 3D models in general, and, in particular, a much wider range with respect to the kind of chemical structures that can be built automatically, with capabilities far beyond standard organic and main-group chemistry.

Structure and engineering of celluloses.

PubMed

Pérez, Serge; Samain, Daniel

2010-01-01

This chapter collates the developments and conclusions of many of the extensive studies that have been conducted on cellulose, with particular emphasis on the structural and morphological features while not ignoring the most recent results derived from the elucidation of unique biosynthetic pathways. The presentation of structural and morphological data gathered together in this chapter follows the historical development of our knowledge of the different structural levels of cellulose and its various organizational levels. These levels concern features such as chain conformation, chain polarity, chain association, crystal polarity, and microfibril structure and organization. This chapter provides some historical landmarks related to the evolution of concepts in the field of biopolymer science, which parallel the developments of novel methods for characterization of complex macromolecular structures. The elucidation of the different structural levels of organization opens the way to relating structure to function and properties. The chemical and biochemical methods that have been developed to dissolve and further modify cellulose chains are briefly covered. Particular emphasis is given to the facets of topochemistry and topoenzymology where the morphological features play a key role in determining unique physicochemical properties. A final chapter addresses what might be considered tomorrow's goal in amplifying the economic importance of cellulose in the context of sustainable development. Selected examples illustrate the types of result that can be obtained when cellulose fibers are no longer viewed as inert substrates, and when the polyhydroxyl nature of their surfaces, as well as their entire structural complexity, are taken into account. Copyright © 2010 Elsevier Inc. All rights reserved.

Knowledge-based fragment binding prediction.

PubMed

Tang, Grace W; Altman, Russ B

2014-04-01

Target-based drug discovery must assess many drug-like compounds for potential activity. Focusing on low-molecular-weight compounds (fragments) can dramatically reduce the chemical search space. However, approaches for determining protein-fragment interactions have limitations. Experimental assays are time-consuming, expensive, and not always applicable. At the same time, computational approaches using physics-based methods have limited accuracy. With increasing high-resolution structural data for protein-ligand complexes, there is now an opportunity for data-driven approaches to fragment binding prediction. We present FragFEATURE, a machine learning approach to predict small molecule fragments preferred by a target protein structure. We first create a knowledge base of protein structural environments annotated with the small molecule substructures they bind. These substructures have low-molecular weight and serve as a proxy for fragments. FragFEATURE then compares the structural environments within a target protein to those in the knowledge base to retrieve statistically preferred fragments. It merges information across diverse ligands with shared substructures to generate predictions. Our results demonstrate FragFEATURE's ability to rediscover fragments corresponding to the ligand bound with 74% precision and 82% recall on average. For many protein targets, it identifies high scoring fragments that are substructures of known inhibitors. FragFEATURE thus predicts fragments that can serve as inputs to fragment-based drug design or serve as refinement criteria for creating target-specific compound libraries for experimental or computational screening.

Knowledge-based Fragment Binding Prediction

PubMed Central

Tang, Grace W.; Altman, Russ B.

2014-01-01

Target-based drug discovery must assess many drug-like compounds for potential activity. Focusing on low-molecular-weight compounds (fragments) can dramatically reduce the chemical search space. However, approaches for determining protein-fragment interactions have limitations. Experimental assays are time-consuming, expensive, and not always applicable. At the same time, computational approaches using physics-based methods have limited accuracy. With increasing high-resolution structural data for protein-ligand complexes, there is now an opportunity for data-driven approaches to fragment binding prediction. We present FragFEATURE, a machine learning approach to predict small molecule fragments preferred by a target protein structure. We first create a knowledge base of protein structural environments annotated with the small molecule substructures they bind. These substructures have low-molecular weight and serve as a proxy for fragments. FragFEATURE then compares the structural environments within a target protein to those in the knowledge base to retrieve statistically preferred fragments. It merges information across diverse ligands with shared substructures to generate predictions. Our results demonstrate FragFEATURE's ability to rediscover fragments corresponding to the ligand bound with 74% precision and 82% recall on average. For many protein targets, it identifies high scoring fragments that are substructures of known inhibitors. FragFEATURE thus predicts fragments that can serve as inputs to fragment-based drug design or serve as refinement criteria for creating target-specific compound libraries for experimental or computational screening. PMID:24762971

Band Structure Engineering and Thermoelectric Properties of Charge-Compensated Filled Skutterudites

PubMed Central

Shi, Xiaoya; Yang, Jiong; Wu, Lijun; Salvador, James R.; Zhang, Cheng; Villaire, William L.; Haddad, Daad; Yang, Jihui; Zhu, Yimei; Li, Qiang

2015-01-01

Thermoelectric properties of semiconductors are intimately related to their electronic band structure, which can be engineered via chemical doping. Dopant Ga in the cage-structured skutterudite Co4Sb12 substitutes Sb sites while occupying the void sites. Combining quantitative scanning transmission electron microscopy and first-principles calculations, we show that Ga dual-site occupancy breaks the symmetry of the Sb-Sb network, splits the deep triply-degenerate conduction bands, and drives them downward to the band edge. The charge-compensating nature of the dual occupancy Ga increases overall filling fraction limit. By imparting this unique band structure feature, and judiciously doping the materials by increasing the Yb content, we promote the Fermi level to a point where carriers are in energetic proximity to these features. Increased participation of these heavier bands in electronic transport leads to increased thermopower and effective mass. Further, the localized distortion from Ga/Sb substitution enhances the phonon scattering to reduce the thermal conductivity effectively. PMID:26456013

Band structure engineering and thermoelectric properties of charge-compensated filled skutterudites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Xiaoya; Yang, Jiong; Wu, Lijun

2015-10-12

Thermoelectric properties of semiconductors are intimately related to their electronic band structure, which can be engineered via chemical doping. Dopant Ga in the cage-structured skutterudite Co 4Sb 12 substitutes Sb sites while occupying the void sites. Combining quantitative scanning transmission electron microscopy and first-principles calculations, we show that Ga dual-site occupancy breaks the symmetry of the Sb-Sb network, splits the deep triply-degenerate conduction bands, and drives them downward to the band edge. The charge-compensating nature of the dual occupancy Ga increases overall filling fraction limit. By imparting this unique band structure feature, and judiciously doping the materials by increasing themore » Yb content, we promote the Fermi level to a point where carriers are in energetic proximity to these features. Increased participation of these heavier bands in electronic transport leads to increased thermopower and effective mass. Further, the localized distortion from Ga/Sb substitution enhances the phonon scattering to reduce the thermal conductivity effectively.« less

Band Structure Engineering and Thermoelectric Properties of Charge-Compensated Filled Skutterudites

NASA Astrophysics Data System (ADS)

Shi, Xiaoya; Yang, Jiong; Wu, Lijun; Salvador, James R.; Zhang, Cheng; Villaire, William L.; Haddad, Daad; Yang, Jihui; Zhu, Yimei; Li, Qiang

2015-10-01

Thermoelectric properties of semiconductors are intimately related to their electronic band structure, which can be engineered via chemical doping. Dopant Ga in the cage-structured skutterudite Co4Sb12 substitutes Sb sites while occupying the void sites. Combining quantitative scanning transmission electron microscopy and first-principles calculations, we show that Ga dual-site occupancy breaks the symmetry of the Sb-Sb network, splits the deep triply-degenerate conduction bands, and drives them downward to the band edge. The charge-compensating nature of the dual occupancy Ga increases overall filling fraction limit. By imparting this unique band structure feature, and judiciously doping the materials by increasing the Yb content, we promote the Fermi level to a point where carriers are in energetic proximity to these features. Increased participation of these heavier bands in electronic transport leads to increased thermopower and effective mass. Further, the localized distortion from Ga/Sb substitution enhances the phonon scattering to reduce the thermal conductivity effectively.

The core contribution of transmission electron microscopy to functional nanomaterials engineering

NASA Astrophysics Data System (ADS)

Carenco, Sophie; Moldovan, Simona; Roiban, Lucian; Florea, Ileana; Portehault, David; Vallé, Karine; Belleville, Philippe; Boissière, Cédric; Rozes, Laurence; Mézailles, Nicolas; Drillon, Marc; Sanchez, Clément; Ersen, Ovidiu

2016-01-01

Research on nanomaterials and nanostructured materials is burgeoning because their numerous and versatile applications contribute to solve societal needs in the domain of medicine, energy, environment and STICs. Optimizing their properties requires in-depth analysis of their structural, morphological and chemical features at the nanoscale. In a transmission electron microscope (TEM), combining tomography with electron energy loss spectroscopy and high-magnification imaging in high-angle annular dark-field mode provides access to all features of the same object. Today, TEM experiments in three dimensions are paramount to solve tough structural problems associated with nanoscale matter. This approach allowed a thorough morphological description of silica fibers. Moreover, quantitative analysis of the mesoporous network of binary metal oxide prepared by template-assisted spray-drying was performed, and the homogeneity of amino functionalized metal-organic frameworks was assessed. Besides, the morphology and internal structure of metal phosphide nanoparticles was deciphered, providing a milestone for understanding phase segregation at the nanoscale. By extrapolating to larger classes of materials, from soft matter to hard metals and/or ceramics, this approach allows probing small volumes and uncovering materials characteristics and properties at two or three dimensions. Altogether, this feature article aims at providing (nano)materials scientists with a representative set of examples that illustrates the capabilities of modern TEM and tomography, which can be transposed to their own research.Research on nanomaterials and nanostructured materials is burgeoning because their numerous and versatile applications contribute to solve societal needs in the domain of medicine, energy, environment and STICs. Optimizing their properties requires in-depth analysis of their structural, morphological and chemical features at the nanoscale. In a transmission electron microscope (TEM), combining tomography with electron energy loss spectroscopy and high-magnification imaging in high-angle annular dark-field mode provides access to all features of the same object. Today, TEM experiments in three dimensions are paramount to solve tough structural problems associated with nanoscale matter. This approach allowed a thorough morphological description of silica fibers. Moreover, quantitative analysis of the mesoporous network of binary metal oxide prepared by template-assisted spray-drying was performed, and the homogeneity of amino functionalized metal-organic frameworks was assessed. Besides, the morphology and internal structure of metal phosphide nanoparticles was deciphered, providing a milestone for understanding phase segregation at the nanoscale. By extrapolating to larger classes of materials, from soft matter to hard metals and/or ceramics, this approach allows probing small volumes and uncovering materials characteristics and properties at two or three dimensions. Altogether, this feature article aims at providing (nano)materials scientists with a representative set of examples that illustrates the capabilities of modern TEM and tomography, which can be transposed to their own research. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05460e

A New Publicly Available Chemical Query Language, CSRML ...

EPA Pesticide Factsheets

A new XML-based query language, CSRML, has been developed for representing chemical substructures, molecules, reaction rules, and reactions. CSRML queries are capable of integrating additional forms of information beyond the simple substructure (e.g., SMARTS) or reaction transformation (e.g., SMIRKS, reaction SMILES) queries currently in use. Chemotypes, a term used to represent advanced CSRML queries for repeated application can be encoded not only with connectivity and topology, but also with properties of atoms, bonds, electronic systems, or molecules. The CSRML language has been developed in parallel with a public set of chemotypes, i.e., the ToxPrint chemotypes, which are designed to provide excellent coverage of environmental, regulatory and commercial use chemical space, as well as to represent features and frameworks believed to be especially relevant to toxicity concerns. A software application, ChemoTyper, has also been developed and made publicly available to enable chemotype searching and fingerprinting against a target structure set. The public ChemoTyper houses the ToxPrint chemotype CSRML dictionary, as well as reference implementation so that the query specifications may be adopted by other chemical structure knowledge systems. The full specifications of the XML standard used in CSRML-based chemotypes are publicly available to facilitate and encourage the exchange of structural knowledge. Paper details specifications for a new XML-based query lan

Synthesis and characterization of polypyrrole and its application for solar cell

NASA Astrophysics Data System (ADS)

Almuntaser, Faisal M. A.; Majumder, Sutripto; Baviskar, Prashant K.; Sali, Jaydeep V.; Sankapal, B. R.

2017-08-01

In this report, the fabrication of a solar cell device with the structures FTO/PPy/PTh/ZnO/Al was performed using wet chemical synthesis methods in open environment. The cost-effective methods like CBD, SILAR, and spin coating have been used for the synthesis. The effect of thickness of PPy active layer on the device performance is investigated. Features such as structural, morphological, and chemical bonding of the layers have been investigated using X-ray diffraction, field emission scanning electron microscopy, and Fourier transform infrared spectroscopy and are discussed herein. Effects of PPy thickness on current-voltage characteristics have been studied under dark and illumination at 1 Sun (100 mW/cm2, AM 1.5 G) condition to study the solar cell performance.

Development of TLSER model and QSAR model for predicting partition coefficients of hydrophobic organic chemicals between low density polyethylene film and water.

PubMed

Liu, Huihui; Wei, Mengbi; Yang, Xianhai; Yin, Cen; He, Xiao

2017-01-01

Partition coefficients are vital parameters for measuring accurately the chemicals concentrations by passive sampling devices. Given the wide use of low density polyethylene (LDPE) film in passive sampling, we developed a theoretical linear solvation energy relationship (TLSER) model and a quantitative structure-activity relationship (QSAR) model for the prediction of the partition coefficient of chemicals between LDPE and water (K pew ). For chemicals with the octanol-water partition coefficient (log K ow ) <8, a TLSER model with V x (McGowan volume) and qA - (the most negative charge on O, N, S, X atoms) as descriptors was developed, but the model had relatively low determination coefficient (R 2 ) and cross-validated coefficient (Q 2 ). In order to further explore the theoretical mechanisms involved in the partition process, a QSAR model with four descriptors (MLOGP (Moriguchi octanol-water partition coeff.), P_VSA_s_3 (P_VSA-like on I-state, bin 3), Hy (hydrophilic factor) and NssO (number of atoms of type ssO)) was established, and statistical analysis indicated that the model had satisfactory goodness-of-fit, robustness and predictive ability. For chemicals with log K OW >8, a TLSER model with V x and a QSAR model with MLOGP as descriptor were developed. This is the first paper to explore the models for highly hydrophobic chemicals. The applicability domain of the models, characterized by the Euclidean distance-based method and Williams plot, covered a large number of structurally diverse chemicals, which included nearly all the common hydrophobic organic compounds. Additionally, through mechanism interpretation, we explored the structural features those governing the partition behavior of chemicals between LDPE and water. Copyright © 2016 Elsevier B.V. All rights reserved.

Structure-guided wavelength tuning in far-red fluorescent proteins

PubMed Central

Ng, Ho-Leung; Lin, Michael Z.

2017-01-01

In recent years, protein engineers have succeeded in tuning the excitation spectra of natural fluorescent proteins from green wavelengths into orange and red wavelengths, resulting in the creation of a series of fluorescent proteins with emission in the far-red portions of the optical spectrum. These results have arisen from the synergistic combination of structural knowledge of fluorescent proteins, chemical intuition, and high-throughput screening methods. Here we review structural features found in autocatalytic far-red fluorescent proteins, and discuss how they add to our understanding of the biophysical mechanisms of wavelength tuning in biological chromophores. PMID:27468111

Molpher: a software framework for systematic chemical space exploration

PubMed Central

2014-01-01

Background Chemical space is virtual space occupied by all chemically meaningful organic compounds. It is an important concept in contemporary chemoinformatics research, and its systematic exploration is vital to the discovery of either novel drugs or new tools for chemical biology. Results In this paper, we describe Molpher, an open-source framework for the systematic exploration of chemical space. Through a process we term ‘molecular morphing’, Molpher produces a path of structurally-related compounds. This path is generated by the iterative application of so-called ‘morphing operators’ that represent simple structural changes, such as the addition or removal of an atom or a bond. Molpher incorporates an optimized parallel exploration algorithm, compound logging and a two-dimensional visualization of the exploration process. Its feature set can be easily extended by implementing additional morphing operators, chemical fingerprints, similarity measures and visualization methods. Molpher not only offers an intuitive graphical user interface, but also can be run in batch mode. This enables users to easily incorporate molecular morphing into their existing drug discovery pipelines. Conclusions Molpher is an open-source software framework for the design of virtual chemical libraries focused on a particular mechanistic class of compounds. These libraries, represented by a morphing path and its surroundings, provide valuable starting data for future in silico and in vitro experiments. Molpher is highly extensible and can be easily incorporated into any existing computational drug design pipeline. PMID:24655571

Molpher: a software framework for systematic chemical space exploration.

PubMed

Hoksza, David; Skoda, Petr; Voršilák, Milan; Svozil, Daniel

2014-03-21

Chemical space is virtual space occupied by all chemically meaningful organic compounds. It is an important concept in contemporary chemoinformatics research, and its systematic exploration is vital to the discovery of either novel drugs or new tools for chemical biology. In this paper, we describe Molpher, an open-source framework for the systematic exploration of chemical space. Through a process we term 'molecular morphing', Molpher produces a path of structurally-related compounds. This path is generated by the iterative application of so-called 'morphing operators' that represent simple structural changes, such as the addition or removal of an atom or a bond. Molpher incorporates an optimized parallel exploration algorithm, compound logging and a two-dimensional visualization of the exploration process. Its feature set can be easily extended by implementing additional morphing operators, chemical fingerprints, similarity measures and visualization methods. Molpher not only offers an intuitive graphical user interface, but also can be run in batch mode. This enables users to easily incorporate molecular morphing into their existing drug discovery pipelines. Molpher is an open-source software framework for the design of virtual chemical libraries focused on a particular mechanistic class of compounds. These libraries, represented by a morphing path and its surroundings, provide valuable starting data for future in silico and in vitro experiments. Molpher is highly extensible and can be easily incorporated into any existing computational drug design pipeline.

Microlithography and resist technology information at your fingertips via SciFinder

NASA Astrophysics Data System (ADS)

Konuk, Rengin; Macko, John R.; Staggenborg, Lisa

1997-07-01

Finding and retrieving the information you need about microlithography and resist technology in a timely fashion can make or break your competitive edge in today's business environment. Chemical Abstracts Service (CAS) provides the most complete and comprehensive database of the chemical literature in the CAplus, REGISTRY, and CASREACT files including 13 million document references, 15 million substance records and over 1.2 million reactions. This includes comprehensive coverage of positive and negative resist formulations and processing, photoacid generation, silylation, single and multilayer resist systems, photomasks, dry and wet etching, photolithography, electron-beam, ion-beam and x-ray lithography technologies and process control, optical tools, exposure systems, radiation sources and steppers. Journal articles, conference proceedings and patents related to microlithography and resist technology are analyzed and indexed by scientific information analysts with strong technical background in these areas. The full CAS database, which is updated weekly with new information, is now available at your desktop, via a convenient, user-friendly tool called 'SciFinder.' Author, subject and chemical substance searching is simplified by SciFinder's smart search features. Chemical substances can be searched by chemical structure, chemical name, CAS registry number or molecular formula. Drawing chemical structures in SciFinder is easy and does not require compliance with CA conventions. Built-in intelligence of SciFinder enables users to retrieve substances with multiple components, tautomeric forms and salts.

Uniform manganese hexacyanoferrate hydrate nanocubes featuring superior performance for low-cost supercapacitors and nonenzymatic electrochemical sensors.

PubMed

Pang, Huan; Zhang, Yizhou; Cheng, Tao; Lai, Wen-Yong; Huang, Wei

2015-10-14

Uniform manganese hexacyanoferrate hydrate nanocubes are prepared via a simple chemical precipitation method at room temperature. Due to both micro/mesopores of the Prussian blue analogue and nanocubic structures, the manganese hexacyanoferrate hydrate nanocubes allow the efficient charge transfer and mass transport for electrolyte solution and chemical species. Thus, the manganese hexacyanoferrate hydrate nanocube electrode shows a good rate capability and cycling stability for electrochemical capacitors. Furthermore, electrodes modified with manganese hexacyanoferrate hydrate nanocubes demonstrate a sensitive electrochemical response to hydrogen peroxide (H2O2) in buffer solutions with a high selectivity.

Sesterterpenes from a common marine sponge, Hyrtios erecta.

PubMed

Crews, P; Bescansa, P

1986-01-01

Eleven sesterterpenes have been characterized from the biotoxic extracts of Hyrtios erecta. Their structures and stereochemistry were established by spectral properties or results from chemical interconversions. Especially valuable for establishing stereochemical features were 13C-nmr methyl shift correlations and analysis of 1H-nmr couplings and chemical shifts. The new scalarane sesterterpenes included 2, 3, 7, 9, and 10a (but 9 and 10a might be artifacts), and they were accompanied by five previously described scalaranes, 1, 4, 5a, 6, and 8, along with hyrtial (11), a novel norsesterterpene. Many of these sesterterpenes exhibited interesting biological activity.

Self-organizing ontology of biochemically relevant small molecules

PubMed Central

2012-01-01

Background The advent of high-throughput experimentation in biochemistry has led to the generation of vast amounts of chemical data, necessitating the development of novel analysis, characterization, and cataloguing techniques and tools. Recently, a movement to publically release such data has advanced biochemical structure-activity relationship research, while providing new challenges, the biggest being the curation, annotation, and classification of this information to facilitate useful biochemical pattern analysis. Unfortunately, the human resources currently employed by the organizations supporting these efforts (e.g. ChEBI) are expanding linearly, while new useful scientific information is being released in a seemingly exponential fashion. Compounding this, currently existing chemical classification and annotation systems are not amenable to automated classification, formal and transparent chemical class definition axiomatization, facile class redefinition, or novel class integration, thus further limiting chemical ontology growth by necessitating human involvement in curation. Clearly, there is a need for the automation of this process, especially for novel chemical entities of biological interest. Results To address this, we present a formal framework based on Semantic Web technologies for the automatic design of chemical ontology which can be used for automated classification of novel entities. We demonstrate the automatic self-assembly of a structure-based chemical ontology based on 60 MeSH and 40 ChEBI chemical classes. This ontology is then used to classify 200 compounds with an accuracy of 92.7%. We extend these structure-based classes with molecular feature information and demonstrate the utility of our framework for classification of functionally relevant chemicals. Finally, we discuss an iterative approach that we envision for future biochemical ontology development. Conclusions We conclude that the proposed methodology can ease the burden of chemical data annotators and dramatically increase their productivity. We anticipate that the use of formal logic in our proposed framework will make chemical classification criteria more transparent to humans and machines alike and will thus facilitate predictive and integrative bioactivity model development. PMID:22221313

Conservation of Dynamics Associated with Biological Function in an Enzyme Superfamily.

PubMed

Narayanan, Chitra; Bernard, David N; Bafna, Khushboo; Gagné, Donald; Chennubhotla, Chakra S; Doucet, Nicolas; Agarwal, Pratul K

2018-03-06

Enzyme superfamily members that share common chemical and/or biological functions also share common features. While the role of structure is well characterized, the link between enzyme function and dynamics is not well understood. We present a systematic characterization of intrinsic dynamics of over 20 members of the pancreatic-type RNase superfamily, which share a common structural fold. This study is motivated by the fact that the range of chemical activity as well as molecular motions of RNase homologs spans over 10 5 folds. Dynamics was characterized using a combination of nuclear magnetic resonance experiments and computer simulations. Phylogenetic clustering led to the grouping of sequences into functionally distinct subfamilies. Detailed characterization of the diverse RNases showed conserved dynamical traits for enzymes within subfamilies. These results suggest that selective pressure for the conservation of dynamical behavior, among other factors, may be linked to the distinct chemical and biological functions in an enzyme superfamily. Copyright © 2018 Elsevier Ltd. All rights reserved.

Unravelling Some of the Structure-Property Relationships in Graphene Oxide at Low Degree of Oxidation.

PubMed

Savazzi, Filippo; Risplendi, Francesca; Mallia, Giuseppe; Harrison, Nicholas M; Cicero, Giancarlo

2018-04-05

Graphene oxide (GO) is a versatile 2D material whose properties can be tuned by changing the type and concentration of oxygen-containing functional groups attached to its surface. However, a detailed knowledge of the dependence of the chemo/physical features of this material on its chemical composition is largely unknown. We combine classical molecular dynamics and density functional theory simulations to predict the structural and electronic properties of GO at low degree of oxidation and suggest a revision of the Lerf-Klinowski model. We find that layer deformation is larger for samples containing high concentrations of epoxy groups and that correspondingly the band gap increases. Targeted chemical modification of the GO surface appears to be an effective route to tailor the electronic properties of the monolayer for given applications. Our simulations also show that the chemical shift of the C-1s XPS peak allows one to unambiguously characterize GO composition, resolving the peak attribution  uncertainty often encountered in experiments.

In-Situ TEM Visualization Of Vacancy Injection And Chemical Partition During Oxidation Of Ni-Cr Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Chong M.; Genc, Arda; Cheng, Huikai

2014-01-14

Oxidation of alloy often involves chemical partition and injection of vacancies. Chemical partition is the consequence of selective oxidation, while injection of vacancies is associated with the differences of diffusivity of cations and anions. It is far from clear as how the injected vacancies behave during oxidation of metal. Using in-situ transmission electron microscopy, we captured unprecedented details on the collective behavior of injected vacancies during oxidation of metal, featuring an initial multi-site oxide nucleation, vacancy supersaturation, nucleation of a single cavity, sinking of vacancies into the cavity and accelerated oxidation of the particle. High sensitive energy dispersive x-ray spectroscopymore » mapping reveals that Cr is preferentially oxidized even at the initial oxidation, leading to a structure that Cr oxide is sandwiched near the inner wall of the hollow particle. The work provides a general guidance on tailoring of nanostructured materials involving multi-ion exchange such as core-shell structured composite nanoparticles.« less

Porous polycarbene-bearing membrane actuator for ultrasensitive weak-acid detection and real-time chemical reaction monitoring.

PubMed

Sun, Jian-Ke; Zhang, Weiyi; Guterman, Ryan; Lin, Hui-Juan; Yuan, Jiayin

2018-04-30

Soft actuators with integration of ultrasensitivity and capability of simultaneous interaction with multiple stimuli through an entire event ask for a high level of structure complexity, adaptability, and/or multi-responsiveness, which is a great challenge. Here, we develop a porous polycarbene-bearing membrane actuator built up from ionic complexation between a poly(ionic liquid) and trimesic acid (TA). The actuator features two concurrent structure gradients, i.e., an electrostatic complexation (EC) degree and a density distribution of a carbene-NH 3 adduct (CNA) along the membrane cross-section. The membrane actuator performs the highest sensitivity among the state-of-the-art soft proton actuators toward acetic acid at 10 -6  mol L -1 (M) level in aqueous media. Through competing actuation of the two gradients, it is capable of monitoring an entire process of proton-involved chemical reactions that comprise multiple stimuli and operational steps. The present achievement constitutes a significant step toward real-life application of soft actuators in chemical sensing and reaction technology.

In-Situ TEM visualization of vacancy injection and chemical partition during oxidation of Ni-Cr nanoparticles

PubMed Central

Wang, Chong-Min; Genc, Arda; Cheng, Huikai; Pullan, Lee; Baer, Donald R.; Bruemmer, Stephen M.

2014-01-01

Oxidation of alloy often involves chemical partition and injection of vacancies. Chemical partition is the consequence of selective oxidation, while injection of vacancies is associated with the differences of diffusivity of cations and anions. It is far from clear as how the injected vacancies behave during oxidation of metal. Using in-situ transmission electron microscopy, we captured unprecedented details on the collective behavior of injected vacancies during oxidation of metal, featuring an initial multi-site oxide nucleation, vacancy supersaturation, nucleation of a single cavity, sinking of vacancies into the cavity and accelerated oxidation of the particle. High sensitive energy dispersive x-ray spectroscopy mapping reveals that Cr is preferentially oxidized even at the initial oxidation, leading to a structure that Cr oxide is sandwiched near the inner wall of the hollow particle. The work provides a general guidance on tailoring of nanostructured materials involving multi-ion exchange such as core-shell structured composite nanoparticles. PMID:24418778

Mass Spectral Library with Search Program, Data Version: NIST v17

National Institute of Standards and Technology Data Gateway

SRD 1A NIST/EPA/NIH Mass Spectral Library with Search Program, Data Version: NIST v17 (PC database for purchase)   Available with full-featured NIST MS Search Program for Windows integrated tools, the NIST '98 is a fully evaluated collection of electron-ionization mass spectra. (147,198 Compounds with Spectra; 147,194 Chemical Structures; 174,948 Spectra )

Simulating the Past, Present and Future of the Upper Troposphere and Lower Stratosphere

NASA Astrophysics Data System (ADS)

Gettelman, Andrew; Hegglin, Michaela

2010-05-01

A comprehensive assessment of coupled chemistry climate model (CCM) performance in the upper troposphere and lower stratosphere has been conducted with 18 models. Both qualitative and quantitative comparisons of model representation of UTLS dynamical, radiative and chemical structure have been conducted, using a collection of quantitative grading techniques. The models are able to reproduce the observed climatology of dynamical, radiative and chemical structure in the tropical and extratropical UTLS, despite relatively coarse vertical and horizontal resolution. Diagnostics of the Tropical Tropopause Layer (TTL), Tropopause Inversion Layer (TIL) and Extra-tropical Transition Layer (ExTL) are analyzed. The results provide new insight into the key processes that govern the dynamics and transport in the tropics and extra-tropicsa. The presentation will explain how models are able to reproduce key features of the UTLS, what features they do not reproduce, and why. Model trends over the historical period are also assessed and interannual variability is included in the metrics. Finally, key trends in the UTLS for the future with a given halogen and greenhouse gas scenario are presented, indicating significant changes in tropopause height and temperature, as well as UTLS ozone concentrations in the 21st century due to climate change and ozone recovery.

Mass Spectrometry Imaging and GC-MS Profiling of the Mammalian Peripheral Sensory-Motor Circuit

NASA Astrophysics Data System (ADS)

Rubakhin, Stanislav S.; Ulanov, Alexander; Sweedler, Jonathan V.

2015-06-01

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has evolved to become an effective discovery tool in science and clinical diagnostics. Here, chemical imaging approaches are applied to well-defined regions of the mammalian peripheral sensory-motor system, including the dorsal root ganglia (DRG) and adjacent nerves. By combining several MSI approaches, analyte coverage is increased and 195 distinct molecular features are observed. Principal component analysis suggests three chemically different regions within the sensory-motor system, with the DRG and adjacent nerve regions being the most distinct. Investigation of these regions using gas chromatography-mass spectrometry corroborate these findings and reveal important metabolic markers related to the observed differences. The heterogeneity of the structurally, physiologically, and functionally connected regions demonstrates the intricate chemical and spatial regulation of their chemical composition.

Features of the electronic structure of FeTe compounds

NASA Astrophysics Data System (ADS)

Grechnev, G. E.; Lyogenkaya, A. A.; Panfilov, A. S.; Logosha, A. V.; Kotlyar, O. V.; Gnezdilov, V. P.; Makarova, I. P.; Chareev, D. A.; Mitrofanova, E. S.

2015-12-01

A theoretical and experimental study of the electronic structure and nature of the chemical bonds in FeTe compounds in antiferromagnetic (AFM) and paramagnetic phases was carried out. It is established that the nature of the chemical bonds is mainly metallic, and the presence of covalent bonds Fe-Te and Te-Te helps to stabilize the structural distortions of the tetragonal phase of FeTe in the low-temperature region. It is found that the bicollinear AFM structure corresponds to the ground state of the FeTe compound and the calculated value of the magnetic moment MFe = -2.4μB is in good agreement with the data from neutron diffraction measurements. At the same time, the Fermi surface (FS) of the low-temperature AFM phase is radically different from the FS of the paramagnetic FeTe. Reconstructing the FS can lead to a sign change of the Hall coefficient observed in FeTe. The calculation results serve as evidence of the fact that the electronic structures and magnetic properties of FeTe are well-described by the model of itinerant d-electrons and the density functional theory (DFT-GGA).

Understanding the structural and chemical changes of plant biomass following steam explosion pretreatment.

PubMed

Auxenfans, Thomas; Crônier, David; Chabbert, Brigitte; Paës, Gabriel

2017-01-01

Biorefining of lignocellulosic biomass has become one of the most valuable alternatives for the production of multi-products such as biofuels. Pretreatment is a prerequisite to increase the enzymatic conversion of the recalcitrant lignocellulose. However, there is still considerable debate regarding the key features of biomass impacting the cellulase accessibility. In this study, we evaluate the structural and chemical features of three different representative biomasses ( Miscanthus × giganteus , poplar and wheat straw), before and after steam explosion pretreatment at increasing severities, by monitoring chemical analysis, SEM, FTIR and 2D NMR. Regardless the biomass type, combined steam explosion pretreatment with dilute sulfuric acid impregnation resulted in significant improvement of the cellulose conversion. Chemical analyses revealed that the pretreatment selectively degraded the hemicellulosic fraction and associated cross-linking ferulic acids. As a result, the pretreated residues contained mostly cellulosic glucose and lignin. In addition, the pretreatment directly affected the cellulose crystallinity but these variations were dependent upon the biomass type. Important chemical modifications also occurred in lignin since the β- O -4' aryl-ether linkages were found to be homolytically cleaved, followed by some recoupling/recondensation to β-β' and β-5' linkages, regardless the biomass type. Finally, 2D NMR analysis of the whole biomass showed that the pretreatment preferentially degraded the syringyl-type lignin fractions in miscanthus and wheat straw while it was not affected in the pretreated poplar samples. Our findings provide an enhanced understanding of parameters impacting biomass recalcitrance, which can be easily generalized to both woody and non-woody biomass species. Results indeed suggest that the hemicellulose removal accompanied by the significant reduction in the cross-linking phenolic acids and the redistribution of lignin are strongly correlated with the enzymatic saccharification, by loosening the cell wall structure thus allowing easier cellulase accessibility. By contrast, we have shown that the changes in the syringyl/guaiacyl ratio and the cellulose crystallinity do not seem to be relevant factors in assessing the enzymatic digestibility. Some biomass type-dependent and easily measurable FTIR factors are highly correlated to saccharification.

Gravitational Instabilities in a Protosolar-like Disc

NASA Astrophysics Data System (ADS)

Evans, Mark Graham

2018-02-01

This thesis presents a study of protoplanetary discs around young, low mass protostars. Such discs are believed to be massive enough to develop gravitational instabilities, which subsequently form spiral structures. The dynamical and chemical evolutions of a protosolar-like, gravitationally unstable disc are explored and the spiral structure in the disc is found to shock-heat material. This affects the chemical composition via enhanced desorption rates and endothermic reaction rates and through global mixing of the disc. As a result, the gravitational instability in the model disc leads to transient and permanent changes in the disc chemistry, and also provides a chemically-rich midplane in contrast to simulations of more evolved discs. Secondly, radiative transfer calculations are performed for the dust continuum, and model-tailored grid construction is found to improve the accuracy of the resultant flux images. Continuum observations of the model disc are synthesised and the spiral structure (driven by the gravitational instability) is shown to be readily detectable with ALMA across a range of frequencies, disc inclinations and dust opacities. The derivation of disc mass from the observed flux densities is explored but the method commonly utilised is found to be unreliable and underestimate the disc mass. Therefore, it is concluded that gravitational instabilities could be retrospectively validated in discs previously thought not massive enough to be self-gravitating. Finally, radiative transfer calculations are performed for molecular line transitions. Methods for improving the accuracy of line flux images are explored and the validity of assuming local thermodynamic equilibrium is assessed. Observations of the line fluxes are synthesised without noise and the spiral structure is found to be traced to an extent by all transitions considered, which is not necessarily congruent with the underlying distribution of the molecular species. The disc is seen in absorption in all transitions considered, due to the global mixing of the disc, which suggests absorption features could be a signature of gravitational instability in young protoplanetary discs. The sensitivities required to detect flux originating in spiral features are determined and it is found that a dedicated observation with ALMA should be capable of spatially resolving spiral structure in a Class 0 disc. Whether the spiral structure can be also be determined from spectral features is explored, which is shown to only be reliable with PV diagrams of nearly edge-on discs. The derivation of protostellar mass from PV diagrams is also explored and found to most likely be unreliable for gravitationally unstable discs.

Phosphatization Associated Features of Ferromanganese Crusts at Lemkein Seamount, Marshall Islands

NASA Astrophysics Data System (ADS)

Choi, J.; Lee, I.; Park, B. K.; Kim, J.

2014-12-01

Old layers of ferromanganese crusts, especially in the Pacific Ocean, have been affected by phosphatization. Ferromanganese crusts on Lemkein seamount in Marshall Islands also are phosphatized (3.3 to 4.2 wt % of P concentration). Furthermore, they have characteristic features that are different from other ferromanganese crusts. These features occur near the phosphorite, which were thought to fill the pore spaces of ferromanganese crusts. Inside the features, ferromanganese crusts are botryoidally precipitated from the round-boundary. The features of the phosphatized lower crusts of Lemkein seamount are observed using microscope and SEM. Elemental compositions of the selected samples were analyzed by SEM-EDS. Based on the observation and analysis of samples, three characteristic structures are identified: (1) phosphate-filled circles, (2) tongue-shaped framboidal crust, and (3) massive framboidal crust. The phosphate-filled circles are mostly composed of phosphorite, and they include trace fossils such as foraminifera. Phosphatized ferromanganese crusts exist at the boundary of this structure. The tongue-shaped crust is connected with the lips downward, and ferromanganese crusts inside the tongue show distinct growth rim. The massive framboidal crust is located below the tongue. Ferromanganese crusts in the massive framboidal crust are enveloped by phosphate, and some of the crusts are phosphatized. Around the structures, Mn oxide phase is concentrated as a shape of corona on BSE image. All of the structures are in the phosphatized crusts that show columnar growth of ferromanganese crusts and have sub-parallel lamination. These observation and chemical analysis of the ferromanganese crusts can provide a clue of diagenetic processes during the formation of ferromanganese crusts.

Dinocyst taphonomy, impact craters, cyst ghosts, and the Paleocene-Eocene thermal maximum (PETM)

USGS Publications Warehouse

Edwards, Lucy E.

2012-01-01

Dinocysts recovered from sediments related to the Chesapeake Bay impact structure in Virginia and the earliest Eocene suboxic environment in Maryland show strange and intriguing details of preservation. Features such as curled processes, opaque debris, breakage, microborings and cyst ghosts, among others, invite speculation about catastrophic depositional processes, rapid burial and biological and chemical decay. Selected specimens from seven cores taken in the coastal plain of Virginia and Maryland show abnormal preservation features in various combinations that merit illustration, description, discussion and further study. Although the depositional environments described are extreme, many of the features discussed are known from, or could be found in, other environments. These environments will show both similarities to and differences from the extreme environments here.

A realistic molecular model of cement hydrates.

PubMed

Pellenq, Roland J-M; Kushima, Akihiro; Shahsavari, Rouzbeh; Van Vliet, Krystyn J; Buehler, Markus J; Yip, Sidney; Ulm, Franz-Josef

2009-09-22

Despite decades of studies of calcium-silicate-hydrate (C-S-H), the structurally complex binder phase of concrete, the interplay between chemical composition and density remains essentially unexplored. Together these characteristics of C-S-H define and modulate the physical and mechanical properties of this "liquid stone" gel phase. With the recent determination of the calcium/silicon (C/S = 1.7) ratio and the density of the C-S-H particle (2.6 g/cm(3)) by neutron scattering measurements, there is new urgency to the challenge of explaining these essential properties. Here we propose a molecular model of C-S-H based on a bottom-up atomistic simulation approach that considers only the chemical specificity of the system as the overriding constraint. By allowing for short silica chains distributed as monomers, dimers, and pentamers, this C-S-H archetype of a molecular description of interacting CaO, SiO2, and H2O units provides not only realistic values of the C/S ratio and the density computed by grand canonical Monte Carlo simulation of water adsorption at 300 K. The model, with a chemical composition of (CaO)(1.65)(SiO2)(H2O)(1.75), also predicts other essential structural features and fundamental physical properties amenable to experimental validation, which suggest that the C-S-H gel structure includes both glass-like short-range order and crystalline features of the mineral tobermorite. Additionally, we probe the mechanical stiffness, strength, and hydrolytic shear response of our molecular model, as compared to experimentally measured properties of C-S-H. The latter results illustrate the prospect of treating cement on equal footing with metals and ceramics in the current application of mechanism-based models and multiscale simulations to study inelastic deformation and cracking.

Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics.

PubMed

Tanzi, Luana; Ramondo, Fabio; Caminiti, Ruggero; Campetella, Marco; Di Luca, Andrea; Gontrani, Lorenzo

2015-09-21

We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations and anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features.

Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics

NASA Astrophysics Data System (ADS)

Tanzi, Luana; Ramondo, Fabio; Caminiti, Ruggero; Campetella, Marco; Di Luca, Andrea; Gontrani, Lorenzo

2015-09-01

We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations and anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features.

