Advances on the nanostructuration of magnetic molecules on surfaces: the case of single-molecule magnets (SMM).

PubMed

Gómez-Segura, Jordi; Veciana, Jaume; Ruiz-Molina, Daniel

2007-09-28

SMMs exhibit slow magnetization relaxation rates characteristic of nanodomain particles whose origin is however on individual molecules. For this reason, they have attracted much interest due to their potential applications in high-density information storage devices and quantum computing applications, where for instance, each molecule can be used as a magnetic bit of information. However, for this to become a reality, several basic studies such as their deposition on surfaces are still highly required. Here we will revise all the experimental approximations that have been so far reported for their addressing, nanostructuration and study on surfaces, from the use of stamps as templates to their anchorage to gold surface through the use of thiol-based ligands. It is also important to emphasize that the results and methodologies described along this review are applicable not only to SMMs but to any molecular material.

Evaluation of the molecular polarizability using the IPPP-CLOPPA-INDO/S method. Application to molecules of biological interest.

PubMed

Botek, Edith; Giribet, Claudia; Ruiz de Azúa, Martín; Martín Negri, Ricardo; Bernik, Delia

2008-07-31

The IPPP-CLOPPA-INDO/S method is introduced to investigate the static molecular polarizability in macromolecules. As an example of application, the polarizability of phospholipidic compounds, with and without the presence of water molecules has been estimated. The IPPP technique was employed to calculate the polarizability of the polar head and the hydrocarbon chains separately to analyze the feasibility of evaluating the total polarizability of the molecule by addition of these two projected results. INDO/S dipole moments of different fragments of the complex molecule were obtained by means of localized molecular orbitals in order to evaluate the charge transfer in the system.

Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications.

PubMed

Laurencin, Cato T; Ashe, Keshia M; Henry, Nicole; Kan, Ho Man; Lo, Kevin W-H

2014-06-01

Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potential clinical applications. New strategies for bone regeneration that involve inexpensive and stable small molecules can obviate these problems and have a significant impact on the treatment of skeletal injury and diseases. Over the past decade, a large number of small molecules with the potential of regenerating skeletal tissue have been reported in the literature. Here, we review this literature, paying specific attention to the prospects for small molecule-based bone-regenerative engineering. We also review the preclinical study of small molecules associated with bone regeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Single-Molecule Detection in Micron-Sized Capillaries

NASA Astrophysics Data System (ADS)

Ball, David A.; Shen, Guoqing; Davis, Lloyd M.

2004-11-01

The detection of individual molecules in solution by laser-induced fluorescence is becoming an increasingly important tool for biophysics research and biotechnology applications. In a typical single-molecule detection (SMD) experiment, diffusion is the dominant mode of transport of fluorophores through the focused laser beam. In order to more rapidly process a large number of slowly diffusing bio-molecules for applications in pharmaceutical drug discovery, a flow can be introduced within a capillary. If the flow speed is sufficient, bio-molecules will be carried through the probe volume significantly faster than by diffusion alone. Here we discuss SMD near the tip of, and in, such micron-sized capillaries, with a high numerical-aperture microscope objective used for confocal-epi-illumination along the axis of the capillary. Problems such as molecular adsorption to the glass are also addressed.

Molecule database framework: a framework for creating database applications with chemical structure search capability

PubMed Central

2013-01-01

Background Research in organic chemistry generates samples of novel chemicals together with their properties and other related data. The involved scientists must be able to store this data and search it by chemical structure. There are commercial solutions for common needs like chemical registration systems or electronic lab notebooks. However for specific requirements of in-house databases and processes no such solutions exist. Another issue is that commercial solutions have the risk of vendor lock-in and may require an expensive license of a proprietary relational database management system. To speed up and simplify the development for applications that require chemical structure search capabilities, I have developed Molecule Database Framework. The framework abstracts the storing and searching of chemical structures into method calls. Therefore software developers do not require extensive knowledge about chemistry and the underlying database cartridge. This decreases application development time. Results Molecule Database Framework is written in Java and I created it by integrating existing free and open-source tools and frameworks. The core functionality includes: • Support for multi-component compounds (mixtures) • Import and export of SD-files • Optional security (authorization) For chemical structure searching Molecule Database Framework leverages the capabilities of the Bingo Cartridge for PostgreSQL and provides type-safe searching, caching, transactions and optional method level security. Molecule Database Framework supports multi-component chemical compounds (mixtures). Furthermore the design of entity classes and the reasoning behind it are explained. By means of a simple web application I describe how the framework could be used. I then benchmarked this example application to create some basic performance expectations for chemical structure searches and import and export of SD-files. Conclusions By using a simple web application it was shown that Molecule Database Framework successfully abstracts chemical structure searches and SD-File import and export to simple method calls. The framework offers good search performance on a standard laptop without any database tuning. This is also due to the fact that chemical structure searches are paged and cached. Molecule Database Framework is available for download on the projects web page on bitbucket: https://bitbucket.org/kienerj/moleculedatabaseframework. PMID:24325762

Molecule database framework: a framework for creating database applications with chemical structure search capability.

PubMed

Kiener, Joos

2013-12-11

Research in organic chemistry generates samples of novel chemicals together with their properties and other related data. The involved scientists must be able to store this data and search it by chemical structure. There are commercial solutions for common needs like chemical registration systems or electronic lab notebooks. However for specific requirements of in-house databases and processes no such solutions exist. Another issue is that commercial solutions have the risk of vendor lock-in and may require an expensive license of a proprietary relational database management system. To speed up and simplify the development for applications that require chemical structure search capabilities, I have developed Molecule Database Framework. The framework abstracts the storing and searching of chemical structures into method calls. Therefore software developers do not require extensive knowledge about chemistry and the underlying database cartridge. This decreases application development time. Molecule Database Framework is written in Java and I created it by integrating existing free and open-source tools and frameworks. The core functionality includes:•Support for multi-component compounds (mixtures)•Import and export of SD-files•Optional security (authorization)For chemical structure searching Molecule Database Framework leverages the capabilities of the Bingo Cartridge for PostgreSQL and provides type-safe searching, caching, transactions and optional method level security. Molecule Database Framework supports multi-component chemical compounds (mixtures).Furthermore the design of entity classes and the reasoning behind it are explained. By means of a simple web application I describe how the framework could be used. I then benchmarked this example application to create some basic performance expectations for chemical structure searches and import and export of SD-files. By using a simple web application it was shown that Molecule Database Framework successfully abstracts chemical structure searches and SD-File import and export to simple method calls. The framework offers good search performance on a standard laptop without any database tuning. This is also due to the fact that chemical structure searches are paged and cached. Molecule Database Framework is available for download on the projects web page on bitbucket: https://bitbucket.org/kienerj/moleculedatabaseframework.

Assigned and unassigned distance geometry: applications to biological molecules and nanostructures

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

Billinge, Simon J. L.; Duxbury, Phillip M.; Gonçalves, Douglas S.

2016-04-04

Here, considering geometry based on the concept of distance, the results found by Menger and Blumenthal originated a body of knowledge called distance geometry. This survey covers some recent developments for assigned and unassigned distance geometry and focuses on two main applications: determination of three-dimensional conformations of biological molecules and nanostructures.

Free-standing few-layered graphene oxide films: selective, steady and lasting permeation of organic molecules with adjustable speeds

NASA Astrophysics Data System (ADS)

Huang, Tao; An, Qi; Luan, Xinglong; Zhang, Qian; Zhang, Yihe

2016-01-01

A variety of small molecules with diameters around 1 nm possess a range of functions, such as antibiotic, antimicrobic, anticoagulant, pesticidal and chemotherapy effects, making these molecules especially useful in various applications ranging from medical treatment to environmental microbiological control. However, the long-term steady delivery (release or permeation) of these small molecules with adjustable and controllable speeds has remained an especially challenging task. In this study, we prepared covalently cross-linked free-standing few-layered GO films using a layer-by-layer technique in combination with photochemical cross-linkages, and achieved a controlled release of positively charged, negatively charged, and zwitterionic small molecules with adjustable and controllable speeds. The steady delivery of the small molecule lasted up to 9 days. Other functionalities, such as graphene-enhanced Raman spectra and electrochemical properties that could also be integrated or employed in delivery systems, were also studied for our films. We expect the special molecular delivery properties of our films to lead to new possibilities in drug/fertilizer delivery and environmental microbiological control applications.A variety of small molecules with diameters around 1 nm possess a range of functions, such as antibiotic, antimicrobic, anticoagulant, pesticidal and chemotherapy effects, making these molecules especially useful in various applications ranging from medical treatment to environmental microbiological control. However, the long-term steady delivery (release or permeation) of these small molecules with adjustable and controllable speeds has remained an especially challenging task. In this study, we prepared covalently cross-linked free-standing few-layered GO films using a layer-by-layer technique in combination with photochemical cross-linkages, and achieved a controlled release of positively charged, negatively charged, and zwitterionic small molecules with adjustable and controllable speeds. The steady delivery of the small molecule lasted up to 9 days. Other functionalities, such as graphene-enhanced Raman spectra and electrochemical properties that could also be integrated or employed in delivery systems, were also studied for our films. We expect the special molecular delivery properties of our films to lead to new possibilities in drug/fertilizer delivery and environmental microbiological control applications. Electronic supplementary information (ESI) available: AFM images of GO and GO films, UV-vis spectra of delayed release, and permeation fidelities. See DOI: 10.1039/c5nr08129g

Challenges and Opportunities for Small-Molecule Fluorescent Probes in Redox Biology Applications.

PubMed

Jiang, Xiqian; Wang, Lingfei; Carroll, Shaina L; Chen, Jianwei; Wang, Meng C; Wang, Jin

2018-02-16

The concentrations of reactive oxygen/nitrogen species (ROS/RNS) are critical to various biochemical processes. Small-molecule fluorescent probes have been widely used to detect and/or quantify ROS/RNS in many redox biology studies and serve as an important complementary to protein-based sensors with unique applications. Recent Advances: New sensing reactions have emerged in probe development, allowing more selective and quantitative detection of ROS/RNS, especially in live cells. Improvements have been made in sensing reactions, fluorophores, and bioavailability of probe molecules. In this review, we will not only summarize redox-related small-molecule fluorescent probes but also lay out the challenges of designing probes to help redox biologists independently evaluate the quality of reported small-molecule fluorescent probes, especially in the chemistry literature. We specifically highlight the advantages of reversibility in sensing reactions and its applications in ratiometric probe design for quantitative measurements in living cells. In addition, we compare the advantages and disadvantages of small-molecule probes and protein-based probes. The low physiological relevant concentrations of most ROS/RNS call for new sensing reactions with better selectivity, kinetics, and reversibility; fluorophores with high quantum yield, wide wavelength coverage, and Stokes shifts; and structural design with good aqueous solubility, membrane permeability, low protein interference, and organelle specificity. Antioxid. Redox Signal. 00, 000-000.

Watching cellular machinery in action, one molecule at a time.

PubMed

Monachino, Enrico; Spenkelink, Lisanne M; van Oijen, Antoine M

2017-01-02

Single-molecule manipulation and imaging techniques have become important elements of the biologist's toolkit to gain mechanistic insights into cellular processes. By removing ensemble averaging, single-molecule methods provide unique access to the dynamic behavior of biomolecules. Recently, the use of these approaches has expanded to the study of complex multiprotein systems and has enabled detailed characterization of the behavior of individual molecules inside living cells. In this review, we provide an overview of the various force- and fluorescence-based single-molecule methods with applications both in vitro and in vivo, highlighting these advances by describing their applications in studies on cytoskeletal motors and DNA replication. We also discuss how single-molecule approaches have increased our understanding of the dynamic behavior of complex multiprotein systems. These methods have shown that the behavior of multicomponent protein complexes is highly stochastic and less linear and deterministic than previously thought. Further development of single-molecule tools will help to elucidate the molecular dynamics of these complex systems both inside the cell and in solutions with purified components. © 2017 Monachino et al.

[Biophysics of single molecules].

PubMed

Serdiuk, I N; Deriusheva, E I

2011-01-01

The modern methods of research of biological molecules whose application led to the development of a new field of science, biophysics of single molecules, are reviewed. The measurement of the characteristics of single molecules enables one to reveal their individual features, and it is just for this reason that much more information can be obtained from one molecule than from the entire ensample of molecules. The high sensitivity of the methods considered in detail makes it possible to come close to the solution of the basic problem of practical importance, namely, the determination of the nucleotide sequence of a single DNA molecule.

Molecules coating magnetic nanoparticles for oil-field applications

NASA Astrophysics Data System (ADS)

Zuluaga, Sebastian; Manchanda, Priyanka; Pantelides, Sokrates

Magnetic nanoparticles have recently attracted significant attention in scientific and industrial communities due to their use in the fields of catalysis, spintronics, biomedical applications, and oil recovery and reservoir characterization. However, these nanoparticles have to be protected with a coating layer of molecules that prevents the nanoparticles from oxidation, which is known to occur in air, and from agglomeration into larger nanoparticles. Therefore, the binding of the molecules to the nanoparticles is critical before a large scale implementation can be done. Here we report results of density functional theory calculations on several molecules (methylamine, acetic acid, boronic acid, ethyl phosphate, and ethyl trihydroxysilane) and magnetic nanoparticles (Fe3O4, NiFe2O4, and Fe3C). We focus on two main points: 1) the bond strength between the organic molecule and the nano particle, and 2) how, H2O and H+ in the oil well may facilitate the desorption of the molecules. The results show that H+ and H2O molecules facilitate the desorption of molecules reducing the bond strength by several eV. On the other hand, the results allow us to identify and design molecules that exhibit the best performance in protecting each nanoparticle. Supported by a Grant from the Petroleum Institute, Abu Dhabi.

Improved Dye Stability in Single-Molecule Fluorescence Experiments

NASA Astrophysics Data System (ADS)

EcheverrÍa Aitken, Colin; Marshall, R. Andrew; Pugi, Joseph D.

Complex biological systems challenge existing single-molecule methods. In particular, dye stability limits observation time in singlemolecule fluorescence applications. Current approaches to improving dye performance involve the addition of enzymatic oxygen scavenging systems and small molecule additives. We present an enzymatic oxygen scavenging system that improves dye stability in single-molecule experiments. Compared to the currently-employed glucose-oxidase/catalase system, the protocatechuate-3,4-dioxygenase system achieves lower dissolved oxygen concentration and stabilizes single Cy3, Cy5, and Alexa488 fluorophores. Moreover, this system possesses none of the limitations associated with the glucose oxidase/catalase system. We also tested the effects of small molecule additives in this system. Biological reducing agents significantly destabilize the Cy5 fluorophore as a function of reducing potential. In contrast, anti-oxidants stabilize the Cy3 and Alexa488 fluorophores. We recommend use of the protocatechuate-3,4,-dioxygenase system with antioxidant additives, and in the absence of biological reducing agents. This system should have wide application to single-molecule fluorescence experiments.

Detection of gas molecules on single Mn adatom adsorbed graphyne: a DFT-D study

NASA Astrophysics Data System (ADS)

Lu, Zhansheng; Lv, Peng; Ma, Dongwei; Yang, Xinwei; Li, Shuo; Yang, Zongxian

2018-02-01

As one of the prominent applications in intelligent systems, gas sensing technology has attracted great interest in both industry and academia. In the current study, the pristine graphyne (GY) without and with a single Mn atom is investigated to detect the gas molecules (CO, CH4, CO2, NH3, NO and O2). The pristine GY is promising to detect O2 molecules because of its chemical adsorption on GY with large electron transfer. The great stability of the Mn/GY is found, and the Mn atom prefers to anchor at the alkyne ring as a single atom. Upon single Mn atom anchoring, the sensitivity and selectivity of GY based gas sensors is significantly improved for various molecules, except CH4. The recovery time of the Mn/GY after detecting the gas molecules may help to appraise the detection efficiency for the Mn/GY. The current study will help to understand the mechanism of detecting the gas molecules, and extend the potentially fascinating applications of GY-based materials.

Sensitivity of BN nano-cages to caffeine and nicotine molecules

NASA Astrophysics Data System (ADS)

Soltani, Alireza; Baei, Mohammad T.; Tazikeh Lemeski, E.; Shahini, Malihe

2014-12-01

Adsorption of caffeine and nicotine molecules over B12N12 and B16N16 nano-cages were investigated by using first-principles calculations to define whether BN nano-cages are applicable for filtering or sensing caffeine and nicotine molecules. The chemisorption energy of nicotine molecule on BN nano-cages is very stronger than caffeine molecule. Upon the adsorption of caffeine and nicotine molecules, the electronic properties of the BN nano-cages can be significantly changed, being too much sensitized on the caffeine and nicotine adsorptions.

A rhenium tris-carbonyl derivative as a model molecule for incorporation into phospholipid assemblies for skin applications.