Recent Developments in Toxico-Cheminformatics; Supporting ...

EPA Pesticide Factsheets

EPA's National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through the harnessing of legacy toxicity data, creation of data linkages, and generation of new high-content and high-thoughput screening data. In association with EPA's ToxCast, ToxRefDB, and ACToR projects, the DSSTox project provides cheminformatics support and, in addition, is improving public access to quality structure-annotated chemical toxicity information in less summarized forms than traditionally employed in SAR modeling, and in ways that facilitate data-mining and data read-across. The latest DSSTox version of the Carcinogenic Potency Database file (CPDBAS) illustrates ways in which various summary definitions of carcinogenic activity can be employed in modeling and data mining. DSSTox Structure-Browser provides structure searchability across all published DSSTox toxicity-related inventory, and is enabling linkages between previously isolated toxicity data resources associated with environmental and industrial chemicals. The public DSSTox inventory also has been integrated into PubChem, allowing a user to take full advantage of PubChem structure-activity and bioassay clustering features. Phase I of the ToxCast project is generating high-throughput screening data from several hundred biochemical and cell-based assays for a set of 320 chemicals, mostly pesticide actives with rich toxicology profiles. Incorporating

Statistical Analysis of Crystallization Database Links Protein Physico-Chemical Features with Crystallization Mechanisms

PubMed Central

Fusco, Diana; Barnum, Timothy J.; Bruno, Andrew E.; Luft, Joseph R.; Snell, Edward H.; Mukherjee, Sayan; Charbonneau, Patrick

2014-01-01

X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds through knowledge-informed empiricism. Better physico-chemical understanding remains elusive because of the large number of variables involved, hence little guidance is available to systematically identify solution conditions that promote crystallization. To help determine relationships between macromolecular properties and their crystallization propensity, we have trained statistical models on samples for 182 proteins supplied by the Northeast Structural Genomics consortium. Gaussian processes, which capture trends beyond the reach of linear statistical models, distinguish between two main physico-chemical mechanisms driving crystallization. One is characterized by low levels of side chain entropy and has been extensively reported in the literature. The other identifies specific electrostatic interactions not previously described in the crystallization context. Because evidence for two distinct mechanisms can be gleaned both from crystal contacts and from solution conditions leading to successful crystallization, the model offers future avenues for optimizing crystallization screens based on partial structural information. The availability of crystallization data coupled with structural outcomes analyzed through state-of-the-art statistical models may thus guide macromolecular crystallization toward a more rational basis. PMID:24988076

Statistical analysis of crystallization database links protein physico-chemical features with crystallization mechanisms.

PubMed

Fusco, Diana; Barnum, Timothy J; Bruno, Andrew E; Luft, Joseph R; Snell, Edward H; Mukherjee, Sayan; Charbonneau, Patrick

2014-01-01

X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds through knowledge-informed empiricism. Better physico-chemical understanding remains elusive because of the large number of variables involved, hence little guidance is available to systematically identify solution conditions that promote crystallization. To help determine relationships between macromolecular properties and their crystallization propensity, we have trained statistical models on samples for 182 proteins supplied by the Northeast Structural Genomics consortium. Gaussian processes, which capture trends beyond the reach of linear statistical models, distinguish between two main physico-chemical mechanisms driving crystallization. One is characterized by low levels of side chain entropy and has been extensively reported in the literature. The other identifies specific electrostatic interactions not previously described in the crystallization context. Because evidence for two distinct mechanisms can be gleaned both from crystal contacts and from solution conditions leading to successful crystallization, the model offers future avenues for optimizing crystallization screens based on partial structural information. The availability of crystallization data coupled with structural outcomes analyzed through state-of-the-art statistical models may thus guide macromolecular crystallization toward a more rational basis.

Potentiometric and spectroscopic study of the interaction of 3d transition metal ions with inositol hexakisphosphate

NASA Astrophysics Data System (ADS)

Veiga, Nicolás; Macho, Israel; Gómez, Kerman; González, Gabriel; Kremer, Carlos; Torres, Julia

2015-10-01

Among myo-inositol phosphates, the most abundant in nature is the myo-inositol hexakisphosphate, InsP6. Although it is known to be vital to cell functioning, the biochemical research into its metabolism needs chemical and structural analysis of all the protonation, complexation and precipitation processes that it undergoes in the biological media. In view of its high negative charge at physiological level, our group has been leading a thorough research into the InsP6 chemical and structural behavior in the presence of the alkali and alkaline earth metal ions essential for life. The aim of this article is to extend these studies, dealing with the chemical and structural features of the InsP6 interaction with biologically relevant 3d transition metal ions (Fe(II), Fe(III), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II)), in a non-interacting medium and under simulated physiological conditions. The metal-complex stability constants were determined by potentiometry, showing under ligand-excess conditions the formation of mononuclear species in different protonation states. Under metal ion excess, polymetallic species were detected for Fe(II), Fe(III), Zn(II) and Cu(II). Additionally, the 31P NMR and UV-vis spectroscopic studies provided interesting structural aspects of the strong metal ion-InsP6 interaction.

Metabolic biotransformation half-lives in fish: QSAR modeling and consensus analysis.

PubMed

Papa, Ester; van der Wal, Leon; Arnot, Jon A; Gramatica, Paola

2014-02-01

Bioaccumulation in fish is a function of competing rates of chemical uptake and elimination. For hydrophobic organic chemicals bioconcentration, bioaccumulation and biomagnification potential are high and the biotransformation rate constant is a key parameter. Few measured biotransformation rate constant data are available compared to the number of chemicals that are being evaluated for bioaccumulation hazard and for exposure and risk assessment. Three new Quantitative Structure-Activity Relationships (QSARs) for predicting whole body biotransformation half-lives (HLN) in fish were developed and validated using theoretical molecular descriptors that seek to capture structural characteristics of the whole molecule and three data set splitting schemes. The new QSARs were developed using a minimal number of theoretical descriptors (n=9) and compared to existing QSARs developed using fragment contribution methods that include up to 59 descriptors. The predictive statistics of the models are similar thus further corroborating the predictive performance of the different QSARs; Q(2)ext ranges from 0.75 to 0.77, CCCext ranges from 0.86 to 0.87, RMSE in prediction ranges from 0.56 to 0.58. The new QSARs provide additional mechanistic insights into the biotransformation capacity of organic chemicals in fish by including whole molecule descriptors and they also include information on the domain of applicability for the chemical of interest. Advantages of consensus modeling for improving overall prediction and minimizing false negative errors in chemical screening assessments, for identifying potential sources of residual error in the empirical HLN database, and for identifying structural features that are not well represented in the HLN dataset to prioritize future testing needs are illustrated. © 2013.

An ensemble model of QSAR tools for regulatory risk assessment.

PubMed

Pradeep, Prachi; Povinelli, Richard J; White, Shannon; Merrill, Stephen J

2016-01-01

Quantitative structure activity relationships (QSARs) are theoretical models that relate a quantitative measure of chemical structure to a physical property or a biological effect. QSAR predictions can be used for chemical risk assessment for protection of human and environmental health, which makes them interesting to regulators, especially in the absence of experimental data. For compatibility with regulatory use, QSAR models should be transparent, reproducible and optimized to minimize the number of false negatives. In silico QSAR tools are gaining wide acceptance as a faster alternative to otherwise time-consuming clinical and animal testing methods. However, different QSAR tools often make conflicting predictions for a given chemical and may also vary in their predictive performance across different chemical datasets. In a regulatory context, conflicting predictions raise interpretation, validation and adequacy concerns. To address these concerns, ensemble learning techniques in the machine learning paradigm can be used to integrate predictions from multiple tools. By leveraging various underlying QSAR algorithms and training datasets, the resulting consensus prediction should yield better overall predictive ability. We present a novel ensemble QSAR model using Bayesian classification. The model allows for varying a cut-off parameter that allows for a selection in the desirable trade-off between model sensitivity and specificity. The predictive performance of the ensemble model is compared with four in silico tools (Toxtree, Lazar, OECD Toolbox, and Danish QSAR) to predict carcinogenicity for a dataset of air toxins (332 chemicals) and a subset of the gold carcinogenic potency database (480 chemicals). Leave-one-out cross validation results show that the ensemble model achieves the best trade-off between sensitivity and specificity (accuracy: 83.8 % and 80.4 %, and balanced accuracy: 80.6 % and 80.8 %) and highest inter-rater agreement [kappa ( κ ): 0.63 and 0.62] for both the datasets. The ROC curves demonstrate the utility of the cut-off feature in the predictive ability of the ensemble model. This feature provides an additional control to the regulators in grading a chemical based on the severity of the toxic endpoint under study.

An ensemble model of QSAR tools for regulatory risk assessment

DOE PAGES

Pradeep, Prachi; Povinelli, Richard J.; White, Shannon; ...

2016-09-22

Quantitative structure activity relationships (QSARs) are theoretical models that relate a quantitative measure of chemical structure to a physical property or a biological effect. QSAR predictions can be used for chemical risk assessment for protection of human and environmental health, which makes them interesting to regulators, especially in the absence of experimental data. For compatibility with regulatory use, QSAR models should be transparent, reproducible and optimized to minimize the number of false negatives. In silico QSAR tools are gaining wide acceptance as a faster alternative to otherwise time-consuming clinical and animal testing methods. However, different QSAR tools often make conflictingmore » predictions for a given chemical and may also vary in their predictive performance across different chemical datasets. In a regulatory context, conflicting predictions raise interpretation, validation and adequacy concerns. To address these concerns, ensemble learning techniques in the machine learning paradigm can be used to integrate predictions from multiple tools. By leveraging various underlying QSAR algorithms and training datasets, the resulting consensus prediction should yield better overall predictive ability. We present a novel ensemble QSAR model using Bayesian classification. The model allows for varying a cut-off parameter that allows for a selection in the desirable trade-off between model sensitivity and specificity. The predictive performance of the ensemble model is compared with four in silico tools (Toxtree, Lazar, OECD Toolbox, and Danish QSAR) to predict carcinogenicity for a dataset of air toxins (332 chemicals) and a subset of the gold carcinogenic potency database (480 chemicals). Leave-one-out cross validation results show that the ensemble model achieves the best trade-off between sensitivity and specificity (accuracy: 83.8 % and 80.4 %, and balanced accuracy: 80.6 % and 80.8 %) and highest inter-rater agreement [kappa (κ): 0.63 and 0.62] for both the datasets. The ROC curves demonstrate the utility of the cut-off feature in the predictive ability of the ensemble model. In conclusion, this feature provides an additional control to the regulators in grading a chemical based on the severity of the toxic endpoint under study.« less

Teaching structure: student use of software tools for understanding macromolecular structure in an undergraduate biochemistry course.

PubMed

Jaswal, Sheila S; O'Hara, Patricia B; Williamson, Patrick L; Springer, Amy L

2013-01-01

Because understanding the structure of biological macromolecules is critical to understanding their function, students of biochemistry should become familiar not only with viewing, but also with generating and manipulating structural representations. We report a strategy from a one-semester undergraduate biochemistry course to integrate use of structural representation tools into both laboratory and homework activities. First, early in the course we introduce the use of readily available open-source software for visualizing protein structure, coincident with modules on amino acid and peptide bond properties. Second, we use these same software tools in lectures and incorporate images and other structure representations in homework tasks. Third, we require a capstone project in which teams of students examine a protein-nucleic acid complex and then use the software tools to illustrate for their classmates the salient features of the structure, relating how the structure helps explain biological function. To ensure engagement with a range of software and database features, we generated a detailed template file that can be used to explore any structure, and that guides students through specific applications of many of the software tools. In presentations, students demonstrate that they are successfully interpreting structural information, and using representations to illustrate particular points relevant to function. Thus, over the semester students integrate information about structural features of biological macromolecules into the larger discussion of the chemical basis of function. Together these assignments provide an accessible introduction to structural representation tools, allowing students to add these methods to their biochemical toolboxes early in their scientific development. © 2013 by The International Union of Biochemistry and Molecular Biology.

Feature Selection for Chemical Sensor Arrays Using Mutual Information

PubMed Central

Wang, X. Rosalind; Lizier, Joseph T.; Nowotny, Thomas; Berna, Amalia Z.; Prokopenko, Mikhail; Trowell, Stephen C.

2014-01-01

We address the problem of feature selection for classifying a diverse set of chemicals using an array of metal oxide sensors. Our aim is to evaluate a filter approach to feature selection with reference to previous work, which used a wrapper approach on the same data set, and established best features and upper bounds on classification performance. We selected feature sets that exhibit the maximal mutual information with the identity of the chemicals. The selected features closely match those found to perform well in the previous study using a wrapper approach to conduct an exhaustive search of all permitted feature combinations. By comparing the classification performance of support vector machines (using features selected by mutual information) with the performance observed in the previous study, we found that while our approach does not always give the maximum possible classification performance, it always selects features that achieve classification performance approaching the optimum obtained by exhaustive search. We performed further classification using the selected feature set with some common classifiers and found that, for the selected features, Bayesian Networks gave the best performance. Finally, we compared the observed classification performances with the performance of classifiers using randomly selected features. We found that the selected features consistently outperformed randomly selected features for all tested classifiers. The mutual information filter approach is therefore a computationally efficient method for selecting near optimal features for chemical sensor arrays. PMID:24595058

Quantification of microscopic surface features of single point diamond turned optics with subsequent chemical polishing

NASA Astrophysics Data System (ADS)

Cardenas, Nelson; Kyrish, Matthew; Taylor, Daniel; Fraelich, Margaret; Lechuga, Oscar; Claytor, Richard; Claytor, Nelson

2015-03-01

Electro-Chemical Polishing is routinely used in the anodizing industry to achieve specular surface finishes of various metals products prior to anodizing. Electro-Chemical polishing functions by leveling the microscopic peaks and valleys of the substrate, thereby increasing specularity and reducing light scattering. The rate of attack is dependent of the physical characteristics (height, depth, and width) of the microscopic structures that constitute the surface finish. To prepare the sample, mechanical polishing such as buffing or grinding is typically required before etching. This type of mechanical polishing produces random microscopic structures at varying depths and widths, thus the electropolishing parameters are determined in an ad hoc basis. Alternatively, single point diamond turning offers excellent repeatability and highly specific control of substrate polishing parameters. While polishing, the diamond tool leaves behind an associated tool mark, which is related to the diamond tool geometry and machining parameters. Machine parameters such as tool cutting depth, speed and step over can be changed in situ, thus providing control of the spatial frequency of the microscopic structures characteristic of the surface topography of the substrate. By combining single point diamond turning with subsequent electro-chemical etching, ultra smooth polishing of both rotationally symmetric and free form mirrors and molds is possible. Additionally, machining parameters can be set to optimize post polishing for increased surface quality and reduced processing times. In this work, we present a study of substrate surface finish based on diamond turning tool mark spatial frequency with subsequent electro-chemical polishing.

Thermo-mechanical evaluation of carbon-carbon primary structure for SSTO vehicles

NASA Astrophysics Data System (ADS)

Croop, Harold C.; Lowndes, Holland B.; Hahn, Steven E.; Barthel, Chris A.

1998-01-01

An advanced development program to demonstrate carbon-carbon composite structure for use as primary load carrying structure has entered the experimental validation phase. The component being evaluated is a wing torque box section for a single-stage-to-orbit (SSTO) vehicle. The validation or demonstration component features an advanced carbon-carbon design incorporating 3D woven graphite preforms, integral spars, oxidation inhibited matrix, chemical vapor deposited (CVD) oxidation protection coating, and ceramic matrix composite fasteners. The validation component represents the culmination of a four phase design and fabrication development effort. Extensive developmental testing was performed to verify material properties and integrity of basic design features before committing to fabrication of the full scale box. The wing box component is now being set up for testing in the Air Force Research Laboratory Structural Test Facility at Wright-Patterson Air Force Base, Ohio. One of the important developmental tests performed in support of the design and planned testing of the full scale box was the fabrication and test of a skin/spar trial subcomponent. The trial subcomponent incorporated critical features of the full scale wing box design. This paper discusses the results of the trial subcomponent test which served as a pathfinder for the upcoming full scale box test.

Overcoming computational uncertainties to reveal chemical sensitivity in single molecule conduction calculations.

PubMed

Solomon, Gemma C; Reimers, Jeffrey R; Hush, Noel S

2005-06-08

In the calculation of conduction through single molecule's approximations about the geometry and electronic structure of the system are usually made in order to simplify the problem. Previously [G. C. Solomon, J. R. Reimers, and N. S. Hush, J. Chem. Phys. 121, 6615 (2004)], we have shown that, in calculations employing cluster models for the electrodes, proper treatment of the open-shell nature of the clusters is the most important computational feature required to make the results sensitive to variations in the structural and chemical features of the system. Here, we expand this and establish a general hierarchy of requirements involving treatment of geometrical approximations. These approximations are categorized into two classes: those associated with finite-dimensional methods for representing the semi-infinite electrodes, and those associated with the chemisorption topology. We show that ca. 100 unique atoms are required in order to properly characterize each electrode: using fewer atoms leads to nonsystematic variations in conductivity that can overwhelm the subtler changes. The choice of binding site is shown to be the next most important feature, while some effects that are difficult to control experimentally concerning the orientations at each binding site are actually shown to be insignificant. Verification of this result provides a general test for the precision of computational procedures for molecular conductivity. Predictions concerning the dependence of conduction on substituent and other effects on the central molecule are found to be meaningful only when they exceed the uncertainties of the effects associated with binding-site variation.

Overcoming computational uncertainties to reveal chemical sensitivity in single molecule conduction calculations

NASA Astrophysics Data System (ADS)

Solomon, Gemma C.; Reimers, Jeffrey R.; Hush, Noel S.

2005-06-01

In the calculation of conduction through single molecule's approximations about the geometry and electronic structure of the system are usually made in order to simplify the problem. Previously [G. C. Solomon, J. R. Reimers, and N. S. Hush, J. Chem. Phys. 121, 6615 (2004)], we have shown that, in calculations employing cluster models for the electrodes, proper treatment of the open-shell nature of the clusters is the most important computational feature required to make the results sensitive to variations in the structural and chemical features of the system. Here, we expand this and establish a general hierarchy of requirements involving treatment of geometrical approximations. These approximations are categorized into two classes: those associated with finite-dimensional methods for representing the semi-infinite electrodes, and those associated with the chemisorption topology. We show that ca. 100 unique atoms are required in order to properly characterize each electrode: using fewer atoms leads to nonsystematic variations in conductivity that can overwhelm the subtler changes. The choice of binding site is shown to be the next most important feature, while some effects that are difficult to control experimentally concerning the orientations at each binding site are actually shown to be insignificant. Verification of this result provides a general test for the precision of computational procedures for molecular conductivity. Predictions concerning the dependence of conduction on substituent and other effects on the central molecule are found to be meaningful only when they exceed the uncertainties of the effects associated with binding-site variation.

Synthesis, Crystal Structures and Properties of Ferrocenyl Bis-Amide Derivatives Yielded via the Ugi Four-Component Reaction.

PubMed

Zhao, Mei; Shao, Guang-Kui; Huang, Dan-Dan; Lv, Xue-Xin; Guo, Dian-Shun

2017-05-04

Ten ferrocenyl bis-amide derivatives were successfully synthesized via the Ugi four-component reaction by treating ferrocenecarboxylic acid with diverse aldehydes, amines, and isocyanides in methanol solution. Their chemical structures were fully characterized by IR, NMR, HR-MS, and X-ray diffraction analyses. They feature unique molecular morphologies and create a 14-membered ring motif in the centro-symmetric dimers generated in the solid state. Moreover, the electrochemical behavior of these ferrocenyl bis-amides was assessed by cyclic voltammetry.

Highly birefringent polymer microstructured optical fibers embedded in composite materials

NASA Astrophysics Data System (ADS)

Lesiak, P.; SzelÄ g, M.; Kuczkowski, M.; Domański, A. W.; Woliński, T. R.

2013-05-01

Composite structures are made from two or more constituent materials with significantly different physical or chemical properties and they remain separate and distinct in a macroscopic level within the finished structure. This feature allows for introducing highly birefringent polymer microstructured optical fibers into the composite material. These new fibers can consist of only two polymer materials (PMMA and PC) with similar value of the Young modulus as the composite material so any stresses induced in the composite material can be easily measured by the proposed embedded fiber optic sensors.

Morphological and structural studies of CBD-CdS thin films by microscopy and diffraction techniques

NASA Astrophysics Data System (ADS)

Martínez, M. A.; Guillén, C.; Herrero, J.

1998-10-01

The influence of cadmium salt and thiourea concentrations on the morphological and structural properties of chemical bath-deposited CdS thin films has been investigated. Two different feature regimes have been distinguished: an inner continuous layer grown directly on the glass and independent on the deposition conditions, and other porous overlayer, more dependent on the chemical concentrations. Root mean square, RMS, and average roughnesses, Ra, as quantified by AFM, are about 10-13 nm and 7-11 nm, respectively, for all CdS samples tested. These films are sulphur-poor, decreasing S/Cd atomic ratio from 0.82 at low cadmium salt, 1 mM, and high thiourea concentrations, 100 mM, down to 0.76 at higher [Cd 2+], 5 mM, and lower [TU], 10 mM.

Evaluating and enhancing quantum capacitance in graphene-based electrodes from first principles

NASA Astrophysics Data System (ADS)

Ogitsu, Tadashi; Otani, Minoru; Lee, Jonathan; Bagge-Hansen, Michael; Biener, Juergen; Wood, Brandon

2013-03-01

Graphene derivatives are attractive as supercapacitor electrodes because they are lightweight, chemically inert, have high surface area and conductivity, and are stable in electrolyte solutions. Nevertheless, devising reliable strategies for improving energy density relies on an understanding of the specific factors that control electrode performance. We use density-functional theory calculations of pristine and defective graphene to extract quantum capacitance, as well as to identify specific limiting factors. The effect of structural point defects and strain-related morphological changes on the density of states is also evaluated. The results are combined with predicted and measured in situ X-ray absorption spectra in order to give insight into the structural and chemical features present in synthesized carbon aerogel samples. Performed under the auspices of the U.S. DOE by LLNL under Contract DE-AC52-07NA27344.

From QSAR to QSIIR: Searching for Enhanced Computational Toxicology Models

PubMed Central

Zhu, Hao

2017-01-01

Quantitative Structure Activity Relationship (QSAR) is the most frequently used modeling approach to explore the dependency of biological, toxicological, or other types of activities/properties of chemicals on their molecular features. In the past two decades, QSAR modeling has been used extensively in drug discovery process. However, the predictive models resulted from QSAR studies have limited use for chemical risk assessment, especially for animal and human toxicity evaluations, due to the low predictivity of new compounds. To develop enhanced toxicity models with independently validated external prediction power, novel modeling protocols were pursued by computational toxicologists based on rapidly increasing toxicity testing data in recent years. This chapter reviews the recent effort in our laboratory to incorporate the biological testing results as descriptors in the toxicity modeling process. This effort extended the concept of QSAR to Quantitative Structure In vitro-In vivo Relationship (QSIIR). The QSIIR study examples provided in this chapter indicate that the QSIIR models that based on the hybrid (biological and chemical) descriptors are indeed superior to the conventional QSAR models that only based on chemical descriptors for several animal toxicity endpoints. We believe that the applications introduced in this review will be of interest and value to researchers working in the field of computational drug discovery and environmental chemical risk assessment. PMID:23086837

Structural features, substrate specificity, kinetic properties of insect α-amylase and specificity of plant α-amylase inhibitors.

PubMed

Kaur, Rimaljeet; Kaur, Narinder; Gupta, Anil Kumar

2014-11-01

α-Amylase is an important digestive enzyme required for the optimal growth and development of insects. Several insect α-amylases had been purified and their physical and chemical properties were characterized. Insect α-amylases of different orders display variability in structure, properties and substrate specificity. Such diverse properties of amylases could be due to different feeding habits and gut environment of insects. In this review, structural features and properties of several insect α-amylases were compared. This could be helpful in exploring the diversity in characteristics of α-amylase between the members of the same class (insecta). Properties like pH optima are reflected in enzyme structural features. In plants, α-amylase inhibitors (α-AIs) occur as part of natural defense mechanisms against pests by interfering in their digestion process and thus could also provide access to new pest management strategies. AIs are quite specific in their action; therefore, these could be employed according to their effectiveness against target amylases. Potential of transgenics with α-AIs has also been discussed for insect resistance and controlling infestation. The differences in structural features of insect α-amylases provided reasons for their efficient functioning at different pH and the specificity towards various substrates. Various proteinaceous and non-proteinaceous inhibitors discussed could be helpful in controlling pest infestation. In depth detailed studies are required on proteinaceous α-AI-α-amylase interaction at different pH's as well as the insect proteinase action on these inhibitors before selecting the α-AI for making transgenics resistant to particular insect. Copyright © 2014 Elsevier Inc. All rights reserved.

FT-Raman investigation of milled-wood lignins : softwood, hardwood, and chemically modified black spruce lignins

Treesearch

Umesh P. Agarwal; James D. McSweeny; Sally A. Ralph

2011-01-01

Raman spectroscopy is being increasingly applied to study wood and other lignin-containing biomass/biomaterials. Lignin’s contribution to the Raman spectra of such materials needs to be understood in the context of various lignin structures, substructures, and functional groups so that lignin-specific features could be identified and the spectral information could be...

Informing the Human Plasma Protein Binding of Environmental Chemicals by Machine Learning in the Pharmaceutical Space: Applicability Domain and Limits of Predictability.

PubMed

Ingle, Brandall L; Veber, Brandon C; Nichols, John W; Tornero-Velez, Rogelio

2016-11-28

The free fraction of a xenobiotic in plasma (F ub ) is an important determinant of chemical adsorption, distribution, metabolism, elimination, and toxicity, yet experimental plasma protein binding data are scarce for environmentally relevant chemicals. The presented work explores the merit of utilizing available pharmaceutical data to predict F ub for environmentally relevant chemicals via machine learning techniques. Quantitative structure-activity relationship (QSAR) models were constructed with k nearest neighbors (kNN), support vector machines (SVM), and random forest (RF) machine learning algorithms from a training set of 1045 pharmaceuticals. The models were then evaluated with independent test sets of pharmaceuticals (200 compounds) and environmentally relevant ToxCast chemicals (406 total, in two groups of 238 and 168 compounds). The selection of a minimal feature set of 10-15 2D molecular descriptors allowed for both informative feature interpretation and practical applicability domain assessment via a bounded box of descriptor ranges and principal component analysis. The diverse pharmaceutical and environmental chemical sets exhibit similarities in terms of chemical space (99-82% overlap), as well as comparable bias and variance in constructed learning curves. All the models exhibit significant predictability with mean absolute errors (MAE) in the range of 0.10-0.18F ub . The models performed best for highly bound chemicals (MAE 0.07-0.12), neutrals (MAE 0.11-0.14), and acids (MAE 0.14-0.17). A consensus model had the highest accuracy across both pharmaceuticals (MAE 0.151-0.155) and environmentally relevant chemicals (MAE 0.110-0.131). The inclusion of the majority of the ToxCast test sets within the AD of the consensus model, coupled with high prediction accuracy for these chemicals, indicates the model provides a QSAR for F ub that is broadly applicable to both pharmaceuticals and environmentally relevant chemicals.

Understanding the differences in molecular conformation of carbohydrate and protein in endosperm tissues of grains with different biodegradation kinetics using advanced synchrotron technology

NASA Astrophysics Data System (ADS)

Yu, P.; Block, H. C.; Doiron, K.

2009-01-01

Conventional "wet" chemical analyses rely heavily on the use of harsh chemicals and derivatization, thereby altering native seed structures leaving them unable to detect any original inherent structures within an intact tissue sample. A synchrotron is a giant particle accelerator that turns electrons into light (million times brighter than sunlight) which can be used to study the structure of materials at the molecular level. Synchrotron radiation-based Fourier transform IR microspectroscopy (SR-FTIRM) has been developed as a rapid, direct, non-destructive and bioanalytical technique. This technique, taking advantage of the brightness of synchrotron light and a small effective source size, is capable of exploring the molecular chemistry within the microstructures of a biological tissue without the destruction of inherent structures at ultraspatial resolutions within cellular dimensions. This is in contrast to traditional 'wet' chemical methods, which, during processing for analysis, often result in the destruction of the intrinsic structures of feeds. To date there has been very little application of this technique to the study of plant seed tissue in relation to nutrient utilization. The objective of this study was to use novel synchrotron radiation-based technology (SR-FTIRM) to identify the differences in the molecular chemistry and conformation of carbohydrate and protein in various plant seed endosperms within intact tissues at cellular and subcellular level from grains with different biodegradation kinetics. Barley grain (cv. Harrington) with a high rate (31.3%/h) and extent (78%), corn grain (cv. Pioneer) with a low rate (9.6%/h) and extent of (57%), and wheat grain (cv. AC Barrie) with an intermediate rate (23%/h) and extent (72%) of ruminal DM degradation were selected for evaluation. SR-FTIRM evaluations were performed at the National Synchrotron Light Source at the Brookhaven National Laboratory (Brookhaven, NY). The molecular structure spectral analysis involved the fingerprint regions of ca. 1720-1485 cm -1 (attributed to protein amide I C dbnd O and C sbnd N stretching; amide II N sbnd H bending and C sbnd N stretching), ca. 1650-950 cm -1 (non-structural CHO starch in endosperms), and ca. 1185-800 cm -1 (attributed to total CHO C sbnd O stretching vibrations) together with agglomerative hierarchical cluster and principal component analyses. Analyses involving the protein amide I features consistently identified differences between all three grains. Other analyses involving carbohydrate features were able to differentiate between wheat and barley but failed however to differentiate between wheat and corn. These results suggest that SR-FTIRM plus the multivariate analyses can be used to identify spectral features associated with the molecular structure of endosperm from grains with different biodegradation kinetics, especially in relation to protein structure. The Novel synchrotron radiation-based bioanalytical technique provides a new approach for plant seed structural molecular studies at ultraspatial resolution and within intact tissue in relation to nutrient availability.

Computational Insight into Protein Tyrosine Phosphatase 1B Inhibition: A Case Study of the Combined Ligand- and Structure-Based Approach.

PubMed

Zhang, Xiangyu; Jiang, Hailun; Li, Wei; Wang, Jian; Cheng, Maosheng

2017-01-01

Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for treating cancer, obesity, and type 2 diabetes. In our work, the way of combined ligand- and structure-based approach was applied to analyze the characteristics of PTP1B enzyme and its interaction with competitive inhibitors. Firstly, the pharmacophore model of PTP1B inhibitors was built based on the common feature of sixteen compounds. It was found that the pharmacophore model consisted of five chemical features: one aromatic ring (R) region, two hydrophobic (H) groups, and two hydrogen bond acceptors (A). To further elucidate the binding modes of these inhibitors with PTP1B active sites, four docking programs (AutoDock 4.0, AutoDock Vina 1.0, standard precision (SP) Glide 9.7, and extra precision (XP) Glide 9.7) were used. The characteristics of the active sites were then described by the conformations of the docking results. In conclusion, a combination of various pharmacophore features and the integration information of structure activity relationship (SAR) can be used to design novel potent PTP1B inhibitors.

Magnetoconductance signatures of subband structure in semiconductor nanowires

NASA Astrophysics Data System (ADS)

Holloway, Gregory; Haapamaki, Chris; Lapierre, Ray; Baugh, Jonathan

2015-03-01

Understanding the subband structure due to radial confinement in semiconductor nanowires can benefit technologies ranging from optical sensors to quantum information processing. An axial magnetic field couples to the orbital angular momentum, giving rise to non-trivial features in electronic transport as a function of magnetic field. Previous reports focused on conduction electrons confined to a thin shell near the nanowire surface, which lead to flux-periodic energies and conductance oscillations. Here, we calculate the eigenstates for more general radial potentials with moderate to low surface band bending such that electrons are distributed more uniformly across the nanowire cross-section. It is found that the energy spectrum becomes aperiodic in both gate voltage and magnetic field as the radial potential becomes flatter. The behavior of an energy level is dictated by its angular momentum, and this allows, in principle, each state to be identified based on its dependence on magnetic field and the chemical potential. We experimentally investigate a short-channel InAs nanowire FET in search of conductance features that reveal this subband structure. A quantitative measure for assigning conductance features to specific transverse states is introduced and applied to this device.

Evaluation of food-relevant chemicals in the ToxCast high ...

EPA Pesticide Factsheets

There are thousands of chemicals that are directly added to or come in contact with food, many of which have undergone little to no toxicological evaluation. The ToxCast high-throughput screening (HTS) program has evaluated over 1,800 chemicals in concentration-response across ~820 assay endpoints and continues to grow; with all data completely available to the public, this resource serves as a unique opportunity to evaluate the bioactivity of chemicals in vitro. This study investigated the chemical landscape of the food-relevant chemical universe using cheminformatics analyses, and subsequently evaluated the bioactivity of food-relevant chemicals included in the ToxCast HTS program. Initially, a list of 9,437 food-relevant chemicals was compiled by comprehensively mining publicly available sources for direct food additives, food contact substances, indirect food additives, and pesticides. Of these food-relevant chemicals, 4,638 were associated with curated structure definition files amenable to defining physical/chemical features used to generate chemical fingerprints. Clustering was conducted based on the chemical fingerprints using a self-organizing map approach. This revealed that pesticides, food contact substances, and direct food additives generally clustered apart from one another, supporting that these categories reflect not only different uses but also distinct chemistries. Subsequently, 967 of the 9,437 food-relevant chemicals were identified in the T

Feature Analysis of ToxCast Compounds

EPA Science Inventory

ToxCast was initiated by the US Environmental Protection Agency (EPA) to prioritize environmental chemicals for toxicity testing. Phase I generated data for 309 unique chemicals, mostly pesticide actives, that span diverse chemical feature/property space, as determined by quantu...

A DNA-Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition.

PubMed

Favalli, Nicholas; Biendl, Stefan; Hartmann, Marco; Piazzi, Jacopo; Sladojevich, Filippo; Gräslund, Susanne; Brown, Peter J; Näreoja, Katja; Schüler, Herwig; Scheuermann, Jörg; Franzini, Raphael; Neri, Dario

2018-06-01

A DNA-encoded chemical library (DECL) with 1.2 million compounds was synthesized by combinatorial reaction of seven central scaffolds with two sets of 343×492 building blocks. Library screening by affinity capture revealed that for some target proteins, the chemical nature of building blocks dominated the selection results, whereas for other proteins, the central scaffold also crucially contributed to ligand affinity. Molecules based on a 3,5-bis(aminomethyl)benzoic acid core structure were found to bind human serum albumin with a K d value of 6 nm, while compounds with the same substituents on an equidistant but flexible l-lysine scaffold showed 140-fold lower affinity. A 18 nm tankyrase-1 binder featured l-lysine as linking moiety, while molecules based on d-Lysine or (2S,4S)-amino-l-proline showed no detectable binding to the target. This work suggests that central scaffolds which predispose the orientation of chemical building blocks toward the protein target may enhance the screening productivity of encoded libraries. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microbial-Catalyzed Biotransformation of Multifunctional Triterpenoids Derived from Phytonutrients

PubMed Central

Shah, Syed Adnan Ali; Tan, Huey Ling; Sultan, Sadia; Mohd Faridz, Muhammad Afifi Bin; Mohd Shah, Mohamad Azlan Bin; Nurfazilah, Sharifah; Hussain, Munawar

2014-01-01

Microbial-catalyzed biotransformations have considerable potential for the generation of an enormous variety of structurally diversified organic compounds, especially natural products with complex structures like triterpenoids. They offer efficient and economical ways to produce semi-synthetic analogues and novel lead molecules. Microorganisms such as bacteria and fungi could catalyze chemo-, regio- and stereospecific hydroxylations of diverse triterpenoid substrates that are extremely difficult to produce by chemical routes. During recent years, considerable research has been performed on the microbial transformation of bioactive triterpenoids, in order to obtain biologically active molecules with diverse structures features. This article reviews the microbial modifications of tetranortriterpenoids, tetracyclic triterpenoids and pentacyclic triterpenoids. PMID:25003642

Differential role of molten globule and protein folding in distinguishing unique features of botulinum neurotoxin.

PubMed

Kumar, Raj; Kukreja, Roshan V; Cai, Shuowei; Singh, Bal R

2014-06-01

Botulinum neurotoxins (BoNTs) are proteins of great interest not only because of their extreme toxicity but also paradoxically for their therapeutic applications. All the known serotypes (A-G) have varying degrees of longevity and potency inside the neuronal cell. Differential chemical modifications such as phosphorylation and ubiquitination have been suggested as possible mechanisms for their longevity, but the molecular basis of the longevity remains unclear. Since the endopeptidase domain (light chain; LC) of toxin apparently survives inside the neuronal cells for months, it is important to examine the structural features of this domain to understand its resistance to intracellular degradation. Published crystal structures (both botulinum neurotoxins and endopeptidase domain) have not provided adequate explanation for the intracellular longevity of the domain. Structural features obtained from spectroscopic analysis of LCA and LCB were similar, and a PRIME (PReImminent Molten Globule Enzyme) conformation appears to be responsible for their optimal enzymatic activity at 37°C. LCE, on the other hand, was although optimally active at 37°C, but its active conformation differed from the PRIME conformation of LCA and LCB. This study establishes and confirms our earlier finding that an optimally active conformation of these proteins in the form of PRIME exists for the most poisonous poison, botulinum neurotoxin. There are substantial variations in the structural and functional characteristics of these active molten globule related structures among the three BoNT endopeptidases examined. These differential conformations of LCs are important in understanding the fundamental structural features of proteins, and their possible connection to intracellular longevity could provide significant clues for devising new countermeasures and effective therapeutics. Copyright © 2014 Elsevier B.V. All rights reserved.

Reading PDB: perception of molecules from 3D atomic coordinates.

PubMed

Urbaczek, Sascha; Kolodzik, Adrian; Groth, Inken; Heuser, Stefan; Rarey, Matthias

2013-01-28

The analysis of small molecule crystal structures is a common way to gather valuable information for drug development. The necessary structural data is usually provided in specific file formats containing only element identities and three-dimensional atomic coordinates as reliable chemical information. Consequently, the automated perception of molecular structures from atomic coordinates has become a standard task in cheminformatics. The molecules generated by such methods must be both chemically valid and reasonable to provide a reliable basis for subsequent calculations. This can be a difficult task since the provided coordinates may deviate from ideal molecular geometries due to experimental uncertainties or low resolution. Additionally, the quality of the input data often differs significantly thus making it difficult to distinguish between actual structural features and mere geometric distortions. We present a method for the generation of molecular structures from atomic coordinates based on the recently published NAOMI model. By making use of this consistent chemical description, our method is able to generate reliable results even with input data of low quality. Molecules from 363 Protein Data Bank (PDB) entries could be perceived with a success rate of 98%, a result which could not be achieved with previously described methods. The robustness of our approach has been assessed by processing all small molecules from the PDB and comparing them to reference structures. The complete data set can be processed in less than 3 min, thus showing that our approach is suitable for large scale applications.

Modeling the Biodegradability of Chemical Compounds Using the Online CHEmical Modeling Environment (OCHEM).

PubMed

Vorberg, Susann; Tetko, Igor V

2014-01-01

Biodegradability describes the capacity of substances to be mineralized by free-living bacteria. It is a crucial property in estimating a compound's long-term impact on the environment. The ability to reliably predict biodegradability would reduce the need for laborious experimental testing. However, this endpoint is difficult to model due to unavailability or inconsistency of experimental data. Our approach makes use of the Online Chemical Modeling Environment (OCHEM) and its rich supply of machine learning methods and descriptor sets to build classification models for ready biodegradability. These models were analyzed to determine the relationship between characteristic structural properties and biodegradation activity. The distinguishing feature of the developed models is their ability to estimate the accuracy of prediction for each individual compound. The models developed using seven individual descriptor sets were combined in a consensus model, which provided the highest accuracy. The identified overrepresented structural fragments can be used by chemists to improve the biodegradability of new chemical compounds. The consensus model, the datasets used, and the calculated structural fragments are publicly available at http://ochem.eu/article/31660. © 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Chemical ordering in substituted fluorite oxides: a computational investigation of Ho2Zr2O7 and RE2Th2O7 (RE=Ho, Y, Gd, Nd, La).