PubMed

Fernández, Estibalitz; Rodríguez, Gelen; Hostachy, Sarah; Clède, Sylvain; Cócera, Mercedes; Sandt, Christophe; Lambert, François; de la Maza, Alfonso; Policar, Clotilde; López, Olga

2015-07-01

A rhenium tris-carbonyl derivative (fac-[Re(CO)3Cl(2-(1-dodecyl-1H-1,2,3,triazol-4-yl)-pyridine)]) was incorporated into phospholipid assemblies, called bicosomes, and the penetration of this molecule into skin was monitored using Fourier-transform infrared microspectroscopy (FTIR). To evaluate the capacity of bicosomes to promote the penetration of this derivative, the skin penetration of the Re(CO)3 derivative dissolved in dimethyl sulfoxide (DMSO), a typical enhancer, was also studied. Dynamic light scattering results (DLS) showed an increase in the size of the bicosomes with the incorporation of the Re(CO)3 derivative, and the FTIR microspectroscopy showed that the Re(CO)3 derivative incorporated in bicosomes penetrated deeper into the skin than when dissolved in DMSO. When this molecule was applied on the skin using the bicosomes, 60% of the Re(CO)3 derivative was retained in the stratum corneum (SC) and 40% reached the epidermis (Epi). Otherwise, the application of this molecule via DMSO resulted in 95% of the Re(CO)3 derivative being in the SC and only 5% reaching the Epi. Using a Re(CO)3 derivative with a dodecyl-chain as a model molecule, it was possible to determine the distribution of molecules with similar physicochemical characteristics in the skin using bicosomes. This fact makes these nanostructures promising vehicles for the application of lipophilic molecules inside the skin. Copyright © 2015 Elsevier B.V. All rights reserved.

Diels-Alder Trapping of Photochemically Generated o-Xylenols: Application in the Synthesis of Novel Organic Molecules and Polymers

NASA Technical Reports Server (NTRS)

Meador, Michael A.

2003-01-01

Bis(o-xylenol) equivalents are useful synthetic intermediates in the construction of polymers and hydroxyl substituted organic molecules which can organize by hydrogen bonded self-assembly into unique supramolecular structures. These polymers and supramolecular materials have potential use as coatings and thin films in aerospace, electronic and biomedical applications.

New Wind in Old Sails: Novel Applications of Triphos-based Transition Metal Complexes as Homogeneous Catalysts for Small Molecules and Renewables Activation.

PubMed

Mellone, Irene; Bertini, Federica; Gonsalvi, Luca; Guerriero, Antonella; Peruzzini, Maurizio

2015-01-01

Recent developments in the coordination chemistry and applications of Ru-triphos [triphos = 1,1,1-tris-(diphenylphosphinomethyl)ethane] systems are reviewed, highlighting their role as active and selective homogenous catalysts for small molecule activation, biomass conversions and in carbon dioxide utilization-related processes.

Synthesis of many different types of organic small molecules using one automated process.

PubMed

Li, Junqi; Ballmer, Steven G; Gillis, Eric P; Fujii, Seiko; Schmidt, Michael J; Palazzolo, Andrea M E; Lehmann, Jonathan W; Morehouse, Greg F; Burke, Martin D

2015-03-13

Small-molecule synthesis usually relies on procedures that are highly customized for each target. A broadly applicable automated process could greatly increase the accessibility of this class of compounds to enable investigations of their practical potential. Here we report the synthesis of 14 distinct classes of small molecules using the same fully automated process. This was achieved by strategically expanding the scope of a building block-based synthesis platform to include even C(sp3)-rich polycyclic natural product frameworks and discovering a catch-and-release chromatographic purification protocol applicable to all of the corresponding intermediates. With thousands of compatible building blocks already commercially available, many small molecules are now accessible with this platform. More broadly, these findings illuminate an actionable roadmap to a more general and automated approach for small-molecule synthesis. Copyright © 2015, American Association for the Advancement of Science.

Entangling and disentangling many-electron quantum systems with an electric field

NASA Astrophysics Data System (ADS)

Sajjan, Manas; Head-Marsden, Kade; Mazziotti, David A.

2018-06-01

We show that the electron correlation of a molecular system can be enhanced or diminished through the application of a homogeneous electric field antiparallel or parallel to the system's intrinsic dipole moment. More generally, we prove that any external stimulus that significantly changes the expectation value of a one-electron operator with nondegenerate minimum and maximum eigenvalues can be used to control the degree of a molecule's electron correlation. Computationally, the effect is demonstrated in HeH+, MgH+, BH, HCN, H2O , HF, formaldehyde, and a fluorescent dye. Furthermore, we show in calculations with an array of formaldehyde (CH2O ) molecules that the field can control not only the electron correlation of a single formaldehyde molecule but also the entanglement among formaldehyde molecules. The quantum control of correlation and entanglement has potential applications in the design of molecules with tunable properties and the stabilization of qubits in quantum computations.

Antibody-Mediated Small Molecule Detection Using Programmable DNA-Switches.

PubMed

Rossetti, Marianna; Ippodrino, Rudy; Marini, Bruna; Palleschi, Giuseppe; Porchetta, Alessandro

2018-06-13

The development of rapid, cost-effective, and single-step methods for the detection of small molecules is crucial for improving the quality and efficiency of many applications ranging from life science to environmental analysis. Unfortunately, current methodologies still require multiple complex, time-consuming washing and incubation steps, which limit their applicability. In this work we present a competitive DNA-based platform that makes use of both programmable DNA-switches and antibodies to detect small target molecules. The strategy exploits both the advantages of proximity-based methods and structure-switching DNA-probes. The platform is modular and versatile and it can potentially be applied for the detection of any small target molecule that can be conjugated to a nucleic acid sequence. Here the rational design of programmable DNA-switches is discussed, and the sensitive, rapid, and single-step detection of different environmentally relevant small target molecules is demonstrated.

Lasers '81

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

Collins, C.B.

1982-01-01

Progress in lasers is discussed. The subjects addressed include: excimer lasers, surface spectroscopy, modern laser spectroscopy, free electron lasers, cavities and propagation, lasers in medicine, X-ray and gamma ray lasers, laser spectroscopy of small molecules and clusters, optical bistability, excitons, nonlinear optics in the X-ray and gamma ray regions, collective atomic phenomena, tunable IR lasers, far IR/submillimeter lasers, and laser-assisted collisions. Also treated are: special applications, multiphoton processes in atoms and small molecules, nuclear pumped lasers, material processing and applications, polarization, high energy lasers, laser chemistry, IR molecular lasers, laser applications of collision and dissociation phenomena, solid state laser materials,more » phase conjugation, advances in laser technology for fusion, metal vapor lasers, picosecond phenomena, laser ranging and geodesy, and laser photochemistry of complex molecules.« less

Analytical Applications Of High-Resolution Molecular Fluorescence Spectroscopy In Low Temperature Solid Matrices

NASA Astrophysics Data System (ADS)

Hofstraat, Johannes W.; van Zeijl, W. J.; Smedes, F.; Ariese, Freek; Gooijer, Cees; Velthorst, Nel H.; Locher, R.; Renn, Alois; Wild, Urs P.

1989-05-01

High-resolution fluorescence spectroscopy may be used to obtain highly specific, vibrationally resolved spectral signatures of molecules. Two techniques are presented that both make use of low temperature, solid matrices. In Shpol'skii spectroscopy highly resolved spectra are obtained by employing n-alkanes as solvents that form neat crystalline matrices at low temperatures in which the guest molecules occupy well defined substitutional sites. Fluorescence line-narrowing spectroscopy is based on the application of selective (mostly laser-) excitation of the guest molecules. Principles and analytical applications of both techniques will be discussed. Specific attention will be paid to the determination of pyrene in bird meat by means of Shpol'skii spectroscopy and to the possibilities of applying two-dimensional fluorescence line-narrowing spectroscopy.

Soil concentration of glyphosate and AMPA under rice cultivation with contrasting levels of fertilization

NASA Astrophysics Data System (ADS)

Rey Montoya, Tania; Micaela Biassoni, María; Graciela Herber, Luciana; De Geronimo, Eduardo; Aparicio, Virginia

2017-04-01

Rice (Oryza sativa) is the world's most important crop species and occupies c. 150 mill ha. The province of Corrientes in Argentina leads the national production of rice cultivation. Glyphosate is a non-selective herbicide commonly used to control weeds. The molecule is inactivated once applied due to its adsorption in the soil, and once desorbed is degraded by soil microflora resulting in sarcosine and aminomethylphosphoric acid (AMPA) molecules. The objective of this investigation was to compare glyphosate and AMPA concentration in soil under different levels of fertilization along the growth season of the rice crop. A field experiment following a completely randomized design was carried out with four replicates. We evaluated four levels of fertilization (0-18-40): Control: 0 kg ha-1, Dose 1: 120 kg ha-1, Dose 2: 150 kg ha-1, Dose 3: 180 kg ha-1; and two levels of Glyphosate: with (Gly) or without (No) application. Four sampling moments were defined: pre-sowing (taken as reference), vegetative stage (V4, 30 days after application), in floral primordial differentiation-DPF (80 days post-application), and at physiological maturity-MF (125 days after application). Flooding was applied in V4 after sampling. The method used for determination and quantification was by ultra high-pressure liquid chromatography coupled to ESI UHPLC-MS / MS tandem mass spectrometer (+/-) (Acquit-Quattro Premier). We found that glyphosate and AMPA varied their concentration in soil according to the time of sampling. Detected levels of both molecules at pre-sowing indicate the persistence of this herbicide from earlier crop seasons. The highest concentration was measured in MF followed by V4. Interestingly, AMPA concentration showed higher values in V4 without application compared to the treatment with glyphosate application. On the other hand, in flooded soil both molecules presented a decrease in their concentration probably because of their dilution in water, increasing it again after the irrigation was suspended. The ratio between the concentration of glyphosate and AMPA molecules was positive, this means that to a greater presence of the original molecule, the greater the content of the metabolite, even after 125 days of the application of the herbicide.

Characteristic effects onto C13H12N2O3 molecule dissolved in solvents of argon plasma at atmospheric pressure

NASA Astrophysics Data System (ADS)

Tanışlı, Murat; Taşal, Erol

2017-07-01

We could easily argue that the decomposition of the chemical chain molecules is a compelling application when it comes to the atmospheric pressure plasma. In this paper, we have investigated the effect of the atmospheric pressure argon plasma on 4-((2-methoxyphenyl)diazenyl)benzene-1,3,-diol molecule (abbreviated as 4MBD) at room temperature. 4MBD molecule is one of the industrial dye molecules used widely. When considering the ecological life, this molecule is very harmful and dangerous. As such, we suggest a new decomposing method for such molecules. Atmospheric pressure plasma jet is principally treated for the breakdown of the molecule in question. Fourier transform infrared spectrometry and UV-Vis spectrophotometry tools are used to characterization of the molecules subsequent to the plasma applications to 4MBD molecule in ethanol and methanol solvents. The atmospheric-pressure plasma jet of argon (Ar) as non-equilibrium has been formed by ac-power generator with frequency—24 kHz and voltage—12 kV. Characterizations for solutions prepared with ethanol and methanol solvents of 4MBD molecule have been examined after applying ( duration 3 min) the atmospheric pressure plasma jet. The molecule is broken at 6C-7N-8N=9C stretching peak in consequence of the plasma treatment. The new plasma photo-products for ethanol and methanol solutions are produced as 6C-7N-8N=9C (strong, varying) and 12C=17O (strong, wide) stretching peaks. Also, the bathochromic drifts are discerned.

[The principle and application of the single-molecule real-time sequencing technology].

PubMed

Yanhu, Liu; Lu, Wang; Li, Yu

2015-03-01

Last decade witnessed the explosive development of the third-generation sequencing strategy, including single-molecule real-time sequencing (SMRT), true single-molecule sequencing (tSMSTM) and the single-molecule nanopore DNA sequencing. In this review, we summarize the principle, performance and application of the SMRT sequencing technology. Compared with the traditional Sanger method and the next-generation sequencing (NGS) technologies, the SMRT approach has several advantages, including long read length, high speed, PCR-free and the capability of direct detection of epigenetic modifications. However, the disadvantage of its low accuracy, most of which resulted from insertions and deletions, is also notable. So, the raw sequence data need to be corrected before assembly. Up to now, the SMRT is a good fit for applications in the de novo genomic sequencing and the high-quality assemblies of small genomes. In the future, it is expected to play an important role in epigenetics, transcriptomic sequencing, and assemblies of large genomes.

Small-Molecule Binding Aptamers: Selection Strategies, Characterization, and Applications

PubMed Central

Ruscito, Annamaria; DeRosa, Maria C.

2016-01-01

Aptamers are single-stranded, synthetic oligonucleotides that fold into 3-dimensional shapes capable of binding non-covalently with high affinity and specificity to a target molecule. They are generated via an in vitro process known as the Systematic Evolution of Ligands by EXponential enrichment, from which candidates are screened and characterized, and then used in various applications. These applications range from therapeutic uses to biosensors for target detection. Aptamers for small molecule targets such as toxins, antibiotics, molecular markers, drugs, and heavy metals will be the focus of this review. Their accurate detection is needed for the protection and wellbeing of humans and animals. However, the small molecular weights of these targets, including the drastic size difference between the target and the oligonucleotides, make it challenging to select, characterize, and apply aptamers for their detection. Thus, recent (since 2012) notable advances in small molecule aptamers, which have overcome some of these challenges, are presented here, while defining challenges that still exist are discussed. PMID:27242994

Why trash don't pass? pharmaceutical licensing and safety performance of drugs.

PubMed

Banerjee, Tannista; Nayak, Arnab

2017-01-01

This paper examines how asymmetric information in pharmaceutical licensing affects the safety standards of licensed drugs. Pharmaceutical companies often license potential drug molecules at different stages of drug development from other pharmaceutical or biotechnology companies and complete the remaining of research stages before submitting the new drug application(NDA) to the food and drug administration. The asymmetric information associated with the quality of licensed molecules might result in the molecules which are less likely to succeed to be licensed out, while those with greater potential of success being held internally for development. We identify the NDAs submitted between 1993 and 2004 where new molecular entities were acquired through licensing. Controlling for other drug area specific and applicant firm specific factors, we investigate whether drugs developed with licensed molecules face higher probability of safety based recall and ultimate withdrawal from the market than drugs developed internally. Results suggest the opposite of Akerlof's (Q J Econ 84:488-500, 1970) lemons problem. Licensed molecules rather have less probability of facing safety based recalls and ultimate withdrawal from the market comparing to internally developed drug molecules. This suggests that biotechnology and small pharmaceutical firms specializing in pharmaceutical research are more efficient in developing good potential molecules because of their concentrated research. Biotechnology firms license out good potential molecules because it increases their market value and reputation. In addition, results suggest that both the number of previous approved drugs in the disease area, and also the applicant firms' total number of previous approvals in all disease areas reduce the probability that an additional approved drug in the same drug area will potentially be harmful.

Inhibitors of voltage-gated sodium channel Nav1.7: patent applications since 2010.

PubMed

Sun, Shaoyi; Cohen, Charles J; Dehnhardt, Christoph M

2014-09-01

There has been intense interest in developing inhibitors of the sodium channel Nav1.7 because genetic studies have established very strong validation for the efficacy to alleviate both inflammatory and neuropathic pain. This review summarizes patent applications targeting Nav1.7 since 2010 until May, 2014. We have classified the patents into three categories as follows: small molecules with well-defined molecular selectivity among sodium channel isoforms; biologicals with well-defined molecular selectivity; and, small molecules that inhibit Nav1.7 with unknown molecular selectivity. Most of the review is dedicated to small molecule selective compounds.

Graphane versus graphene: a computational investigation of the interaction of nucleobases, aminoacids, heterocycles, small molecules (CO2, H2O, NH3, CH4, H2), metal ions and onium ions.

PubMed

Umadevi, Deivasigamani; Narahari Sastry, G

2015-11-11

Graphane has emerged as a two-dimensional hydrocarbon with interesting physical properties and potential applications. Understanding the interaction of graphane with various molecules and ions is crucial to appreciate its potential applications. We investigated the interaction of nucleobases, aminoacids, saturated and unsaturated heterocycles, small molecules, metal ions and onium ions with graphane by using density functional theory calculations. The preferred orientations of these molecules and ions on the graphane surface have been analysed. The binding energies of graphane with these molecules have been compared with the corresponding binding energies of graphene. Our results reveal that graphane forms stable complexes with all the molecules and ions yet showing lesser binding affinity when compared to graphene. As an exemption, the preferential strong binding of H2O with graphane than graphene reveals the fact that graphane is more hydrophilic than graphene. Charge transfer between graphane and the molecules and ions have been found to be an important factor in determining the binding strength of the complexes. The effect of the interaction of these molecules and ions on the HOMO-LUMO energy gap of graphane has also been investigated.

Methods And Devices For Characterizing Duplex Nucleic Acid Molecules

DOEpatents

Akeson, Mark; Vercoutere, Wenonah; Haussler, David; Winters-Hilt, Stephen

2005-08-30

Methods and devices are provided for characterizing a duplex nucleic acid, e.g., a duplex DNA molecule. In the subject methods, a fluid conducting medium that includes a duplex nucleic acid molecule is contacted with a nanopore under the influence of an applied electric field and the resulting changes in current through the nanopore caused by the duplex nucleic acid molecule are monitored. The observed changes in current through the nanopore are then employed as a set of data values to characterize the duplex nucleic acid, where the set of data values may be employed in raw form or manipulated, e.g., into a current blockade profile. Also provided are nanopore devices for practicing the subject methods, where the subject nanopore devices are characterized by the presence of an algorithm which directs a processing means to employ monitored changes in current through a nanopore to characterize a duplex nucleic acid molecule responsible for the current changes. The subject methods and devices find use in a variety of applications, including, among other applications, the identification of an analyte duplex DNA molecule in a sample, the specific base sequence at a single nulceotide polymorphism (SNP), and the sequencing of duplex DNA molecules.