PubMed

Solomon, Jonathan M; Shamblin, Jacob; Lang, Maik; Navrotsky, Alexandra; Asta, Mark

2016-12-12

Fluorite-structured oxides find widespread use for applications spanning nuclear energy and waste containment, energy conversion, and sensing. In such applications the host tetravalent cation is often partially substituted by trivalent cations, with an associated formation of charge-compensating oxygen vacancies. The stability and properties of such materials are known to be influenced strongly by chemical ordering of the cations and vacancies, and the nature of such ordering and associated energetics are thus of considerable interest. Here we employ density-functional theory (DFT) calculations to study the structure and energetics of cation and oxygen-vacancy ordering in Ho 2 Zr 2 O 7 . In a recent neutron total scattering study, solid solutions in this system were reported to feature local chemical ordering based on the fluorite-derivative weberite structure. The calculations show a preferred chemical ordering qualitatively consistent with these findings, and yield values for the ordering energy of 9.5 kJ/mol-cation. Similar DFT calculations are applied to additional RE 2 Th 2 O 7 fluorite compounds, spanning a range of values for the ratio of the tetravalent and trivalent (RE) cation radii. The results demonstrate that weberite-type order becomes destabilized with increasing values of this size ratio, consistent with an increasing energetic preference for the tetravalent cations to have higher oxygen coordination.

Chemical ordering in substituted fluorite oxides: a computational investigation of Ho2Zr2O7 and RE2Th2O7 (RE=Ho, Y, Gd, Nd, La)

NASA Astrophysics Data System (ADS)

Solomon, Jonathan M.; Shamblin, Jacob; Lang, Maik; Navrotsky, Alexandra; Asta, Mark

2016-12-01

Fluorite-structured oxides find widespread use for applications spanning nuclear energy and waste containment, energy conversion, and sensing. In such applications the host tetravalent cation is often partially substituted by trivalent cations, with an associated formation of charge-compensating oxygen vacancies. The stability and properties of such materials are known to be influenced strongly by chemical ordering of the cations and vacancies, and the nature of such ordering and associated energetics are thus of considerable interest. Here we employ density-functional theory (DFT) calculations to study the structure and energetics of cation and oxygen-vacancy ordering in Ho2Zr2O7. In a recent neutron total scattering study, solid solutions in this system were reported to feature local chemical ordering based on the fluorite-derivative weberite structure. The calculations show a preferred chemical ordering qualitatively consistent with these findings, and yield values for the ordering energy of 9.5 kJ/mol-cation. Similar DFT calculations are applied to additional RE2Th2O7 fluorite compounds, spanning a range of values for the ratio of the tetravalent and trivalent (RE) cation radii. The results demonstrate that weberite-type order becomes destabilized with increasing values of this size ratio, consistent with an increasing energetic preference for the tetravalent cations to have higher oxygen coordination.

Characterization of products from hydrothermal carbonization of pine.

PubMed

Wu, Qiong; Yu, Shitao; Hao, Naijia; Wells, Tyrone; Meng, Xianzhi; Li, Mi; Pu, Yunqiao; Liu, Shouxin; Ragauskas, Arthur J

2017-11-01

This study aims to reveal the structural features and reaction pathways for solid-liquid products from hydrothermal carbonization of Loblolly pine, where the solid products can be used as catalysts, adsorbents and electrode materials while liquid products can be treated yielding fuels and platform chemicals. Results revealed when treated at 240°C, cellulose and hemicellulose were degraded, in part, to 5-hydroxy-methyl furfural and furfural which were further transformed to aromatic structures via ring opening and Diels Alder reactions. Lignin degradation and formation of carbon-carbon bonds, forming aromatic motifs in the presence of furanic compounds connected via aliphatic bridges, ether or condensation reactions. After hydrothermal treatment, condensed aromatic carbon materials with methoxy groups were recovered with high fixed carbon content and HHV. The recovered liquid products are lignin-like value-added chemicals consisting of furfural and polyaromatic structure with alkanes and carboxyl, their total hydroxyl group content decreased when increasing reaction time. Copyright © 2017 Elsevier Ltd. All rights reserved.

From Protein Structure to Small-Molecules: Recent Advances and Applications to Fragment-Based Drug Discovery.

PubMed

Ferreira, Leonardo G; Andricopulo, Adriano D

2017-01-01

Fragment-based drug discovery (FBDD) is a broadly used strategy in structure-guided ligand design, whereby low-molecular weight hits move from lead-like to drug-like compounds. Over the past 15 years, an increasingly important role of the integration of these strategies into industrial and academic research platforms has been successfully established, allowing outstanding contributions to drug discovery. One important factor for the current prominence of FBDD is the better coverage of the chemical space provided by fragment-like libraries. The development of the field relies on two features: (i) the growing number of structurally characterized drug targets and (ii) the enormous chemical diversity available for experimental and virtual screenings. Indeed, fragment-based campaigns have contributed to address major challenges in lead optimization, such as the appropriate physicochemical profile of clinical candidates. This perspective paper outlines the usefulness and applications of FBDD approaches in medicinal chemistry and drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Characterization of products from hydrothermal carbonization of pine

DOE PAGES

Wu, Qiong; Yu, Shitao; Hao, Naijia; ...

2017-07-27

This study aims to reveal the structural features and reaction pathways for solid–liquid products from hydrothermal carbonization of Loblolly pine, where the solid products can be used as catalysts, adsorbents and electrode materials while liquid products can be treated yielding fuels and platform chemicals. Results revealed when treated at 240 °C, cellulose and hemicellulose were degraded, in part, to 5-hydroxy-methyl furfural and furfural which were further transformed to aromatic structures via ring opening and Diels Alder reactions. Lignin degradation and formation of carbon–carbon bonds, forming aromatic motifs in the presence of furanic compounds connected via aliphatic bridges, ether or condensationmore » reactions. After hydrothermal treatment, condensed aromatic carbon materials with methoxy groups were recovered with high fixed carbon content and HHV. As a result, the recovered liquid products are lignin-like value-added chemicals consisting of furfural and polyaromatic structure with alkanes and carboxyl, their total hydroxyl group content decreased when increasing reaction time.« less

COMPUTER-AIDED DRUG DISCOVERY AND DEVELOPMENT (CADDD): in silico-chemico-biological approach

PubMed Central

Kapetanovic, I.M.

2008-01-01

It is generally recognized that drug discovery and development are very time and resources consuming processes. There is an ever growing effort to apply computational power to the combined chemical and biological space in order to streamline drug discovery, design, development and optimization. In biomedical arena, computer-aided or in silico design is being utilized to expedite and facilitate hit identification, hit-to-lead selection, optimize the absorption, distribution, metabolism, excretion and toxicity profile and avoid safety issues. Commonly used computational approaches include ligand-based drug design (pharmacophore, a 3-D spatial arrangement of chemical features essential for biological activity), structure-based drug design (drug-target docking), and quantitative structure-activity and quantitative structure-property relationships. Regulatory agencies as well as pharmaceutical industry are actively involved in development of computational tools that will improve effectiveness and efficiency of drug discovery and development process, decrease use of animals, and increase predictability. It is expected that the power of CADDD will grow as the technology continues to evolve. PMID:17229415

Investigation of composition and structure of spongy and hard bone tissue using FTIR spectroscopy, XRD and SEM

NASA Astrophysics Data System (ADS)

Al-Akhras, M.-Ali H.; Hasan Qaseer, M. K.; Albiss, B. A.; Alebrhim, M. Anwar; Gezawa, Umar S.

2018-02-01

Valuable structural and chemical features can be obtained for spongy and hard bone by infrared spectroscopy and X-ray diffraction. A better understanding of chemical and structural differences between spongy and hard bone is a very important contributor to bone quality. Our data according to IR data showed that the collagen cross-links occurred to be higher in spongy bone, and crystallinity was lower in spongy bone. Deconvolution of the infrared band near 870 cm-1 reveals evidence for A2-type carbonate substitution on hydroxyapatite of spongy bone in addition to the A and B type carbonate substitution that are also found in hard bone. IR and XRD data confirmed the results of each other since full width at half maximum of 002-apatite pattern of XRD showed that the crystallinity was lower in spongy bone. The microstructure was examined by using scanning electron microscope and the result showed that the lattice of thin threads in spongy bone and is less dense than hard bone.

Ta-Nb-Mo-W refractory high-entropy alloys: Anomalous ordering behavior and its intriguing electronic origin

DOE PAGES

Singh, Prashant; Smirnov, A. V.; Johnson, Duane D.

2018-05-31

From electronic-structure-based thermodynamic linear response, we establish chemical ordering behavior in complex solid solutions versus how Gibbs' space is traversed—applying it on prototype refractory A2 Ta-Nb-Mo-W high-entropy alloys. Near ideal stoichiometry, this alloy has anomalous, intricate chemical ordering tendencies, with long-ranged chemical interactions that produce competing short-range order (SRO) with a crossover to spinodal segregation. This atypical SRO arises from canonical band behavior that, with alloying, creates features near the Fermi surface (well defined even with disorder) that change to simple commensurate SRO with (un)filling of these states. In conclusion, our results reveal how complexity and competing electronic effects controlmore » ordering in these alloys.« less

Ta-Nb-Mo-W refractory high-entropy alloys: Anomalous ordering behavior and its intriguing electronic origin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Prashant; Smirnov, A. V.; Johnson, Duane D.

From electronic-structure-based thermodynamic linear response, we establish chemical ordering behavior in complex solid solutions versus how Gibbs' space is traversed—applying it on prototype refractory A2 Ta-Nb-Mo-W high-entropy alloys. Near ideal stoichiometry, this alloy has anomalous, intricate chemical ordering tendencies, with long-ranged chemical interactions that produce competing short-range order (SRO) with a crossover to spinodal segregation. This atypical SRO arises from canonical band behavior that, with alloying, creates features near the Fermi surface (well defined even with disorder) that change to simple commensurate SRO with (un)filling of these states. In conclusion, our results reveal how complexity and competing electronic effects controlmore » ordering in these alloys.« less

Electroactive nanoparticle directed assembly of functionalized graphene nanosheets into hierarchical structures with hybrid compositions for flexible supercapacitors

NASA Astrophysics Data System (ADS)

Choi, Bong Gill; Huh, Yun Suk; Hong, Won Hi; Erickson, David; Park, Ho Seok

2013-04-01

Hierarchical structures of hybrid materials with the controlled compositions have been shown to offer a breakthrough for energy storage and conversion. Here, we report the integrative assembly of chemically modified graphene (CMG) building blocks into hierarchical complex structures with the hybrid composition for high performance flexible pseudocapacitors. The formation mechanism of hierarchical CMG/Nafion/RuO2 (CMGNR) microspheres, which is triggered by the cooperative interplay during the in situ synthesis of RuO2 nanoparticles (NPs), was extensively investigated. In particular, the hierarchical CMGNR microspheres consisting of the aggregates of CMG/Nafion (CMGN) nanosheets and RuO2 NPs provided large surface area and facile ion accessibility to storage sites, while the interconnected nanosheets offered continuous electron pathways and mechanical integrity. The synergistic effect of CMGNR hybrids on the supercapacitor (SC) performance was derived from the hybrid composition of pseudocapacitive RuO2 NPs with the conductive CMGNs as well as from structural features. Consequently, the CMGNR-SCs showed a specific capacitance as high as 160 F g-1, three-fold higher than that of conventional graphene SCs, and a capacitance retention of >95% of the maximum value even after severe bending and 1000 charge-discharge tests due to the structural and compositional features.Hierarchical structures of hybrid materials with the controlled compositions have been shown to offer a breakthrough for energy storage and conversion. Here, we report the integrative assembly of chemically modified graphene (CMG) building blocks into hierarchical complex structures with the hybrid composition for high performance flexible pseudocapacitors. The formation mechanism of hierarchical CMG/Nafion/RuO2 (CMGNR) microspheres, which is triggered by the cooperative interplay during the in situ synthesis of RuO2 nanoparticles (NPs), was extensively investigated. In particular, the hierarchical CMGNR microspheres consisting of the aggregates of CMG/Nafion (CMGN) nanosheets and RuO2 NPs provided large surface area and facile ion accessibility to storage sites, while the interconnected nanosheets offered continuous electron pathways and mechanical integrity. The synergistic effect of CMGNR hybrids on the supercapacitor (SC) performance was derived from the hybrid composition of pseudocapacitive RuO2 NPs with the conductive CMGNs as well as from structural features. Consequently, the CMGNR-SCs showed a specific capacitance as high as 160 F g-1, three-fold higher than that of conventional graphene SCs, and a capacitance retention of >95% of the maximum value even after severe bending and 1000 charge-discharge tests due to the structural and compositional features. Electronic supplementary information (ESI) available: Electrodeposition procedure, TEM, SEM, and AFM images, XPS, FT-IR, and XRD spectra, mechanical strain-stress curve, textural and conductive properties, and impedance spectroscopy. See DOI: 10.1039/c3nr33674c

Accurate prediction of personalized olfactory perception from large-scale chemoinformatic features.

PubMed

Li, Hongyang; Panwar, Bharat; Omenn, Gilbert S; Guan, Yuanfang

2018-02-01

The olfactory stimulus-percept problem has been studied for more than a century, yet it is still hard to precisely predict the odor given the large-scale chemoinformatic features of an odorant molecule. A major challenge is that the perceived qualities vary greatly among individuals due to different genetic and cultural backgrounds. Moreover, the combinatorial interactions between multiple odorant receptors and diverse molecules significantly complicate the olfaction prediction. Many attempts have been made to establish structure-odor relationships for intensity and pleasantness, but no models are available to predict the personalized multi-odor attributes of molecules. In this study, we describe our winning algorithm for predicting individual and population perceptual responses to various odorants in the DREAM Olfaction Prediction Challenge. We find that random forest model consisting of multiple decision trees is well suited to this prediction problem, given the large feature spaces and high variability of perceptual ratings among individuals. Integrating both population and individual perceptions into our model effectively reduces the influence of noise and outliers. By analyzing the importance of each chemical feature, we find that a small set of low- and nondegenerative features is sufficient for accurate prediction. Our random forest model successfully predicts personalized odor attributes of structurally diverse molecules. This model together with the top discriminative features has the potential to extend our understanding of olfactory perception mechanisms and provide an alternative for rational odorant design.

Integrative Chemical-Biological Read-Across Approach for Chemical Hazard Classification

PubMed Central

Low, Yen; Sedykh, Alexander; Fourches, Denis; Golbraikh, Alexander; Whelan, Maurice; Rusyn, Ivan; Tropsha, Alexander

2013-01-01

Traditional read-across approaches typically rely on the chemical similarity principle to predict chemical toxicity; however, the accuracy of such predictions is often inadequate due to the underlying complex mechanisms of toxicity. Here we report on the development of a hazard classification and visualization method that draws upon both chemical structural similarity and comparisons of biological responses to chemicals measured in multiple short-term assays (”biological” similarity). The Chemical-Biological Read-Across (CBRA) approach infers each compound's toxicity from those of both chemical and biological analogs whose similarities are determined by the Tanimoto coefficient. Classification accuracy of CBRA was compared to that of classical RA and other methods using chemical descriptors alone, or in combination with biological data. Different types of adverse effects (hepatotoxicity, hepatocarcinogenicity, mutagenicity, and acute lethality) were classified using several biological data types (gene expression profiling and cytotoxicity screening). CBRA-based hazard classification exhibited consistently high external classification accuracy and applicability to diverse chemicals. Transparency of the CBRA approach is aided by the use of radial plots that show the relative contribution of analogous chemical and biological neighbors. Identification of both chemical and biological features that give rise to the high accuracy of CBRA-based toxicity prediction facilitates mechanistic interpretation of the models. PMID:23848138

Materials prediction via classification learning

DOE PAGES

Balachandran, Prasanna V.; Theiler, James; Rondinelli, James M.; ...

2015-08-25

In the paradigm of materials informatics for accelerated materials discovery, the choice of feature set (i.e. attributes that capture aspects of structure, chemistry and/or bonding) is critical. Ideally, the feature sets should provide a simple physical basis for extracting major structural and chemical trends and furthermore, enable rapid predictions of new material chemistries. Orbital radii calculated from model pseudopotential fits to spectroscopic data are potential candidates to satisfy these conditions. Although these radii (and their linear combinations) have been utilized in the past, their functional forms are largely justified with heuristic arguments. Here we show that machine learning methods naturallymore » uncover the functional forms that mimic most frequently used features in the literature, thereby providing a mathematical basis for feature set construction without a priori assumptions. We apply these principles to study two broad materials classes: (i) wide band gap AB compounds and (ii) rare earth-main group RM intermetallics. The AB compounds serve as a prototypical example to demonstrate our approach, whereas the RM intermetallics show how these concepts can be used to rapidly design new ductile materials. In conclusion, our predictive models indicate that ScCo, ScIr, and YCd should be ductile, whereas each was previously proposed to be brittle.« less

Materials Prediction via Classification Learning

PubMed Central

Balachandran, Prasanna V.; Theiler, James; Rondinelli, James M.; Lookman, Turab

2015-01-01

In the paradigm of materials informatics for accelerated materials discovery, the choice of feature set (i.e. attributes that capture aspects of structure, chemistry and/or bonding) is critical. Ideally, the feature sets should provide a simple physical basis for extracting major structural and chemical trends and furthermore, enable rapid predictions of new material chemistries. Orbital radii calculated from model pseudopotential fits to spectroscopic data are potential candidates to satisfy these conditions. Although these radii (and their linear combinations) have been utilized in the past, their functional forms are largely justified with heuristic arguments. Here we show that machine learning methods naturally uncover the functional forms that mimic most frequently used features in the literature, thereby providing a mathematical basis for feature set construction without a priori assumptions. We apply these principles to study two broad materials classes: (i) wide band gap AB compounds and (ii) rare earth-main group RM intermetallics. The AB compounds serve as a prototypical example to demonstrate our approach, whereas the RM intermetallics show how these concepts can be used to rapidly design new ductile materials. Our predictive models indicate that ScCo, ScIr, and YCd should be ductile, whereas each was previously proposed to be brittle. PMID:26304800

Improved method for predicting protein fold patterns with ensemble classifiers.

PubMed

Chen, W; Liu, X; Huang, Y; Jiang, Y; Zou, Q; Lin, C

2012-01-27

Protein folding is recognized as a critical problem in the field of biophysics in the 21st century. Predicting protein-folding patterns is challenging due to the complex structure of proteins. In an attempt to solve this problem, we employed ensemble classifiers to improve prediction accuracy. In our experiments, 188-dimensional features were extracted based on the composition and physical-chemical property of proteins and 20-dimensional features were selected using a coupled position-specific scoring matrix. Compared with traditional prediction methods, these methods were superior in terms of prediction accuracy. The 188-dimensional feature-based method achieved 71.2% accuracy in five cross-validations. The accuracy rose to 77% when we used a 20-dimensional feature vector. These methods were used on recent data, with 54.2% accuracy. Source codes and dataset, together with web server and software tools for prediction, are available at: http://datamining.xmu.edu.cn/main/~cwc/ProteinPredict.html.

Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gombar, V.K.; Enslein, K.; Hart, J.B.

1991-09-01

A quantitative structure-activity relationship (QSAR) model has been developed to estimate maximum tolerated doses (MTD) from structural features of chemicals and the corresponding oral acute lethal doses (LD50) as determined in male rats. The model is based on a set of 269 diverse chemicals which have been tested under the National Cancer Institute/National Toxicology Program (NCI/NTP) protocols. The rat oral LD50 value was the strongest predictor. Additionally, 22 structural descriptors comprising nine substructural MOLSTAC(c) keys, three molecular connectivity indices, and sigma charges on 10 molecular fragments were identified as endpoint predictors. The model explains 76% of the variance and ismore » significant (F = 35.7) at p less than 0.0001 with a standard error of the estimate of 0.40 in the log (1/mol) units used in Hansch-type equations. Cross-validation showed that the difference between the average deleted residual square (0.179) and the model residual square (0.160) was not significant (t = 0.98).« less

AN OVERVIEW OF COMPUTATIONAL LIFE SCIENCE DATABASES & EXCHANGE FORMATS OF RELEVANCE TO CHEMICAL BIOLOGY RESEARCH

PubMed Central

Hall, Aaron Smalter; Shan, Yunfeng; Lushington, Gerald; Visvanathan, Mahesh

2016-01-01

Databases and exchange formats describing biological entities such as chemicals and proteins, along with their relationships, are a critical component of research in life sciences disciplines, including chemical biology wherein small information about small molecule properties converges with cellular and molecular biology. Databases for storing biological entities are growing not only in size, but also in type, with many similarities between them and often subtle differences. The data formats available to describe and exchange these entities are numerous as well. In general, each format is optimized for a particular purpose or database, and hence some understanding of these formats is required when choosing one for research purposes. This paper reviews a selection of different databases and data formats with the goal of summarizing their purposes, features, and limitations. Databases are reviewed under the categories of 1) protein interactions, 2) metabolic pathways, 3) chemical interactions, and 4) drug discovery. Representation formats will be discussed according to those describing chemical structures, and those describing genomic/proteomic entities. PMID:22934944

An overview of computational life science databases & exchange formats of relevance to chemical biology research.

PubMed

Smalter Hall, Aaron; Shan, Yunfeng; Lushington, Gerald; Visvanathan, Mahesh

2013-03-01

Databases and exchange formats describing biological entities such as chemicals and proteins, along with their relationships, are a critical component of research in life sciences disciplines, including chemical biology wherein small information about small molecule properties converges with cellular and molecular biology. Databases for storing biological entities are growing not only in size, but also in type, with many similarities between them and often subtle differences. The data formats available to describe and exchange these entities are numerous as well. In general, each format is optimized for a particular purpose or database, and hence some understanding of these formats is required when choosing one for research purposes. This paper reviews a selection of different databases and data formats with the goal of summarizing their purposes, features, and limitations. Databases are reviewed under the categories of 1) protein interactions, 2) metabolic pathways, 3) chemical interactions, and 4) drug discovery. Representation formats will be discussed according to those describing chemical structures, and those describing genomic/proteomic entities.

Prediction of chemical biodegradability using support vector classifier optimized with differential evolution.

PubMed

Cao, Qi; Leung, K M

2014-09-22

Reliable computer models for the prediction of chemical biodegradability from molecular descriptors and fingerprints are very important for making health and environmental decisions. Coupling of the differential evolution (DE) algorithm with the support vector classifier (SVC) in order to optimize the main parameters of the classifier resulted in an improved classifier called the DE-SVC, which is introduced in this paper for use in chemical biodegradability studies. The DE-SVC was applied to predict the biodegradation of chemicals on the basis of extensive sample data sets and known structural features of molecules. Our optimization experiments showed that DE can efficiently find the proper parameters of the SVC. The resulting classifier possesses strong robustness and reliability compared with grid search, genetic algorithm, and particle swarm optimization methods. The classification experiments conducted here showed that the DE-SVC exhibits better classification performance than models previously used for such studies. It is a more effective and efficient prediction model for chemical biodegradability.

Environmental Chemistry Compound Identification Using High ...

EPA Pesticide Factsheets

There is a growing need for rapid chemical screening and prioritization to inform regulatory decision-making on thousands of chemicals in the environment. We have previously used high-resolution mass spectrometry to examine household vacuum dust samples using liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS). Using a combination of exact mass, isotope distribution, and isotope spacing, molecular features were matched with a list of chemical formulas from the EPA’s Distributed Structure-Searchable Toxicity (DSSTox) database. This has further developed our understanding of how openly available chemical databases, together with the appropriate searches, could be used for the purpose of compound identification. We report here on the utility of the EPA’s iCSS Chemistry Dashboard for the purpose of compound identification using searches against a database of over 720,000 chemicals. We also examine the benefits of QSAR prediction for the purpose of retention time prediction to allow for alignment of both chromatographic and mass spectral properties. This abstract does not reflect U.S. EPA policy presentation at the Eastern Analytical Symposium.

Chemical compass model of avian magnetoreception.

PubMed

Maeda, Kiminori; Henbest, Kevin B; Cintolesi, Filippo; Kuprov, Ilya; Rodgers, Christopher T; Liddell, Paul A; Gust, Devens; Timmel, Christiane R; Hore, P J

2008-05-15

Approximately 50 species, including birds, mammals, reptiles, amphibians, fish, crustaceans and insects, are known to use the Earth's magnetic field for orientation and navigation. Birds in particular have been intensively studied, but the biophysical mechanisms that underlie the avian magnetic compass are still poorly understood. One proposal, based on magnetically sensitive free radical reactions, is gaining support despite the fact that no chemical reaction in vitro has been shown to respond to magnetic fields as weak as the Earth's ( approximately 50 muT) or to be sensitive to the direction of such a field. Here we use spectroscopic observation of a carotenoid-porphyrin-fullerene model system to demonstrate that the lifetime of a photochemically formed radical pair is changed by application of < or =50 microT magnetic fields, and to measure the anisotropic chemical response that is essential for its operation as a chemical compass sensor. These experiments establish the feasibility of chemical magnetoreception and give insight into the structural and dynamic design features required for optimal detection of the direction of the Earth's magnetic field.

[Pulmonary reaction after furazidin (Furagin). Case report].

PubMed

Zielonka, T M; Demkow, U; Kuś, J

1997-05-01

For the first time in Poland we present the case of pulmonary reaction to furazidin which is by chemical structure closely related to nitrofurantoin. 63 years old woman presented generalized symptoms of acute hypersensitivity reaction induced by furazidin as well as features of chronic pulmonary fibrosis. After few months of treatment with this drug patients complained of weight loss, dyspnea on effort, non-productive cough, chills and fever. Radiological and functional evaluation of respiratory system confirmed features of lung fibrosis. Drug provocation test was positive. In vitro furazidin in low concentrations stimulated proliferation of patient's lymphocytes. After cessation of treatment we have observed rapid improvement of clinical, radiological, biochemical and functional parameters.

Avalanche for shape and feature-based virtual screening with 3D alignment

NASA Astrophysics Data System (ADS)

Diller, David J.; Connell, Nancy D.; Welsh, William J.

2015-11-01

This report introduces a new ligand-based virtual screening tool called Avalanche that incorporates both shape- and feature-based comparison with three-dimensional (3D) alignment between the query molecule and test compounds residing in a chemical database. Avalanche proceeds in two steps. The first step is an extremely rapid shape/feature based comparison which is used to narrow the focus from potentially millions or billions of candidate molecules and conformations to a more manageable number that are then passed to the second step. The second step is a detailed yet still rapid 3D alignment of the remaining candidate conformations to the query conformation. Using the 3D alignment, these remaining candidate conformations are scored, re-ranked and presented to the user as the top hits for further visualization and evaluation. To provide further insight into the method, the results from two prospective virtual screens are presented which show the ability of Avalanche to identify hits from chemical databases that would likely be missed by common substructure-based or fingerprint-based search methods. The Avalanche method is extended to enable patent landscaping, i.e., structural refinements to improve the patentability of hits for deployment in drug discovery campaigns.

The Significance of Interfacial Water Structure in Soluble Salt Flotation Systems.

PubMed

Hancer, M.; Celik, M. S.; Miller, J. D.

2001-03-01

Flotation of soluble salts with dodecyl amine hydrochloride (DAH) and sodium dodecyl sulfate (SDS) collectors has demonstrated that the interfacial water structure and hydration states of soluble salt surfaces together with the precipitation tendency of the corresponding collector salts are of considerable importance in explaining their flotation behavior. In particular, the high concentration of ions in these soluble salt brines and their hydration appear to modify the bulk and interfacial structure of water as revealed by contact angle measurements and this effect is shown to be an important feature in the flotation chemistry of soluble salt minerals including alkali halide and alkali oxyanion salts. Depending on characteristic chemical features (salt type), the salt can serve either as a structure maker, in which intermolecular hydrogen bonding between water molecules is facilitated, or as a structure breaker, in which intermolecular hydrogen bonding between water molecules is disrupted. For structure making salts the brine completely wets the salt surface and no contact angle can be measured. For structure breaking salts the brine does not completely wet the salt surface and a finite contact angle is measured. In this regard it has been found that soluble salt flotation either with the cationic DAH or anionic SDS collector is possible only if the salt is a structure breaker. Copyright 2001 Academic Press.

Humic Substances in Organic Wastes and their Effects on Amended Soils

NASA Astrophysics Data System (ADS)

Senesi, N.; Ciavatta, C.; Plaza, C.

2009-04-01

Soil humic substances (HS) are universally recognized to play a major role in a wide number of agronomic and environmental processes. For example, soil HS are able to bind mineral particles together, thus promoting a good soil structure, constitute an important source of nutrients for plants and microorganisms, contribute largely to the acid-base buffering capacity of soils, and exert a marked control on the biological availability, physico-chemical behavior, and environmental fate of toxic metal ions and xenobiotics. For these reasons, the knowledge of the short- and long-term effects of organic amendments on the status, quality, and reactivity of indigenous soil HS is of paramount importance. The objective of this presentation is to provide an overview of the chemical and physico-chemical data available in the literature for the evaluation of the effects of organic wastes of various origin and nature used as soil amendments on the composition, structure, and chemical reactivity of native soil HS. In general, HS-like components of organic wastes are typically characterized by a relatively larger presence of aliphatic, amide, and polysaccharide structures, simple structural components of wide molecular heterogeneity, smaller contents of oxygen, acidic functional groups, and organic free radicals, and smaller degrees of aromatic ring polycondensation, polymerization, and humification than native soil HS. Further, with respect to native soil HS, HS-like fractions from organic wastes generally exhibit smaller binding capacities and affinities for metal ions and organic xenobiotics. Appropriate treatment processes of raw organic wastes able to produce environmentally safe and agronomically efficient soil amendments, such as composting, yield HS-like fractions characterized by chemical and physico-chemical features that approach those of native soil HS. In general, aliphatic, polysaccharide, and lignin structures and S- and N-containing groups of the HS-like fractions of organic wastes can be partially incorporated into native soil HS determining modifications at various extents of their composition, structure, and chemistry. The changes occurred in amended soil HS are more evident when untreated organic materials are used. However, with increasing time after land application, the effects observed become less and less apparent with a clear trend to approach the molecular properties typical of native soil HS.

Inducamides A–C, Chlorinated Alkaloids from an RNA Polymerase Mutant Strain of Streptomyces sp.

PubMed Central

2015-01-01

Inducamides A–C (1–3), three new chlorinated alkaloids featuring an amide skeleton generated by a tryptophan fragment and a 6-methylsalicylic acid unit, were isolated from a chemically induced mutant strain of Streptomyces sp. with the inducamides only being produced in the mutant strain. Their structures, including stereochemistry, were determined by spectroscopic analysis, Marfey’s method, and CD spectroscopy. PMID:25338006

Electronic laboratory notebook: the academic point of view.

PubMed

Rudolphi, Felix; Goossen, Lukas J

2012-02-27

Based on a requirement analysis and alternative design considerations, a platform-independent electronic laboratory notebook (ELN) has been developed that specifically targets academic users. Its intuitive design and numerous productivity features motivate chemical researchers and students to record their data electronically. The data are stored in a highly structured form that offers substantial benefits over laboratory notebooks written on paper with regard to data retrieval, data mining, and exchange of results.

The influence of glacial meltwater on alpine aquatic ecosystems: a review.

PubMed

Slemmons, Krista E H; Saros, Jasmine E; Simon, Kevin

2013-10-01

The recent and rapid recession of alpine glaciers over the last 150 years has major implications for associated aquatic communities. Glacial meltwater shapes many of the physical features of high altitude lakes and streams, producing turbid environments with distinctive hydrology patterns relative to nival systems. Over the past decade, numerous studies have investigated the chemical and biological effects of glacial meltwater on freshwater ecosystems. Here, we review these studies across both lake and stream ecosystems. Focusing on alpine regions mainly in the Northern Hemisphere, we present examples of how glacial meltwater can affect habitat by altering physical and chemical features of aquatic ecosystems, and review the subsequent effects on the biological structure and function of lakes and streams. Collectively or separately, these factors can drive the overall distribution, diversity and behavior of primary producers, triggering cascading effects throughout the food web. We conclude by proposing areas for future research, particularly in regions where glaciers are soon projected to disappear.

Comparison of seven types of thermo-chemical pretreatments on the structural features and anaerobic digestion of sunflower stalks.

PubMed

Monlau, F; Barakat, A; Steyer, J P; Carrere, H

2012-09-01

Sunflower stalks can be used for the production of methane, but their recalcitrant structure requires the use of thermo-chemical pretreatments. Two thermal (55 and 170°C) and five thermo-chemical pretreatments (NaOH, H(2)O(2), Ca(OH)(2), HCl and FeCl(3)) were carried out, followed by anaerobic digestion. The highest methane production (259 ± 6 mL CH(4)g(-1) VS) was achieved after pretreatment at 55°C with 4% NaOH for 24h. Acidic pretreatments at 170°C removed more than 90% of hemicelluloses and uronic acids whereas alkaline and oxidative pretreatments were more effective in dissolving lignin. However, no pretreatment was effective in reducing the crystallinity of cellulose. Methane production rate was positively correlated with the amount of solubilized matter whereas methane potential was negatively correlated with the amount of lignin. Considering that the major challenge is obtaining increased methane potential, alkaline pretreatments can be recommended in order to optimize the anaerobic digestion of lignocellulosic substrates. Copyright © 2012 Elsevier Ltd. All rights reserved.

Luminescence studies of HgCdTe- and InAsSb-based quantum-well structures

NASA Astrophysics Data System (ADS)

Izhnin, I. I.; Izhnin, A. I.; Fitsych, O. I.; Voitsekhovskii, A. V.; Gorn, D. I.; Semakova, A. A.; Bazhenov, N. L.; Mynbaev, K. D.; Zegrya, G. G.

2018-04-01

Results of photoluminescence studies of single-quantum-well HgCdTe-based structures and electroluminescence studies of multiple-quantum-well InAsSb-based structures are reported. HgCdTe structures were grown with molecular beam epitaxy on GaAs substrates. InAsSb-based structures were grown with metal-organic chemical vapor deposition on InAs substrates. The common feature of luminescence spectra of all the structures was the presence of peaks with the energy much larger than that of calculated optical transitions between the first quantization levels for electrons and heavy holes. Possibility of observation of optical transitions between the quantization levels of electrons and first and/or second heavy and light hole levels is discussed in the paper in relation to the specifics of the electronic structure of the materials under consideration.

Exploring the atomic structure of 1.8nm monolayer-protected gold clusters with aberration-corrected STEM.

PubMed

Liu, Jian; Jian, Nan; Ornelas, Isabel; Pattison, Alexander J; Lahtinen, Tanja; Salorinne, Kirsi; Häkkinen, Hannu; Palmer, Richard E

2017-05-01

Monolayer-protected (MP) Au clusters present attractive quantum systems with a range of potential applications e.g. in catalysis. Knowledge of the atomic structure is needed to obtain a full understanding of their intriguing physical and chemical properties. Here we employed aberration-corrected scanning transmission electron microscopy (ac-STEM), combined with multislice simulations, to make a round-robin investigation of the atomic structure of chemically synthesised clusters with nominal composition Au 144 (SCH 2 CH 2 Ph) 60 provided by two different research groups. The MP Au clusters were "weighed" by the atom counting method, based on their integrated intensities in the high angle annular dark field (HAADF) regime and calibrated exponent of the Z dependence. For atomic structure analysis, we compared experimental images of hundreds of clusters, with atomic resolution, against a variety of structural models. Across the size range 123-151 atoms, only 3% of clusters matched the theoretically predicted Au 144 (SR) 60 structure, while a large proportion of the clusters were amorphous (i.e. did not match any model structure). However, a distinct ring-dot feature, characteristic of local icosahedral symmetry, was observed in about 20% of the clusters. Copyright © 2017. Published by Elsevier B.V.

Testing the limits of sensitivity in a solid-state structural investigation by combined X-ray powder diffraction, solid-state NMR, and molecular modelling.

PubMed

Filip, Xenia; Borodi, Gheorghe; Filip, Claudiu

2011-10-28

A solid state structural investigation of ethoxzolamide is performed on microcrystalline powder by using a multi-technique approach that combines X-ray powder diffraction (XRPD) data analysis based on direct space methods with information from (13)C((15)N) solid-state Nuclear Magnetic Resonance (SS-NMR) and molecular modeling. Quantum chemical computations of the crystal were employed for geometry optimization and chemical shift calculations based on the Gauge Including Projector Augmented-Wave (GIPAW) method, whereas a systematic search in the conformational space was performed on the isolated molecule using a molecular mechanics (MM) approach. The applied methodology proved useful for: (i) removing ambiguities in the XRPD crystal structure determination process and further refining the derived structure solutions, and (ii) getting important insights into the relationship between the complex network of non-covalent interactions and the induced supra-molecular architectures/crystal packing patterns. It was found that ethoxzolamide provides an ideal case study for testing the accuracy with which this methodology allows to distinguish between various structural features emerging from the analysis of the powder diffraction data. This journal is © the Owner Societies 2011

Initiation structure of oblique detonation waves behind conical shocks

NASA Astrophysics Data System (ADS)

Yang, Pengfei; Ng, Hoi Dick; Teng, Honghui; Jiang, Zonglin

2017-08-01

The understanding of oblique detonation dynamics has both inherent basic research value for high-speed compressible reacting flow and propulsion application in hypersonic aerospace systems. In this study, the oblique detonation structures formed by semi-infinite cones are investigated numerically by solving the unsteady, two-dimensional axisymmetric Euler equations with a one-step irreversible Arrhenius reaction model. The present simulation results show that a novel wave structure, featured by two distinct points where there is close-coupling between the shock and combustion front, is depicted when either the cone angle or incident Mach number is reduced. This structure is analyzed by examining the variation of the reaction length scale and comparing the flow field with that of planar, wedge-induced oblique detonations. Further simulations are performed to study the effects of chemical length scale and activation energy, which are both found to influence the formation of this novel structure. The initiation mechanism behind the conical shock is discussed to investigate the interplay between the effect of the Taylor-Maccoll flow, front curvature, and energy releases from the chemical reaction in conical oblique detonations. The observed flow fields are interpreted by means of the energetic limit as in the critical regime for initiation of detonation.

Further exploration of the conformational space of α-synuclein fibrils: solid-state NMR assignment of a high-pH polymorph.

PubMed

Verasdonck, Joeri; Bousset, Luc; Gath, Julia; Melki, Ronald; Böckmann, Anja; Meier, Beat H

2016-04-01

Polymorphism is a common and important phenomenon for protein fibrils which has been linked to the appearance of strains in prion and other neurodegenerative diseases. Parkinson disease is a frequently occurring neurodegenerative pathology, tightly associated with the formation of Lewy bodies. These deposits mainly consist of α-synuclein in fibrillar, β-sheet-rich form. α-synuclein is known to form numerous different polymorphs, which show distinct structural features. Here, we describe the chemical shift assignments, and derive the secondary structure, of a polymorph that was fibrillized at higher-than-physiological pH conditions. The fibrillar core contains residues 40-95, with both the C- and N-terminus not showing any ordered, rigid parts. The chemical shifts are similar to those recorded previously for an assigned polymorph that was fibrillized at neutral pH.

Enhancement mechanism of field electron emission properties in hybrid carbon nanotubes with tree- and wing-like features

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, G.M.; School of Materials Science and Engineering, The University of New South Wales, NSW 2052; Yang, C.C., E-mail: ccyang@unsw.edu.a

2009-12-15

In this work, the tree-like carbon nanotubes (CNTs) with branches of different diameters and the wing-like CNTs with graphitic-sheets of different densities were synthesized by using plasma enhanced chemical vapor deposition. The nanostructures of the as-prepared hybrid carbon materials were characterized by scanning electron microscopy and transmission electron microscopy. The structural dependence of field electron emission (FEE) property was also investigated. It is found that both of the tree- and wing-like CNTs exhibit a lower turn-on field and higher emission current density than the pristine CNTs, which can be ascribed to the effects of branch size, crystal orientation, and graphitic-sheetmore » density. - Graphical abstract: Tree-like carbon nanotubes (CNTs) with branches and the wing-like CNTs with graphitic-sheets were synthesized by using plasma enhanced chemical vapor deposition. The structural dependence of field electron emission property was also investigated.« less

Anharmonic vibrational spectroscopy, NBO charges and global chemical reactivity studies on the charge transfer PDCA-.AHMP+ single crystal using DFT calculations

NASA Astrophysics Data System (ADS)

Faizan, Mohd; Afroz, Ziya; Bhat, Sheeraz Ahmad; Alam, Mohamad Jane; Ahmad, Shabbir; Ahmad, Afaq

2018-04-01

The charge transfer (CT) complex of the 2-amino-4-hydroxy-6-methylpyrimidine and 2,3 pyrazinedicarboxylic acid (PDCA-.AHMP+) was synthesized and its single crystal was grown by solution method. The structure of the crystalline complex has been investigated by single crystal X-ray diffraction (SCXRD). The vibrational features of the complex have been studied with the help of FTIR spectra and DFT computation. The anharmonic corrections in vibrational frequencies are made using the GVPT2 method at B3LYP/6-311++G(d,p) level of theory. The frontier molecular orbitals and global chemical reactivity have been calculated to understand the pharmacological aspect of the synthesized crystal. Furthermore, Hirshfeld electrostatic potential (ESP) surface, void space in the crystal structure and natural as well as Mulliken atomic charges are studied.