Programmed self-assembly of large π-conjugated molecules into electroactive one-dimensional nanostructures

PubMed Central

Yamamoto, Yohei

2012-01-01

Electroactive one-dimensional (1D) nano-objects possess inherent unidirectional charge and energy transport capabilities along with anisotropic absorption and emission of light, which are of great advantage for the development of nanometer-scale electronics and optoelectronics. In particular, molecular nanowires formed by self-assembly of π-conjugated molecules attract increasing attention for application in supramolecular electronics. This review introduces recent topics related to electroactive molecular nanowires. The nanowires are classified into four categories with respect to the electronic states of the constituent molecules: electron donors, acceptors, donor–acceptor pairs and miscellaneous molecules that display interesting electronic properties. Although many challenges still remain for practical use, state-of-the-art 1D supramolecular nanomaterials have already brought significant advances to both fundamental chemical sciences and technological applications. PMID:27877488

Single-molecule spectroscopic methods.

PubMed

Haustein, Elke; Schwille, Petra

2004-10-01

Being praised for the mere fact of enabling the detection of individual fluorophores a dozen years ago, single-molecule techniques nowadays represent standard methods for the elucidation of the structural rearrangements of biologically relevant macromolecules. Single-molecule-sensitive techniques, such as fluorescence correlation spectroscopy, allow real-time access to a multitude of molecular parameters (e.g. diffusion coefficients, concentration and molecular interactions). As a result of various recent advances, this technique shows promise even for intracellular applications. Fluorescence imaging can reveal the spatial localization of fluorophores on nanometer length scales, whereas fluorescence resonance energy transfer supports a wide range of different applications, including real-time monitoring of conformational rearrangements (as in protein folding). Still in their infancy, single-molecule spectroscopic methods thus provide unprecedented insights into basic molecular mechanisms. Copyright 2004 Elsevier Ltd.

Single-molecule pull-down (SiMPull) for new-age biochemistry: methodology and biochemical applications of single-molecule pull-down (SiMPull) for probing biomolecular interactions in crude cell extracts.

PubMed

Aggarwal, Vasudha; Ha, Taekjip

2014-11-01

Macromolecular interactions play a central role in many biological processes. Protein-protein interactions have mostly been studied by co-immunoprecipitation, which cannot provide quantitative information on all possible molecular connections present in the complex. We will review a new approach that allows cellular proteins and biomolecular complexes to be studied in real-time at the single-molecule level. This technique is called single-molecule pull-down (SiMPull), because it integrates principles of conventional immunoprecipitation with the powerful single-molecule fluorescence microscopy. SiMPull is used to count how many of each protein is present in the physiological complexes found in cytosol and membranes. Concurrently, it serves as a single-molecule biochemical tool to perform functional studies on the pulled-down proteins. In this review, we will focus on the detailed methodology of SiMPull, its salient features and a wide range of biological applications in comparison with other biosensing tools. © 2014 WILEY Periodicals, Inc.

Optoelectrical Cooling of Formaldehyde to Sub-Millikelvin Temperatures

NASA Astrophysics Data System (ADS)

Zeppenfeld, Martin

2016-05-01

Due to their strong long-range dipole-dipole interactions and large number of internal states, polar molecules cooled to ultracold temperatures enable fascinating applications ranging from ultracold chemistry to investigation of dipolar quantum gases. However, realizing a simple and general technique to cool molecules to ultracold temperatures, akin to laser cooling of atoms, has been a formidable challenge. We present results for opto-electrical Sisyphus cooling applied to formaldehyde (H2 CO). In this generally applicable cooling scheme, molecules repeatedly move up and down electric field gradients of a trapping potential in different rotational states to efficiently extract kinetic energy. A total of about 300,000 molecules are thereby cooled by a factor of 1000 to 400uK, resulting in a record-large ensemble of ultracold molecules. In addition to cooling of the motional degrees of freedom, optical pumping via a vibrational transition allows us to control the internal rotational state. We thereby achieve a purity of over 80% of formaldehyde molecules in a single rotational M-sublevel. Our experiment provides an excellent starting point for precision spectroscopy and investigation of ultracold collisions.

Single molecule-level study of donor-acceptor interactions and nanoscale environment in blends

NASA Astrophysics Data System (ADS)

Quist, Nicole; Grollman, Rebecca; Rath, Jeremy; Robertson, Alex; Haley, Michael; Anthony, John; Ostroverkhova, Oksana

2017-02-01

Organic semiconductors have attracted considerable attention due to their applications in low-cost (opto)electronic devices. The most successful organic materials for applications that rely on charge carrier generation, such as solar cells, utilize blends of several types of molecules. In blends, the local environment strongly influences exciton and charge carrier dynamics. However, relationship between nanoscale features and photophysics is difficult to establish due to the lack of necessary spatial resolution. We use functionalized fluorinated pentacene (Pn) molecule as single molecule probes of intermolecular interactions and of the nanoscale environment in blends containing donor and acceptor molecules. Single Pn donor (D) molecules were imaged in PMMA in the presence of acceptor (A) molecules using wide-field fluorescence microscopy. Two sample configurations were realized: (i) a fixed concentration of Pn donor molecules, with increasing concentration of acceptor molecules (functionalized indenflouorene or PCBM) and (ii) a fixed concentration of acceptor molecules with an increased concentration of the Pn donor. The D-A energy transfer and changes in the donor emission due to those in the acceptor- modified polymer morphology were quantified. The increase in the acceptor concentration was accompanied by enhanced photobleaching and blinking of the Pn donor molecules. To better understand the underlying physics of these processes, we modeled photoexcited electron dynamics using Monte Carlo simulations. The simulated blinking dynamics were then compared to our experimental data, and the changes in the transition rates were related to the changes in the nanoscale environment. Our study provides insight into evolution of nanoscale environment during the formation of bulk heterojunctions.

An electrostatic elliptical mirror for neutral polar molecules.

PubMed

González Flórez, A Isabel; Meek, Samuel A; Haak, Henrik; Conrad, Horst; Santambrogio, Gabriele; Meijer, Gerard

2011-11-14

Focusing optics for neutral molecules finds application in shaping and steering molecular beams. Here we present an electrostatic elliptical mirror for polar molecules consisting of an array of microstructured gold electrodes deposited on a glass substrate. Alternating positive and negative voltages applied to the electrodes create a repulsive potential for molecules in low-field-seeking states. The equipotential lines are parallel to the substrate surface, which is bent in an elliptical shape. The mirror is characterized by focusing a beam of metastable CO molecules and the results are compared to the outcome of trajectory simulations.

Molecular communication and networking: opportunities and challenges.

PubMed

Nakano, Tadashi; Moore, Michael J; Wei, Fang; Vasilakos, Athanasios V; Shuai, Jianwei

2012-06-01

The ability of engineered biological nanomachines to communicate with biological systems at the molecular level is anticipated to enable future applications such as monitoring the condition of a human body, regenerating biological tissues and organs, and interfacing artificial devices with neural systems. From the viewpoint of communication theory and engineering, molecular communication is proposed as a new paradigm for engineered biological nanomachines to communicate with the natural biological nanomachines which form a biological system. Distinct from the current telecommunication paradigm, molecular communication uses molecules as the carriers of information; sender biological nanomachines encode information on molecules and release the molecules in the environment, the molecules then propagate in the environment to receiver biological nanomachines, and the receiver biological nanomachines biochemically react with the molecules to decode information. Current molecular communication research is limited to small-scale networks of several biological nanomachines. Key challenges to bridge the gap between current research and practical applications include developing robust and scalable techniques to create a functional network from a large number of biological nanomachines. Developing networking mechanisms and communication protocols is anticipated to introduce new avenues into integrating engineered and natural biological nanomachines into a single networked system. In this paper, we present the state-of-the-art in the area of molecular communication by discussing its architecture, features, applications, design, engineering, and physical modeling. We then discuss challenges and opportunities in developing networking mechanisms and communication protocols to create a network from a large number of bio-nanomachines for future applications.

CEST: from basic principles to applications, challenges and opportunities

PubMed Central

Vinogradov, Elena; Sherry, A Dean; Lenkinski, Robert E

2012-01-01

Chemical Exchange Saturation Transfer (CEST) offers a new type of contrast for MRI that is molecule specific. In this approach, a slowly exchanging NMR active nucleus, typically a proton, possessing a chemical shift distinct from water is selectively saturated and the saturated spin is transferred to the bulk water via chemical exchange. Many molecules can act as CEST agents, both naturally occurring endogenous molecules and new types of exogenous agents. A large variety of molecules have been demonstrated as potential agents, including small diamagnetic molecules, complexes of paramagnetic ions, endogenous macromolecules, dendrimers and liposomes. In this review we described the basic principles of the CEST experiment, with emphasis on the similarity to earlier saturation transfer experiments described in the literature. Interest in quantitative CEST has also resulted in the development of new exchange-sensitive detection schemes. Some emerging clinical applications of CEST are described and the challenges and opportunities associated with translation of these methods to the clinical environment are discussed. PMID:23273841

Bioorthogonal cyclization-mediated in situ self-assembly of small-molecule probes for imaging caspase activity in vivo

NASA Astrophysics Data System (ADS)

Ye, Deju; Shuhendler, Adam J.; Cui, Lina; Tong, Ling; Tee, Sui Seng; Tikhomirov, Grigory; Felsher, Dean W.; Rao, Jianghong

2014-06-01

Directed self-assembly of small molecules in living systems could enable a myriad of applications in biology and medicine, and already this has been used widely to synthesize supramolecules and nano/microstructures in solution and in living cells. However, controlling the self-assembly of synthetic small molecules in living animals is challenging because of the complex and dynamic in vivo physiological environment. Here we employ an optimized first-order bioorthogonal cyclization reaction to control the self-assembly of a fluorescent small molecule, and demonstrate its in vivo applicability by imaging caspase-3/7 activity in human tumour xenograft mouse models of chemotherapy. The fluorescent nanoparticles assembled in situ were imaged successfully in both apoptotic cells and tumour tissues using three-dimensional structured illumination microscopy. This strategy combines the advantages offered by small molecules with those of nanomaterials and should find widespread use for non-invasive imaging of enzyme activity in vivo.

Single molecule tools for enzymology, structural biology, systems biology and nanotechnology: an update

PubMed Central

Widom, Julia R.; Dhakal, Soma; Heinicke, Laurie A.; Walter, Nils G.

2015-01-01

Toxicology is the highly interdisciplinary field studying the adverse effects of chemicals on living organisms. It requires sensitive tools to detect such effects. After their initial implementation during the 1990s, single-molecule fluorescence detection tools were quickly recognized for their potential to contribute greatly to many different areas of scientific inquiry. In the intervening time, technical advances in the field have generated ever-improving spatial and temporal resolution, and have enabled the application of single-molecule fluorescence to increasingly complex systems, such as live cells. In this review, we give an overview of the optical components necessary to implement the most common versions of single-molecule fluorescence detection. We then discuss current applications to enzymology and structural studies, systems biology, and nanotechnology, presenting the technical considerations that are unique to each area of study, along with noteworthy recent results. We also highlight future directions that have the potential to revolutionize these areas of study by further exploiting the capabilities of single-molecule fluorescence microscopy. PMID:25212907

Delivery of large biopharmaceuticals from cardiovascular stents: a review

PubMed Central

Takahashi, Hironobu; Letourneur, Didier; Grainger, David W.

2008-01-01

This review focuses on the new and emerging large-molecule bioactive agents delivered from stent surfaces in drug-eluting stents (DES) to inhibit vascular restenosis in the context of interventional cardiology. New therapeutic agents representing proteins, nucleic acids (small interfering RNAs and large DNA plasmids), viral delivery vectors and even engineered cell therapies require specific delivery designs distinct from traditional smaller molecule approaches on DES. While small molecules are currently the clinical standard for coronary stenting, extension of the DES to other lesion types, peripheral vasculature and non-vasculature therapies will seek to deliver an increasingly sophisticated armada of drug types. This review describes many of the larger molecule and biopharmaceutical approaches reported recently for stent-based delivery with the challenges associated with formulating and delivering these drug classes compared to the current small molecule drugs. It also includes perspectives on possible future applications that may improve safety and efficacy and facilitate diversification of the DES to other clinical applications. PMID:17929968

Computational design of molecules for an all-quinone redox flow battery† †Electronic supplementary information (ESI) available: The list of computationally predicted candidate quinone molecules with interesting redox properties. See DOI: 10.1039/c4sc03030c Click here for additional data file.

PubMed Central

Er, Süleyman; Suh, Changwon; Marshak, Michael P.

2015-01-01

Inspired by the electron transfer properties of quinones in biological systems, we recently showed that quinones are also very promising electroactive materials for stationary energy storage applications. Due to the practically infinite chemical space of organic molecules, the discovery of additional quinones or other redox-active organic molecules for energy storage applications is an open field of inquiry. Here, we introduce a high-throughput computational screening approach that we applied to an accelerated study of a total of 1710 quinone (Q) and hydroquinone (QH2) (i.e., two-electron two-proton) redox couples. We identified the promising candidates for both the negative and positive sides of organic-based aqueous flow batteries, thus enabling an all-quinone battery. To further aid the development of additional interesting electroactive small molecules we also provide emerging quantitative structure-property relationships. PMID:29560173

Hierarchical virtual screening approaches in small molecule drug discovery.

PubMed

Kumar, Ashutosh; Zhang, Kam Y J

2015-01-01

Virtual screening has played a significant role in the discovery of small molecule inhibitors of therapeutic targets in last two decades. Various ligand and structure-based virtual screening approaches are employed to identify small molecule ligands for proteins of interest. These approaches are often combined in either hierarchical or parallel manner to take advantage of the strength and avoid the limitations associated with individual methods. Hierarchical combination of ligand and structure-based virtual screening approaches has received noteworthy success in numerous drug discovery campaigns. In hierarchical virtual screening, several filters using ligand and structure-based approaches are sequentially applied to reduce a large screening library to a number small enough for experimental testing. In this review, we focus on different hierarchical virtual screening strategies and their application in the discovery of small molecule modulators of important drug targets. Several virtual screening studies are discussed to demonstrate the successful application of hierarchical virtual screening in small molecule drug discovery. Copyright © 2014 Elsevier Inc. All rights reserved.

Method and apparatus for passive optical dosimeter comprising caged dye molecules

DOEpatents

Sandison, David R.

2001-07-03

A new class of ultraviolet dosimeters is made possible by exposing caged dye molecules, which generate a dye molecule on exposure to ultraviolet radiation, to an exterior environment. Applications include sunburn monitors, characterizing the UV exposure history of UV-sensitive materials, especially including structural plastics, and use in disposable `one-use` optical equipment, especially medical devices.

Chemical Modification of Cyclodextrin and Amylose by Click Reaction and Its Application to the Synthesis of Poly-alkylamine-Modified Antibacterial Sugars.

PubMed

Yamamura, Hatsuo

2017-01-01

Cyclodextrin (CD) can be chemically modified into desired and sophisticated functional molecules. However, poly-modification often produces complicated mixtures, resulting in a low yield of the desired product. As the most promising procedure to solve such problems and to achieve poly-modification of the CD molecule, we present here the Huisgen 1,3-dipolar cycloaddition, known as a click reaction. This review will describe the results of our microwave-assisted click reaction for the poly-modification of CD and amylose molecules, and its application to the study of synthetic membrane active antibacterial derivatives.

Towards new uses of botulinum toxin as a novel therapeutic tool.

PubMed

Pickett, Andy; Perrow, Karen

2011-01-01

The uses of botulinum toxin in the fields of neurology, ophthalmology, urology, rehabilitation medicine and aesthetic applications have been revolutionary for the treatment of patients. This non-invasive therapeutic has continually been developed since first discovered in the 1970s as a new approach to what were previously surgical treatments. As these applications develop, so also the molecules are developing into tools with new therapeutic properties in specific clinical areas. This review examines how the botulinum toxin molecule is being adapted to new therapeutic uses and also how new areas of use for the existing molecules are being identified. Prospects for future developments are also considered.

Thymoquinone, as an anticancer molecule: from basic research to clinical investigation

PubMed Central

Asaduzzaman Khan, Md.; Tania, Mousumi; Fu, Shangyi; Fu, Junjiang

2017-01-01

Thymoquinone is an anticancer phytochemical commonly found in black cumin. In this review, we discuss the potential of thymoquinone as anticancer molecule, its mechanism of action and future usage in clinical applications. Thymoquinone exhibits anticancer activity via numerous mechanisms of action, specifically by showing selective antioxidant and oxidant activity, interfering with DNA structure, affecting carcinogenic signaling molecules/pathways and immunomodulation. In vitro activity of thymoquinone has been further implicated in animal models of cancer; however, no clinical application has been proven yet. This is the optimum time to focus on clinical trials for developing thymoquinone as a future drug in cancer therapeutics. PMID:28881699

Thymoquinone, as an anticancer molecule: from basic research to clinical investigation.