3rd annual symposium of chemical and pharmaceutical structure analysis.

PubMed

Weng, Naidong; Zheng, Jenny; Lee, Mike

2012-08-01

The 3rd Annual Symposium on Chemical and Pharmaceutical Structure Analysis was once again held in Shanghai, where a rich history of 'East meets West' continued. This meeting is dedicated to bringing together scientists from pharmaceutical companies, academic institutes, CROs and instrument vendors to discuss current challenges and opportunities on the forefront of pharmaceutical research and development. The diversified symposia and roundtables are highly interactive events where scientists share their experiences and visions in a collegial setting. The symposium highlighted speakers and sessions that provided first-hand experiences as well as the latest guidance and industrial/regulatory thinking, which was reflected by the theme of this year's meeting 'From Bench to Decision Making - from Basics to Application.' In addition to the highly successful Young Scientist Excellence Award, new events were featured at this year's meeting, such as the Executive Roundtable and the inaugural Innovator Award.

Effect of growth parameters on the optical properties of ZnO nanostructures grown by simple solution methods

NASA Astrophysics Data System (ADS)

Kothari, Anjana

2017-05-01

ZnO, a wide band gap semiconductor is of significant interest for a range of practical applications. One of the highly attractive features of ZnO is to grow variety of nanostructures by using low-cost techniques. In this paper, we report deposition of ZnO nanostructure rod-arrays (NRA) via low-temperature, solution-based deposition techniques such as chemical bath deposition (CBD) and microwave-assisted chemical bath deposition (MACBD). A detailed study of film deposition parameters such as variation in concentration of precursors and deposition temperature has been carried out. Compositional and structural study of the films has been done by X-ray Diffractometer to know the phase and purity of the final product. Morphological study of these structures has been carried out by Scanning Electron Microscopy. Optical study such as transmittance and diffuse reflectance of the films has been carried out as a function of growth parameters.

Recent Progress in Monolithic Silica Columns for High-Speed and High-Selectivity Separations.

PubMed

Ikegami, Tohru; Tanaka, Nobuo

2016-06-12

Monolithic silica columns have greater (through-pore size)/(skeleton size) ratios than particulate columns and fixed support structures in a column for chemical modification, resulting in high-efficiency columns and stationary phases. This review looks at how the size range of monolithic silica columns has been expanded, how high-efficiency monolithic silica columns have been realized, and how various methods of silica surface functionalization, leading to selective stationary phases, have been developed on monolithic silica supports, and provides information on the current status of these columns. Also discussed are the practical aspects of monolithic silica columns, including how their versatility can be improved by the preparation of small-sized structural features (sub-micron) and columns (1 mm ID or smaller) and by optimizing reaction conditions for in situ chemical modification with various restrictions, with an emphasis on recent research results for both topics.

Molecular structure, chemical reactivity, nonlinear optical activity and vibrational spectroscopic studies on 6-(4-n-heptyloxybenzyoloxy)-2-hydroxybenzylidene)amino)-2H-chromen-2-one: A combined density functional theory and experimental approach

NASA Astrophysics Data System (ADS)

Pegu, David; Deb, Jyotirmoy; Saha, Sandip Kumar; Paul, Manoj Kumar; Sarkar, Utpal

2018-05-01

In this work, we have synthesized new coumarin Schiff base molecule, viz., 6-(4-n-heptyloxybenzyoloxy)-2-hydroxybenzylidene)amino)-2H-chromen-2-one and characterized its structural, electronic and spectroscopic properties experimentally and theoretically. The theoretical analysis of UV-visible absorption spectra reflects a red shift in the absorption maximum in comparison to the experimental results. Most of the vibrational assignments of infrared and Raman spectra predicted using density functional theory approach match well with the experimental findings. Further, the chemical reactivity analysis confirms that solvent highly affects the reactivity of the studied compound. The large hyperpolarizability value of the compound concludes that the system exhibits significant nonlinear optical features and thus, points out their possibility in designing material with high nonlinear activity.

Probing the chemical interaction space governed by 4-aminosubstituted benzenesulfonamides and carbonic anhydrase isoforms.

PubMed

Rasti, Behnam; Heravi, Yeganeh Entezari

2018-06-01

Isoform diversity, critical physiological roles and involvement in major diseases/disorders such as glaucoma, epilepsy, Alzheimer's disease, obesity, and cancers have made carbonic anhydrase (CA), one of the most interesting case studies in the field of computer aided drug design. Since applying non-selective inhibitors can result in major side effects, there have been considerable efforts so far to achieve selective inhibitors for different isoforms of CA. Using proteochemometrics approach, the chemical interaction space governed by a group of 4-amino-substituted benzenesulfonamides and human CAs has been explored in the present study. Several validation methods have been utilized to assess the validity, robustness and predictivity power of the proposed proteochemometric model. Our model has offered major structural information that can be applied to design new selective inhibitors for distinct isoforms of CA. To prove the applicability of the proposed model, new compounds have been designed based on the offered discriminative structural features.

Crystal Graph Convolutional Neural Networks for an Accurate and Interpretable Prediction of Material Properties

NASA Astrophysics Data System (ADS)

Xie, Tian; Grossman, Jeffrey C.

2018-04-01

The use of machine learning methods for accelerating the design of crystalline materials usually requires manually constructed feature vectors or complex transformation of atom coordinates to input the crystal structure, which either constrains the model to certain crystal types or makes it difficult to provide chemical insights. Here, we develop a crystal graph convolutional neural networks framework to directly learn material properties from the connection of atoms in the crystal, providing a universal and interpretable representation of crystalline materials. Our method provides a highly accurate prediction of density functional theory calculated properties for eight different properties of crystals with various structure types and compositions after being trained with 1 04 data points. Further, our framework is interpretable because one can extract the contributions from local chemical environments to global properties. Using an example of perovskites, we show how this information can be utilized to discover empirical rules for materials design.

Predicting Drug-induced Hepatotoxicity Using QSAR and Toxicogenomics Approaches

PubMed Central

Low, Yen; Uehara, Takeki; Minowa, Yohsuke; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro; Sedykh, Alexander; Muratov, Eugene; Fourches, Denis; Zhu, Hao; Rusyn, Ivan; Tropsha, Alexander

2014-01-01

Quantitative Structure-Activity Relationship (QSAR) modeling and toxicogenomics are used independently as predictive tools in toxicology. In this study, we evaluated the power of several statistical models for predicting drug hepatotoxicity in rats using different descriptors of drug molecules, namely their chemical descriptors and toxicogenomic profiles. The records were taken from the Toxicogenomics Project rat liver microarray database containing information on 127 drugs (http://toxico.nibio.go.jp/datalist.html). The model endpoint was hepatotoxicity in the rat following 28 days of exposure, established by liver histopathology and serum chemistry. First, we developed multiple conventional QSAR classification models using a comprehensive set of chemical descriptors and several classification methods (k nearest neighbor, support vector machines, random forests, and distance weighted discrimination). With chemical descriptors alone, external predictivity (Correct Classification Rate, CCR) from 5-fold external cross-validation was 61%. Next, the same classification methods were employed to build models using only toxicogenomic data (24h after a single exposure) treated as biological descriptors. The optimized models used only 85 selected toxicogenomic descriptors and had CCR as high as 76%. Finally, hybrid models combining both chemical descriptors and transcripts were developed; their CCRs were between 68 and 77%. Although the accuracy of hybrid models did not exceed that of the models based on toxicogenomic data alone, the use of both chemical and biological descriptors enriched the interpretation of the models. In addition to finding 85 transcripts that were predictive and highly relevant to the mechanisms of drug-induced liver injury, chemical structural alerts for hepatotoxicity were also identified. These results suggest that concurrent exploration of the chemical features and acute treatment-induced changes in transcript levels will both enrich the mechanistic understanding of sub-chronic liver injury and afford models capable of accurate prediction of hepatotoxicity from chemical structure and short-term assay results. PMID:21699217

Survey of marine natural product structure revisions: a synergy of spectroscopy and chemical synthesis

PubMed Central

Suyama, Takashi L.; Gerwick, William H.; McPhail, Kerry L.

2011-01-01

The structural assignment of new natural product molecules supports research in a multitude of disciplines that may lead to new therapeutic agents and or new understanding of disease biology. However, reports of numerous structural revisions, even of recently elucidated natural products, inspired the present survey of techniques used in structural misassignments and subsequent revisions in the context of constitutional or configurational errors. Given the comparatively recent development of marine natural products chemistry, coincident with the modern spectroscopy, it is of interest to consider the relative roles of spectroscopy and chemical synthesis in the structure elucidation and revision of those marine natural products which were initially misassigned. Thus, a tabulated review of all marine natural product structural revisions from 2005 to 2010 is organized according to structural motif revised. Misassignments of constitution are more frequent than perhaps anticipated by reliance on HMBC and other advanced NMR experiments, especially considering the full complement of all natural products. However, these techniques also feature prominently in structural revisions, specifically of marine natural products. Nevertheless, as is the case for revision of relative and absolute configuration, total synthesis is a proven partner for marine, as well as terrestrial, natural products structure elucidation. It also becomes apparent that considerable ‘detective work’ remains in structure elucidation, in spite of the spectacular advances in spectroscopic techniques. PMID:21715178

Ultrastructural analysis of chemical synapses and gap junctions between Drosophila brain neurons in culture.

PubMed

Oh, Hyun-Woo; Campusano, Jorge M; Hilgenberg, Lutz G W; Sun, Xicui; Smith, Martin A; O'Dowd, Diane K

2008-02-15

Dissociated cultures from many species have been important tools for exploring factors that regulate structure and function of central neuronal synapses. We have previously shown that cells harvested from brains of late stage Drosophila pupae can regenerate their processes in vitro. Electrophysiological recordings demonstrate the formation of functional synaptic connections as early as 3 days in vitro (DIV), but no information about synapse structure is available. Here, we report that antibodies against pre-synaptic proteins Synapsin and Bruchpilot result in punctate staining of regenerating neurites. Puncta density increases as neuritic plexuses develop over the first 4 DIV. Electron microscopy reveals that closely apposed neurites can form chemical synapses with both pre- and postsynaptic specializations characteristic of many inter-neuronal synapses in the adult brain. Chemical synapses in culture are restricted to neuritic processes and some neurite pairs form reciprocal synapses. GABAergic synapses have a significantly higher percentage of clear core versus granular vesicles than non-GABA synapses. Gap junction profiles, some adjacent to chemical synapses, suggest that neurons in culture can form purely electrical as well as mixed synapses, as they do in the brain. However, unlike adult brain, gap junctions in culture form between neuronal somata as well as neurites, suggesting soma ensheathing glia, largely absent in culture, regulate gap junction location in vivo. Thus pupal brain cultures, which support formation of interneuronal synapses with structural features similar to synapses in adult brain, are a useful model system for identifying intrinsic and extrinsic regulators of central synapse structure as well as function.

Nanometer-resolved chemical analyses of femtosecond laser-induced periodic surface structures on titanium

NASA Astrophysics Data System (ADS)

Kirner, Sabrina V.; Wirth, Thomas; Sturm, Heinz; Krüger, Jörg; Bonse, Jörn

2017-09-01

The chemical characteristics of two different types of laser-induced periodic surface structures (LIPSS), so-called high and low spatial frequency LIPSS (HSFL and LSFL), formed upon irradiation of titanium surfaces by multiple femtosecond laser pulses in air (30 fs, 790 nm, 1 kHz), are analyzed by various optical and electron beam based surface analytical techniques, including micro-Raman spectroscopy, energy dispersive X-ray analysis, X-ray photoelectron spectroscopy, and Auger electron spectroscopy. The latter method was employed in a high-resolution mode being capable of spatially resolving even the smallest HSFL structures featuring spatial periods below 100 nm. In combination with an ion sputtering technique, depths-resolved chemical information of superficial oxidation processes was obtained, revealing characteristic differences between the two different types of LIPSS. Our results indicate that a few tens of nanometer shallow HSFL are formed on top of a ˜150 nm thick graded superficial oxide layer without sharp interfaces, consisting of amorphous TiO2 and partially crystallized Ti2O3. The larger LSFL structures with periods close to the irradiation wavelength originate from the laser-interaction with metallic titanium. They are covered by a ˜200 nm thick amorphous oxide layer, which consists mainly of TiO2 (at the surface) and other titanium oxide species of lower oxidation states underneath.

EPA DSSTox and ToxCast Project Updates: Generating New ...

EPA Pesticide Factsheets

EPA’s National Center for Computational Toxicology is generating data and capabilities to support a new paradigm for toxicity screening and prediction. The DSSTox project is improving public access to quality structure-annotated chemical toxicity information in less summarized forms than traditionally employed in SAR modeling, and in ways that facilitate data-mining and data read-across. The DSSTox Structure-Browser provides structure searchability across the full published DSSTox toxicity-related inventory, enables linkages to and from previously isolated toxicity data resources (soon to include public microarray resources GEO, ArrayExpress, and CEBS), and provides link-outs to cross-indexed public resources such as PubChem, ChemSpider, and ACToR. The published DSSTox inventory and bioassay information also have been integrated into PubChem allowing a user to take full advantage of PubChem structure-activity and bioassay clustering features. Phase I of the ToxCastTM project has generated high-throughput screening (HTS) data from several hundred biochemical and cell-based assays for a set of 320 chemicals, mostly pesticide actives, with rich toxicology profiles. DSSTox and ACToR are providing the primary cheminformatics support for ToxCastTM and collaborative efforts with the National Toxicology Program’s HTS Program and the NIH Chemical Genomics Center. DSSTox will also be a primary vehicle for publishing ToxCastTM ToxRef summarized bioassay data for use

Femtosecond laser structuring of silver-containing glass: Silver redistribution, selective etching, and surface topology engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Desmoulin, Jean-Charles; Petit, Yannick; Cardinal, Thierry, E-mail: thierry.cardinal@icmcb.cnrs.fr

2015-12-07

Femtosecond direct laser writing in silver-containing phosphate glasses allows for the three-dimensional (3D) implementation of complex photonic structures. Sample translation along or perpendicular to the direction of the beam propagation has been performed, which led to the permanent formation of fluorescent structures, either corresponding to a tubular shape or to two parallel planes at the vicinity of the interaction voxel, respectively. These optical features are related to significant modifications of the local material chemistry. Indeed, silver depletion areas with a diameter below 200 nm were evidenced at the center of the photo-produced structures while photo-produced luminescence properties are attributed to themore » formation of silver clusters around the multiphoton interaction voxel. The laser-triggered oxidation-reduction processes and the associated photo-induced silver redistribution are proposed to be at the origin of the observed original 3D luminescent structures. Thanks to such material structuring, surface engineering has been also demonstrated. Selective surface chemical etching of the glass has been obtained subsequently to laser writing at the location of the photo-produced structures, revealing features with nanometric depth profiles and radial dimensions strongly related to the spatial distributions of the silver clusters.« less

Structural studies on choline-carboxylate bio-ionic liquids by x-ray scattering and molecular dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanzi, Luana; Ramondo, Fabio, E-mail: fabio.ramondo@univaq.it; Caminiti, Ruggero

2015-09-21

We report a X-ray diffraction and molecular dynamics study on three choline-based bio-ionic liquids, choline formate, [Ch] [For], choline propanoate, [Ch][Pro], and choline butanoate, [Ch][But]. For the first time, this class of ionic liquids has been investigated by X-ray diffraction. Experimental and theoretical structure factors have been compared for each term of the series. Local structural organization has been obtained from ab initio calculations through static models of isolated ion pairs and dynamic simulations of small portions of liquids through twelve, ten, and nine ion pairs for [Ch][For], [Ch][Pro], and [Ch][But], respectively. All the theoretical models indicate that cations andmore » anions are connected by strong hydrogen bonding and form stable ion pairs in the liquid that are reminiscent of the static ab initio ion pairs. Different structural aspects may affect the radial distribution function, like the local structure of ion pairs and the conformation of choline. When small portions of liquids have been simulated by dynamic quantum chemical methods, some key structural features of the X-ray radial distribution function were well reproduced whereas the classical force fields here applied did not entirely reproduce all the observed structural features.« less

New software for statistical analysis of Cambridge Structural Database data

PubMed Central

Sykes, Richard A.; McCabe, Patrick; Allen, Frank H.; Battle, Gary M.; Bruno, Ian J.; Wood, Peter A.

2011-01-01

A collection of new software tools is presented for the analysis of geometrical, chemical and crystallographic data from the Cambridge Structural Database (CSD). This software supersedes the program Vista. The new functionality is integrated into the program Mercury in order to provide statistical, charting and plotting options alongside three-dimensional structural visualization and analysis. The integration also permits immediate access to other information about specific CSD entries through the Mercury framework, a common requirement in CSD data analyses. In addition, the new software includes a range of more advanced features focused towards structural analysis such as principal components analysis, cone-angle correction in hydrogen-bond analyses and the ability to deal with topological symmetry that may be exhibited in molecular search fragments. PMID:22477784

Analysis of Surface and Bulk Behavior in Ni-Pd Alloys

NASA Technical Reports Server (NTRS)

Bozzolo, Guillermo; Noebe, Rondald D.

2003-01-01

The most salient features of the surface structure and bulk behavior of Ni-Pd alloys have been studied using the BFS method for alloys. Large-scale atomistic simulations were performed to investigate surface segregation profiles as a function of temperature, crystal face, and composition. Pd enrichment of the first layer was observed in (111) and (100) surfaces, and enrichment of the top two layers occurred for (110) surfaces. In all cases, the segregation profile shows alternate planes enriched and depleted in Pd. In addition, the phase structure of bulk Ni-Pd alloys as a function of temperature and composition was studied. A weak ordering tendency was observed at low temperatures, which helps explain the compositional oscillations in the segregation profiles. Finally, based on atom-by-atom static energy calculations, a comprehensive explanation for the observed surface and bulk features will be presented in terms of competing chemical and strain energy effects.

QSAR, docking and ADMET studies of artemisinin derivatives for antimalarial activity targeting plasmepsin II, a hemoglobin-degrading enzyme from P. falciparum.

PubMed

Qidwai, Tabish; Yadav, Dharmendra K; Khan, Feroz; Dhawan, Sangeeta; Bhakuni, R S

2012-01-01

This work presents the development of quantitative structure activity relationship (QSAR) model to predict the antimalarial activity of artemisinin derivatives. The structures of the molecules are represented by chemical descriptors that encode topological, geometric, and electronic structure features. Screening through QSAR model suggested that compounds A24, A24a, A53, A54, A62 and A64 possess significant antimalarial activity. Linear model is developed by the multiple linear regression method to link structures to their reported antimalarial activity. The correlation in terms of regression coefficient (r(2)) was 0.90 and prediction accuracy of model in terms of cross validation regression coefficient (rCV(2)) was 0.82. This study indicates that chemical properties viz., atom count (all atoms), connectivity index (order 1, standard), ring count (all rings), shape index (basic kappa, order 2), and solvent accessibility surface area are well correlated with antimalarial activity. The docking study showed high binding affinity of predicted active compounds against antimalarial target Plasmepsins (Plm-II). Further studies for oral bioavailability, ADMET and toxicity risk assessment suggest that compound A24, A24a, A53, A54, A62 and A64 exhibits marked antimalarial activity comparable to standard antimalarial drugs. Later one of the predicted active compound A64 was chemically synthesized, structure elucidated by NMR and in vivo tested in multidrug resistant strain of Plasmodium yoelii nigeriensis infected mice. The experimental results obtained agreed well with the predicted values.

A review on principles, theory and practices of 2D-QSAR.

PubMed

Roy, Kunal; Das, Rudra Narayan

2014-01-01

The central axiom of science purports the explanation of every natural phenomenon using all possible logics coming from pure as well as mixed scientific background. The quantitative structure-activity relationship (QSAR) analysis is a study correlating the behavioral manifestation of compounds with their structures employing the interdisciplinary knowledge of chemistry, mathematics, biology as well as physics. Several studies have attempted to mathematically correlate the chemistry and property (physicochemical/ biological/toxicological) of molecules using various computationally or experimentally derived quantitative parameters termed as descriptors. The dimensionality of the descriptors depends on the type of algorithm employed and defines the nature of QSAR analysis. The most interesting feature of predictive QSAR models is that the behavior of any new or even hypothesized molecule can be predicted by the use of the mathematical equations. The phrase "2D-QSAR" signifies development of QSAR models using 2D-descriptors. Such predictor variables are the most widely practised ones because of their simple and direct mathematical algorithmic nature involving no time consuming energy computations and having reproducible operability. 2D-descriptors have a deluge of contributions in extracting chemical attributes and they are also capable of representing the 3D molecular features to some extent; although in no case they should be considered as the ultimate one, since they often suffer from the problems of intercorrelation, insufficient chemical information as well as lack of interpretation. However, by following rational approaches, novel 2D-descriptors may be developed to obviate various existing problems giving potential 2D-QSAR equations, thereby solving the innumerable chemical mysteries still unexplored.

Structural analysis of hierarchically organized zeolites

PubMed Central

Mitchell, Sharon; Pinar, Ana B.; Kenvin, Jeffrey; Crivelli, Paolo; Kärger, Jörg; Pérez-Ramírez, Javier

2015-01-01

Advances in materials synthesis bring about many opportunities for technological applications, but are often accompanied by unprecedented complexity. This is clearly illustrated by the case of hierarchically organized zeolite catalysts, a class of crystalline microporous solids that has been revolutionized by the engineering of multilevel pore architectures, which combine unique chemical functionality with efficient molecular transport. Three key attributes, the crystal, the pore and the active site structure, can be expected to dominate the design process. This review examines the adequacy of the palette of techniques applied to characterize these distinguishing features and their catalytic impact. PMID:26482337

Principal component analysis as a tool for library design: a case study investigating natural products, brand-name drugs, natural product-like libraries, and drug-like libraries.

PubMed

Wenderski, Todd A; Stratton, Christopher F; Bauer, Renato A; Kopp, Felix; Tan, Derek S

2015-01-01

Principal component analysis (PCA) is a useful tool in the design and planning of chemical libraries. PCA can be used to reveal differences in structural and physicochemical parameters between various classes of compounds by displaying them in a convenient graphical format. Herein, we demonstrate the use of PCA to gain insight into structural features that differentiate natural products, synthetic drugs, natural product-like libraries, and drug-like libraries, and show how the results can be used to guide library design.

Metal-assisted chemical etching using sputtered gold: a simple route to black silicon

NASA Astrophysics Data System (ADS)

Kurek, Agnieszka; Barry, Seán T.

2011-08-01

We report an accessible and simple method of producing 'black silicon' with aspect ratios as high as 8 using common laboratory equipment. Gold was sputtered to a thickness of 8 nm using a low-vacuum sputter coater. The structures were etched into silicon substrates using an aqueous H2O2/HF solution, and the gold was then removed using aqua regia. Ultrasonication was necessary to produce columnar structures, and an etch time of 24 min gave a velvety, non-reflective surface. The surface features after 24 min etching were uniformly microstructured over an area of square centimetres.

Principal Component Analysis as a Tool for Library Design: A Case Study Investigating Natural Products, Brand-Name Drugs, Natural Product-Like Libraries, and Drug-Like Libraries

PubMed Central

Wenderski, Todd A.; Stratton, Christopher F.; Bauer, Renato A.; Kopp, Felix; Tan, Derek S.

2015-01-01

Principal component analysis (PCA) is a useful tool in the design and planning of chemical libraries. PCA can be used to reveal differences in structural and physicochemical parameters between various classes of compounds by displaying them in a convenient graphical format. Herein, we demonstrate the use of PCA to gain insight into structural features that differentiate natural products, synthetic drugs, natural product-like libraries, and drug-like libraries, and show how the results can be used to guide library design. PMID:25618349

Presumed magnetic biosignatures observed in magnetite derived from abiotic reductive alteration of nanogoethite

NASA Astrophysics Data System (ADS)

Till, Jessica L.; Guyodo, Yohan; Lagroix, France; Morin, Guillaume; Menguy, Nicolas; Ona-Nguema, Georges

2017-03-01

The oriented chains of nanoscale Fe-oxide particles produced by magnetotactic bacteria are a striking example of biomineralization. Several distinguishing features of magnetite particles that comprise bacterial magnetosomes have been proposed to collectively constitute a biosignature of magnetotactic bacteria (Thomas-Keprta et al., 2001). These features include high crystallinity, chemical purity, a single-domain magnetic structure, well-defined crystal morphology, and arrangement of particles in chain structures. Here, we show that magnetite derived from the inorganic breakdown of nanocrystalline goethite exhibits magnetic properties and morphologies remarkably similar to those of biogenic magnetite from magnetosomes. During heating in reducing conditions, oriented nanogoethite aggregates undergo dehydroxylation and transform into stoichiometric magnetite. We demonstrate that highly crystalline single-domain magnetite with euhedral grain morphologies produced abiogenically from goethite meets several of the biogenicity criteria commonly used for the identification of magnetofossils. Furthermore, the suboxic conditions necessary for magnetofossil preservation in sediments are conducive to the reductive alteration of nanogoethite, as well as the preservation of detrital magnetite originally formed from goethite. The findings of this study have potential implications for the identification of biogenic magnetite, particularly in older sediments where diagenesis commonly disrupts the chain structure of magnetosomes. Our results indicate that isolated magnetofossils cannot be positively distinguished from inorganic magnetite on the basis of their magnetic properties and morphology, and that intact chain structures remain the only reliable distinguishing feature of fossil magnetosomes.

Crystal structure, stoichiometry, and dielectric relaxation in Bi 3.32Nb 7.09O 22.7 and structurally related ternary phases

NASA Astrophysics Data System (ADS)

Grey, I. E.; Vanderah, T. A.; Mumme, W. G.; Roth, R. S.; Guzman, J.; Nino, J. C.; Levin, I.

2008-03-01

The crystal structure of the phase previously reported to occur at 4:9 Bi 2O 3:Nb 2O 5 has been determined using single-crystal X-ray and powder neutron diffraction ( P6 3/ mmc; a=7.4363(1) Å, c=19.7587(5) Å; Z=2). The structural study combined with phase equilibrium analyses indicate that the actual composition is Bi 3.32Nb 7.09O 22.7. This binary compound is the end-member of a family of four phases which form along a line between it and the pyrochlore phase field in the Bi 2O 3:Fe 2O 3:Nb 2O 5 system. The structures are derived from the parent pyrochlore end-member by chemical twinning, and can also be described as unit-cell intergrowths of the pyrochlore and hexagonal tungsten bronze (HTB) structures. The dielectric properties of the three chemically twinned pyrochlore phases, Bi 3.32Nb 7.09O 22.7, Bi 9.3Fe 1.1Nb 16.9O 57.8 and Bi 5.67FeNb 10O 35, were characterized. All exhibit low-temperature, broad dielectric relaxation similar to that of the Bi-Fe-Nb-O pyrochlore. At 1 MHz and ≈175 K the observed relative permittivites were 345, 240, and 205, respectively, compared to 125 for the Bi-Fe-Nb-O pyrochlore. The higher relative permittivities observed for the chemically twinned pyrochlore derivatives are ascribed to the presence of HTB blocks in their structures: The Bi atoms located in the HTB blocks feature highly asymmetric coordination environments compared to pyrochlore, and the magnitude of the relative permittivity increases with the proportion of Bi located within the HTB portions of the structures.

Gene-Transformation-Induced Changes in Chemical Functional Group Features and Molecular Structure Conformation in Alfalfa Plants Co-Expressing Lc-bHLH and C1-MYB Transcriptive Flavanoid Regulatory Genes: Effects of Single-Gene and Two-Gene Insertion.

PubMed

Heendeniya, Ravindra G; Yu, Peiqiang

2017-03-20

Alfalfa ( Medicago sativa L.) genotypes transformed with Lc-bHLH and Lc transcription genes were developed with the intention of stimulating proanthocyanidin synthesis in the aerial parts of the plant. To our knowledge, there are no studies on the effect of single-gene and two-gene transformation on chemical functional groups and molecular structure changes in these plants. The objective of this study was to use advanced molecular spectroscopy with multivariate chemometrics to determine chemical functional group intensity and molecular structure changes in alfalfa plants when co-expressing Lc-bHLH and C1-MYB transcriptive flavanoid regulatory genes in comparison with non-transgenic (NT) and AC Grazeland (ACGL) genotypes. The results showed that compared to NT genotype, the presence of double genes ( Lc and C1 ) increased ratios of both the area and peak height of protein structural Amide I/II and the height ratio of α-helix to β-sheet. In carbohydrate-related spectral analysis, the double gene-transformed alfalfa genotypes exhibited lower peak heights at 1370, 1240, 1153, and 1020 cm -1 compared to the NT genotype. Furthermore, the effect of double gene transformation on carbohydrate molecular structure was clearly revealed in the principal component analysis of the spectra. In conclusion, single or double transformation of Lc and C1 genes resulted in changing functional groups and molecular structure related to proteins and carbohydrates compared to the NT alfalfa genotype. The current study provided molecular structural information on the transgenic alfalfa plants and provided an insight into the impact of transgenes on protein and carbohydrate properties and their molecular structure's changes.

Vibrational structure of the S 2 (1B u) excited state of diphenyloctatetraene observed by femtosecond stimulated Raman spectroscopy

NASA Astrophysics Data System (ADS)

Kukura, Philipp; McCamant, David W.; Davis, Paul H.; Mathies, Richard A.

2003-11-01

Femtosecond time-resolved stimulated Raman spectroscopy (FSRS) is used to study the vibrational structure and dynamics of the S 2 state of diphenyloctatetraene. Strong vibrational features at 1184, 1259 and 1578 cm -1 whose linewidths are determined by the S 2 electronic lifetime are observed at early times after photoexcitation at 397 nm. Kinetic analysis of the integrated Raman intensities as well as the transient absorption reveals an exponential decay of the S 2 state on the order of 100 fs. These results demonstrate the ability of FSRS to study the vibrational structure of excited state and chemical reaction dynamics on the femtosecond timescale.

Fine line structures of ceramic films formed by patterning of metalorganic precursors using photolithography and ion beams

NASA Astrophysics Data System (ADS)

Hung, L. S.; Zheng, L. R.

1992-05-01

Fine line structures of ceramic thin films were fabricated by patterning of metalorganic precursors using photolithography and ion beams. A trilevel structure was developed with an outer resist layer to transfer patterns, a silver delineated layer as an implantation mask, and a planar resist layer protecting the precursor film from chemical attacking and sputtering. Ion irradiation through the Ag stencil rendered metal carboxylates insoluble in 2-ethylhexanoic acid, permitting patterning of the precursor film with patterning features on micron scales. The potential of this technique was demonstrated in patterning of Bi2Sr2CaCu2O(8+x) and Pb(Zr(0.53)Ti(0.47) thin films.

A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design.

PubMed

Li, Shiliang; Song, Yuwei; Liu, Xiaofeng; Li, Honglin

2016-01-01

The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly exploited to maximize hit rate and improve efficiency at the beginning of the drug discovery and drug development pipeline. This paper presented a valid methodology for fast target-focused combinatorial library design in both reaction-based and production-based ways with the library creating rates of approximately 70,000 molecules per second. Simple, quick and convenient operating procedures are the specific features of the method. SHAFTS, a hybrid 3D similarity calculation software, was embedded to help refine the size of the libraries and improve hit rates. Two target-focused (p38-focused and COX2-focused) libraries were constructed efficiently in this study. This rapid library enumeration method is portable and applicable to any other targets for good chemical starting points identification collaborated with either structure-based or ligand-based virtual screening.

Influence of chemical disorder on energy dissipation and defect evolution in advanced alloys

DOE PAGES

Zhang, Yanwen; Jin, Ke; Xue, Haizhou; ...

2016-08-01

We report that historically, alloy development with better radiation performance has been focused on traditional alloys with one or two principal element(s) and minor alloying elements, where enhanced radiation resistance depends on microstructural or nanoscale features to mitigate displacement damage. In sharp contrast to traditional alloys, recent advances of single-phase concentrated solid solution alloys (SP-CSAs) have opened up new frontiers in materials research. In these alloys, a random arrangement of multiple elemental species on a crystalline lattice results in disordered local chemical environments and unique site-to-site lattice distortions. Based on closely integrated computational and experimental studies using a novel setmore » of SP-CSAs in a face-centered cubic structure, we have explicitly demonstrated that increasing chemical disorder can lead to a substantial reduction in electron mean free paths, as well as electrical and thermal conductivity, which results in slower heat dissipation in SP-CSAs. The chemical disorder also has a significant impact on defect evolution under ion irradiation. Considerable improvement in radiation resistance is observed with increasing chemical disorder at electronic and atomic levels. Finally, the insights into defect dynamics may provide a basis for understanding elemental effects on evolution of radiation damage in irradiated materials and may inspire new design principles of radiation-tolerant structural alloys for advanced energy systems.« less

Comparative analyses of structural features and scaffold diversity for purchasable compound libraries.

PubMed

Shang, Jun; Sun, Huiyong; Liu, Hui; Chen, Fu; Tian, Sheng; Pan, Peichen; Li, Dan; Kong, Dexin; Hou, Tingjun

2017-04-21

Large purchasable screening libraries of small molecules afforded by commercial vendors are indispensable sources for virtual screening (VS). Selecting an optimal screening library for a specific VS campaign is quite important to improve the success rates and avoid wasting resources in later experimental phases. Analysis of the structural features and molecular diversity for different screening libraries can provide valuable information to the decision making process when selecting screening libraries for VS. In this study, the structural features and scaffold diversity of eleven purchasable screening libraries and Traditional Chinese Medicine Compound Database (TCMCD) were analyzed and compared. Their scaffold diversity represented by the Murcko frameworks and Level 1 scaffolds was characterized by the scaffold counts and cumulative scaffold frequency plots, and visualized by Tree Maps and SAR Maps. The analysis demonstrates that, based on the standardized subsets with similar molecular weight distributions, Chembridge, ChemicalBlock, Mucle, TCMCD and VitasM are more structurally diverse than the others. Compared with all purchasable screening libraries, TCMCD has the highest structural complexity indeed but more conservative molecular scaffolds. Moreover, we found that some representative scaffolds were important components of drug candidates against different drug targets, such as kinases and guanosine-binding protein coupled receptors, and therefore the molecules containing pharmacologically important scaffolds found in screening libraries might be potential inhibitors against the relevant targets. This study may provide valuable perspective on which purchasable compound libraries are better for you to screen. Graphical abstract Selecting diverse compound libraries with scaffold analyses.

Predicting drug side-effect profiles: a chemical fragment-based approach

PubMed Central

2011-01-01

Background Drug side-effects, or adverse drug reactions, have become a major public health concern. It is one of the main causes of failure in the process of drug development, and of drug withdrawal once they have reached the market. Therefore, in silico prediction of potential side-effects early in the drug discovery process, before reaching the clinical stages, is of great interest to improve this long and expensive process and to provide new efficient and safe therapies for patients. Results In the present work, we propose a new method to predict potential side-effects of drug candidate molecules based on their chemical structures, applicable on large molecular databanks. A unique feature of the proposed method is its ability to extract correlated sets of chemical substructures (or chemical fragments) and side-effects. This is made possible using sparse canonical correlation analysis (SCCA). In the results, we show the usefulness of the proposed method by predicting 1385 side-effects in the SIDER database from the chemical structures of 888 approved drugs. These predictions are performed with simultaneous extraction of correlated ensembles formed by a set of chemical substructures shared by drugs that are likely to have a set of side-effects. We also conduct a comprehensive side-effect prediction for many uncharacterized drug molecules stored in DrugBank, and were able to confirm interesting predictions using independent source of information. Conclusions The proposed method is expected to be useful in various stages of the drug development process. PMID:21586169

Prediction of cancer cell sensitivity to natural products based on genomic and chemical properties.

PubMed

Yue, Zhenyu; Zhang, Wenna; Lu, Yongming; Yang, Qiaoyue; Ding, Qiuying; Xia, Junfeng; Chen, Yan

2015-01-01

Natural products play a significant role in cancer chemotherapy. They are likely to provide many lead structures, which can be used as templates for the construction of novel drugs with enhanced antitumor activity. Traditional research approaches studied structure-activity relationship of natural products and obtained key structural properties, such as chemical bond or group, with the purpose of ascertaining their effect on a single cell line or a single tissue type. Here, for the first time, we develop a machine learning method to comprehensively predict natural products responses against a panel of cancer cell lines based on both the gene expression and the chemical properties of natural products. The results on two datasets, training set and independent test set, show that this proposed method yields significantly better prediction accuracy. In addition, we also demonstrate the predictive power of our proposed method by modeling the cancer cell sensitivity to two natural products, Curcumin and Resveratrol, which indicate that our method can effectively predict the response of cancer cell lines to these two natural products. Taken together, the method will facilitate the identification of natural products as cancer therapies and the development of precision medicine by linking the features of patient genomes to natural product sensitivity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Solomon, Jonathan M.; Shamblin, Jacob; Lang, Maik

Fluorite-structured oxides find widespread use for applications spanning nuclear energy and waste containment, energy conversion, and sensing. In such applications the host tetravalent cation is often partially substituted by trivalent cations, with an associated formation of charge-compensating oxygen vacancies. The stability and properties of such materials are known to be influenced strongly by chemical ordering of the cations and vacancies, and the nature of such ordering and associated energetics are thus of considerable interest. Here we employ density-functional theory (DFT) calculations to study the structure and energetics of cation and oxygen-vacancy ordering in Ho 2Zr 2O 7. In a recentmore » neutron total scattering study, solid solutions in this system were reported to feature local chemical ordering based on the fluorite-derivative weberite structure. The calculations show a preferred chemical ordering qualitatively consistent with these findings, and yield values for the ordering energy of 9.5 kJ/mol-cation. Similar DFT calculations are applied to additional RE 2Th 2O 7'' fluorite compounds, spanning a range of values for the ratio of the tetravalent and trivalent (RE) cation radii. Finally, the results demonstrate that weberite-type order becomes destabilized with increasing values of this size ratio, consistent with an increasing energetic preference for the tetravalent cations to have higher oxygen coordination.« less

Electrochemical assembly of organic molecules by the reduction of iodonium salts

DOEpatents

Dirk, Shawn M [Albuquerque, NM; Howell, Stephen W [Albuquerque, NM; Wheeler, David R [Albuquerque, NM

2009-06-23

Methods are described for the electrochemical assembly of organic molecules on silicon, or other conducting or semiconducting substrates, using iodonium salt precursors. Iodonium molecules do not assemble on conducting surfaces without a negative bias. Accordingly, the iodonium salts are preferred for patterning applications that rely on direct writing with negative bias. The stability of the iodonium molecule to acidic conditions allows them to be used with standard silicon processing. As a directed assembly process, the use of iodonium salts provides for small features while maintaining the ability to work on a surface and create structures on a wafer level. Therefore, the process is amenable for mass production. Furthermore, the assembled monolayer (or multilayer) is chemically robust, allowing for subsequent chemical manipulations and the introduction of various molecular functionalities for various chemical and biological applications.

Structure-performance relationships of phenyl cinnamic acid derivatives as MALDI-MS matrices for sulfatide detection.

PubMed

Tambe, Suparna; Blott, Henning; Fülöp, Annabelle; Spang, Nils; Flottmann, Dirk; Bräse, Stefan; Hopf, Carsten; Junker, Hans-Dieter

2017-02-01

A key aspect for the further development of matrix-assisted laser desorption ionization (MALDI)-mass spectrometry (MS) is a better understanding of the working principles of MALDI matrices. To address this issue, a chemical compound library of 59 structurally related cinnamic acid derivatives was synthesized. Potential MALDI matrices were evaluated with sulfatides, a class of anionic lipids which are abundant in complex brain lipid mixtures. For each matrix relative mean S/N ratios of sulfatides were determined against 9-aminoacridine as a reference matrix using negative ion mass spectrometry with 355 and 337 nm laser systems. The comparison of matrix features with their corresponding relative mean S/N ratios for sulfatide detection identified correlations between matrix substitution patterns, their chemical functionality, and their MALDI-MS performance. Crystal structures of six selected matrices provided structural insight in hydrogen bond interactions in the solid state. Principal component analysis allowed the additional identification of correlation trends between structural and physical matrix properties like number of exchangeable protons at the head group, MW, logP, UV-Vis, and sulfatide detection sensitivity. Graphical abstract Design, synthesis and mass spectrometric evaluation of MALDI-MS matrix compound libraries allows the identification of matrix structure - MALDI-MS performance relationships using multivariate statistics as a tool.

NMR studies of protein-nucleic acid interactions.

PubMed

Varani, Gabriele; Chen, Yu; Leeper, Thomas C

2004-01-01

Protein-DNA and protein-RNA complexes play key functional roles in every living organism. Therefore, the elucidation of their structure and dynamics is an important goal of structural and molecular biology. Nuclear magnetic resonance (NMR) studies of protein and nucleic acid complexes have common features with studies of protein-protein complexes: the interaction surfaces between the molecules must be carefully delineated, the relative orientation of the two species needs to be accurately and precisely determined, and close intermolecular contacts defined by nuclear Overhauser effects (NOEs) must be obtained. However, differences in NMR properties (e.g., chemical shifts) and biosynthetic pathways for sample productions generate important differences. Chemical shift differences between the protein and nucleic acid resonances can aid the NMR structure determination process; however, the relatively limited dispersion of the RNA ribose resonances makes the process of assigning intermolecular NOEs more difficult. The analysis of the resulting structures requires computational tools unique to nucleic acid interactions. This chapter summarizes the most important elements of the structure determination by NMR of protein-nucleic acid complexes and their analysis. The main emphasis is on recent developments (e.g., residual dipolar couplings and new Web-based analysis tools) that have facilitated NMR studies of these complexes and expanded the type of biological problems to which NMR techniques of structural elucidation can now be applied.

Directed self-assembly of block copolymer films on atomically-thin graphene chemical patterns

DOE PAGES

Chang, Tzu-Hsuan; Xiong, Shisheng; Jacobberger, Robert M.; ...

2016-08-16

Directed self-assembly of block copolymers is a scalable method to fabricate well-ordered patterns over the wafer scale with feature sizes below the resolution of conventional lithography. Typically, lithographically-defined prepatterns with varying chemical contrast are used to rationally guide the assembly of block copolymers. The directed self-assembly to obtain accurate registration and alignment is largely influenced by the assembly kinetics. Furthermore, a considerably broad processing window is favored for industrial manufacturing. Using an atomically-thin layer of graphene on germanium, after two simple processing steps, we create a novel chemical pattern to direct the assembly of polystyreneblock-poly(methyl methacrylate). Faster assembly kinetics aremore » observed on graphene/germanium chemical patterns than on conventional chemical patterns based on polymer mats and brushes. This new chemical pattern allows for assembly on a wide range of guiding periods and along designed 90° bending structures. We also achieve density multiplication by a factor of 10, greatly enhancing the pattern resolution. Lastly, the rapid assembly kinetics, minimal topography, and broad processing window demonstrate the advantages of inorganic chemical patterns composed of hard surfaces.« less

On the Certain Topological Indices of Titania Nanotube TiO2[m, n

NASA Astrophysics Data System (ADS)

Javaid, M.; Liu, Jia-Bao; Rehman, M. A.; Wang, Shaohui

2017-07-01

A numeric quantity that characterises the whole structure of a molecular graph is called the topological index that predicts the physical features, chemical reactivities, and boiling activities of the involved chemical compound in the molecular graph. In this article, we give new mathematical expressions for the multiple Zagreb indices, the generalised Zagreb index, the fourth version of atom-bond connectivity (ABC4) index, and the fifth version of geometric-arithmetic (GA5) index of TiO2[m, n]. In addition, we compute the latest developed topological index called by Sanskruti index. At the end, a comparison is also included to estimate the efficiency of the computed indices. Our results extended some known conclusions.

Anticancer properties of polysaccharides isolated from fungi of the Basidiomycetes class.

PubMed

Lemieszek, Marta; Rzeski, Wojciech

2012-01-01

Basidiomycete mushrooms represent a valuable source of biologically active compounds with anticancer properties. This feature is primarily attributed to polysaccharides and their derivatives. The anticancer potential of polysaccharides is linked to their origin, composition and chemical structure, solubility and method of isolation. Moreover, their activity can be significantly increased by chemical modifications. Anticancer effects of polysaccharides can be expressed indirectly (immunostimulation) or directly (cell proliferation inhibition and/or apoptosis induction). Among the wide range of polysaccharides with documented anticancer properties, lentinan, polysaccharide-K (PSK) and schizophyllan deserve special attention. These polysaccharides for many years have been successfully applied in cancer treatment and their mechanism of action is the best known.

Shell Biorefinery: Dream or Reality?

PubMed

Chen, Xi; Yang, Huiying; Yan, Ning

2016-09-12

Shell biorefinery, referring to the fractionation of crustacean shells into their major components and the transformation of each component into value-added chemicals and materials, has attracted growing attention in recent years. Since the large quantities of waste shells remain underexploited, their valorization can potentially bring both ecological and economic benefits. This Review provides an overview of the current status of shell biorefinery. It first describes the structural features of crustacean shells, including their composition and their interactions. Then, various fractionation methods for the shells are introduced. The last section is dedicated to the valorization of chitin and its derivatives for chemicals, porous carbon materials and functional polymers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical ordering in substituted fluorite oxides: a computational investigation of Ho 2Zr 2O 7 and RE 2Th 2O 7 (RE=Ho, Y, Gd, Nd, La)

DOE PAGES

Solomon, Jonathan M.; Shamblin, Jacob; Lang, Maik; ...

2016-12-12

Fluorite-structured oxides find widespread use for applications spanning nuclear energy and waste containment, energy conversion, and sensing. In such applications the host tetravalent cation is often partially substituted by trivalent cations, with an associated formation of charge-compensating oxygen vacancies. The stability and properties of such materials are known to be influenced strongly by chemical ordering of the cations and vacancies, and the nature of such ordering and associated energetics are thus of considerable interest. Here we employ density-functional theory (DFT) calculations to study the structure and energetics of cation and oxygen-vacancy ordering in Ho 2Zr 2O 7. In a recentmore » neutron total scattering study, solid solutions in this system were reported to feature local chemical ordering based on the fluorite-derivative weberite structure. The calculations show a preferred chemical ordering qualitatively consistent with these findings, and yield values for the ordering energy of 9.5 kJ/mol-cation. Similar DFT calculations are applied to additional RE 2Th 2O 7'' fluorite compounds, spanning a range of values for the ratio of the tetravalent and trivalent (RE) cation radii. Finally, the results demonstrate that weberite-type order becomes destabilized with increasing values of this size ratio, consistent with an increasing energetic preference for the tetravalent cations to have higher oxygen coordination.« less

Clinical and laboratory evaluation of microstructural changes in the physical, mechanical and chemical properties of dental filling materials under the influence of an electromagnetic field.

PubMed

Moiseeva, Natalia S; Kunin, Anatoly A

2018-03-01

Restorative filling materials used for dental caries prevention and treatment consist of various components including monomers or oligomers, which play a significant role in forming the main structure of these materials, as well as in characterising their physical, mechanical and chemical properties. The necessity for the development and improvement of structural characteristics of polymeric dental filling materials intended for caries prevention and their life duration increase served as the initiating factor of our research. According to the research purpose and challenges, we studied the changes in the physical, mechanical and chemical properties of composite filling materials with and without electromagnetic field influence. The investigations in vivo include the study of microstructural features of polymeric filling materials by scanning electron microscopy (SEM) and the investigations in vitro include the study of sealed and extracted human teeth chips by using X-ray spectral analysis. We also evaluated the changes in the strength characteristics of dental filling materials with and without electromagnetic field influence. The analysis of the obtained data indicates the presence of structural changes in polymeric dental filling materials, including the material microstructure condensation confirmed by the SEM results, an increase in the strength and adhesion characteristics and certain regularities of the chemical elemental composition concentration change in the area of hard tooth tissue and dental filling material. These scientific data will provide tooth caries prevention and promote the increase of treatment quality.

Chemical ordering in substituted fluorite oxides: a computational investigation of Ho2Zr2O7 and RE2Th2O7 (RE=Ho, Y, Gd, Nd, La)

PubMed Central

Solomon, Jonathan M.; Shamblin, Jacob; Lang, Maik; Navrotsky, Alexandra; Asta, Mark

2016-01-01

Fluorite-structured oxides find widespread use for applications spanning nuclear energy and waste containment, energy conversion, and sensing. In such applications the host tetravalent cation is often partially substituted by trivalent cations, with an associated formation of charge-compensating oxygen vacancies. The stability and properties of such materials are known to be influenced strongly by chemical ordering of the cations and vacancies, and the nature of such ordering and associated energetics are thus of considerable interest. Here we employ density-functional theory (DFT) calculations to study the structure and energetics of cation and oxygen-vacancy ordering in Ho2Zr2O7. In a recent neutron total scattering study, solid solutions in this system were reported to feature local chemical ordering based on the fluorite-derivative weberite structure. The calculations show a preferred chemical ordering qualitatively consistent with these findings, and yield values for the ordering energy of 9.5 kJ/mol-cation. Similar DFT calculations are applied to additional RE2Th2O7 fluorite compounds, spanning a range of values for the ratio of the tetravalent and trivalent (RE) cation radii. The results demonstrate that weberite-type order becomes destabilized with increasing values of this size ratio, consistent with an increasing energetic preference for the tetravalent cations to have higher oxygen coordination. PMID:27941870

Accuracy of Small Base Metal Dental Castings,

DTIC Science & Technology

1980-07-10

onre r puf~ eece an dif bydo:k itse Base metal al oy, c s ii.ing c ucyicatin nesmncatn ecnqe an.DISRBTOTTMN in( sten te hiquestatetrdISoc20itifrntrmRpr...34alternatives" to conventional dental golds. Determination and evaluation of composition , structure, physical and chemical properties, biologic features...maxillary right first molar was made from an industrial grade silicone . Then the tooth was machined to receive a full crown cast restoration. The tapered

Thermal-chemical Mantle Convection Models With Adaptive Mesh Refinement

NASA Astrophysics Data System (ADS)

Leng, W.; Zhong, S.

2008-12-01

In numerical modeling of mantle convection, resolution is often crucial for resolving small-scale features. New techniques, adaptive mesh refinement (AMR), allow local mesh refinement wherever high resolution is needed, while leaving other regions with relatively low resolution. Both computational efficiency for large- scale simulation and accuracy for small-scale features can thus be achieved with AMR. Based on the octree data structure [Tu et al. 2005], we implement the AMR techniques into the 2-D mantle convection models. For pure thermal convection models, benchmark tests show that our code can achieve high accuracy with relatively small number of elements both for isoviscous cases (i.e. 7492 AMR elements v.s. 65536 uniform elements) and for temperature-dependent viscosity cases (i.e. 14620 AMR elements v.s. 65536 uniform elements). We further implement tracer-method into the models for simulating thermal-chemical convection. By appropriately adding and removing tracers according to the refinement of the meshes, our code successfully reproduces the benchmark results in van Keken et al. [1997] with much fewer elements and tracers compared with uniform-mesh models (i.e. 7552 AMR elements v.s. 16384 uniform elements, and ~83000 tracers v.s. ~410000 tracers). The boundaries of the chemical piles in our AMR code can be easily refined to the scales of a few kilometers for the Earth's mantle and the tracers are concentrated near the chemical boundaries to precisely trace the evolvement of the boundaries. It is thus very suitable for our AMR code to study the thermal-chemical convection problems which need high resolution to resolve the evolvement of chemical boundaries, such as the entrainment problems [Sleep, 1988].

Uniform manganese hexacyanoferrate hydrate nanocubes featuring superior performance for low-cost supercapacitors and nonenzymatic electrochemical sensors

NASA Astrophysics Data System (ADS)

Pang, Huan; Zhang, Yizhou; Cheng, Tao; Lai, Wen-Yong; Huang, Wei

2015-09-01

Uniform manganese hexacyanoferrate hydrate nanocubes are prepared via a simple chemical precipitation method at room temperature. Due to both micro/mesopores of the Prussian blue analogue and nanocubic structures, the manganese hexacyanoferrate hydrate nanocubes allow the efficient charge transfer and mass transport for electrolyte solution and chemical species. Thus, the manganese hexacyanoferrate hydrate nanocube electrode shows a good rate capability and cycling stability for electrochemical capacitors. Furthermore, electrodes modified with manganese hexacyanoferrate hydrate nanocubes demonstrate a sensitive electrochemical response to hydrogen peroxide (H2O2) in buffer solutions with a high selectivity.Uniform manganese hexacyanoferrate hydrate nanocubes are prepared via a simple chemical precipitation method at room temperature. Due to both micro/mesopores of the Prussian blue analogue and nanocubic structures, the manganese hexacyanoferrate hydrate nanocubes allow the efficient charge transfer and mass transport for electrolyte solution and chemical species. Thus, the manganese hexacyanoferrate hydrate nanocube electrode shows a good rate capability and cycling stability for electrochemical capacitors. Furthermore, electrodes modified with manganese hexacyanoferrate hydrate nanocubes demonstrate a sensitive electrochemical response to hydrogen peroxide (H2O2) in buffer solutions with a high selectivity. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04322k

Chemical kinetics of octane sensitivity in a spark-ignition engine (Chemical Kinetics of Octane Sensitivity in a Spark Ignition Engine)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westbrook, Charles K.; Mehl, Marco; Pitz, William J.

This article uses a chemical kinetic modeling approach to study the influences of fuel molecular structure on Octane Sensitivity (OS) in Spark Ignition (SI) engines. Octane Sensitivity has the potential to identify fuels that can be used in next-generation high compression, turbocharged SI engines to avoid unwanted knocking conditions and extend the range of operating conditions that can be used in such engines. While the concept of octane numbers of different fuels has been familiar for many years, the variations of their values and their role in determining Octane Sensitivity have not been addressed previously in terms of the basicmore » structures of the fuel molecules. In particular, the importance of electron delocalization on low temperature hydrocarbon reactivity and its role in determining OS in engine fuel is described here for the first time. Finally, the role of electron delocalization on fuel reactivity and Octane Sensitivity is illustrated for a very wide range of engine fuel types, including n-alkane, 1-olefin, n-alcohol, and n-alkyl benzenes, and the unifying features of these fuels and their common trends, using existing detailed chemical kinetic reaction mechanisms that have been collected and unified to produce an overall model with unprecedented capabilities.« less

Chemical kinetics of octane sensitivity in a spark-ignition engine (Chemical Kinetics of Octane Sensitivity in a Spark Ignition Engine)

DOE PAGES

Westbrook, Charles K.; Mehl, Marco; Pitz, William J.; ...

2016-07-11

This article uses a chemical kinetic modeling approach to study the influences of fuel molecular structure on Octane Sensitivity (OS) in Spark Ignition (SI) engines. Octane Sensitivity has the potential to identify fuels that can be used in next-generation high compression, turbocharged SI engines to avoid unwanted knocking conditions and extend the range of operating conditions that can be used in such engines. While the concept of octane numbers of different fuels has been familiar for many years, the variations of their values and their role in determining Octane Sensitivity have not been addressed previously in terms of the basicmore » structures of the fuel molecules. In particular, the importance of electron delocalization on low temperature hydrocarbon reactivity and its role in determining OS in engine fuel is described here for the first time. Finally, the role of electron delocalization on fuel reactivity and Octane Sensitivity is illustrated for a very wide range of engine fuel types, including n-alkane, 1-olefin, n-alcohol, and n-alkyl benzenes, and the unifying features of these fuels and their common trends, using existing detailed chemical kinetic reaction mechanisms that have been collected and unified to produce an overall model with unprecedented capabilities.« less

SEM viewing of gypsiferous material and study of their influence on electrical resistivity

NASA Astrophysics Data System (ADS)

Dafalla, M.; Fouzan, F. Al

2012-04-01

The gypsum rich material is often linked to the cavity formation due to the high solubility of cal-cium carbonate in the presence of acidic media. This work is dedicated to a close-up look to the structure of materials rich of gypsum and material of less or traces of sulfate ions. Electrical resistivity measurements were conducted along extended lines on sections involving cavities and the resulting profiles were examined for any changes. Forms and features of gypsum and minerals containing sulfates were studied and compared to sam-ples tested using SEM (scanning electron microscope). The chemical analyses (EDAX) using electron beam was carried out and the elements present within these samples were established. Quantitative chemical testing for some parameters including sulfate ions was carried out. Structural forms variation and changes are studied in view of the chemical composition. The electrical resistivity was measured using Syscal R1 electerical resis-tivity equipment for several spots near surface. Statistical correlations between sulfate ions content and elec-trical resistivity, for near surface soils, is presented. This study is aiming at utilizing the geophysical testing methods of sulfate rich soils and predicting future cavity formation in areas of high risk to cavities due to chemical weathering.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yanwen; Jin, Ke; Xue, Haizhou

We report that historically, alloy development with better radiation performance has been focused on traditional alloys with one or two principal element(s) and minor alloying elements, where enhanced radiation resistance depends on microstructural or nanoscale features to mitigate displacement damage. In sharp contrast to traditional alloys, recent advances of single-phase concentrated solid solution alloys (SP-CSAs) have opened up new frontiers in materials research. In these alloys, a random arrangement of multiple elemental species on a crystalline lattice results in disordered local chemical environments and unique site-to-site lattice distortions. Based on closely integrated computational and experimental studies using a novel setmore » of SP-CSAs in a face-centered cubic structure, we have explicitly demonstrated that increasing chemical disorder can lead to a substantial reduction in electron mean free paths, as well as electrical and thermal conductivity, which results in slower heat dissipation in SP-CSAs. The chemical disorder also has a significant impact on defect evolution under ion irradiation. Considerable improvement in radiation resistance is observed with increasing chemical disorder at electronic and atomic levels. Finally, the insights into defect dynamics may provide a basis for understanding elemental effects on evolution of radiation damage in irradiated materials and may inspire new design principles of radiation-tolerant structural alloys for advanced energy systems.« less

Local electronic structure and photoelectrochemical activity of partial chemically etched Ti-doped hematite

NASA Astrophysics Data System (ADS)

Rioult, Maxime; Belkhou, Rachid; Magnan, Hélène; Stanescu, Dana; Stanescu, Stefan; Maccherozzi, Francesco; Rountree, Cindy; Barbier, Antoine

2015-11-01

The direct conversion of solar light into chemical energy or fuel through photoelectrochemical water splitting is promising as a clean hydrogen production solution. Ti-doped hematite (Ti:α-Fe2O3) is a potential key photoanode material, which despite its optimal band gap, excellent chemical stability, abundance, non-toxicity and low cost, still has to be improved. Here we give evidence of a drastic improvement of the water splitting performances of Ti-doped hematite photoanodes upon a HCl wet-etching. In addition to the topography investigation by atomic force microscopy, a detailed determination of the local electronic structure has been carried out in order to understand the phenomenon and to provide new insights in the understanding of solar water splitting. Using synchrotron radiation based spectromicroscopy (X-PEEM), we investigated the X-ray absorption spectral features at the L3 Fe edge of the as grown surface and of the wet-etched surface on the very same sample thanks to patterning. We show that HCl wet etching leads to substantial surface modifications of the oxide layer including increased roughness and chemical reduction (presence of Fe2 +) without changing the band gap. We demonstrate that these changes are profitable and correlated to the drastic changes of the photocatalytic activity.

Response of Phlebotomus papatasi to visual, physical and chemical attraction features in the field.

USDA-ARS?s Scientific Manuscript database

In this study, 27 CDC traps were modified with various attractive features and compared with a CDC trap with no light source or baits to evaluate the effects on attraction to Phlebotomus papatasi (Scopoli). Attractive features included CO2, lights, colored trap bodies, heat, moisture, chemical lures...

Structural Biology of Non-Ribosomal Peptide Synthetases

PubMed Central

Miller, Bradley R.; Gulick, Andrew M.

2016-01-01

Summary The non-ribosomal peptide synthetases are modular enzymes that catalyze synthesis of important peptide products from a variety of standard and non-proteinogenic amino acid substrates. Within a single module are multiple catalytic domains that are responsible for incorporation of a single residue. After the amino acid is activated and covalently attached to an integrated carrier protein domain, the substrates and intermediates are delivered to neighboring catalytic domains for peptide bond formation or, in some modules, chemical modification. In the final module, the peptide is delivered to a terminal thioesterase domain that catalyzes release of the peptide product. This multi-domain modular architecture raises questions about the structural features that enable this assembly line synthesis in an efficient manner. The structures of the core component domains have been determined and demonstrate insights into the catalytic activity. More recently, multi-domain structures have been determined and are providing clues to the features of these enzyme systems that govern the functional interaction between multiple domains. This chapter describes the structures of NRPS proteins and the strategies that are being used to assist structural studies of these dynamic proteins, including careful consideration of domain boundaries for generation of truncated proteins and the use of mechanism-based inhibitors that trap interactions between the catalytic and carrier protein domains. PMID:26831698

Visualizing spatial correlation: structural and electronic orders in iron-based superconductors on atomic scale

NASA Astrophysics Data System (ADS)

Maksov, Artem; Ziatdinov, Maxim; Li, Li; Sefat, Athena; Maksymovych, Petro; Kalinin, Sergei

Crystalline matter on the nanoscale level often exhibits strongly inhomogeneous structural and electronic orders, which have a profound effect on macroscopic properties. This may be caused by subtle interplay between chemical disorder, strain, magnetic, and structural order parameters. We present a novel approach based on combination of high resolution scanning tunneling microscopy/spectroscopy (STM/S) and deep data style analysis for automatic separation, extraction, and correlation of structural and electronic behavior which might lead us to uncovering the underlying sources of inhomogeneity in in iron-based family of superconductors (FeSe, BaFe2As2) . We identify STS spectral features using physically robust Bayesian linear unmixing, and show their direct relevance to the fundamental physical properties of the system, including electronic states associated with individual defects and impurities. We collect structural data from individual unit cells on the crystalline lattice, and calculate both global and local indicators of spatial correlation with electronic features, demonstrating, for the first time, a direct quantifiable connection between observed structural order parameters extracted from the STM data and electronic order parameters identified within the STS data. This research was sponsored by the Division of Materials Sciences and Engineering, Office of Science, Basic Energy Sciences, US DOE.

Growth and characterization of organic layers deposited on porous-patterned Si surface

NASA Astrophysics Data System (ADS)

Gorbach, Tamara Ya.; Smertenko, Petro S.; Olkhovik, G. P.; Wisz, Grzegorz

2017-01-01

The organic layers with the thickness from a few nanometers up to few micrometers have been deposited from the chemical solution at room temperature on porous patterned Si surfaces using two medical solutions: thiamine diphosphide (pH=1÷2) and metamizole sodium (pH=6÷7). Based on evolution of morphology, structural and compositional features obtained by scanning electron microscopy, X-ray analysis, reflectance high energy electron diffraction the grown mechanisms in thin organic layers are discussed in the terms of terrace-step-kink model whereas self-organized assemblies evaluated more thick layers. Transport mechanism features and possible photovoltaic properties are discussed on the base of differential current-voltage characteristics.

Structure and bonding in beta-HMX-characterization of a trans-annular N...N interaction.

PubMed

Zhurova, Elizabeth A; Zhurov, Vladimir V; Pinkerton, A Alan

2007-11-14

Chemical bonding in the beta-phase of the 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX) crystal based on the experimental electron density obtained from X-ray diffraction data at 20 K, and solid state theoretical calculations, has been analyzed in terms of the quantum theory of atoms in molecules. Features of the intra- and intermolecular bond critical points and the oxygen atom lone-pair locations are discussed. An unusual N...N bonding interaction across the 8-membered ring has been discovered and characterized. Hydrogen bonding, O...O and O...C intermolecular interactions are reported. Atomic charges and features of the electrostatic potential are discussed.

Magnitude Differences in Bioactive Compounds, Chemical Functional Groups, Fatty Acid Profiles, Nutrient Degradation and Digestion, Molecular Structure, and Metabolic Characteristics of Protein in Newly Developed Yellow-Seeded and Black-Seeded Canola Lines.

PubMed

Theodoridou, Katerina; Zhang, Xuewei; Vail, Sally; Yu, Peiqiang

2015-06-10

Recently, new lines of yellow-seeded (CS-Y) and black-seeded canola (CS-B) have been developed with chemical and structural alteration through modern breeding technology. However, no systematic study was found on the bioactive compounds, chemical functional groups, fatty acid profiles, inherent structure, nutrient degradation and absorption, or metabolic characteristics between the newly developed yellow- and black-seeded canola lines. This study aimed to systematically characterize chemical, structural, and nutritional features in these canola lines. The parameters accessed include bioactive compounds and antinutrition factors, chemical functional groups, detailed chemical and nutrient profiles, energy value, nutrient fractions, protein structure, degradation kinetics, intestinal digestion, true intestinal protein supply, and feed milk value. The results showed that the CS-Y line was lower (P ≤ 0.05) in neutral detergent fiber (122 vs 154 g/kg DM), acid detergent fiber (61 vs 99 g/kg DM), lignin (58 vs 77 g/kg DM), nonprotein nitrogen (56 vs 68 g/kg DM), and acid detergent insoluble protein (11 vs 35 g/kg DM) than the CS-B line. There was no difference in fatty acid profiles except C20:1 eicosenoic acid content (omega-9) which was in lower in the CS-Y line (P < 0.05) compared to the CS-B line. The glucosinolate compounds differed (P < 0.05) in terms of 4-pentenyl, phenylethyl, 3-CH3-indolyl, and 3-butenyl glucosinolates (2.9 vs 1.0 μmol/g) between the CS-Y and CS-B lines. For bioactive compounds, total polyphenols tended to be different (6.3 vs 7.2 g/kg DM), but there were no differences in erucic acid and condensed tannins with averages of 0.3 and 3.1 g/kg DM, respectively. When protein was portioned into five subfractions, significant differences were found in PA, PB1 (65 vs 79 g/kg CP), PB2, and PC fractions (10 vs 33 g/kg CP), indicating protein degradation and supply to small intestine differed between two new lines. In terms of protein structure spectral profile, there were no significant differences in functional groups of amides I and II, α helix, and β-sheet structure as well as their ratio between the two new lines, indicating no difference in protein structure makeup and conformation between the two lines. In terms of energy values, there were significant differences in total digestible nutrient (TDN; 149 vs 133 g/kg DM), metabolizable energy (ME; 58 vs 52 MJ/kg DM), and net energy for lactation (NEL; 42 vs 37 MJ/kg DM) between CS-Y and CS-B lines. For in situ rumen degradation kinetics, the two lines differed in soluble fraction (S; 284 vs 341 g/kg CP), potential degradation fraction (D; 672 vs 590 g/kg CP), and effective degraded organic matter (EDOM; 710 vs 684 g/kg OM), but no difference in degradation rate. CS-Y had higher digestibility of rumen bypass protein in the intestine than CS-B (566 vs 446 g/kg of RUP, P < 0.05). Modeling nutrient supply results showed that microbial protein synthesis (MCP; 148 vs 171 g/kg DM) and rumen protein degraded balance (DPB; 108 vs 127 g/kg DM) were lower in the CS-Y line, but there were no differences in total truly digested protein in small intestine (DVE) and feed milk value (FMV) between the two lines. In conclusion, the new yellow line had different nutritional, chemical, and structural features compared to the black line. CS-Y provided better nutrient utilization and availability.

Evolutionarily Conserved Linkage between Enzyme Fold, Flexibility, and Catalysis

PubMed Central

Ramanathan, Arvind; Agarwal, Pratul K.

2011-01-01

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme–substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme–substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design. PMID:22087074

Evolutionarily conserved linkage between enzyme fold, flexibility, and catalysis.

PubMed

Ramanathan, Arvind; Agarwal, Pratul K

2011-11-01

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme-substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme-substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramanathan, Arvind; Agarwal, Pratul K

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function.more » Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design.« less

In-Silico Analysis of Binding Site Features and Substrate Selectivity in Plant Flavonoid-3-O Glycosyltransferases (F3GT) through Molecular Modeling, Docking and Dynamics Simulation Studies

PubMed Central

Sharma, Ranu; Panigrahi, Priyabrata; Suresh, C.G.

2014-01-01

Flavonoids are a class of plant secondary metabolites that act as storage molecules, chemical messengers, as well as participate in homeostasis and defense processes. They possess pharmaceutical properties important for cancer treatment such as antioxidant and anti-tumor activities. The drug-related properties of flavonoids can be improved by glycosylation. The enzymes glycosyltransferases (GTs) glycosylate acceptor molecules in a regiospecific manner with the help of nucleotide sugar donor molecules. Several plant GTs have been characterized and their amino acid sequences determined. However, three-dimensional structures of only a few are reported. Here, phylogenetic analysis using amino acid sequences have identified a group of GTs with the same regiospecific activity. The structures of these closely related GTs were modeled using homologous GT structures. Their substrate binding sites were elaborated by docking flavonoid acceptor and UDP-sugar donor molecules in the modeled structures. Eight regions near the acceptor binding site in the N- and C- terminal domain of GTs have been identified that bind and specifically glycosylate the 3-OH group of acceptor flavonoids. Similarly, a conserved motif in the C-terminal domain is known to bind a sugar donor substrate. In certain GTs, the substitution of a specific glutamine by histidine in this domain changes the preference of sugar from glucose to galactose as a result of changed pattern of interactions. The molecular modeling, docking, and molecular dynamics simulation studies have revealed the chemical and topological features of the binding site and thus provided insights into the basis of acceptor and donor recognition by GTs. PMID:24667893

Identification of critical chemical features for Aurora kinase-B inhibitors using Hip-Hop, virtual screening and molecular docking

NASA Astrophysics Data System (ADS)

Sakkiah, Sugunadevi; Thangapandian, Sundarapandian; John, Shalini; Lee, Keun Woo

2011-01-01

This study was performed to find the selective chemical features for Aurora kinase-B inhibitors using the potent methods like Hip-Hop, virtual screening, homology modeling, molecular dynamics and docking. The best hypothesis, Hypo1 was validated toward a wide range of test set containing the selective inhibitors of Aurora kinase-B. Homology modeling and molecular dynamics studies were carried out to perform the molecular docking studies. The best hypothesis Hypo1 was used as a 3D query to screen the chemical databases. The screened molecules from the databases were sorted based on ADME and drug like properties. The selective hit compounds were docked and the hydrogen bond interactions with the critical amino acids present in Aurora kinase-B were compared with the chemical features present in the Hypo1. Finally, we suggest that the chemical features present in the Hypo1 are vital for a molecule to inhibit the Aurora kinase-B activity.

A combined Fisher and Laplacian score for feature selection in QSAR based drug design using compounds with known and unknown activities.

PubMed

Valizade Hasanloei, Mohammad Amin; Sheikhpour, Razieh; Sarram, Mehdi Agha; Sheikhpour, Elnaz; Sharifi, Hamdollah

2018-02-01

Quantitative structure-activity relationship (QSAR) is an effective computational technique for drug design that relates the chemical structures of compounds to their biological activities. Feature selection is an important step in QSAR based drug design to select the most relevant descriptors. One of the most popular feature selection methods for classification problems is Fisher score which aim is to minimize the within-class distance and maximize the between-class distance. In this study, the properties of Fisher criterion were extended for QSAR models to define the new distance metrics based on the continuous activity values of compounds with known activities. Then, a semi-supervised feature selection method was proposed based on the combination of Fisher and Laplacian criteria which exploits both compounds with known and unknown activities to select the relevant descriptors. To demonstrate the efficiency of the proposed semi-supervised feature selection method in selecting the relevant descriptors, we applied the method and other feature selection methods on three QSAR data sets such as serine/threonine-protein kinase PLK3 inhibitors, ROCK inhibitors and phenol compounds. The results demonstrated that the QSAR models built on the selected descriptors by the proposed semi-supervised method have better performance than other models. This indicates the efficiency of the proposed method in selecting the relevant descriptors using the compounds with known and unknown activities. The results of this study showed that the compounds with known and unknown activities can be helpful to improve the performance of the combined Fisher and Laplacian based feature selection methods.

A combined Fisher and Laplacian score for feature selection in QSAR based drug design using compounds with known and unknown activities

NASA Astrophysics Data System (ADS)

Valizade Hasanloei, Mohammad Amin; Sheikhpour, Razieh; Sarram, Mehdi Agha; Sheikhpour, Elnaz; Sharifi, Hamdollah

2018-02-01

Quantitative structure-activity relationship (QSAR) is an effective computational technique for drug design that relates the chemical structures of compounds to their biological activities. Feature selection is an important step in QSAR based drug design to select the most relevant descriptors. One of the most popular feature selection methods for classification problems is Fisher score which aim is to minimize the within-class distance and maximize the between-class distance. In this study, the properties of Fisher criterion were extended for QSAR models to define the new distance metrics based on the continuous activity values of compounds with known activities. Then, a semi-supervised feature selection method was proposed based on the combination of Fisher and Laplacian criteria which exploits both compounds with known and unknown activities to select the relevant descriptors. To demonstrate the efficiency of the proposed semi-supervised feature selection method in selecting the relevant descriptors, we applied the method and other feature selection methods on three QSAR data sets such as serine/threonine-protein kinase PLK3 inhibitors, ROCK inhibitors and phenol compounds. The results demonstrated that the QSAR models built on the selected descriptors by the proposed semi-supervised method have better performance than other models. This indicates the efficiency of the proposed method in selecting the relevant descriptors using the compounds with known and unknown activities. The results of this study showed that the compounds with known and unknown activities can be helpful to improve the performance of the combined Fisher and Laplacian based feature selection methods.

Chemical Bonding in Sulfide Minerals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaughan, David J.; Rosso, Kevin M.

An understanding of chemical bonding and electronic structure in sulfide minerals is central to any attempt at understanding their crystal structures, stabilities and physical properties. It is also an essential precursor to understanding reactivity through modeling surface structure at the molecular scale. In recent decades, there have been remarkable advances in first principles (ab initio) methods for the quantitative calculation of electronic structure. These advances have been made possible by the very rapid development of high performance computers. Several review volumes that chart the applications of these developments in mineralogy and geochemistry are available (Tossell and Vaughan, 1992; Cygan andmore » Kubicki, 2001). An important feature of the sulfide minerals is the diversity of their electronic structures, as evidenced by their electrical and magnetic properties (see Pearce et al. 2006, this volume). Thus, sulfide minerals range from insulators through semiconductors to metals, and exhibit every type of magnetic behavior. This has presented problems for those attempting to develop bonding models for sulfides, and also led to certain misconceptions regarding the kinds of models that may be appropriate. In this chapter, chemical bonding and electronic structure models for sulfides are reviewed with emphasis on more recent developments. Although the fully ab initio quantitative methods are now capable of a remarkable degree of sophistication in terms of agreement with experiment and potential to interpret and predict behavior with varying conditions, both qualitative and more simplistic quantitative approaches will also be briefly discussed. This is because we believe that the insights which they provide are still helpful to those studying sulfide minerals. In addition to the application of electronic structure models and calculations to solid sulfides, work on sulfide mineral surfaces (Rosso and Vaughan 2006a,b) and solution complexes and clusters (Rickard and Luther, 2006) are discussed in detail later in this volume.« less

Simple mechanisms of early life - simulation model on the origin of semi-cells.

PubMed

Klein, Adrian; Bock, Martin; Alt, Wolfgang

2017-01-01

The development of first cellular structures played an important role in the early evolution of life. Early evolution of life probably took place on a molecular level in a reactive environment. The iron-sulfur theory postulates the formation of cell-like structures on catalytic surfaces. Experiments show that H 2 S together with FeS and other metallic centers drive auto-catalytic surface reactions, in which organic molecules such as pyruvic and amino acids occur. It is questionable which mechanisms are needed to form cell-like structures under these conditions. To address this question, we implemented a model system featuring the fundamentals of molecular dynamics: heat, attraction, repulsion and formation of covalent bonds. Our basic model exhibits a series of essential processes: self-organization of lipid micelles and bilayers, formation of fluid filled cavities, flux of molecules along membranes, transport of energized groups towards sinks and whole colonies of cell-like structures on a larger scale. The results demonstrate that only a few features are sufficient for discovering hitherto non described phenomena of self-assembly and dynamics of cell-like structures as candidates for early evolving proto-cells. Significance statement The quest for a possible origin of life continues to be one of the most fascinating problems in biology. In one theoretical scenario, early life originated from a solution of reactive chemicals in the ancient deep sea, similar to conditions as to be found in thermal vents. Experiments have shown that a variety of organic molecules, the building blocks of life, form under these conditions. Based on such experiments, the iron-sulfur theory postulates the growth of cell-like structures at certain catalytic surfaces. For an explanation and proof of such a process we have developed a computer model simulating molecular assembly of lipid bilayers and formation of semi-cell cavities. The results demonstrate the possibility of cell-like self-organization under appropriate physico-chemical conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Bulk measurements of messy chemistries are needed for a theory of the origins of life

NASA Astrophysics Data System (ADS)

Guttenberg, Nicholas; Virgo, Nathaniel; Chandru, Kuhan; Scharf, Caleb; Mamajanov, Irena

2017-11-01

A feature of many of the chemical systems plausibly involved in the origins of terrestrial life is that they are complex and messy-producing a wide range of compounds via a wide range of mechanisms. However, the fundamental behaviour of such systems is currently not well understood; we do not have the tools to make statistical predictions about such complex chemical networks. This is, in part, due to a lack of quantitative data from which such a theory could be built; specifically, functional measurements of messy chemical systems. Here, we propose that the pantheon of experimental approaches to the origins of life should be expanded to include the study of `functional measurements'-the direct study of bulk properties of chemical systems and their interactions with other compounds, the formation of structures and other behaviours, even in cases where the precise composition and mechanisms are unknown. This article is part of the themed issue 'Reconceptualizing the origins of life'.

Design of chemical space networks on the basis of Tversky similarity

NASA Astrophysics Data System (ADS)

Wu, Mengjun; Vogt, Martin; Maggiora, Gerald M.; Bajorath, Jürgen

2016-01-01

Chemical space networks (CSNs) have been introduced as a coordinate-free representation of chemical space. In CSNs, nodes represent compounds and edges pairwise similarity relationships. These network representations are mostly used to navigate sections of biologically relevant chemical space. Different types of CSNs have been designed on the basis of alternative similarity measures including continuous numerical similarity values or substructure-based similarity criteria. CSNs can be characterized and compared on the basis of statistical concepts from network science. Herein, a new CSN design is introduced that is based upon asymmetric similarity assessment using the Tversky coefficient and termed TV-CSN. Compared to other CSNs, TV-CSNs have unique features. While CSNs typically contain separate compound communities and exhibit small world character, many TV-CSNs are also scale-free in nature and contain hubs, i.e., extensively connected central compounds. Compared to other CSNs, these hubs are a characteristic of TV-CSN topology. Hub-containing compound communities are of particular interest for the exploration of structure-activity relationships.

Reaction Decoder Tool (RDT): extracting features from chemical reactions.

PubMed

Rahman, Syed Asad; Torrance, Gilliean; Baldacci, Lorenzo; Martínez Cuesta, Sergio; Fenninger, Franz; Gopal, Nimish; Choudhary, Saket; May, John W; Holliday, Gemma L; Steinbeck, Christoph; Thornton, Janet M

2016-07-01

Extracting chemical features like Atom-Atom Mapping (AAM), Bond Changes (BCs) and Reaction Centres from biochemical reactions helps us understand the chemical composition of enzymatic reactions. Reaction Decoder is a robust command line tool, which performs this task with high accuracy. It supports standard chemical input/output exchange formats i.e. RXN/SMILES, computes AAM, highlights BCs and creates images of the mapped reaction. This aids in the analysis of metabolic pathways and the ability to perform comparative studies of chemical reactions based on these features. This software is implemented in Java, supported on Windows, Linux and Mac OSX, and freely available at https://github.com/asad/ReactionDecoder : asad@ebi.ac.uk or s9asad@gmail.com. © The Author 2016. Published by Oxford University Press.

Understanding ligninase-mediated reactions of endocrine disrupting chemicals in water: reaction rates and quantitative structure-activity relationships.

PubMed

Mao, Liang; Colosi, Lisa M; Gao, Shixiang; Huang, Qingguo

2011-07-15

We have verified in our previous work that lignin peroxidase (LiP) mediates effective removal of selected natural and synthetic estrogens. The efficiency of these reactions was greatly enhanced in the presence of veratryl alcohol (VA), a chemical that is produced along with LiP by certain white rot fungi, for example, Phanerochaete chrysosporium. In this study, we systematically evaluated the kinetic behaviors of LiP-mediated reactions for six endocrine disrupting compounds (EDCs), that is, steroid estrogens and their structural analogs, in both the presence and absence of VA. Resulting kinetic parameters were then correlated with structural features of LiP/substrate binding complexes, as quantified using molecular simulation, to create quantitative structure-activity relationship (QSAR) equations. These equations suggest that binding distance between a substrate's phenolic proton and δN of HIS47's imidazole ring plays an important role in modulating substrate reactivity toward LiP in both the presence and absence of VA. This information provides insight into an important enzymatic reaction process that occurs in the natural environment affecting EDC transformation, a process that may be used in engineered systems to achieve EDC removal from water.