PubMed

Asaduzzaman Khan, Md; Tania, Mousumi; Fu, Shangyi; Fu, Junjiang

2017-08-01

Thymoquinone is an anticancer phytochemical commonly found in black cumin. In this review, we discuss the potential of thymoquinone as anticancer molecule, its mechanism of action and future usage in clinical applications. Thymoquinone exhibits anticancer activity via numerous mechanisms of action, specifically by showing selective antioxidant and oxidant activity, interfering with DNA structure, affecting carcinogenic signaling molecules/pathways and immunomodulation. In vitro activity of thymoquinone has been further implicated in animal models of cancer; however, no clinical application has been proven yet. This is the optimum time to focus on clinical trials for developing thymoquinone as a future drug in cancer therapeutics.

Defining RNA-Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA.

PubMed

Velagapudi, Sai Pradeep; Luo, Yiling; Tran, Tuan; Haniff, Hafeez S; Nakai, Yoshio; Fallahi, Mohammad; Martinez, Gustavo J; Childs-Disney, Jessica L; Disney, Matthew D

2017-03-22

RNA drug targets are pervasive in cells, but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross-Linking and Isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of noncoding RNAs.

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.

Computational design of molecules for an all-quinone redox flow battery.

PubMed

Er, Süleyman; Suh, Changwon; Marshak, Michael P; Aspuru-Guzik, Alán

2015-02-01

Inspired by the electron transfer properties of quinones in biological systems, we recently showed that quinones are also very promising electroactive materials for stationary energy storage applications. Due to the practically infinite chemical space of organic molecules, the discovery of additional quinones or other redox-active organic molecules for energy storage applications is an open field of inquiry. Here, we introduce a high-throughput computational screening approach that we applied to an accelerated study of a total of 1710 quinone (Q) and hydroquinone (QH 2 ) ( i.e. , two-electron two-proton) redox couples. We identified the promising candidates for both the negative and positive sides of organic-based aqueous flow batteries, thus enabling an all-quinone battery. To further aid the development of additional interesting electroactive small molecules we also provide emerging quantitative structure-property relationships.

Structure and thermodynamics of asymmetric molecules: Application to linear triatomic dipolar molecules

NASA Astrophysics Data System (ADS)

Nichols, Albert L., III; Calef, Daniel F.

A new method to solve the reference HNC equations is developed to treat systems with both asymmetric short-range and long-range interactions. This method is motivated by the work of Patey and co-workers and uses Lado's free-energy minimizing optimization criteria for the reference HNC approximation. The properties of several fluids composed of linear triatomic molecules with various dipole moments or hard-sphere molecules with different-length dipoles are investigated.

Applications of Fluorogens with Rotor Structures in Solar Cells.

PubMed

Ong, Kok-Haw; Liu, Bin

2017-05-29

Solar cells are devices that convert light energy into electricity. To drive greater adoption of solar cell technologies, higher cell efficiencies and reductions in manufacturing cost are necessary. Fluorogens containing rotor structures may be helpful in addressing some of these challenges due to their unique twisted structures and photophysics. In this review, we discuss the applications of rotor-containing molecules as dyes for luminescent down-shifting layers and luminescent solar concentrators, where their aggregation-induced emission properties and large Stokes shifts are highly desirable. We also discuss the applications of molecules containing rotors in third-generation solar cell technologies, namely dye-sensitized solar cells and organic photovoltaics, where the twisted 3-dimensional rotor structures are used primarily for aggregation control. Finally, we discuss perspectives on the future role of molecules containing rotor structures in solar cell technologies.

Compressive Force Spectroscopy: From Living Cells to Single Proteins.

PubMed

Wang, Jiabin; Liu, Meijun; Shen, Yi; Sun, Jielin; Shao, Zhifeng; Czajkowsky, Daniel Mark

2018-03-23

One of the most successful applications of atomic force microscopy (AFM) in biology involves monitoring the effect of force on single biological molecules, often referred to as force spectroscopy. Such studies generally entail the application of pulling forces of different magnitudes and velocities upon individual molecules to resolve individualistic unfolding/separation pathways and the quantification of the force-dependent rate constants. However, a less recognized variation of this method, the application of compressive force, actually pre-dates many of these "tensile" force spectroscopic studies. Further, beyond being limited to the study of single molecules, these compressive force spectroscopic investigations have spanned samples as large as living cells to smaller, multi-molecular complexes such as viruses down to single protein molecules. Correspondingly, these studies have enabled the detailed characterization of individual cell states, subtle differences between seemingly identical viral structures, as well as the quantification of rate constants of functionally important, structural transitions in single proteins. Here, we briefly review some of the recent achievements that have been obtained with compressive force spectroscopy using AFM and highlight exciting areas of its future development.

Rhodamine/Nanodiamond as a System Model for Drug Carrier.

PubMed

Reina, G; Orlanducci, S; Cairone, C; Tamburri, E; Lenti, S; Cianchetta, I; Rossi, M; Terranova, M L

2015-02-01

In this paper we present some strategies that are being developed in our labs towards enabling nanodiamond-based applications for drug delivery. Rhodamine B (RhB) has been choosen as model molecule to study the loading of nanodiamonds with active moieties and the conditions for their controlled release. In order to test the chemical/physical interactions between functionalized detonation nanodiamond (DND) and complex molecules, we prepared and tested different RhB@DND systems, with RhB adsorbed or linked by ionic bonding to the DND surface. The chemical state of the DND surfaces before conjugation with the RhB molecules, and the chemical features of the DND-RhB interactions have been deeply analysed by coupling DND with Au nanoparticles and taking advantage of surface enhanced Raman spectroscopy SERS. The effects due to temperature and pH variations on the process of RhB release from the DND carrier have been also investigated. The amounts of released molecules are consistent with those required for effective drug action in conventional therapeutic applications, and this makes the DND promising nanostructured cargos for drug delivery applications.

Quantitative evaluation of cross correlation between two finite-length time series with applications to single-molecule FRET.

PubMed

Hanson, Jeffery A; Yang, Haw

2008-11-06

The statistical properties of the cross correlation between two time series has been studied. An analytical expression for the cross correlation function's variance has been derived. On the basis of these results, a statistically robust method has been proposed to detect the existence and determine the direction of cross correlation between two time series. The proposed method has been characterized by computer simulations. Applications to single-molecule fluorescence spectroscopy are discussed. The results may also find immediate applications in fluorescence correlation spectroscopy (FCS) and its variants.

[Progresses in screening active compounds from herbal medicine by affinity chromatography].

PubMed

Feng, Ying-shu; Tong, Shan-shan; Xu, Xi-ming; Yu, Jiang-nan

2015-03-01

Affinity chromatography is a chromatographic method for separating molecules using the binding characteristics of the stationary phase with potential drug molecules. This method can be performed as a high throughput screening method and a chromatographic separation method to screen a variety of active drugs. This paper summarizes the history of affinity chromatography, screening technology of affinity chromatography, and application of affinity chromatography in screening bio-active compounds in herbal medicines, and then discusses its application prospects, in order to broaden applications of the affinity chromatography in drug screening.

Development of novel vaccines using DNA shuffling and screening strategies.

PubMed

Locher, Christopher P; Soong, Nay Wei; Whalen, Robert G; Punnonen, Juha

2004-02-01

DNA shuffling and screening technologies recombine and evolve genes in vitro to rapidly obtain molecules with improved biological activity and fitness. In this way, genes from related strains are bred like plants or livestock and their successive progeny are selected. These technologies have also been called molecular breeding-directed molecular evolution. Recent developments in bioinformatics-assisted computer programs have facilitated the design, synthesis and analysis of DNA shuffled libraries of chimeric molecules. New applications in vaccine development are among the key features of DNA shuffling and screening technologies because genes from several strains or antigenic variants of pathogens can be recombined to create novel molecules capable of inducing immune responses that protect against infections by multiple strains of pathogens. In addition, molecules such as co-stimulatory molecules and cytokines have been evolved to have improved T-cell proliferation and cytokine production compared with the wild-type human molecules. These molecules can be used to immunomodulate vaccine responsiveness and have multiple applications in infectious diseases, cancer, allergy and autoimmunity. Moreover, DNA shuffling and screening technologies can facilitate process development of vaccine manufacturing through increased expression of recombinant polypeptides and viruses. Therefore, DNA shuffling and screening technologies can overcome some of the challenges that vaccine development currently faces.