Molecular modeling of the microstructure evolution during carbon fiber processing

NASA Astrophysics Data System (ADS)

Desai, Saaketh; Li, Chunyu; Shen, Tongtong; Strachan, Alejandro

2017-12-01

The rational design of carbon fibers with desired properties requires quantitative relationships between the processing conditions, microstructure, and resulting properties. We developed a molecular model that combines kinetic Monte Carlo and molecular dynamics techniques to predict the microstructure evolution during the processes of carbonization and graphitization of polyacrylonitrile (PAN)-based carbon fibers. The model accurately predicts the cross-sectional microstructure of the fibers with the molecular structure of the stabilized PAN fibers and physics-based chemical reaction rates as the only inputs. The resulting structures exhibit key features observed in electron microcopy studies such as curved graphitic sheets and hairpin structures. In addition, computed X-ray diffraction patterns are in good agreement with experiments. We predict the transverse moduli of the resulting fibers between 1 GPa and 5 GPa, in good agreement with experimental results for high modulus fibers and slightly lower than those of high-strength fibers. The transverse modulus is governed by sliding between graphitic sheets, and the relatively low value for the predicted microstructures can be attributed to their perfect longitudinal texture. Finally, the simulations provide insight into the relationships between chemical kinetics and the final microstructure; we observe that high reaction rates result in porous structures with lower moduli.

New Toxico-Cheminformatics & Computational Toxicology ...

EPA Pesticide Factsheets

EPA’s National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction. The DSSTox project is improving public access to quality structure-annotated chemical toxicity information in less summarized forms than traditionally employed in SAR modeling, and in ways that facilitate data-mining, and data read-across. The DSSTox Structure-Browser provides structure searchability across all published DSSTox toxicity-related inventory, and is enabling linkages between previously isolated toxicity data resources. As of early March 2008, the public DSSTox inventory has been integrated into PubChem, allowing a user to take full advantage of PubChem structure-activity and bioassay clustering features. The most recent DSSTox version of the Carcinogenic Potency Database file (CPDBAS) illustrates ways in which various summary definitions of carcinogenic activity can be employed in modeling and data mining. Phase I of the ToxCastTM project is generating high-throughput screening data from several hundred biochemical and cell-based assays for a set of 320 chemicals, mostly pesticide actives, with rich toxicology profiles. Incorporating and expanding traditional SAR concepts into this new high-throughput and data-rich world pose conceptual and practical challenges, but also holds great promise for improving predictive capabilities.

Electrical current at micro-/macro-scale of undoped and nitrogen-doped MWPECVD diamond films

NASA Astrophysics Data System (ADS)

Cicala, G.; Velardi, L.; Senesi, G. S.; Picca, R. A.; Cioffi, N.

2017-12-01

Chemical, structural, morphological and micro-/macro-electrical properties of undoped and nitrogen-(N-)doped diamond films are determined by X-ray photoelectron spectroscopy, Raman and photoluminescence spectroscopies, field emission scanning electron microscopy, atomic force microscopy, scanning capacitance microscopy (SCM) and two points technique for I-V characteristics, respectively. The characterization results are very useful to examine and understand the relationship among these properties. The effect of the nitrogen incorporation in diamond films is investigated through the evolution of the chemical, structural, morphological and topographical features and of the electrical behavior. The distribution of the electrical current is first assessed at millimeter scale on the surface of diamond films and then at micrometer scale on small regions in order to establish the sites where the carriers preferentially move. Specifically, the SCM images indicate a non-uniform distribution of carriers on the morphological structures mainly located along the grain boundaries. A good agreement is found by comparing the electrical currents at the micro- and macro-scale. This work aims to highlight phenomena such as photo- and thermionic emission from N-doped diamond useful for microelectronic engineering.

Antifeedant effect of polygodial and drimenol derivatives against Spodoptera frugiperda and Epilachna paenulata and quantitative structure-activity analysis.

PubMed

Montenegro, Iván J; Del Corral, Soledad; Diaz Napal, Georgina N; Carpinella, María C; Mellado, Marco; Madrid, Alejandro M; Villena, Joan; Palacios, Sara M; Cuellar, Mauricio A

2018-07-01

The antifeedant activity of 18 sesquiterpenoids of the drimane family (polygodial, drimenol and derivatives) was investigated. Polygodial, drimanic and nordrimanic derivatives were found to exert antifeedant effects against two insect species, Spodoptera frugiperda and Epilachna paenulata, which are pests of agronomic interest, indicating that they have potential as biopesticide agents. Among the 18 compounds tested, the epoxynordrimane compound (11) and isonordrimenone (4) showed the highest activity [50% effective concentration (EC 50 ) = 23.28 and 25.63 nmol cm - 2 , respectively, against S. frugiperda, and 50.50 and 59.00 nmol/cm 2 , respectively, against E. paenulata]. The results suggest that drimanic compounds have potential as new agents against S. frugiperda and E. paenulata. A quantitative structure-activity relationship (QSAR) analysis of the whole series, supported by electronic studies, suggested that drimanic compounds have structural features necessary for increasing antifeedant activity, namely a C-9 carbonyl group and an epoxide at C-8 and C-9. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Structure of naturally hydrated ferrihydrite revealed through neutron diffraction and first-principles modeling

NASA Astrophysics Data System (ADS)

Chappell, Helen F.; Thom, William; Bowron, Daniel T.; Faria, Nuno; Hasnip, Philip J.; Powell, Jonathan J.

2017-08-01

Ferrihydrite, with a ``two-line'' x-ray diffraction pattern (2L-Fh), is the most amorphous of the iron oxides and is ubiquitous in both terrestrial and aquatic environments. It also plays a central role in the regulation and metabolism of iron in bacteria, algae, higher plants, and animals, including humans. In this study, we present a single-phase model for ferrihydrite that unifies existing analytical data while adhering to fundamental chemical principles. The primary particle is small (20-50 Å) and has a dynamic and variably hydrated surface, which negates long-range order; collectively, these features have hampered complete characterization and frustrated our understanding of the mineral's reactivity and chemical/biochemical function. Near and intermediate range neutron diffraction (NIMROD) and first-principles density functional theory (DFT) were employed in this study to generate and interpret high-resolution data of naturally hydrated, synthetic 2L-Fh at standard temperature. The structural optimization overcomes transgressions of coordination chemistry inherent within previously proposed structures, to produce a robust and unambiguous single-phase model.

Multiple conformations of the cytidine repressor DNA-binding domain coalesce to one upon recognition of a specific DNA surface.

PubMed

Moody, Colleen L; Tretyachenko-Ladokhina, Vira; Laue, Thomas M; Senear, Donald F; Cocco, Melanie J

2011-08-09

The cytidine repressor (CytR) is a member of the LacR family of bacterial repressors with distinct functional features. The Escherichia coli CytR regulon comprises nine operons whose palindromic operators vary in both sequence and, most significantly, spacing between the recognition half-sites. This suggests a strong likelihood that protein folding would be coupled to DNA binding as a mechanism to accommodate the variety of different operator architectures to which CytR is targeted. Such coupling is a common feature of sequence-specific DNA-binding proteins, including the LacR family repressors; however, there are no significant structural rearrangements upon DNA binding within the three-helix DNA-binding domains (DBDs) studied to date. We used nuclear magnetic resonance (NMR) spectroscopy to characterize the CytR DBD free in solution and to determine the high-resolution structure of a CytR DBD monomer bound specifically to one DNA half-site of the uridine phosphorylase (udp) operator. We find that the free DBD populates multiple distinct conformations distinguished by up to four sets of NMR peaks per residue. This structural heterogeneity is previously unknown in the LacR family. These stable structures coalesce into a single, more stable udp-bound form that features a three-helix bundle containing a canonical helix-turn-helix motif. However, this structure differs from all other LacR family members whose structures are known with regard to the packing of the helices and consequently their relative orientations. Aspects of CytR activity are unique among repressors; we identify here structural properties that are also distinct and that might underlie the different functional properties. © 2011 American Chemical Society

The pivotal role of mass spectrometry in determining the presence of chemical contaminants in food raw materials.

PubMed

Mohamed, Rayane; Guy, Philippe A

2011-01-01

During recent years, a rising interest from consumers and various governmental organizations towards the quality of food has continuously been observed. Human intervention across the different stages of the food supply chain can lead to the presence of several types of chemical contaminants in food-based products. On a normal daily consumption basis, some of these chemicals are not harmful; however, for those that present a risk to consumers, legislation rules were established to specify tolerance levels or in some cases the total forbiddance of these specific contaminants. Hence, the use of appropriate analytical tools is recommended to properly identify chemical contaminants. In that context, mass spectrometry (MS)-based techniques coupled or not to chromatography offer a vast panel of features such as sensitivity, selectivity, quantification at trace levels, and/or structural elucidation. Because of the complexity of food-based matrices, sample preparation is a crucial step before final detection. In the present manuscript, we review the contribution and the potentialities of MS-based techniques to ensure the absence of chemical contaminants in food-based products. Copyright © 2011 Wiley Periodicals, Inc.

Influence of the physicochemical and aromatic properties on the chemical reactivity and its relation with carcinogenic and anticoagulant effect of 17β-aminoestrogens

NASA Astrophysics Data System (ADS)

Soriano-Correa, Catalina; Raya, Angélica; Barrientos-Salcedo, Carolina; Esquivel, Rodolfo O.

2014-06-01

Activity of steroid hormones is dependent upon a number of factors, as solubility, transport and metabolism. The functional differences caused by structural modifications could exert an influence on the chemical reactivity and biological effect. The goal of this work is to study the influence of the physicochemical and aromatic properties on the chemical reactivity and its relation with the carcinogenic risk that can associate with the anticoagulant effect of 17β-aminoestrogens using quantum-chemical descriptors at the DFT-B3LYP, BH&HLYP and M06-2X levels. The relative acidity of (H1) of the hydroxyl group increases with electron-withdrawing groups. Electron-donor groups favor the basicity. The steric hindrance of the substituents decreases the aromatic character and consequently diminution the carcinogenic effect. Density descriptors: hardness, electrophilic index, atomic charges, molecular orbitals, electrostatic potential and their geometric parameters permit analyses of the chemical reactivity and physicochemical features and to identify some reactive sites of 17β-aminoestrogens.

High performance polymer chemical hydrogel-based electrode binder materials for direct borohydride fuel cells

NASA Astrophysics Data System (ADS)

Choudhury, Nurul A.; Ma, Jia; Sahai, Yogeshwar; Buchheit, Rudolph G.

Novel, cost-effective, high-performance, and environment-friendly electrode binders, comprising polyvinyl alcohol chemical hydrogel (PCH) and chitosan chemical hydrogel (CCH), are reported for direct borohydride fuel cells (DBFCs). PCH and CCH binders-based electrodes have been fabricated using a novel, simple, cost-effective, time-effective, and environmentally benign technique. Morphologies and electrochemical performance in DBFCs of the chemical hydrogel binder-based electrodes have been compared with those of Nafion ® binder-based electrodes. Relationships between the performance of binders in DBFCs with structural features of the polymers and the polymer-based chemical hydrogels are discussed. The CCH binder exhibited better performance than a Nafion ® binder whereas the PCH binder exhibited comparable performance to Nafion ® in DBFCs operating at elevated cell temperatures. The better performance of CCH binder at higher operating cell temperatures has been ascribed to the hydrophilic nature and water retention characteristics of chitosan. DBFCs employing CCH binder-based electrodes and a Nafion ®-117 membrane as an electrolyte exhibited a maximum peak power density of about 589 mW cm -2 at 70 °C.

Structure of the glycosyl-phosphatidylinositol membrane anchor of acetylcholinesterase from the electric organ of the electric-fish, Torpedo californica.

PubMed Central

Mehlert, A; Varon, L; Silman, I; Homans, S W; Ferguson, M A

1993-01-01

The structure of the glycan moiety of the glycosyl-phosphatidylinositol (GPI) membrane anchor from Torpedo californica (electric fish) electric-organ acetylcholinesterase was solved using n.m.r., methylation analysis and chemical and enzymic micro-sequencing. Two structures were found to be present: Glc alpha 1-2Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6myo-inositol and Glc alpha 1-2Man alpha 1-2Man alpha 1-6(GalNAc beta 1-4)Man alpha 1-4GlcN alpha 1-6myo-inositol. The presence of glucose in this GPI anchor structure is a novel feature. The anchor was also shown to contain 2.3 residues of ethanolamine per molecule. PMID:8257440

Crystal structure of guanidinium hexafluoridovanadate(III), (CN3H6)3[VF6]: an unusual hybrid compound related to perovskite.

PubMed

Black, Cameron; Lightfoot, Philip

2017-03-01

Vanadium fluorides with novel crystal-chemical features and interesting physical properties can be prepared by solvothermal synthetic routes. The title compound, guanidinium hexafluoridovanadate(III), has a cubic structure (space group Pa-3), exhibiting isolated regular VF 6 octahedral units, which are hydrogen bonded to protonated guanidinium moieties. Although the VF 6 octahedral units are not linked directly together, there are structural similarities between this crystal structure and those of the wider family of perovskite materials, in particular, hybrid perovskites based on extended ligands such as cyanide. In this context, the octahedral tilt system of the present compound is of interest and demonstrates that unusual tilt systems can be mediated via `molecular' linkers which allow only supramolecular rather than covalent interactions.

Impact of annealing on features of BCP coating on NiTi shape memory alloy: Preparation and physicochemical characterization

NASA Astrophysics Data System (ADS)

Dulski, Mateusz; Dudek, Karolina; Grelowski, Michał; Kubacki, Jerzy; Hertlein, Justyna; Wojtyniak, Marcin; Goryczka, Tomasz

2018-04-01

A multifunctional composite structure consisting of resorbable tricalcium phosphate with non-resorbable hydroxyapatite and NiTi shape memory alloy (SMA) has been manufactured to develop a biocompatible system for long-term implant applications. The hybrid system has been vacuum sintered to consolidate and form chemical binding between phosphate biomaterials and NiTi SMA. In this context, the impact of sintering on biomaterial's features in relation to initial material has been analyzed using a combination of structural and surface sensitive approaches. Moreover, a partial decomposition of the NiTi parent phase to the equilibrium Ti2Ni with cubic structure, and non-equilibrium Ti3Ni4 with hexagonal structure has been detected. Moreover, a sintering has provided a reconstruction of the orthophosphate surface through the disintegration of calcium phosphate material and increase of hydroxyapatite with smaller particles in volume. The biomaterial surface has become more enriched in calcium in relation to the initial composition, with a simultaneous decline of the roughness parameters due to the gradual consolidation of orthophosphates. Finally, surface modification accompanied with heat treatment has led to an increase of surface Young's modulus as an effect of partial recrystallization of calcium phosphates.

Algorithm, applications and evaluation for protein comparison by Ramanujan Fourier transform.

PubMed

Zhao, Jian; Wang, Jiasong; Hua, Wei; Ouyang, Pingkai

2015-12-01

The amino acid sequence of a protein determines its chemical properties, chain conformation and biological functions. Protein sequence comparison is of great importance to identify similarities of protein structures and infer their functions. Many properties of a protein correspond to the low-frequency signals within the sequence. Low frequency modes in protein sequences are linked to the secondary structures, membrane protein types, and sub-cellular localizations of the proteins. In this paper, we present Ramanujan Fourier transform (RFT) with a fast algorithm to analyze the low-frequency signals of protein sequences. The RFT method is applied to similarity analysis of protein sequences with the Resonant Recognition Model (RRM). The results show that the proposed fast RFT method on protein comparison is more efficient than commonly used discrete Fourier transform (DFT). RFT can detect common frequencies as significant feature for specific protein families, and the RFT spectrum heat-map of protein sequences demonstrates the information conservation in the sequence comparison. The proposed method offers a new tool for pattern recognition, feature extraction and structural analysis on protein sequences. Copyright © 2015 Elsevier Ltd. All rights reserved.

Growth-dissolution-regrowth transitions of Fe3O4 nanoparticles as building blocks for 3D magnetic nanoparticle clusters under hydrothermal conditions.

PubMed

Lin, Mouhong; Huang, Haoliang; Liu, Zuotao; Liu, Yingju; Ge, Junbin; Fang, Yueping

2013-12-10

Magnetic nanoparticle clusters (MNCs) are a class of secondary structural materials that comprise chemically defined nanoparticles assembled into clusters of defined size. Herein, MNCs are fabricated through a one-pot solvothermal reaction featuring self-limiting assembly of building blocks and the controlled reorganization process. Such growth-dissolution-regrowth fabrication mechanism overcomes some limitations of conventional solvothermal fabrication methods with regard to restricted available feature size and structural complexity, which can be extended to other oxides (as long as one can be chelated by EDTA-2Na). Based on this method, the nanoparticle size of MNCs is tuned between 6.8 and 31.2 nm at a fixed cluster diameter of 120 nm, wherein the critical size for superparamagnetic-ferromagnetic transition is estimated from 13.5 to 15.7 nm. Control over the nature and secondary structure of MNCs gives an excellent model system to understand the nanoparticle size-dependent magnetic properties of MNCs. MNCs have potential applications in many different areas, while this work evaluates their cytotoxicity and Pb(2+) adsorption capacity as initial application study.

Molecular recognition principles and stationary-phase characteristics of topoisomer-selective chemoaffinity materials for chromatographic separation of circular plasmid DNA topoisomers.

PubMed

Mahut, Marek; Lindner, Wolfgang; Lämmerhofer, Michael

2012-01-18

We recently discovered the molecular recognition capability of a quinine carbamate ligand attached to silica as a powerful chemoaffinity material for the chromatographic separation of circular plasmid topoisomers of different linking numbers. In this paper we develop structure-selectivity relationship studies to figure out the essential structural features for topoisomer recognition. By varying different moieties of the original cinchonan-derived selector, it was shown that intercalation by the quinoline moiety of the ligand as assumed initially as the working hypothesis is not an essential feature for topoisomer recognition during chromatography. We found that the key elements for topoisomer selectivity are the presence of a rigid weak anion-exchange site and a H-donor site separated from each other in a defined distance by a 4-atom spacer. Additionally, incorporation of the weak anion-exchange site into a cyclic ring structure provides greater rigidity of the ligand molecule and turned out to be advantageous, if not mandatory, for (close to) baseline separation. © 2011 American Chemical Society

The Role of Feature Selection and Statistical Weighting in ...

EPA Pesticide Factsheets

Our study assesses the value of both in vitro assay and quantitative structure activity relationship (QSAR) data in predicting in vivo toxicity using numerous statistical models and approaches to process the data. Our models are built on datasets of (i) 586 chemicals for which both in vitro and in vivo data are currently available in EPA’s Toxcast and ToxRefDB databases, respectively, and (ii) 769 chemicals for which both QSAR data and in vivo data exist. Similar to a previous study (based on just 309 chemicals, Thomas et al. 2012), after converting the continuous values from each dataset to binary values, the majority of more than 1,000 in vivo endpoints are poorly predicted. Even for the endpoints that are well predicted (about 40 with an F1 score of >0.75), imbalances in in vivo endpoint data or cytotoxicity across in vitro assays may be skewing results. In order to better account for these types of considerations, we examine best practices in data preprocessing and model fitting in real-world contexts where data are rife with imperfections. We discuss options for dealing with missing data, including omitting observations, aggregating variables, and imputing values. We also examine the impacts of feature selection (from both a statistical and biological perspective) on performance and efficiency, and we weight outcome data to reduce endpoint imbalances to account for potential chemical selection bias and assess revised performance. For example, initial weig

Mechanical Properties and Failure of Biopolymers: Atomistic Reactions to Macroscale Response

PubMed Central

Jung, GangSeob; Qin, Zhao

2017-01-01

The behavior of chemical bonding under various mechanical loadings is an intriguing mechanochemical property of biological materials, and the property plays a critical role in determining their deformation and failure mechanisms. Because of their astonishing mechanical properties and roles in constituting the basis of a variety of physiologically relevant materials, biological protein materials have been intensively studied. Understanding the relation between chemical bond networks (structures) and their mechanical properties offers great possibilities to enable new materials design in nanotechnology and new medical treatments for human diseases. Here we focus on how the chemical bonds in biological systems affect mechanical properties and how they change during mechanical deformation and failure. Three representative cases of biomaterials related to the human diseases are discussed in case studies, including: amyloids, intermediate filaments, and collagen, each describing mechanochemical features and how they relate to the pathological conditions at multiple scales. PMID:26108895

Multifunctional porous solids derived from tannins

NASA Astrophysics Data System (ADS)

Celzard, Alain; Fierro, Vanessa; Pizzi, Antonio; Zhao, Weigang

2013-03-01

Tannins are extremely valuable, non toxic, wood extractives combining reactivity towards aldehydes, low cost, natural origin and easy handling. When polymerized in the presence of suitable chemicals including blowing agent, ultra lightweight rigid tannin-based foams are obtained. If pyrolyzed under inert gas, reticulated carbon foams having the same pore structure and the same density are obtained. The most remarkable features of tannin-based foams are the following: mechanical resistance similar to, or higher than, that of commercial phenolic foams, tuneable pore size and permeability, infusibility, very low thermal conductivity, cheapness, ecological character, high resistance to flame and to chemicals. Carbon foams have even better properties and are also electrically conducting. Consequently, various applications are suggested for organic foams: cores of sandwich composite panels, sound and shock absorbers and thermal insulators, whereas carbon foams can be used as porous electrodes, filters for molten metals and corrosive chemicals, catalyst supports and adsorbents.

On the outside looking in: redefining the role of analytical chemistry in the biosciences.

PubMed

Hare, Dominic J; New, Elizabeth J

2016-07-12

Biomedical research has moved on from the study of the structure of organs, cells and organelles. Today, the key questions that must be addressed to understand the body in health and disease are related to fundamental biochemistry: the distribution and speciation of chemicals, the regulation of chemical reactions, and the control of chemical environments. To see advances in this field, it is essential for analytical chemists to actively engage in this process, from beginning to end. In this Feature Article, we review the progress that has been made towards gaining an understanding of the chemistry of the body, while commenting on the intrinsic disconnect between new innovations in the field of analytical chemistry and practical application within the biosciences. We identify the challenges that prevent chemists from making a greater impact in this field, and highlight key steps for moving forward.

Approaches to Establishing the Chemical Structure of Extraterrestrial Organic Solids

NASA Technical Reports Server (NTRS)

Cody, G. D.; Alexander, C. M. OD.; Wirick, Susan

2003-01-01

The majority of extraterrestrial organic matter in carbonaceous chondrites resides in a chemically complex, insoluble and perhaps macromolecular phase. We have been applying a series of independent solid state NMR experiments that are designed to provide a self consistent chemical characterization of this complex material. To date we have thoroughly analyzed 8 organic residues from different meteorites, including a CR2 (EET92042), CIl(Orgueil), CM2 (Murchison), Tagish Lake, CM2 (AlH83100), CM2 (Cold Bokkefeld), CM2 (Mighei), CM3 (Y86720). In fig 1. (1)H to (13)C cross polarization NMR spectra of four of these are shown. Note that there exists an enormous range in chemistry exhibited in organic solid [evident by the breadth of the spectral features both in the aliphatic region (sp(sup 3)) and the aromatic region (sp(sup 2))]. There is also considerable differences in the carbon chemistry across the meteorite groups.

A DFT investigation on geometry and chemical bonding of isoelectronic Si8N6V-, Si8N6Cr, and Si8N6Mn+ clusters

NASA Astrophysics Data System (ADS)

Tam, Nguyen Minh; Pham, Hung Tan; Cuong, Ngo Tuan; Tung, Nguyen Thanh

2017-10-01

The geometric feature and chemical bonding of isoelectronic systems Si8N6Mq (M = V, Cr, Mn and q = -1, 0, 1, respectively) are investigated by means of density-functional-theory calculations. The encapsulated form is found for all ground-state structures, where the metal atom locates at the central site of the hollow Si8N6 cage. The Si8N6 cage is established by adding two Si atoms to a distorted Si6N6 prism, which is a combination of Si4N2 and Si2N4 strings. Chemical bonding of Si8N6Mq systems is explored by using the electron localization indicator and theory of atom in molecule, revealing the vital role of metal center in stabilizing the clusters.

Factors contributing to the immunogenicity of meningococcal conjugate vaccines

PubMed Central

Bröker, Michael; Berti, Francesco; Costantino, Paolo

2016-01-01

ABSTRACT Various glycoprotein conjugate vaccines have been developed for the prevention of invasive meningococcal disease, having significant advantages over pure polysaccharide vaccines. One of the most important features of the conjugate vaccines is the induction of a T-cell dependent immune response, which enables both the induction of immune memory and a booster response after repeated immunization. The nature of the carrier protein to which the polysaccharides are chemically linked, is often regarded as the main component of the vaccine in determining its immunogenicity. However, other factors can have a significant impact on the vaccine's profile. In this review, we explore the physico-chemical properties of meningococcal conjugate vaccines, which can significantly contribute to the vaccine's immunogenicity. We demonstrate that the carrier is not the sole determining factor of the vaccine's profile, but, moreover, that the conjugate vaccine's immunogenicity is the result of multiple physico-chemical structures and characteristics. PMID:26934310

Training HBCU Faculty and Students in Prostate Cancer (PC) Research: Signal Transduction and Receptor-Inhibitor Interactions in the Progress of PC

DTIC Science & Technology

2008-03-01

thiocinnamide, and 4-[(3-bromophenyl) amino ]-6- propionylamidoquinazoline have been completed. We continue to crystallize samples of tyrosine kinase...been developed last year identify the geometric relationship between structural features of a set of molecules known to act as tyrosine kinase...L. Klein Stevens, “A Crystallographic Study of ErbB2 Tyrosine Kinase Inhibitors”, 230th American Chemical Society National Meeting, Washington, DC

Functional conjugated pyridines via main-group element tuning.

PubMed

Stolar, Monika; Baumgartner, Thomas

2018-03-29

Pyridine-based materials have seen widespread attention for the development of n-type organic materials. In recent years, the incorporation of main-group elements has also explored significant advantages for the development and tunability of organic conjugated materials. The unique chemical and electronic structure of main-group elements has led to several enhancements in conventional organic materials. This Feature article highlights recent main-group based pyridine materials by discussing property enhancements and application in organic electronics.

Laser applications to chemical, security, and environmental analysis: introduction to the feature issue.

PubMed

Seeger, Thomas; Dreier, Thomas; Chen, Weidong; Kearny, Sean; Kulatilaka, Waruna

2017-04-10

This Applied Optics feature issue on laser applications to chemical, security, and environmental analysis (LACSEA) highlights papers presented at the LACSEA 2016 Fifteenth Topical Meeting sponsored by the Optical Society of America.

Inforna 2.0: A Platform for the Sequence-Based Design of Small Molecules Targeting Structured RNAs.

PubMed

Disney, Matthew D; Winkelsas, Audrey M; Velagapudi, Sai Pradeep; Southern, Mark; Fallahi, Mohammad; Childs-Disney, Jessica L

2016-06-17

The development of small molecules that target RNA is challenging yet, if successful, could advance the development of chemical probes to study RNA function or precision therapeutics to treat RNA-mediated disease. Previously, we described Inforna, an approach that can mine motifs (secondary structures) within target RNAs, which is deduced from the RNA sequence, and compare them to a database of known RNA motif-small molecule binding partners. Output generated by Inforna includes the motif found in both the database and the desired RNA target, lead small molecules for that target, and other related meta-data. Lead small molecules can then be tested for binding and affecting cellular (dys)function. Herein, we describe Inforna 2.0, which incorporates all known RNA motif-small molecule binding partners reported in the scientific literature, a chemical similarity searching feature, and an improved user interface and is freely available via an online web server. By incorporation of interactions identified by other laboratories, the database has been doubled, containing 1936 RNA motif-small molecule interactions, including 244 unique small molecules and 1331 motifs. Interestingly, chemotype analysis of the compounds that bind RNA in the database reveals features in small molecule chemotypes that are privileged for binding. Further, this updated database expanded the number of cellular RNAs to which lead compounds can be identified.

Designed protein reveals structural determinants of extreme kinetic stability

PubMed Central

Broom, Aron; Ma, S. Martha; Xia, Ke; Rafalia, Hitesh; Trainor, Kyle; Colón, Wilfredo; Gosavi, Shachi; Meiering, Elizabeth M.

2015-01-01

The design of stable, functional proteins is difficult. Improved design requires a deeper knowledge of the molecular basis for design outcomes and properties. We previously used a bioinformatics and energy function method to design a symmetric superfold protein composed of repeating structural elements with multivalent carbohydrate-binding function, called ThreeFoil. This and similar methods have produced a notably high yield of stable proteins. Using a battery of experimental and computational analyses we show that despite its small size and lack of disulfide bonds, ThreeFoil has remarkably high kinetic stability and its folding is specifically chaperoned by carbohydrate binding. It is also extremely stable against thermal and chemical denaturation and proteolytic degradation. We demonstrate that the kinetic stability can be predicted and modeled using absolute contact order (ACO) and long-range order (LRO), as well as coarse-grained simulations; the stability arises from a topology that includes many long-range contacts which create a large and highly cooperative energy barrier for unfolding and folding. Extensive data from proteomic screens and other experiments reveal that a high ACO/LRO is a general feature of proteins with strong resistances to denaturation and degradation. These results provide tractable approaches for predicting resistance and designing proteins with sufficient topological complexity and long-range interactions to accommodate destabilizing functional features as well as withstand chemical and proteolytic challenge. PMID:26554002

The in vivo structure of biological membranes and evidence for lipid domains

DOE PAGES

Nickels, Jonathan D.; Chatterjee, Sneha; Stanley, Christopher B.; ...

2017-05-23

Examining the fundamental structure and processes of living cells at the nanoscale poses a unique analytical challenge, as cells are dynamic, chemically diverse, and fragile. A case in point is the cell membrane, which is too small to be seen directly with optical microscopy and provides little observational contrast for other methods. As a consequence, nanoscale characterization of the membrane has been performed ex vivo or in the presence of exogenous labels used to enhance contrast and impart specificity. Here, we introduce an isotopic labeling strategy in the gram-positive bacterium Bacillus subtilis to investigate the nanoscale structure and organization ofmore » its plasma membrane in vivo. Through genetic and chemical manipulation of the organism, we labeled the cell and its membrane independently with specific amounts of hydrogen (H) and deuterium (D). These isotopes have different neutron scattering properties without altering the chemical composition of the cells. From neutron scattering spectra, we confirmed that the B. subtilis cell membrane is lamellar and determined that its average hydrophobic thickness is 24.3 ± 0.9 Ångstroms (Å). Furthermore, by creating neutron contrast within the plane of the membrane using a mixture of H- and D-fatty acids, we detected lateral features smaller than 40 nm that are consistent with the notion of lipid rafts. These experiments—performed under biologically relevant conditions—answer long-standing questions in membrane biology and illustrate a fundamentally new approach for systematic in vivo investigations of cell membrane structure.« less

The in vivo structure of biological membranes and evidence for lipid domains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nickels, Jonathan D.; Chatterjee, Sneha; Stanley, Christopher B.

Examining the fundamental structure and processes of living cells at the nanoscale poses a unique analytical challenge, as cells are dynamic, chemically diverse, and fragile. A case in point is the cell membrane, which is too small to be seen directly with optical microscopy and provides little observational contrast for other methods. As a consequence, nanoscale characterization of the membrane has been performed ex vivo or in the presence of exogenous labels used to enhance contrast and impart specificity. Here, we introduce an isotopic labeling strategy in the gram-positive bacterium Bacillus subtilis to investigate the nanoscale structure and organization ofmore » its plasma membrane in vivo. Through genetic and chemical manipulation of the organism, we labeled the cell and its membrane independently with specific amounts of hydrogen (H) and deuterium (D). These isotopes have different neutron scattering properties without altering the chemical composition of the cells. From neutron scattering spectra, we confirmed that the B. subtilis cell membrane is lamellar and determined that its average hydrophobic thickness is 24.3 ± 0.9 Ångstroms (Å). Furthermore, by creating neutron contrast within the plane of the membrane using a mixture of H- and D-fatty acids, we detected lateral features smaller than 40 nm that are consistent with the notion of lipid rafts. These experiments—performed under biologically relevant conditions—answer long-standing questions in membrane biology and illustrate a fundamentally new approach for systematic in vivo investigations of cell membrane structure.« less

The in vivo structure of biological membranes and evidence for lipid domains.

PubMed

Nickels, Jonathan D; Chatterjee, Sneha; Stanley, Christopher B; Qian, Shuo; Cheng, Xiaolin; Myles, Dean A A; Standaert, Robert F; Elkins, James G; Katsaras, John

2017-05-01

Examining the fundamental structure and processes of living cells at the nanoscale poses a unique analytical challenge, as cells are dynamic, chemically diverse, and fragile. A case in point is the cell membrane, which is too small to be seen directly with optical microscopy and provides little observational contrast for other methods. As a consequence, nanoscale characterization of the membrane has been performed ex vivo or in the presence of exogenous labels used to enhance contrast and impart specificity. Here, we introduce an isotopic labeling strategy in the gram-positive bacterium Bacillus subtilis to investigate the nanoscale structure and organization of its plasma membrane in vivo. Through genetic and chemical manipulation of the organism, we labeled the cell and its membrane independently with specific amounts of hydrogen (H) and deuterium (D). These isotopes have different neutron scattering properties without altering the chemical composition of the cells. From neutron scattering spectra, we confirmed that the B. subtilis cell membrane is lamellar and determined that its average hydrophobic thickness is 24.3 ± 0.9 Ångstroms (Å). Furthermore, by creating neutron contrast within the plane of the membrane using a mixture of H- and D-fatty acids, we detected lateral features smaller than 40 nm that are consistent with the notion of lipid rafts. These experiments-performed under biologically relevant conditions-answer long-standing questions in membrane biology and illustrate a fundamentally new approach for systematic in vivo investigations of cell membrane structure.

A Novel Concept for the Search and Retrieval of the Derwent Markush Resource Database.

PubMed

Barth, Andreas; Stengel, Thomas; Litterst, Edwin; Kraut, Hans; Matuszczyk, Henry; Ailer, Franz; Hajkowski, Steve

2016-05-23

The representation of and search for generic chemical structures (Markush) remains a continuing challenge. Several research groups have addressed this problem, and over time a limited number of practical solutions have been proposed. Today there are two large commercial providers of Markush databases: Chemical Abstracts Service (CAS) and Thomson Reuters. The Thomson Reuters "Derwent" Markush database is currently offered via the online services Questel and STN and as a data feed for in-house use. The aim of this paper is to briefly review the existing Markush systems (databases plus search engines) and to describe our new approach for the implementation of the Derwent Markush Resource on STN. Our new approach demonstrates the integration of the Derwent Markush Resource database into the existing chemistry-focused STN platform without loss of detail. This provides compatibility with other structure and Markush databases on STN and at the same time makes it possible to deploy the specific features and functions of the Derwent approach. It is shown that the different Markush languages developed by CAS and Derwent can be combined into a single general Markush description. In this concept the generic nodes are grouped together in a unique hierarchy where all chemical elements and fragments can be integrated. As a consequence, both systems are searchable using a single structure query. Moreover, the presented concept could serve as a promising starting point for a common generalized description of Markush structures.

Advanced understanding on electronic structure of molecular semiconductors and their interfaces

NASA Astrophysics Data System (ADS)

Akaike, Kouki

2018-03-01

Understanding the electronic structure of organic semiconductors and their interfaces is critical to optimizing functionalities for electronics applications, by rational chemical design and appropriate combination of device constituents. The unique electronic structure of a molecular solid is characterized as (i) anisotropic electrostatic fields that originate from molecular quadrupoles, (ii) interfacial energy-level lineup governed by simple electrostatics, and (iii) weak intermolecular interactions that make not only structural order but also energy distributions of the frontier orbitals sensitive to atmosphere and interface growth. This article shows an overview on these features with reference to the improved understanding of the orientation-dependent electronic structure, comprehensive mechanisms of molecular doping, and energy-level alignment. Furthermore, the engineering of ionization energy by the control of the electrostatic fields and work function of practical electrodes by contact-induced doping is briefly described for the purpose of highlighting how the electronic structure impacts the performance of organic devices.

Chemical function based pharmacophore generation of endothelin-A selective receptor antagonists.

PubMed

Funk, Oliver F; Kettmann, Viktor; Drimal, Jan; Langer, Thierry

2004-05-20

Both quantitative and qualitative chemical function based pharmacophore models of endothelin-A (ET(A)) selective receptor antagonists were generated by using the two algorithms HypoGen and HipHop, respectively, which are implemented in the Catalyst molecular modeling software. The input for HypoGen is a training set of 18 ET(A) antagonists exhibiting IC(50) values ranging between 0.19 nM and 67 microM. The best output hypothesis consists of five features: two hydrophobic (HY), one ring aromatic (RA), one hydrogen bond acceptor (HBA), and one negative ionizable (NI) function. The highest scoring Hip Hop model consists of six features: three hydrophobic (HY), one ring aromatic (RA), one hydrogen bond acceptor (HBA), and one negative ionizable (NI). It is the result of an input of three highly active, selective, and structurally diverse ET(A) antagonists. The predictive power of the quantitative model could be approved by using a test set of 30 compounds, whose activity values spread over 6 orders of magnitude. The two pharmacophores were tested according to their ability to extract known endothelin antagonists from the 3D molecular structure database of Derwent's World Drug Index. Thereby the main part of selective ET(A) antagonistic entries was detected by the two hypotheses. Furthermore, the pharmacophores were used to screen the Maybridge database. Six compounds were chosen from the output hit lists for in vitro testing of their ability to displace endothelin-1 from its receptor. Two of these are new potential lead compounds because they are structurally novel and exhibit satisfactory activity in the binding assay.

Selective host molecules obtained by dynamic adaptive chemistry.

PubMed

Matache, Mihaela; Bogdan, Elena; Hădade, Niculina D

2014-02-17

Up till 20 years ago, in order to endow molecules with function there were two mainstream lines of thought. One was to rationally design the positioning of chemical functionalities within candidate molecules, followed by an iterative synthesis-optimization process. The second was the use of a "brutal force" approach of combinatorial chemistry coupled with advanced screening for function. Although both methods provided important results, "rational design" often resulted in time-consuming efforts of modeling and synthesis only to find that the candidate molecule was not performing the designed job. "Combinatorial chemistry" suffered from a fundamental limitation related to the focusing of the libraries employed, often using lead compounds that limit its scope. Dynamic constitutional chemistry has developed as a combination of the two approaches above. Through the rational use of reversible chemical bonds together with a large plethora of precursor libraries, one is now able to build functional structures, ranging from quite simple molecules up to large polymeric structures. Thus, by introduction of the dynamic component within the molecular recognition processes, a new perspective of deciphering the world of the molecular events has aroused together with a new field of chemistry. Since its birth dynamic constitutional chemistry has continuously gained attention, in particular due to its ability to easily create from scratch outstanding molecular structures as well as the addition of adaptive features. The fundamental concepts defining the dynamic constitutional chemistry have been continuously extended to currently place it at the intersection between the supramolecular chemistry and newly defined adaptive chemistry, a pivotal feature towards evolutive chemistry. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A tandem regression-outlier analysis of a ligand cellular system for key structural modifications around ligand binding.

PubMed

Lin, Ying-Ting

2013-04-30

A tandem technique of hard equipment is often used for the chemical analysis of a single cell to first isolate and then detect the wanted identities. The first part is the separation of wanted chemicals from the bulk of a cell; the second part is the actual detection of the important identities. To identify the key structural modifications around ligand binding, the present study aims to develop a counterpart of tandem technique for cheminformatics. A statistical regression and its outliers act as a computational technique for separation. A PPARγ (peroxisome proliferator-activated receptor gamma) agonist cellular system was subjected to such an investigation. Results show that this tandem regression-outlier analysis, or the prioritization of the context equations tagged with features of the outliers, is an effective regression technique of cheminformatics to detect key structural modifications, as well as their tendency of impact to ligand binding. The key structural modifications around ligand binding are effectively extracted or characterized out of cellular reactions. This is because molecular binding is the paramount factor in such ligand cellular system and key structural modifications around ligand binding are expected to create outliers. Therefore, such outliers can be captured by this tandem regression-outlier analysis.

Structure-activity relationships of pentamidine-affected ion channel trafficking and dofetilide mediated rescue.

PubMed

Varkevisser, R; Houtman, M J C; Linder, T; de Git, K C G; Beekman, H D M; Tidwell, R R; Ijzerman, A P; Stary-Weinzinger, A; Vos, M A; van der Heyden, M A G

2013-07-01

Drug interference with normal hERG protein trafficking substantially reduces the channel density in the plasma membrane and thereby poses an arrhythmic threat. The chemical substructures important for hERG trafficking inhibition were investigated using pentamidine as a model drug. Furthermore, the relationship between acute ion channel block and correction of trafficking by dofetilide was studied. hERG and K(IR)2.1 trafficking in HEK293 cells was evaluated by Western blot and immunofluorescence microscopy after treatment with pentamidine and six pentamidine analogues, and correction with dofetilide and four dofetilide analogues that displayed different abilities to inhibit IKr . Molecular dynamics simulations were used to address mode, number and type of interactions between hERG and dofetilide analogues. Structural modifications of pentamidine differentially affected plasma membrane levels of hERG and K(IR)2.1. Modification of the phenyl ring or substituents directly attached to it had the largest effect, affirming the importance of these chemical residues in ion channel binding. PA-4 had the mildest effects on both ion channels. Dofetilide corrected pentamidine-induced hERG, but not K(IR)2.1 trafficking defects. Dofetilide analogues that displayed high channel affinity, mediated by pi-pi stacks and hydrophobic interactions, also restored hERG protein levels, whereas analogues with low affinity were ineffective. Drug-induced trafficking defects can be minimized if certain chemical features are avoided or 'synthesized out'; this could influence the design and development of future drugs. Further analysis of such features in hERG trafficking correctors may facilitate the design of a non-blocking corrector for trafficking defective hERG proteins in both congenital and acquired LQTS. © 2013 The British Pharmacological Society.

Structure-activity relationships of pentamidine-affected ion channel trafficking and dofetilide mediated rescue

PubMed Central

Varkevisser, R; Houtman, M J C; Linder, T; de Git, K C G; Beekman, H D M; Tidwell, R R; IJzerman, A P; Stary-Weinzinger, A; Vos, M A; van der Heyden, M A G

2013-01-01

Background and Purpose Drug interference with normal hERG protein trafficking substantially reduces the channel density in the plasma membrane and thereby poses an arrhythmic threat. The chemical substructures important for hERG trafficking inhibition were investigated using pentamidine as a model drug. Furthermore, the relationship between acute ion channel block and correction of trafficking by dofetilide was studied. Experimental Approach hERG and KIR2.1 trafficking in HEK293 cells was evaluated by Western blot and immunofluorescence microscopy after treatment with pentamidine and six pentamidine analogues, and correction with dofetilide and four dofetilide analogues that displayed different abilities to inhibit IKr. Molecular dynamics simulations were used to address mode, number and type of interactions between hERG and dofetilide analogues. Key Results Structural modifications of pentamidine differentially affected plasma membrane levels of hERG and KIR2.1. Modification of the phenyl ring or substituents directly attached to it had the largest effect, affirming the importance of these chemical residues in ion channel binding. PA-4 had the mildest effects on both ion channels. Dofetilide corrected pentamidine-induced hERG, but not KIR2.1 trafficking defects. Dofetilide analogues that displayed high channel affinity, mediated by pi-pi stacks and hydrophobic interactions, also restored hERG protein levels, whereas analogues with low affinity were ineffective. Conclusions and Implications Drug-induced trafficking defects can be minimized if certain chemical features are avoided or ‘synthesized out’; this could influence the design and development of future drugs. Further analysis of such features in hERG trafficking correctors may facilitate the design of a non-blocking corrector for trafficking defective hERG proteins in both congenital and acquired LQTS. PMID:23586323

Nanolayered Features of Collagen-like Peptides

NASA Technical Reports Server (NTRS)

Valluzzi, Regina; Bini, Elisabetta; Haas, Terry; Cebe, Peggy; Kaplan, David L.

2003-01-01

We have been investigating collagen-like model oligopeptides as molecular bases for complex ordered biomimetic materials. The collagen-like molecules incorporate aspects of native collagen sequence and secondary structure. Designed modifications to native primary and secondary structure have been incorporated to control the nanostructure and microstructure of the collagen-like materials produced. We find that the collagen-like molecules form a number of lyotropic rod liquid crystalline phases, which because of their strong temperature dependence in the liquid state can also be viewed as solvent intercalated thermotropic liquid crystals. The liquid crystalline phases formed by the molecules can be captured in the solid state by drying off solvent, resulting in solid nanopatterned (chemically and physically) thermally stable (to greater than 100 C) materials. Designed sequences which stabilize smectic phases have allowed a variety of nanoscale multilayered biopolymeric materials to be developed. Preliminary investigations suggest that chemical patterns running perpendicular to the smectic layer plane can be functionalized and used to localize a variety of organic, inorganic, and organometallic moieties in very simple multilayered nanocomposites. The phase behavior of collagen-like oligopeptide materials is described, emphasizing the correlation between mesophase, molecular orientation, and chemical patterning at the microscale and nanoscale. In many cases, the textures observed for smectic and hexatic phase collagens are remarkably similar to the complex (and not fully understood) helicoids observed in biological collagen-based tissues. Comparisons between biological morphologies and collagen model liquid crystalline (and solidified materials) textures may help us understand the molecular features which impart order and function to the extracellular matrix and to collagen-based mineralized tissues. Initial studies have utilized synthetic collagen-like peptides while future work will also focus on similar sequences generated via genetic engineering methods.

Mixed-linker UiO-66: structure-property relationships revealed by a combination of high-resolution powder X-ray diffraction and density functional theory calculations.

PubMed

Taddei, Marco; Tiana, Davide; Casati, Nicola; van Bokhoven, Jeroen A; Smit, Berend; Ranocchiari, Marco

2017-01-04

The use of mixed-linker metal-organic frameworks (MIXMOFs) is one of the most effective strategies to modulate the physical-chemical properties of MOFs without affecting the overall crystal structure. In many instances, MIXMOFs have been recognized as solid solutions, with random distribution of ligands, in agreement with the empirical rule known as Vegard's law. In this work, we have undertaken a study combining high-resolution powder X-ray diffraction (HR-PXRD) and density functional theory (DFT) calculations with the aim of understanding the reasons why UiO-66-based amino- and bromo-functionalized MIXMOFs (MIXUiO-66) undergo cell expansion obeying Vegard's law and how this behaviour is related to their physical-chemical properties. DFT calculations predict that the unit cell in amino-functionalized UiO-66 experiences only minor expansion as a result of steric effects, whereas major modification to the electronic features of the framework leads to weaker metal-linker interaction and consequently to the loss of stability at higher degrees of functionalization. For bromo-functionalized UiO-66, steric repulsion due to the size of bromine yields a large cell expansion, but the electronic features remain very similar to pristine UiO-66, preserving the stability of the framework upon functionalization. MIXUiO-66 obtained by either direct synthesis or by post-synthetic exchange shows Vegard-like behaviour, suggesting that both preparation methods yield solid solutions, but the thermal stability and the textural properties of the post-synthetic exchanged materials do not display a clear dependence on the chemical composition, as observed for the MOFs obtained by direct synthesis.

Hillasides A and B, two new cytotoxic triterpene glycosides from the sea cucumber Holothuria hilla Lesson.

PubMed

Wu, Jun; Yi, Yang-Hua; Tang, Hai-Feng; Wu, Hou-Ming; Zhou, Zhen-Rong

2007-01-01

Two new triterpene glycosides, hillasides A (1) and B (2), were isolated from the sea cucumber H. hilla Lesson, together with one known glycoside holothuria B (3). Their structures were deduced by extensive spectral analysis and chemical evidences. The presence of conjugated double bonds [22E,24-diene] in the aglycone of 1 is a rare structural feature among sea cucumber glycosides. The two glycosides showed significant cytotoxicity against eight human tumour cell lines (A-549, MCF-7, IA9, CAKI-1, PC-3, KB, KB-VIN and HCT-8) with IC(50) in the range of 0.1-3.8 microg/ml.

TiO2 synthesized by microwave assisted solvothermal method: Experimental and theoretical evaluation

NASA Astrophysics Data System (ADS)

Moura, K. F.; Maul, J.; Albuquerque, A. R.; Casali, G. P.; Longo, E.; Keyson, D.; Souza, A. G.; Sambrano, J. R.; Santos, I. M. G.

2014-02-01

In this study, a microwave assisted solvothermal method was used to synthesize TiO2 with anatase structure. The synthesis was done using Ti (IV) isopropoxide and ethanol without templates or alkalinizing agents. Changes in structural features were observed with increasing time of synthesis and evaluated using periodic quantum chemical calculations. The anatase phase was obtained after only 1 min of reaction besides a small amount of brookite phase. Experimental Raman spectra are in accordance with the theoretical one. Micrometric spheres constituted by nanometric particles were obtained for synthesis from 1 to 30 min, while spheres and sticks were observed after 60 min.

Use of Small Angle Neutron Scattering to Study Various Properties of Wool and Mohair Fibres

DOE Office of Scientific and Technical Information (OSTI.GOV)

Franklyn, C. B.; Toeroek, Gy.

2011-12-13

To maintain a competitive edge in the wool and mohair industry, a detailed knowledge and understanding of the properties of wool fibres is essential. Standard techniques are used to determine fibre diameter, length and strength; however, properties such as hydroscopicity, lustre and changes in fibre structure following chemical or mechanical treatment are not so well understood. The unique capabilities of small angle neutron scattering to study changes in the supermolecular structure of wool fibres, particularly at the level of the microfibril-matrix complex, have been used to provide previously unknown features of the fibres. The results of these studies are presented.

Al-centered icosahedral ordering in Cu46Zr46Al8 bulk metallic glass

NASA Astrophysics Data System (ADS)

Fang, H. Z.; Hui, X.; Chen, G. L.; Liu, Z. K.

2009-03-01

Icosahedral short-range order, of which Al atoms are caged in the center of icosahedra with Cu and Zr atoms being the vertices, has been evidenced in the Cu46Zr46Al8 glassy structure by ab initio molecular dynamics simulation. These Al-centered clusters distribute irregularly in the three-dimensional space and form a "backbone" structure of the Cu46Zr46Al8 glass alloy. It is suggested that this kind of local structural feature is attributed to the requirement of efficient dense packing and the chemical affinity between Zr-Zr, Zr-Al, and Cu-Zr atoms. Our calculated results are found to be in good agreement with the experimental data.

Structure-activity relationships for skin sensitization: recent improvements to Derek for Windows.

PubMed

Langton, Kate; Patlewicz, Grace Y; Long, Anthony; Marchant, Carol A; Basketter, David A

2006-12-01

Derek for Windows (DfW) is a knowledge-based expert system that predicts the toxicity of a chemical from its structure. Its predictions are based in part on alerts that describe structural features or toxicophores associated with toxicity. Recently, improvements have been made to skin sensitization alerts within the DfW knowledge base in collaboration with Unilever. These include modifications to the alerts describing the skin sensitization potential of aldehydes, 1,2-diketones, and isothiazolinones and consist of enhancements to the toxicophore definition, the mechanistic classification, and the extent of supporting evidence provided. The outcomes from this collaboration demonstrate the importance of updating and refining computer models for the prediction of skin sensitization as new information from experimental and theoretical studies becomes available.

Chromophoric Nucleoside Analogues: Synthesis and Characterization of 6-Aminouracil-Based Nucleodyes.

PubMed

Freeman, Noam S; Moore, Curtis E; Wilhelmsson, L Marcus; Tor, Yitzhak

2016-06-03

Nucleodyes, visibly colored chromophoric nucleoside analogues, are reported. Design criteria are outlined and the syntheses of cytidine and uridine azo dye analogues derived from 6-aminouracil are described. Structural analysis shows that the nucleodyes are sound structural analogues of their native nucleoside counterparts, and photophysical studies demonstrate that the nucleodyes are sensitive to microenvironmental changes. Quantum chemical calculations are presented as a valuable complementary tool for the design of strongly absorbing nucleodyes, which overlap with the emission of known fluorophores. Förster critical distance (R0) calculations determine that the nucleodyes make good FRET pairs with both 2-aminopurine (2AP) and pyrrolocytosine (PyC). Additionally, unique tautomerization features exhibited by 5-(4-nitrophenylazo)-6-oxocytidine (8) are visualized by an extraordinary crystal structure.

QSAR modeling for predicting mutagenic toxicity of diverse chemicals for regulatory purposes.

PubMed

Basant, Nikita; Gupta, Shikha

2017-06-01

The safety assessment process of chemicals requires information on their mutagenic potential. The experimental determination of mutagenicity of a large number of chemicals is tedious and time and cost intensive, thus compelling for alternative methods. We have established local and global QSAR models for discriminating low and high mutagenic compounds and predicting their mutagenic activity in a quantitative manner in Salmonella typhimurium (TA) bacterial strains (TA98 and TA100). The decision treeboost (DTB)-based classification QSAR models discriminated among two categories with accuracies of >96% and the regression QSAR models precisely predicted the mutagenic activity of diverse chemicals yielding high correlations (R 2 ) between the experimental and model-predicted values in the respective training (>0.96) and test (>0.94) sets. The test set root mean squared error (RMSE) and mean absolute error (MAE) values emphasized the usefulness of the developed models for predicting new compounds. Relevant structural features of diverse chemicals that were responsible and influence the mutagenic activity were identified. The applicability domains of the developed models were defined. The developed models can be used as tools for screening new chemicals for their mutagenicity assessment for regulatory purpose.

Plant antiherbivore defenses in Fabaceae species of the Chaco.

PubMed

Lima, T E; Sartori, A L B; Rodrigues, M L M

2017-01-01

The establishment and maintenance of plant species in the Chaco, one of the widest continuous areas of forests in the South American with sharp climatic variations, are possibly related to biological features favoring plants with particular defenses. This study assesses the physical and chemical defenses mechanisms against herbivores of vegetative and reproductive organs. Its analyses of 12 species of Fabaceae (Leguminosae) collected in remnants of Brazilian Chaco shows that 75% present structural defense characters and 50% have chemical defense - defense proteins in their seeds, like protease inhibitors and lectins. Physical defenses occur mainly on branches (78% of the species), leaves (67%), and reproductive organs (56%). The most common physical characters are trichomes and thorns, whose color represents a cryptic character since it does not contrast with the other plant structures. Defense proteins occur in different concentrations and molecular weight classes in the seeds of most species. Protease inhibitors are reported for the first time in seeds of: Albizia niopoides, Anadenanthera colubrina, Mimosa glutinosa, Prosopis rubriflora, and Poincianella pluviosa. The occurrence of physical and chemical defenses in members of Fabaceae indicate no associations between defense characters in these plant species of the Chaco.

Thermo-mechanical cyclic testing of carbon-carbon primary structure for an SSTO vehicle

NASA Astrophysics Data System (ADS)

Croop, Harold C.; Leger, Kenneth B.; Lowndes, Holland B.; Hahn, Steven E.; Barthel, Chris A.

1999-01-01

An advanced carbon-carbon structural component is being experimentally evaluated for use as primary load carrying structure for future single-stage-to-orbit (SSTO) vehicles. The component is a wing torque box section featuring an advanced, three-spar design. This design features 3D-woven, angle-interlock skins, 3D integrally woven spar webs and caps, oxidation inhibited matrix, chemical vapor deposited (CVD) oxidation protection coating, and ceramic matrix composite fasteners. The box spar caps are nested into the skins which, when processed together through the carbon-carbon processing cycle, resulted in monolithic box halves. The box half sections were then joined at the spar web intersections using ceramic matrix composite fasteners. This method of fabrication eliminated fasteners through both the upper and lower skins. Development of the carbon-carbon wing box structure was accomplished in a four phase design and fabrication effort, conducted by Boeing, Information, Space and Defense Systems, Seattle, WA, under contract to the Air Force Research Laboratory (AFRL). The box is now set up for testing and will soon begin cyclic loads testing in the AFRL Structural Test Facility at Wright-Patterson Air Force Base (WPAFB), OH. This paper discusses the latest test setup accomplishments and the results of the pre-cyclic loads testing performed to date.

Electroactive nanoparticle directed assembly of functionalized graphene nanosheets into hierarchical structures with hybrid compositions for flexible supercapacitors.

PubMed

Choi, Bong Gill; Huh, Yun Suk; Hong, Won Hi; Erickson, David; Park, Ho Seok

2013-05-07

Hierarchical structures of hybrid materials with the controlled compositions have been shown to offer a breakthrough for energy storage and conversion. Here, we report the integrative assembly of chemically modified graphene (CMG) building blocks into hierarchical complex structures with the hybrid composition for high performance flexible pseudocapacitors. The formation mechanism of hierarchical CMG/Nafion/RuO2 (CMGNR) microspheres, which is triggered by the cooperative interplay during the in situ synthesis of RuO2 nanoparticles (NPs), was extensively investigated. In particular, the hierarchical CMGNR microspheres consisting of the aggregates of CMG/Nafion (CMGN) nanosheets and RuO2 NPs provided large surface area and facile ion accessibility to storage sites, while the interconnected nanosheets offered continuous electron pathways and mechanical integrity. The synergistic effect of CMGNR hybrids on the supercapacitor (SC) performance was derived from the hybrid composition of pseudocapacitive RuO2 NPs with the conductive CMGNs as well as from structural features. Consequently, the CMGNR-SCs showed a specific capacitance as high as 160 F g(-1), three-fold higher than that of conventional graphene SCs, and a capacitance retention of >95% of the maximum value even after severe bending and 1000 charge-discharge tests due to the structural and compositional features.

High-resolution charge carrier mobility mapping of heterogeneous organic semiconductors

NASA Astrophysics Data System (ADS)

Button, Steven W.; Mativetsky, Jeffrey M.

2017-08-01

Organic electronic device performance is contingent on charge transport across a heterogeneous landscape of structural features. Methods are therefore needed to unravel the effects of local structure on overall electrical performance. Using conductive atomic force microscopy, we construct high-resolution out-of-plane hole mobility maps from arrays of 5000 to 16 000 current-voltage curves. To demonstrate the efficacy of this non-invasive approach for quantifying and mapping local differences in electrical performance due to structural heterogeneities, we investigate two thin film test systems, one bearing a heterogeneous crystal structure [solvent vapor annealed 5,11-Bis(triethylsilylethynyl)anthradithiophene (TES-ADT)—a small molecule organic semiconductor] and one bearing a heterogeneous chemical composition [p-DTS(FBTTh2)2:PC71BM—a high-performance organic photovoltaic active layer]. TES-ADT shows nearly an order of magnitude difference in hole mobility between semicrystalline and crystalline areas, along with a distinct boundary between the two regions, while p-DTS(FBTTh2)2:PC71BM exhibits subtle local variations in hole mobility and a nanoscale domain structure with features below 10 nm in size. We also demonstrate mapping of the built-in potential, which plays a significant role in organic light emitting diode and organic solar cell operation.

MUFOLD-SS: New deep inception-inside-inception networks for protein secondary structure prediction.

PubMed

Fang, Chao; Shang, Yi; Xu, Dong

2018-05-01

Protein secondary structure prediction can provide important information for protein 3D structure prediction and protein functions. Deep learning offers a new opportunity to significantly improve prediction accuracy. In this article, a new deep neural network architecture, named the Deep inception-inside-inception (Deep3I) network, is proposed for protein secondary structure prediction and implemented as a software tool MUFOLD-SS. The input to MUFOLD-SS is a carefully designed feature matrix corresponding to the primary amino acid sequence of a protein, which consists of a rich set of information derived from individual amino acid, as well as the context of the protein sequence. Specifically, the feature matrix is a composition of physio-chemical properties of amino acids, PSI-BLAST profile, and HHBlits profile. MUFOLD-SS is composed of a sequence of nested inception modules and maps the input matrix to either eight states or three states of secondary structures. The architecture of MUFOLD-SS enables effective processing of local and global interactions between amino acids in making accurate prediction. In extensive experiments on multiple datasets, MUFOLD-SS outperformed the best existing methods and other deep neural networks significantly. MUFold-SS can be downloaded from http://dslsrv8.cs.missouri.edu/~cf797/MUFoldSS/download.html. © 2018 Wiley Periodicals, Inc.

Structural relaxation in a binary metallic melt: Molecular dynamics computer simulation of undercooled Al80Ni20

NASA Astrophysics Data System (ADS)

Das, Subir K.; Horbach, Jürgen; Voigtmann, Thomas

2008-08-01

Molecular dynamics computer simulations are performed to study structure and structural relaxation in the glassforming metallic alloy Al80Ni20 . The interactions between the particles are modeled by an effective potential of the embedded atom type. Our model of Al80Ni20 exhibits chemical short-range order (CSRO) that is reflected in a broad prepeak around a wave number of 1.8Å-1 in the partial static structure factor for the Ni-Ni correlations. The CSRO is due to the preference of Ni atoms to have Al rather than Ni atoms as nearest neighbors. By analyzing incoherent and coherent intermediate scattering functions as well as self-diffusion constants and shear viscosity, we discuss how the chemical ordering is reflected in the dynamics of the deeply undercooled melt. The q dependence of the α relaxation time as well as the Debye-Waller factor for the Al-Al correlations show oscillations at the location of the prepeak in the partial static structure factor for the Ni-Ni correlations. The latter feature of the Debye-Waller factor is well reproduced by a calculation in the framework of the mode coupling theory (MCT) of the glass transition, using the partial static structure factors from the simulation as input. We also check the validity of the Stokes-Einstein-Sutherland formula that relates the self-diffusion coefficients with the shear viscosity. We show that it breaks down already far above the mode coupling critical temperature Tc . The failure of the Stokes-Einstein-Sutherland relation is not related to the specific chemical ordering in Al80Ni20 .

Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents.

PubMed

Zheng, Suqing; Santosh Laxmi, Y R; David, Emilie; Dinkova-Kostova, Albena T; Shiavoni, Katherine H; Ren, Yanqing; Zheng, Ying; Trevino, Isaac; Bumeister, Ronald; Ojima, Iwao; Wigley, W Christian; Bliska, James B; Mierke, Dale F; Honda, Tadashi

2012-05-24

Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-α and IL-1β with potencies that are higher than those of bardoxolone methyl and TBE-31.

Self-assembly of Nano-rods in Photosensitive Phase Separation

NASA Astrophysics Data System (ADS)

Liu, Ya; Kuksenok, Olga; Maresov, Egor; Balazs, Anna

2012-02-01

Computer simulations reveal how photo-induced chemical reactions in polymeric mixtures can be exploited to create long-range order in materials whose features range from the sub-micron to the nanoscale. The process is initiated by shining a spatially uniform light on a photosensitive AB binary blend, which thereby undergoes both a reversible chemical reaction and phase separation. When a well-collimated, higher intensity light is rastered over the sample, the system forms defect-free, spatially periodic structures. We now build on this approach by introducing nanorods that have a preferential affinity for one the phases in a binary mixture. By rastering over the sample with the higher intensity light, we can create ordered arrays of rods within periodically ordered materials in essentially one processing step.

Multicomponent patterned ultrathin carbon nanomembranes by laser ablation

NASA Astrophysics Data System (ADS)

Frese, Natalie; Scherr, Julian; Beyer, André; Terfort, Andreas; Gölzhäuser, Armin; Hampp, Norbert; Rhinow, Daniel

2018-01-01

Carbon nanomembranes (CNMs) are a class of two-dimensional materials, which are obtained by electron beam-induced crosslinking of aromatic self-assembled monolayers (SAMs) on solid substrates. CNMs made from a single type of precursor molecule are uniform with homogeneous chemical and physical properties. We have developed a method for the fabrication of internally patterned CNMs resembling a key feature of biological membranes. Direct laser patterning is used to obtain multicomponent patterned SAMs on gold, which are subsequently crosslinked by electron irradiation. We demonstrate that the structure of internally patterned CNMs is preserved upon transfer to different substrates. The method enables rapid fabrication of patterned 2D materials with local variations in chemical and physical properties on the micrometer to centimeter scale.

Fabrication and characterization of microstructures created in thermally deposited arsenic trisulfide by multiphoton lithography

NASA Astrophysics Data System (ADS)

Schwarz, Casey M.; Grabill, Chris N.; Richardson, Gerald D.; Labh, Shreya; Lewis, Anna M.; Vyas, Aadit; Gleason, Benn; Rivero-Baleine, Clara; Richardson, Kathleen A.; Pogrebnyakov, Alexej; Mayer, Theresa S.; Kuebler, Stephen M.

2017-04-01

A detailed study of multiphoton lithography (MPL) in arsenic trisulfide (As2S3) films and the effects on nanoscale morphology, chemical networking, and the appearance of the resulting features by the chemical composition, deposition rate, etch processing, and inclusion of an antireflection (AR) layer of As2Se3 between the substrate and the As2S3 layer is reported. MPL was used to photo-pattern nanostructured arrays in single- and multilayer films. The variation in chemical composition for laser-exposed, UV-exposed, and unexposed films is correlated with the etch response, nanostructure formation, and deposition conditions. Reflection of the focused beam at the substrate back into the film produces standing wave interference that modulates the exposure with distance from the substrate and produces nanobead structures. The interference and the modulation can be controlled by the addition of an AR layer of As2Se3 deposited between the substrate and the As2S3 film. Relative to structures produced in a single-layer As2S3 film having no AR layer, photo-patterning in the multilayer As2S3-on-As2Se3 film yields pillar-shaped structures that are closer to the targeted shape and are narrower (120 versus 320 nm), more uniform, and better adhering to the substrate. Processing methods are demonstrated for fabricating large-area arrays with diffractive optical function.

Room Temperature Sensing Achieved by GaAs Nanowires and oCVD Polymer Coating.

PubMed

Wang, Xiaoxue; Ermez, Sema; Goktas, Hilal; Gradečak, Silvija; Gleason, Karen

2017-06-01

Novel structures comprised of GaAs nanowire arrays conformally coated with conducting polymers (poly(3,4-ethylenedioxythiophene) (PEDOT) or poly(3,4-ethylenedioxythiophene-co-3-thiophene acetic acid) display both sensitivity and selectivity to a variety of volatile organic chemicals. A key feature is room temperature operation, so that neither a heater nor the power it would consume, is required. It is a distinct difference from traditional metal oxide sensors, which typically require elevated operational temperature. The GaAs nanowires are prepared directly via self-seeded metal-organic chemical deposition, and conducting polymers are deposited on GaAs nanowires using oxidative chemical vapor deposition (oCVD). The range of thickness for the oCVD layer is between 100 and 200 nm, which is controlled by changing the deposition time. X-ray diffraction analysis indicates an edge-on alignment of the crystalline structure of the PEDOT coating layer on GaAs nanowires. In addition, the positive correlation between the improvement of sensitivity and the increasing nanowire density is demonstrated. Furthermore, the effect of different oCVD coating materials is studied. The sensing mechanism is also discussed with studies considering both nanowire density and polymer types. Overall, the novel structure exhibits good sensitivity and selectivity in gas sensing, and provides a promising platform for future sensor design. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of structure-reactivity descriptors and biological activity spectra of 4-(6-methoxy-2-naphthyl)-2-butanone using spectroscopic techniques

NASA Astrophysics Data System (ADS)

Agrawal, Megha; Deval, Vipin; Gupta, Archana; Sangala, Bagvanth Reddy; Prabhu, S. S.

2016-10-01

The structure and several spectroscopic features along with reactivity parameters of the compound 4-(6-methoxy-2-naphthyl)-2-butanone (Nabumetone) have been studied using experimental techniques and tools derived from quantum chemical calculations. Structure optimization is followed by force field calculations based on density functional theory (DFT) at the B3LYP/6-311++G(d,p) level of theory. The vibrational spectra have been interpreted with the aid of normal coordinate analysis. UV-visible spectrum and the effect of solvent have been discussed. The electronic properties such as HOMO and LUMO energies have been determined by TD-DFT approach. In order to understand various aspects of pharmacological sciences several new chemical reactivity descriptors - chemical potential, global hardness and electrophilicity have been evaluated. Local reactivity descriptors - Fukui functions and local softnesses have also been calculated to find out the reactive sites within molecule. Aqueous solubility and lipophilicity have been calculated which are crucial for estimating transport properties of organic molecules in drug development. Estimation of biological effects, toxic/side effects has been made on the basis of prediction of activity spectra for substances (PASS) prediction results and their analysis by Pharma Expert software. Using the THz-TDS technique, the frequency-dependent absorptions of NBM have been measured in the frequency range up to 3 THz.

Harmonised framework for ecological risk assessment of sediments from ports and estuarine zones of North and South Atlantic.

PubMed

Choueri, R B; Cesar, A; Abessa, D M S; Torres, R J; Riba, I; Pereira, C D S; Nascimento, M R L; Morais, R D; Mozeto, A A; DelValls, T A

2010-04-01

This paper presents a harmonised framework of sediment quality assessment and dredging material characterisation for estuaries and port zones of North and South Atlantic. This framework, based on the weight-of-evidence approach, provides a structure and a process for conducting sediment/dredging material assessment that leads to a decision. The main structure consists of "step 1" (examination of available data); "step 2" (chemical characterisation and toxicity assessment); "decision 1" (any chemical level higher than reference values? are sediments toxic?); "step 3" (assessment of benthic community structure); "step 4" (integration of the results); "decision 2" (are sediments toxic or benthic community impaired?); "step 5" (construction of the decision matrix) and "decision 3" (is there environmental risk?). The sequence of assessments may be interrupted when the information obtained is judged to be sufficient for a correct characterisation of the risk posed by the sediments/dredging material. This framework brought novel features compared to other sediment/dredging material risk assessment frameworks: data integration through multivariate analysis allows the identification of which samples are toxic and/or related to impaired benthic communities; it also discriminates the chemicals responsible for negative biological effects; and the framework dispenses the use of a reference area. We demonstrated the successful application of this framework in different port and estuarine zones of the North (Gulf of Cádiz) and South Atlantic (Santos and Paranaguá Estuarine Systems).

Effects of structural and chemical disorders on the vis/UV spectra of carbonaceous interstellar grains

NASA Astrophysics Data System (ADS)

Papoular, Robert J.; Yuan, Shengjun; Roldán, Rafael; Katsnelson, Mikhail I.; Papoular, Renaud

2013-07-01

The recent spectacular progress in the experimental and theoretical understanding of graphene, the basic constituent of graphite, is applied here to compute, from first principles, the ultraviolet extinction of nanoparticles made of stacks of graphene layers. The theory also covers cases where graphene is affected by structural, chemical or orientation disorder, each disorder type being quantitatively defined by a single parameter. The extinction bumps carried by such model materials are found to have positions and widths falling in the same range as the known astronomical 2175 Å features: as the disorder parameter increases, the bump width increases from 0.85 to 2.5 μm-1, while its peak position shifts from 4.65 to 4.75 μm-1. Moderate degrees of disorder are enough to cover the range of widths of the vast majority of observed bumps (0.75 to 1.3 μm-1). Higher degrees account for outliers, also observed in the sky. The introduction of structural or chemical disorder amounts to changing the initial sp2 bondings into sp3 or sp1, so the optical properties of the model material become similar to those of the more or less amorphous carbon-rich materials studied in the laboratory: a-C, a-C:H, HAC, ACH, coals, etc. The present treatment thus bridges gaps between physically different model materials.

Physical-chemical features of non-detergent sulfobetaines active as protein-folding helpers.

PubMed

Expert-Bezançon, Nicole; Rabilloud, Thierry; Vuillard, Laurent; Goldberg, Michel E

2003-01-01

Some non-detergent sulfobetaines had been shown to prevent aggregation and improve the yield of active proteins when added to the buffer during in vitro protein renaturation. With the aim of designing more efficient folding helpers, a series of non-detergent sulfobetaines have been synthesized and their efficiency in improving the renaturation of a variety of proteins (E. coli tryptophan synthase and beta-D-galactosidase, hen lysozyme, bovine serum albumin, a monoclonal antibody) have been investigated. Attempts to correlate the structure of each sulfobetaines with its effect on folding revealed some molecular features that appear important in helping renaturation. This enabled us to design and synthesize new non-detergent sulfobetaines that act as potent folding helpers.

Cesium Platinide Hydride 4Cs 2 Pt-CsH: An Intermetallic Double Salt Featuring Metal Anions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smetana, Volodymyr; Mudring, Anja-Verena

2016-10-24

With Cs9Pt4H a new representative of ionic compounds featuring metal anions can be added to this rare-membered family. Cs 9Pt 4H exhibits a complex crystal structure containing Cs + cations, Pt 2- and H - anions. Being a red, transparent compound its band gap is in the visible range of the electromagnetic spectrum and the ionic type of bonding is confirmed by quantum chemical calculations. This cesium platinide hydride can formally be considered as a double salt of the “alloy” cesium–platinum, or better cesium platinide, Cs2Pt, and the salt cesium hydride CsH according to Cs 9Pt 4H≡4 Cs 2Pt∙CsH.

Biofuels combustion.

PubMed

Westbrook, Charles K

2013-01-01

This review describes major features of current research in renewable fuels derived from plants and from fatty acids. Recent and ongoing fundamental studies of biofuel molecular structure, oxidation reactions, and biofuel chemical properties are reviewed, in addition to combustion applications of biofuels in the major types of engines in which biofuels are used. Biofuels and their combustion are compared with combustion features of conventional petroleum-based fuels. Two main classes of biofuels are described, those consisting of small, primarily alcohol, fuels (particularly ethanol, n-butanol, and iso-pentanol) that are used primarily to replace or supplement gasoline and those derived from fatty acids and used primarily to replace or supplement conventional diesel fuels. Research efforts on so-called second- and third-generation biofuels are discussed briefly.

Complex supramolecular interfacial tessellation through convergent multi-step reaction of a dissymmetric simple organic precursor

NASA Astrophysics Data System (ADS)

Zhang, Yi-Qi; Paszkiewicz, Mateusz; Du, Ping; Zhang, Liding; Lin, Tao; Chen, Zhi; Klyatskaya, Svetlana; Ruben, Mario; Seitsonen, Ari P.; Barth, Johannes V.; Klappenberger, Florian

2018-03-01

Interfacial supramolecular self-assembly represents a powerful tool for constructing regular and quasicrystalline materials. In particular, complex two-dimensional molecular tessellations, such as semi-regular Archimedean tilings with regular polygons, promise unique properties related to their nontrivial structures. However, their formation is challenging, because current methods are largely limited to the direct assembly of precursors, that is, where structure formation relies on molecular interactions without using chemical transformations. Here, we have chosen ethynyl-iodophenanthrene (which features dissymmetry in both geometry and reactivity) as a single starting precursor to generate the rare semi-regular (3.4.6.4) Archimedean tiling with long-range order on an atomically flat substrate through a multi-step reaction. Intriguingly, the individual chemical transformations converge to form a symmetric alkynyl-Ag-alkynyl complex as the new tecton in high yields. Using a combination of microscopy and X-ray spectroscopy tools, as well as computational modelling, we show that in situ generated catalytic Ag complexes mediate the tecton conversion.

Structural and optical properties of novel surfactant-coated Yb@TiO2 nanoparticles

NASA Astrophysics Data System (ADS)

Calandra, P.; Lombardo, D.; Pistone, A.; Turco Liveri, V.; Trusso, S.

2011-11-01

In this paper a novel hybrid approach to synthesise composite nanoparticles is presented. It is based on the laser ablation of a bulk target (Yb) immersed in a reversed micellar solution which contains nanoparticles of a different host material (TiO2 nanoparticles) previously synthesised by chemical method. This approach thus exploits the advantages of the chemical synthesis through reversed micellar solution (size control, nanoparticle stabilisation), and of the laser ablation ("clean" synthesis, no side reactions). Central role is played by the microscopic processes controlling the deposition of the ablated Yb atoms onto the surface of TiO2 nanoparticles which actually behave as nucleation seeds. The structural features of the resulting Yb@TiO2 composite nanoparticles have been studied by Transmission Electron Microscopy, whereas their peculiar optical properties have been explored by UV-Vis spectroscopy and steady-state fluorescence. Results consistently show the formation of Yb and TiO2 glued nanodomains to form nearly spherical and non-interacting nanoparticles with enhanced photophysical properties.

Process for preparing essentially colorless polyimide film containing phenoxy-linked diamines

NASA Technical Reports Server (NTRS)

Stclair, A. K.; Stclair, T. L.

1986-01-01

A polyimide film that is approximately 90% transparent at 500 nm, useful for thermal protective coatings and solar cells, and the processes for preparing the same by thermal and chemical conversion are disclosed. An essential feature for achieving maximum optical transparency films requires utilizing recrystallized and/or sublimated specific aromatic diamines and dianhydride monomers and introducing phenoxy or thiophenyl separator groups and isomeric m,m' or o,p'-oriented diamines into the polymer molecular structure. The incorporation of these groups in the polymer structure serves to separate the chromaphoric centers and reduce the formation of inter-chain and intra-chain charge transfer complexes which normally cause absorptions in the UV-visible range. The films may be obtained by hand, brushing, casting, or spraying a layer of polyamic acid solutions onto a surface and thermally converting the applied layer to the polyimide, or the polyamic acid solution can be chemically converted to the polyimide, subsequentially dissolved in an organic solvent, and applied as a polyimide film layer with the solvent therein thermally removed.

Photonic crystal fiber long-period gratings for structural monitoring and chemical sensing

NASA Astrophysics Data System (ADS)

Tang, Jaw-Luen; Wang, Jian-Neng

2008-03-01

We present a simple, low-cost, temperature- and strain-insensitive long-period gratings (LPGs) written in photonic crystal fibers (PCFs) that can be used as sensitive chemical solution sensors or bend sensors for a variety of industrial applications, including civil engineering, aircraft, chemistry, food industry, and biosensing. Three different configurations of PCFs have been used for this study, including a polarization maintaining PCF, a large mode area PCF and an endlessly single mode PCF. These LPGs have been characterized for their sensitivity to temperature, strain, bending, and surrounding refractive index. Transmission spectra of the LPGs were found to exhibit negligible temperature and strain sensitivities, whereas possessing usable sensitivity to refractive index and bending. This type of PCF sensor could in principle be designed for optimum sensitivity to desired measurand(s), while minimizing or removing undesirable cross-sensitivities. The unique sensing features of PCFs are particularly suited for a wide variety of applications in smart structures, embedded materials, telecommunications and sensor systems.

Synthetic Talc and Talc-Like Structures: Preparation, Features and Applications.

PubMed

Claverie, Marie; Dumas, Angela; Carême, Christel; Poirier, Mathilde; Le Roux, Christophe; Micoud, Pierre; Martin, François; Aymonier, Cyril

2018-01-12

This contribution gives a comprehensive review about the progress in preparation methods, properties and applications of the different synthetic talc types: i) crystalline nanotalc synthesized by hydrothermal treatment; ii) amorphous and/or short-range order nanotalc obtained by precipitation, and iii) organic-inorganic hybrid talc-like structures obtained through a sol-gel process or a chemical grafting. Several advantages of nanotalc such as high chemical purity, high surface area, tunable submicronic size, high thermal stability, and hydrophilic character (leading to be the first fluid mineral) are emphasized. Synthetic nanotalc applications are also considered including its use as nanofiller in composite materials, as absorbers of organic compounds, as anticorrosion coatings and as agents for cosmetic applications. Regarding their high industrial application potential, intensive research has been carried out to better understand their behavior and develop processes to produce them. To facilitate further research and development, scientific and technical challenges are discussed in this Review article. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electronically transparent graphene replicas of diatoms: a new technique for the investigation of frustule morphology

PubMed Central

Pan, Zhengwei; Lerch, Sarah J. L.; Xu, Liang; Li, Xufan; Chuang, Yen-Jun; Howe, Jane Y.; Mahurin, Shannon M.; Dai, Sheng; Hildebrand, Mark

2014-01-01

The morphogenesis of the silica cell walls (called frustules) of unicellular algae known as diatoms is one of the most intriguing mysteries of the diatoms. To study frustule morphogenesis, optical, electron and atomic force microscopy has been extensively used to reveal the frustule morphology. However, since silica frustules are opaque, past observations were limited to outer and fracture surfaces, restricting observations of interior structures. Here we show that opaque silica frustules can be converted into electronically transparent graphene replicas, fabricated using chemical vapor deposition of methane. Chemical vapor deposition creates a continuous graphene coating preserving the frustule's shape and fine, complicated internal features. Subsequent dissolution of the silica with hydrofluoric acid yields a free-standing replica of the internal and external native frustule morphologies. Electron microscopy renders these graphene replicas highly transparent, revealing previously unobserved, complex, three-dimensional, interior frustule structures, which lend new insights into the investigation of frustule morphogenesis. PMID:25135739

Chemical structure and anticoagulant activity of highly pyruvylated sulfated galactans from tropical green seaweeds of the order Bryopsidales.

PubMed

Arata, Paula X; Quintana, Irene; Canelón, Dilsia J; Vera, Beatriz E; Compagnone, Reinaldo S; Ciancia, Marina

2015-05-20

Sulfated and pyruvylated galactans were isolated from three tropical species of the Bryopsidales, Penicillus capitatus, Udotea flabellum, and Halimeda opuntia. They represent the only important sulfated polysaccharides present in the cell walls of these highly calcified seaweeds of the suborder Halimedineae. Their structural features were studied by chemical analyses and NMR spectroscopy. Their backbone comprises 3-, 6-, and 3,6-linkages, constituted by major amounts of 3-linked 4,6-O-(1'-carboxy)ethylidene-d-galactopyranose units in part sulfated on C-2. Sulfation on C-2 was not found in galactans from other seaweeds of this order. In addition, a complex sulfation pattern, comprising also 4-, 6-, and 4,6-disulfated galactose units was found. A fraction from P. capitatus, F1, showed a moderate anticoagulant activity, evaluated by general coagulation tests and also kinetics of fibrin formation was assayed. Besides, preliminary results suggest that one of the possible mechanisms involved is direct thrombin inhibition. Copyright © 2014 Elsevier Ltd. All rights reserved.

A petrographic and geochemical investigation into the Gatun structure, a possible Tertiary impact structure near Gamboa, Republic de Panama

NASA Astrophysics Data System (ADS)

Tornabene, L. L.; Ryan, J. G.; Stewart, R. H.

2001-05-01

The Gatun Structure, (Latitude N 09 deg 05' 58.1", Longitude W 79 deg 47' 21.8", situated in the triple-canopy rainforest 10 km to the WSW of the Gamboa and about 2 km south of the Isle of Barbacoas, Republic de Panama), is a partially inundated, quasi-concentric surface feature 2.2km in diameter, which appears in aerial photographs and in radar imagery as an arcuate chain of islands with a raised central feature. Although deeply eroded, the structure possesses traits consistent with complex crater morphology: an elevated circular central uplift feature approximately 500-600 m in diameter and 50m high, and arcuate boundary ridges (a possible rim structure) ranging from 50-100 meters high. Within the central peak, highly altered and fractured siltstone of the Gatuncillo formation (Eocene) are uplifted and exposed through surrounding calcareous units of the Caimito formation (Oligocene), the major target rocks in the structure. The structure is crosscut by numerous dikes of unshocked basalt and basaltic andesite related to volcanism along the Panamanian segment of the Central American arc to the south. Analysis of mineral assemblages of units within the structure, and mineral compositions were measured via SEM-EDS and electron microprobe, using the JEOL SEM-Probe facility at the Center for the Study of Materials in Extreme Conditions (CeSMEC) at Florida International University. Bulk chemical and trace element analysis of whole rock samples were conducted via DC Plasma spectrometry at USF. Occurring concentrically within the structure, are limestones with anomalous spherical glass inclusions, both black and white hypocrystalline glasses (melt rocks?), lithic breccias, and melt-bearing breccias, some of which contain flow banding and evidence of selective melting. Three types of spherules (glass, fluid-drop and lithic), a pyroxene-quartz "necklace" disequilibrium structure and possibly shocked amphibole are all petrographic indicators of a possible impact event. In addition, the presence of maskelynite has been based on petrography, SEM-EDS and by RAMAN spectroscopy. RAMAN results indicated that many plagioclase grains in a blue-green clast bering breccia (suevite?) were highly disordered and amorphous. Considering the distance of the Gatun structure from the explosive volcanism of Panamanian arc (approximately 30 km away), and the presence of spherules, maskelynite and other disequilibrium shock features, an impact origin is our preferred interpretation for the Gatun structure.

13C and 19F solid-state NMR and X-ray crystallographic study of halogen-bonded frameworks featuring nitrogen-containing heterocycles.

PubMed

Szell, Patrick M J; Gabriel, Shaina A; Gill, Russell D D; Wan, Shirley Y H; Gabidullin, Bulat; Bryce, David L

2017-03-01

Halogen bonding is a noncovalent interaction between the electrophilic region of a halogen (σ-hole) and an electron donor. We report a crystallographic and structural analysis of halogen-bonded compounds by applying a combined X-ray diffraction (XRD) and solid-state nuclear magnetic resonance (SSNMR) approach. Single-crystal XRD was first used to characterize the halogen-bonded cocrystals formed between two fluorinated halogen-bond donors (1,4-diiodotetrafluorobenzene and 1,3,5-trifluoro-2,4,6-triiodobenzene) and several nitrogen-containing heterocycles (acridine, 1,10-phenanthroline, 2,3,5,6-tetramethylpyrazine, and hexamethylenetetramine). New structures are reported for the following three cocrystals, all in the P2 1 /c space group: acridine-1,3,5-trifluoro-2,4,6-triiodobenzene (1/1), C 6 F 3 I 3 ·C 13 H 9 N, 1,10-phenanthroline-1,3,5-trifluoro-2,4,6-triiodobenzene (1/1), C 6 F 3 I 3 ·C 12 H 8 N 2 , and 2,3,5,6-tetramethylpyrazine-1,3,5-trifluoro-2,4,6-triiodobenzene (1/1), C 6 F 3 I 3 ·C 8 H 12 N 2 . 13 C and 19 F solid-state magic-angle spinning (MAS) NMR is shown to be a convenient method to characterize the structural features of the halogen-bond donor and acceptor, with chemical shifts attributable to cocrystal formation observed in the spectra of both nuclides. Cross polarization (CP) from 19 F to 13 C results in improved spectral sensitivity in characterizing the perfluorinated halogen-bond donor when compared to conventional 1 H CP. Gauge-including projector-augmented wave density functional theory (GIPAW DFT) calculations of magnetic shielding constants, along with optimization of the XRD structures, provide a final set of structures in best agreement with the experimental 13 C and 19 F chemical shifts. Data for carbons bonded to iodine remain outliers due to well-known relativistic effects.

Activity and conformation of lysozyme in molecular solvents, protic ionic liquids (PILs) and salt-water systems.

PubMed

Wijaya, Emmy C; Separovic, Frances; Drummond, Calum J; Greaves, Tamar L

2016-09-21

Improving protein stabilisation is important for the further development of many applications in the pharmaceutical, specialty chemical, consumer product and agricultural sectors. However, protein stabilization is highly dependent on the solvent environment and, hence, it is very complex to tailor protein-solvent combinations for stable protein maintenance. Understanding solvent features that govern protein stabilization will enable selection or design of suitable media with favourable solution environments to retain protein native conformation. In this work the structural conformation and activity of lysozyme in 29 solvent systems were investigated to determine the role of various solvent features on the stability of the enzyme. The solvent systems consisted of 19 low molecular weight polar solvents and 4 protic ionic liquids (PILs), both at different water content levels, and 6 aqueous salt solutions. Small angle X-ray scattering, Fourier transform infrared spectroscopy and UV-vis spectroscopy were used to investigate the tertiary and secondary structure of lysozyme along with the corresponding activity in various solvation systems. At low non-aqueous solvent concentrations (high water content), the presence of solvents and salts generally maintained lysozyme in its native structure and enhanced its activity. Due to the presence of a net surface charge on lysozyme, electrostatic interactions in PIL-water systems and salt solutions enhanced lysozyme activity more than the specific hydrogen-bond interactions present in non-ionic molecular solvents. At higher solvent concentrations (lower water content), solvents with a propensity to exhibit the solvophobic effect, analogous to the hydrophobic effect in water, retained lysozyme native conformation and activity. This solvophobic effect was observed particularly for solvents which contained hydroxyl moieties. Preferential solvophobic effects along with bulky chemical structures were postulated to result in less competition with water at the specific hydration layer around the protein, thus reducing protein-solvent interactions and retaining lysozyme's native conformation. The structure-property links established in this study are considered to be applicable to other proteins.

Incorporation of local structure into kriging models for the prediction of atomistic properties in the water decamer.

PubMed

Davie, Stuart J; Di Pasquale, Nicodemo; Popelier, Paul L A

2016-10-15

Machine learning algorithms have been demonstrated to predict atomistic properties approaching the accuracy of quantum chemical calculations at significantly less computational cost. Difficulties arise, however, when attempting to apply these techniques to large systems, or systems possessing excessive conformational freedom. In this article, the machine learning method kriging is applied to predict both the intra-atomic and interatomic energies, as well as the electrostatic multipole moments, of the atoms of a water molecule at the center of a 10 water molecule (decamer) cluster. Unlike previous work, where the properties of small water clusters were predicted using a molecular local frame, and where training set inputs (features) were based on atomic index, a variety of feature definitions and coordinate frames are considered here to increase prediction accuracy. It is shown that, for a water molecule at the center of a decamer, no single method of defining features or coordinate schemes is optimal for every property. However, explicitly accounting for the structure of the first solvation shell in the definition of the features of the kriging training set, and centring the coordinate frame on the atom-of-interest will, in general, return better predictions than models that apply the standard methods of feature definition, or a molecular coordinate frame. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc. © 2016 The Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

Pharmacophore modeling and conformational analysis in the gas phase and in aqueous solution of regioisomeric melatonin analogs. A theoretical and experimental study

NASA Astrophysics Data System (ADS)

Mendoza-Figueroa, Humberto; Martínez-Gudiño, Gelacio; Villanueva-Luna, Jorge E.; Trujillo-Serrato, Joel J.; Morales-Ríos, Martha S.

2017-04-01

In this work, 2-(N-acylaminoalkyl)indoles 1a-1d, that incorporate a pMeOBn group at the 3-position of the indole ring were virtual screened as potential melatoninergic ligands by analog-based design study using pharmacophore modeling. Pharmacophore models for melatoninergic agonist and antagonist activity were developed in order to identify the molecular constraints that define the geometric relationship among chemical features in each model. The best hypothesis consisted of six features for agonists and eight features for antagonists. The models suggest that the agonists and antagonists can share the same 3D arrangement for the six common pharmacophoric elements identified: two hydrogen bond acceptors (HBA), one hydrogen bond donor (HBD), one hydrophobic area (H), and two aromatic rings (AR). The extra hydrofobic interaction might be used as criterion for identified the pharmacological antagonist profile. Based on the pharmacophore fit, it was found that structures 1c and 1d show a good structural overlay that meets the requirements for the antagonistic pharmacophore hypothesis. Molecular modeling studies using the PCM solvation model predicted that the most stable conformers of 1a-1d match the antagonist pharmacophore hypothesis in contrast to those in the gas phase. Structures 1a-1c were synthesized only but the activities were not tested.

Effect of growth pressure on the synthesis of vertically aligned carbon nanotubes and their growth termination.

PubMed

Park, Sangeun; Song, Wooseok; Kim, Yooseok; Song, Inkyung; Kim, Sung Hwan; Lee, Su Il; Jang, Sung Won; Parkl, Chong-Yun

2014-07-01

When vertically aligned carbon nanotubes (VACNTs) are synthesized by thermal chemical vapor deposition (TCVD), their structural features such as height and density can be determined by TCVD growth conditions. In this study we investigated the effect of growth pressure on the structural features of VACNTs. Changes in growth pressure significantly affected the height, density, and crystalinity of synthesized VACNTs. In addition, we suggest that the growth termination of VACNTs could be due to the lack of carbon feedstock supply to the center of the VACNT film induced by the pressure-dependent adsorption of amorphous carbon at the edge of the VACNT film. In addition, the field emission characteristics of the VACNT film were carried out. The turn-on voltage of the VACNT film was 1.62 V/microm and the field enhancement factor (beta) was 2478. These results provide useful information for practical applications of VACNTs, such as field emission display and X-ray source.

Olefinic Thermoplastic Elastomer Gels: Combining Polymer Crystallization and Microphase Separation in a Selective Solvent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armstrong, Daniel P.; Mineart, Kenneth P.; Lee, Byeongdu

Since selectively swollen thermoplastic elastomer gels (TPEGs) afford a wide range of beneficial properties that open new doors to developing elastomer-based technologies, in this study we examine the unique structure-property behavior of TPEGs composed of olefinic block copolymers (OBCs). Unlike their styrenic counterparts typically possessing two chemically different blocks, this class of multiblock copolymers consists of linear polyethylene hard blocks and poly(ethylene-co-α-octene) soft blocks, in which case, microphase separation between the hard and the soft blocks is accompanied by crystallization of the hard blocks. We prepare olefinic TPEGs (OTPEGs) through the incorporation of a primarily aliphatic oil that selectively swellsmore » the soft block and investigate the resultant morphological features through the use of polarized light microscopy and small-/wideangle X-ray scattering. These features are correlated with thermal and mechanical property measurements from calorimetry, rheology, and extensiometry to elucidate the roles of crystallization and self-assembly on gel characteristics and establish useful structure-property relationships.« less

Use of fungal proteases and selected sourdough lactic acid bacteria for making wheat bread with an intermediate content of gluten.

PubMed

Rizzello, Carlo Giuseppe; Curiel, José Antonio; Nionelli, Luana; Vincentini, Olimpia; Di Cagno, Raffaella; Silano, Marco; Gobbetti, Marco; Coda, Rossana

2014-02-01

This study was aimed at combining the highest degradation of gluten during wheat flour fermentation with good structural and sensory features of the related bread. As estimated by R5-ELISA, the degree of degradation of immune reactive gluten was ca. 28%. Two-dimensional electrophoresis and RP-FPLC analyses showed marked variations of the protein fractions compared to the untreated flour. The comparison was also extended to in vitro effect of the peptic/tryptic-digests towards K562 and T84 cells. The flour with the intermediate content of gluten (ICG) was used for bread making, and compared to whole gluten (WG) bread. The chemical, structural and sensory features of the ICG bread approached those of the bread made with WG flour. The protein digestibility of the ICG bread was higher than that from WG flour. Also the nutritional quality, as estimated by different indexes, was the highest for ICG bread. Copyright © 2013 Elsevier Ltd. All rights reserved.

Enhanced water repellency of surfaces coated with multiscale carbon structures

NASA Astrophysics Data System (ADS)

Marchalot, Julien; Ramos, Stella. M. M.; Pirat, Christophe; Journet, Catherine

2018-01-01

Low cost and well characterized superhydrophobic surfaces are frequently required for industrial applications. Materials are commonly structured at the micro or nano scale. Surfaces decorated with nanotube derivatives synthesized by plasma enhanced chemical vapor deposition (PECVD) are of particular interest, since suitable modifications in the growth parameters can lead to numerous designs. In this article, we present surfaces that are selected for their specific wetting features with patterns ranging from dense forests to jungles with concave (re-entrant) surface such as flake-like multiscale roughness. Once these surfaces are functionalized adequately, their wetting properties are investigated. Their ability to sustain a superhydrophobic state for sessile water drops is examined. Finally, we propose a design to achieve a robust so-called ;Fakir; state, even for micrometer-sized drops, whereas with classic nanotubes forests it is not achievable. Thus, the drop remains on the apex of the protrusions with a high contact angle and a low contact angle hysteresis, while the surface features demonstrate good mechanical resistance against capillary forces.

Olefinic Thermoplastic Elastomer Gels: Combining Polymer Crystallization and Microphase Separation in a Selective Solvent

DOE PAGES

Armstrong, Daniel P.; Mineart, Kenneth P.; Lee, Byeongdu; ...

2016-11-01

Since selectively swollen thermoplastic elastomer gels (TPEGs) afford a wide range of beneficial properties that open new doors to developing elastomer-based technologies, in this study we examine the unique structure-property behavior of TPEGs composed of olefinic block copolymers (OBCs). Unlike their styrenic counterparts typically possessing two chemically different blocks, this class of multiblock copolymers consists of linear polyethylene hard blocks and poly(ethylene-co-α-octene) soft blocks, in which case, microphase separation between the hard and the soft blocks is accompanied by crystallization of the hard blocks. We prepare olefinic TPEGs (OTPEGs) through the incorporation of a primarily aliphatic oil that selectively swellsmore » the soft block and investigate the resultant morphological features through the use of polarized light microscopy and small-/wideangle X-ray scattering. These features are correlated with thermal and mechanical property measurements from calorimetry, rheology, and extensiometry to elucidate the roles of crystallization and self-assembly on gel characteristics and establish useful structure-property relationships.« less

Biocuration in the structure-function linkage database: the anatomy of a superfamily.

PubMed

Holliday, Gemma L; Brown, Shoshana D; Akiva, Eyal; Mischel, David; Hicks, Michael A; Morris, John H; Huang, Conrad C; Meng, Elaine C; Pegg, Scott C-H; Ferrin, Thomas E; Babbitt, Patricia C

2017-01-01

With ever-increasing amounts of sequence data available in both the primary literature and sequence repositories, there is a bottleneck in annotating molecular function to a sequence. This article describes the biocuration process and methods used in the structure-function linkage database (SFLD) to help address some of the challenges. We discuss how the hierarchy within the SFLD allows us to infer detailed functional properties for functionally diverse enzyme superfamilies in which all members are homologous, conserve an aspect of their chemical function and have associated conserved structural features that enable the chemistry. Also presented is the Enzyme Structure-Function Ontology (ESFO), which has been designed to capture the relationships between enzyme sequence, structure and function that underlie the SFLD and is used to guide the biocuration processes within the SFLD. http://sfld.rbvi.ucsf.edu/. © The Author 2017. Published by Oxford University Press.

Structure of the full-length TRPV2 channel by cryo-EM

NASA Astrophysics Data System (ADS)

Huynh, Kevin W.; Cohen, Matthew R.; Jiang, Jiansen; Samanta, Amrita; Lodowski, David T.; Zhou, Z. Hong; Moiseenkova-Bell, Vera Y.

2016-03-01

Transient receptor potential (TRP) proteins form a superfamily Ca2+-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a `minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2-6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ~5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels.

Structure of the full-length TRPV2 channel by cryo-EM

PubMed Central

Huynh, Kevin W.; Cohen, Matthew R.; Jiang, Jiansen; Samanta, Amrita; Lodowski, David T.; Zhou, Z. Hong; Moiseenkova-Bell, Vera Y.

2016-01-01

Transient receptor potential (TRP) proteins form a superfamily Ca2+-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a ‘minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2–6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ∼5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels. PMID:27021073

Structure of the full-length TRPV2 channel by cryo-EM.

PubMed

Huynh, Kevin W; Cohen, Matthew R; Jiang, Jiansen; Samanta, Amrita; Lodowski, David T; Zhou, Z Hong; Moiseenkova-Bell, Vera Y

2016-03-29

Transient receptor potential (TRP) proteins form a superfamily Ca(2+)-permeable cation channels regulated by a range of chemical and physical stimuli. Structural analysis of a 'minimal' TRP vanilloid subtype 1 (TRPV1) elucidated a mechanism of channel activation by agonists through changes in its outer pore region. Though homologous to TRPV1, other TRPV channels (TRPV2-6) are insensitive to TRPV1 activators including heat and vanilloids. To further understand the structural basis of TRPV channel function, we determined the structure of full-length TRPV2 at ∼5 Å resolution by cryo-electron microscopy. Like TRPV1, TRPV2 contains two constrictions, one each in the pore-forming upper and lower gates. The agonist-free full-length TRPV2 has wider upper and lower gates compared with closed and agonist-activated TRPV1. We propose these newly revealed TRPV2 structural features contribute to diversity of TRPV channels.

Mössbauer spectroscopy of Basal Ganglia

NASA Astrophysics Data System (ADS)

Miglierini, Marcel; Lančok, Adriana; Kopáni, Martin; Boča, Roman

2014-10-01

Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. 57Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding 57Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

Development of approaches to a third-generation carbohydrate-conjugate vaccine against Streptococcus pneumoniae: the search for optimal oligosaccharide ligands

NASA Astrophysics Data System (ADS)

Gening, M. L.; Kurbatova, E. A.; Tsvetkov, Yu E.; Nifantiev, N. E.

2015-11-01

The review addresses the application of synthetic oligosaccharides related to fragments of capsular polysaccharides from different serotypes of the bacterium Streptococcus pneumoniae for the design of third-generation pneumococcal conjugate vaccines. Special focus is given to characteristic features of the chemical structures of oligosaccharides required for the induction of the protective immune response when using synthetic glycoconjugate vaccines based on oligosaccharide ligands and carrier proteins. The bibliography includes 101 references.

Novel cross-linked polystyrenes with large space network as tailor-made catalyst supports for sustainable media

DOE PAGES

Marrocchi, Assunta; Adriaensens, Peter; Bartollini, Elena; ...

2015-10-09

For a novel class of polystyrene-based gel-type resins (SPACeR, SP), containing the large 1,4-bis (4-vinylphenoxy)benzene cross-linker, is introduced; SP-immobilized 1,5,7-triazabicyclo [4.4.0]dec-5-ene (TBD) and triethylamine (TEA) bases are synthesized and characterized in terms of their structural, thermal and morphological features, and their catalytic efficiency in a series of fundamental chemical transformations under solvent-free conditions is investigated.

Mössbauer spectroscopy of Basal Ganglia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miglierini, Marcel, E-mail: marcel.miglierini@stuba.sk; Lančok, Adriana; Kopáni, Martin

2014-10-27

Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. {sup 57}Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding {sup 57}Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

Amino acid–based surfactants: New antimicrobial agents.

PubMed

Pinazo, A; Manresa, M A; Marques, A M; Bustelo, M; Espuny, M J; Pérez, L

2016-02-01

The rapid increase of drug resistant bacteria makes necessary the development of new antimicrobial agents. Synthetic amino acid-based surfactants constitute a promising alternative to conventional antimicrobial compounds given that they can be prepared from renewable raw materials. In this review, we discuss the structural features that promote antimicrobial activity of amino acid-based surfactants. Monocatenary, dicatenary and gemini surfactants that contain different amino acids on the polar head and show activity against bacteria are revised. The synthesis and basic physico-chemical properties have also been included.

Enabling complex nanoscale pattern customization using directed self-assembly.

PubMed

Doerk, Gregory S; Cheng, Joy Y; Singh, Gurpreet; Rettner, Charles T; Pitera, Jed W; Balakrishnan, Srinivasan; Arellano, Noel; Sanders, Daniel P

2014-12-16

Block copolymer directed self-assembly is an attractive method to fabricate highly uniform nanoscale features for various technological applications, but the dense periodicity of block copolymer features limits the complexity of the resulting patterns and their potential utility. Therefore, customizability of nanoscale patterns has been a long-standing goal for using directed self-assembly in device fabrication. Here we show that a hybrid organic/inorganic chemical pattern serves as a guiding pattern for self-assembly as well as a self-aligned mask for pattern customization through cotransfer of aligned block copolymer features and an inorganic prepattern. As informed by a phenomenological model, deliberate process engineering is implemented to maintain global alignment of block copolymer features over arbitrarily shaped, 'masking' features incorporated into the chemical patterns. These hybrid chemical patterns with embedded customization information enable deterministic, complex two-dimensional nanoscale pattern customization through directed self-assembly.

Soft X-Ray Absorption Spectroscopy of High-Abrasion-Furnace Carbon Black

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muramatsu, Yasuji; Harada, Ryusuke; Gullikson, Eric M.

2007-02-02

The soft x-ray absorption spectra of high-abrasion-furnace carbon black were measured to obtain local-structure/chemical-states information of the primary particles and/or crystallites. The soft x-ray absorption spectral features of carbon black represent broader {pi}* and {sigma}* peak structures compared to highly oriented pyrolytic graphite (HOPG). The subtracted spectra between the carbon black and HOPG, (carbon black) - (HOPG), show double-peak structures on both sides of the {pi}* peak. The lower-energy peak, denoted as the 'pre-peak', in the subtracted spectra and the {pi}*/{sigma}* peak intensity ratio in the absorption spectra clearly depend on the specific surface area by nitrogen adsorption (NSA). Therefore,more » it is concluded that the pre-peak intensity and the {pi}*/{sigma}* ratio reflect the local graphitic structure of carbon black.« less

Predict drug permeability to blood–brain-barrier from clinical phenotypes: drug side effects and drug indications

PubMed Central

Gao, Zhen; Chen, Yang; Cai, Xiaoshu; Xu, Rong

2017-01-01

Abstract Motivation: Blood–Brain-Barrier (BBB) is a rigorous permeability barrier for maintaining homeostasis of Central Nervous System (CNS). Determination of compound’s permeability to BBB is prerequisite in CNS drug discovery. Existing computational methods usually predict drug BBB permeability from chemical structure and they generally apply to small compounds passing BBB through passive diffusion. As abundant information on drug side effects and indications has been recorded over time through extensive clinical usage, we aim to explore BBB permeability prediction from a new angle and introduce a novel approach to predict BBB permeability from drug clinical phenotypes (drug side effects and drug indications). This method can apply to both small compounds and macro-molecules penetrating BBB through various mechanisms besides passive diffusion. Results: We composed a training dataset of 213 drugs with known brain and blood steady-state concentrations ratio and extracted their side effects and indications as features. Next, we trained SVM models with polynomial kernel and obtained accuracy of 76.0%, AUC 0.739, and F1 score (macro weighted) 0.760 with Monte Carlo cross validation. The independent test accuracy was 68.3%, AUC 0.692, F1 score 0.676. When both chemical features and clinical phenotypes were available, combining the two types of features achieved significantly better performance than chemical feature based approach (accuracy 85.5% versus 72.9%, AUC 0.854 versus 0.733, F1 score 0.854 versus 0.725; P < e−90). We also conducted de novo prediction and identified 110 drugs in SIDER database having the potential to penetrate BBB, which could serve as start point for CNS drug repositioning research. Availability and Implementation: https://github.com/bioinformatics-gao/CASE-BBB-prediction-Data Contact: rxx@case.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27993785

ToxCast Chemical Landscape: Paving the Road to 21st Century Toxicology.

PubMed

Richard, Ann M; Judson, Richard S; Houck, Keith A; Grulke, Christopher M; Volarath, Patra; Thillainadarajah, Inthirany; Yang, Chihae; Rathman, James; Martin, Matthew T; Wambaugh, John F; Knudsen, Thomas B; Kancherla, Jayaram; Mansouri, Kamel; Patlewicz, Grace; Williams, Antony J; Little, Stephen B; Crofton, Kevin M; Thomas, Russell S

2016-08-15

The U.S. Environmental Protection Agency's (EPA) ToxCast program is testing a large library of Agency-relevant chemicals using in vitro high-throughput screening (HTS) approaches to support the development of improved toxicity prediction models. Launched in 2007, Phase I of the program screened 310 chemicals, mostly pesticides, across hundreds of ToxCast assay end points. In Phase II, the ToxCast library was expanded to 1878 chemicals, culminating in the public release of screening data at the end of 2013. Subsequent expansion in Phase III has resulted in more than 3800 chemicals actively undergoing ToxCast screening, 96% of which are also being screened in the multi-Agency Tox21 project. The chemical library unpinning these efforts plays a central role in defining the scope and potential application of ToxCast HTS results. The history of the phased construction of EPA's ToxCast library is reviewed, followed by a survey of the library contents from several different vantage points. CAS Registry Numbers are used to assess ToxCast library coverage of important toxicity, regulatory, and exposure inventories. Structure-based representations of ToxCast chemicals are then used to compute physicochemical properties, substructural features, and structural alerts for toxicity and biotransformation. Cheminformatics approaches using these varied representations are applied to defining the boundaries of HTS testability, evaluating chemical diversity, and comparing the ToxCast library to potential target application inventories, such as used in EPA's Endocrine Disruption Screening Program (EDSP). Through several examples, the ToxCast chemical library is demonstrated to provide comprehensive coverage of the knowledge domains and target inventories of potential interest to EPA. Furthermore, the varied representations and approaches presented here define local chemistry domains potentially worthy of further investigation (e.g., not currently covered in the testing library or defined by toxicity "alerts") to strategically support data mining and predictive toxicology modeling moving forward.

Intuitive representation of surface properties of biomolecules using BioBlender.

PubMed

Andrei, Raluca Mihaela; Callieri, Marco; Zini, Maria Francesca; Loni, Tiziana; Maraziti, Giuseppe; Pan, Mike Chen; Zoppè, Monica

2012-03-28

In living cells, proteins are in continuous motion and interaction with the surrounding medium and/or other proteins and ligands. These interactions are mediated by protein features such as electrostatic and lipophilic potentials. The availability of protein structures enables the study of their surfaces and surface characteristics, based on atomic contribution. Traditionally, these properties are calculated by physico-chemical programs and visualized as range of colors that vary according to the tool used and imposes the necessity of a legend to decrypt it. The use of color to encode both characteristics makes the simultaneous visualization almost impossible, requiring these features to be visualized in different images. In this work, we describe a novel and intuitive code for the simultaneous visualization of these properties. Recent advances in 3D animation and rendering software have not yet been exploited for the representation of biomolecules in an intuitive, animated form. For our purpose we use Blender, an open-source, free, cross-platform application used professionally for 3D work. On the basis Blender, we developed BioBlender, dedicated to biological work: elaboration of protein motion with simultaneous visualization of their chemical and physical features. Electrostatic and lipophilic potentials are calculated using physico-chemical software and scripts, organized and accessed through BioBlender interface. A new visual code is introduced for molecular lipophilic potential: a range of optical features going from smooth-shiny for hydrophobic regions to rough-dull for hydrophilic ones. Electrostatic potential is represented as animated line particles that flow along field lines, proportional to the total charge of the protein. Our system permits visualization of molecular features and, in the case of moving proteins, their continuous perception, calculated for each conformation during motion. Using real world tactile/sight feelings, the nanoscale world of proteins becomes more understandable, familiar to our everyday life, making it easier to introduce "un-seen" phenomena (concepts) such as hydropathy or charges. Moreover, this representation contributes to gain insight into molecular functions by drawing viewer's attention to the most active regions of the protein. The program, available for Windows, Linux and MacOS, can be downloaded freely from the dedicated website http://www.bioblender.eu.

Intuitive representation of surface properties of biomolecules using BioBlender

PubMed Central

2012-01-01

Background In living cells, proteins are in continuous motion and interaction with the surrounding medium and/or other proteins and ligands. These interactions are mediated by protein features such as electrostatic and lipophilic potentials. The availability of protein structures enables the study of their surfaces and surface characteristics, based on atomic contribution. Traditionally, these properties are calculated by physico-chemical programs and visualized as range of colors that vary according to the tool used and imposes the necessity of a legend to decrypt it. The use of color to encode both characteristics makes the simultaneous visualization almost impossible, requiring these features to be visualized in different images. In this work, we describe a novel and intuitive code for the simultaneous visualization of these properties. Methods Recent advances in 3D animation and rendering software have not yet been exploited for the representation of biomolecules in an intuitive, animated form. For our purpose we use Blender, an open-source, free, cross-platform application used professionally for 3D work. On the basis Blender, we developed BioBlender, dedicated to biological work: elaboration of protein motion with simultaneous visualization of their chemical and physical features. Electrostatic and lipophilic potentials are calculated using physico-chemical software and scripts, organized and accessed through BioBlender interface. Results A new visual code is introduced for molecular lipophilic potential: a range of optical features going from smooth-shiny for hydrophobic regions to rough-dull for hydrophilic ones. Electrostatic potential is represented as animated line particles that flow along field lines, proportional to the total charge of the protein. Conclusions Our system permits visualization of molecular features and, in the case of moving proteins, their continuous perception, calculated for each conformation during motion. Using real world tactile/sight feelings, the nanoscale world of proteins becomes more understandable, familiar to our everyday life, making it easier to introduce "un-seen" phenomena (concepts) such as hydropathy or charges. Moreover, this representation contributes to gain insight into molecular functions by drawing viewer's attention to the most active regions of the protein. The program, available for Windows, Linux and MacOS, can be downloaded freely from the dedicated website http://www.bioblender.eu PMID:22536962

Structural features of a bituminous coal and their changes during low-temperature oxidation and loss of volatiles investigated by advanced solid-state NMR spectroscopy

USGS Publications Warehouse

Mao, J.-D.; Schimmelmann, A.; Mastalerz, Maria; Hatcher, P.G.; Li, Y.

2010-01-01

Quantitative and advanced 13C solid-state NMR techniques were employed to investigate (i) the chemical structure of a high volatile bituminous coal, as well as (ii) chemical structural changes of this coal after evacuation of adsorbed gases, (iii) during oxidative air exposure at room temperature, and (iv) after oxidative heating in air at 75 ??C. The solid-state NMR techniques employed in this study included quantitative direct polarization/magic angle spinning (DP/MAS) at a high spinning speed of 14 kHz, cross polarization/total sideband suppression (CP/TOSS), dipolar dephasing, CH, CH2, and CHn selection, 13C chemical shift anisotropy (CSA) filtering, two-dimensional (2D) 1H-13C heteronuclear correlation NMR (HETCOR), and 2D HETCOR with 1H spin diffusion. With spectral editing techniques, we identified methyl CCH 3, rigid and mobile methylene CCH2C, methine CCH, quaternary Cq, aromatic CH, aromatic carbons bonded to alkyls, small-sized condensed aromatic moieties, and aromatic C-O groups. With direct polarization combined with spectral-editing techniques, we quantified 11 different types of functional groups. 1H-13C 2D HETCOR NMR experiments indicated spatial proximity of aromatic and alkyl moieties in cross-linked structures. The proton spin diffusion experiments indicated that the magnetization was not equilibrated at a 1H spin diffusion time of 5 ms. Therefore, the heterogeneity in spatial distribution of different functional groups should be above 2 nm. Recoupled C-H long-range dipolar dephasing showed that the fraction of large charcoal-like clusters of polycondensed aromatic rings was relatively small. The exposure of this coal to atmospheric oxygen at room temperature for 6 months did not result in obvious chemical structural changes of the coal, whereas heating at 75 ??C in air for 10 days led to oxidation of coal and generated some COO groups. Evacuation removed most volatiles and caused a significant reduction in aliphatic signals in its DP/MAS spectrum. DP/MAS, but not CP/MAS, allowed us to detect the changes during low-temperature oxidation and loss of volatiles. These results demonstrate the applicability of advanced solid-state NMR techniques in chemical characterization of coal. ?? 2010 American Chemical Society.

Laser applications to chemical analysis: an introduction by the feature editors

NASA Astrophysics Data System (ADS)

Jeffries, Jay B.; Ramsey, J. Michael; Lucht, Robert P.

1995-06-01

This issue of Applied Optics features papers on the application of laser technology to chemical analysis. Many of the contributions, although not all, result from papers presented at the Fourth OSA Topical Meeting on Laser Applications to Chemical Analysis, which was held at Jackson Hole, Wyoming, March, 1994. This successful meeting, with nearly one hundred participants, continued the tradition of earlier LACA meetings to focus on the optical science of laser-based measurements of temperature and trace chemical assays in a wide variety of practical applications.

Optimal Magnetorheological Fluid for Finishing of Chemical-Vapor-Deposited Zinc Sulfide

NASA Astrophysics Data System (ADS)

Salzman, Sivan

Magnetorheological finishing (MRF) of polycrystalline, chemical-vapor- deposited zinc sulfide (ZnS) optics leaves visible surface artifacts known as "pebbles". These artifacts are a direct result of the material's inner structure that consists of cone-like features that grow larger (up to a few millimeters in size) as deposition takes place, and manifest on the top deposited surface as "pebbles". Polishing the pebble features from a CVD ZnS substrate to a flat, smooth surface to below 10 nm root-mean-square is challenging, especially for a non-destructive polishing process such as MRF. This work explores ways to improve the surface finish of CVD ZnS processed with MRF through modification of the magnetorheological (MR) fluid's properties. A materials science approach is presented to define the anisotropy of CVD ZnS through a combination of chemical and mechanical experiments and theoretical predictions. Magnetorheological finishing experiments with single crystal samples of ZnS, whose cuts and orientations represent most of the facets known to occur in the polycrystalline CVD ZnS, were performed to explore the influence of material anisotropy on the material removal rate during MRF. By adjusting the fluid's viscosity, abrasive type concentration, and pH to find the chemo-mechanical conditions that equalize removal rates among all single crystal facets during MRF, we established an optimized, novel MR formulation to polish CVD ZnS without degrading the surface finish of the optic.

Chemical and colloidal aspects of collectorless flotation behavior of sulfide and non-sulfide minerals.

PubMed

Aghazadeh, Sajjad; Mousavinezhad, Seyed Kamal; Gharabaghi, Mahdi

2015-11-01

Flotation has been widely used for separation of valuable minerals from gangues based on their surface characterizations and differences in hydrophobicity on mineral surfaces. As hydrophobicity of minerals widely differs from each other, their separation by flotation will become easier. Collectors are chemical materials which are supposed to make selectively valuable minerals hydrophobic. In addition, there are some minerals which based on their surface and structural features are intrinsically hydrophobic. However, their hydrophobicities are not strong enough to be floatable in the flotation cell without collectors such as sulfide minerals, coal, stibnite, and so forth. To float these minerals in a flotation cell, their hydrophobicity should be increased in specific conditions. Various parameters including pH, Eh, size distribution, mill types, mineral types, ore characterization, and type of reaction in flotation cells affect the hydrophobicity of minerals. Surface analysis results show that when sulfide minerals experience specific flotation conditions, the reactions on the surface of these minerals increase the amount of sulfur on the surface. These phenomenons improve the hydrophobicity of these minerals due to strong hydrophobic feature of sulfurs. Collectorless flotation reduces chemical material consumption amount, increases flotation selectivity (grade increases), and affects the equipment quantities; however, it can also have negative effects. Some minerals with poor surface floatability can be increased by adding some ions to the flotation system. Depressing undesirable minerals in flotation is another application of collectorless flotation.

Pharmacological Characterization of Chemically Synthesized Monomeric phi29 pRNA Nanoparticles for Systemic Delivery

PubMed Central

Abdelmawla, Sherine; Guo, Songchuan; Zhang, Limin; Pulukuri, Sai M; Patankar, Prithviraj; Conley, Patrick; Trebley, Joseph; Guo, Peixuan; Li, Qi-Xiang

2011-01-01

Previous studies have shown that the packaging RNA (pRNA) of bacteriophage phi29 DNA packaging motor folds into a compact structure, constituting a RNA nanoparticle that can be modularized with functional groups as a nanodelivery system. pRNA nanoparticles can also be self-assembled by the bipartite approach without altering folding property. The present study demonstrated that 2′-F-modified pRNA nanoparticles were readily manufactured through this scalable bipartite strategy, featuring total chemical synthesis and permitting diverse functional modularizations. The RNA nanoparticles were chemically and metabolically stable and demonstrated a favorable pharmacokinetic (PK) profile in mice (half-life (T1/2): 5–10 hours, clearance (Cl): <0.13 l/kg/hour, volume of distribution (Vd): 1.2 l/kg). It did not induce an interferon (IFN) response nor did it induce cytokine production in mice. Repeat intravenous administrations in mice up to 30 mg/kg did not result in any toxicity. Fluorescent folate-pRNA nanoparticles efficiently and specifically bound and internalized to folate receptor (FR)-bearing cancer cells in vitro. It also specifically and dose-dependently targeted to FR+ xenograft tumor in mice with minimal accumulation in normal tissues. This first comprehensive pharmacological study suggests that the pRNA nanoparticle had all the preferred pharmacological features to serve as an efficient nanodelivery platform for broad medical applications. PMID:21468004

Effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis.

PubMed

Kaczmarczyk-Sedlak, Ilona; Wojnar, Weronika; Zych, Maria; Ozimina-Kamińska, Ewa; Taranowicz, Joanna; Siwek, Agata

2013-01-01

Formononetin is a naturally occurring isoflavone, which can be found in low concentrations in many dietary products, but the greatest sources of this substance are Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, which all belong to Fabaceae family. Due to its structural similarity to 17 β -estradiol, it can mimic estradiol's effect and therefore is considered as a "phytoestrogen." The aim of this study was to examine the effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. 12-week-old female rats were divided into 4 groups: sham-operated, ovariectomized, ovariectomized treated with estradiol (0.2 mg/kg) and ovariectomized treated with formononetin (10 mg/kg). Analyzed substances were administered orally for 4 weeks. Ovariectomy caused osteoporotic changes, which can be observed in bone biomechanical features (decrease of maximum load and fracture load and increase of displacements for maximum and fracture loads) and bone chemical composition (increase of water and organic fraction content, while a decrease of minerals takes place). Supplementation with formononetin resulted in slightly enhanced bone mechanical properties and bone chemistry improvement (significantly lower water content and insignificantly higher mineral fraction content). To summarize, administration of formononetin to ovariectomized rats shows beneficial effect on bone biomechanical features and chemistry; thus, it can prevent osteoporosis development.