Investigation of multi-state charge-storage properties of redox-active organic molecules in silicon-molecular hybrid devices for DRAM and Flash applications

NASA Astrophysics Data System (ADS)

Gowda, Srivardhan Shivappa

Molecular electronics has recently spawned a considerable amount of interest with several molecules possessing charge-conduction and charge-storage properties proposed for use in electronic devices. Hybrid silicon-molecular technology has the promise of augmenting the current silicon technology and provide for a transitional path to future molecule-only technology. The focus of this dissertation work has been on developing a class of hybrid silicon-molecular electronic devices for DRAM and Flash memory applications utilizing redox-active molecules. This work exploits the ability of molecules to store charges with single-electron precision at room temperature. The hybrid devices are fabricated by forming self-assembled monolayers of redox-active molecules on Si and oxide (SiO2 and HfO2) surfaces via formation of covalent linkages. The molecules possess discrete quantum states from which electrons can tunnel to the Si substrate at discrete applied voltages (oxidation process, cell write), leaving behind a positively charged layer of molecules. The reduction (erase) process, which is the process of electrons tunneling back from Si to the molecules, neutralizes the positively charged molecular monolayer. Hybrid silicon-molecular capacitor test structures were electrically characterized with an electrolyte gate using cyclic voltammetry (CyV) and impedance spectroscopy (CV) techniques. The redox voltages, kinetics (write/erase speeds) and charge-retention characteristics were found to be strongly dependent on the Si doping type and densities, and ambient light. It was also determined that the redox energy states in the molecules communicate with the valence band of the Si substrate. This allows tuning of write and read states by modulating minority carriers in n- and p-Si substrates. Ultra-thin dielectric tunnel barriers (SiO2, HfO2) were placed between the molecules and the Si substrate to augment charge-retention for Flash memory applications. The redox response was studied as a function of tunnel oxide thickness, dielectric permittivity and energy barrier, and modified Butler-Volmer expressions were postulated to describe the redox kinetics. The speed vs. retention performance of the devices was improved via asymmetric layered tunnel barriers. The properties of molecules can be tailored by molecular design and synthetic chemistry. In this work, it was demonstrated that an alternate route to tune/enhance the properties of the hybrid device is to engineer the substrate (silicon) component. The molecules were attached to diode surfaces to tune redox voltages and improve charge-retention characteristics. N+ pockets embedded in P-Si well were utilized to obtain multiple states from a two-state molecule. The structure was also employed as a characterization tool in investigating the intrinsic properties of the molecules such as lateral conductivity within the monolayer. Redox molecules were also incorporated on an ultra thin gate-oxide of Si MOSFETs with the intent of studying the interaction of redox states with Si MOSFETs. The discrete molecular states were manifested in the drain current and threshold voltage characteristics of the device. This work demonstrates the multi-state modulation of Si-MOSFETs' drain current via redox-active molecular monolayers. Polymeric films of redox-active molecules were incorporated to improve the charge-density (ON/OFF ratio) and these structures may be employed for multi-state, low-voltage Flash memory applications. The most critical aspect of this research effort is to build a reliable and high density solid state memory technology. To this end, efforts were directed towards replacement of the electrolytic gate, which forms an extremely thin insulating double layer (˜10 nm) at the electrolyte-molecule interface, with a combination of an ultra-thin high-K dielectric layer and a metal gate. Several interesting observations were made in the research approaches towards integration and provided valuable insights into the electrolyte-redox systems. In summary, this work provides fundamental insights into the interaction of redox-energy states with silicon substrate and realistic approaches for exploiting the unique properties of the molecules that may enable solutions for nanoscale high density, low-voltage, long retention and multiple bit memory applications.

Application of Raman spectroscopy technology to studying Sudan I

NASA Astrophysics Data System (ADS)

Li, Gang; Zhang, Guoping; Chen, Chen

2006-06-01

Being an industrial dye, the Sudan I may have a toxic effect after oral intake on the body, and has recently been shown to cause cancer in rats, mice and rabbits. Because China and some other countries have detected the Sudan I in samples of the hot chilli powder and the chilli products, it is necessary to study the characteristics of this dye. As one kind of molecule scattering spectroscopy, Raman spectroscopy is characterized by the frequency excursion caused by interactions of molecules and photons. The frequency excursion reflects the margin between certain two vibrational or rotational energy states, and shows the information of the molecule. Because Raman spectroscopy can provides quick, easy, reproducible, and non-destructive analysis, both qualitative and quantitative, with no sample preparation required, Raman spectroscopy has been a particularly promising technique for analyzing the characteristics and structures of molecules, especially organic ones. Now, it has a broad application in biological, chemical, environmental and industrial applications. This paper firstly introduces Sudan I dye and the Raman spectroscopy technology, and then describes its application to the Sudan I. Secondly, the fingerprint spectra of the Sudan I are respectively assigned and analyzed in detail. Finally, the conclusion that the Raman spectroscopy technology is a powerful tool to determine the Sudan I is drawn.

Unraveling helicase mechanisms one molecule at a time

PubMed Central

Rasnik, Ivan; Myong, Sua; Ha, Taekjip

2006-01-01

Recent years have seen an increasing number of biological applications of single molecule techniques, evolving from a proof of principle type to the more sophisticated studies. Here we compare the capabilities and limitations of different single molecule techniques in studying the activities of helicases. Helicases share a common catalytic activity but present a high variability in kinetic and phenomenological behavior, making their studies ideal in exemplifying the use of the new single molecule techniques to answer biological questions. Unexpected phenomena have also been observed from individual molecules suggesting extended or alternative functionality of helicases in vivo. PMID:16935883

Hyperfine structure of 2Σ molecules containing alkaline-earth-metal atoms

NASA Astrophysics Data System (ADS)

Aldegunde, Jesus; Hutson, Jeremy M.

2018-04-01

Ultracold molecules with both electron spin and an electric dipole moment offer new possibilities in quantum science. We use density-functional theory to calculate hyperfine coupling constants for a selection of molecules important in this area, including RbSr, LiYb, RbYb, CaF, and SrF. We find substantial hyperfine coupling constants for the fermionic isotopes of the alkaline-earth-metal and Yb atoms. We discuss the hyperfine level patterns and Zeeman splittings expected for these molecules. The results will be important both to experiments aimed at forming ultracold open-shell molecules and to their applications.

Production, Manipulation, and Applications of Ultracold Polar Molecules

DTIC Science & Technology

2015-04-30

molecules, cooling, trapping, photoassociation, feshbach resonances, quantum simulation , ultracold collisions, ultracold chemistry, optical lattices...been a multitude of less predictable outcomes: special quantum information processing schemes, uses of entanglement such a spin-squeezing for better...field seeing states to high-field-seeking states (and back) at key points in the magnetic field. The molecules spontaneously emit photons as they are

Depth of focus extended microscope configuration for imaging of incorporated groups of molecules, DNA constructs and clusters inside bacterial cells

NASA Astrophysics Data System (ADS)

Fessl, Tomas; Ben-Yaish, Shai; Vacha, Frantisek; Adamec, Frantisek; Zalevsky, Zeev

2009-07-01

Imaging of small objects such as single molecules, DNA clusters and single bacterial cells is problematic not only due to the lateral resolution that is obtainable in currently existing microscopy but also, and as much fundamentally limiting, due to the lack of sufficient axial depth of focus to have the full object focused simultaneously. Extension in depth of focus is helpful also for single molecule steady state FRET measurements. In this technique it is crucial to obtain data from many well focused molecules, which are often located in different axial depths. In this paper we present the implementation of an all-optical and a real time technique of extension in the depth of focus that may be incorporated in any high NA microscope system and to be used for the above mentioned applications. We demonstrate experimentally how after the integration of special optical element in high NA 100× objective lens of a single molecule imaging microscope system, the depth of focus is significantly improved while maintaining the same lateral resolution in imaging applications of incorporated groups of molecules, DNA constructs and clusters inside bacterial cells.

Organizing and addressing magnetic molecules.

PubMed

Gatteschi, Dante; Cornia, Andrea; Mannini, Matteo; Sessoli, Roberta

2009-04-20

Magnetic molecules ranging from simple organic radicals to single-molecule magnets (SMMs) are intensively investigated for their potential applications in molecule-based information storage and processing. The goal of this Article is to review recent achievements in the organization of magnetic molecules on surfaces and in their individual probing and manipulation. We stress that the inherent fragility and redox sensitivity of most SMM complexes, combined with the noninnocent role played by the substrate, ask for a careful evaluation of the structural and electronic properties of deposited molecules going beyond routine methods for surface analysis. Detailed magnetic information can be directly obtained using X-ray magnetic circular dichroism or newly emerging scanning probe techniques with magnetic detection capabilities.

Spectroscopic characterization of Venus at the single molecule level.

PubMed

David, Charlotte C; Dedecker, Peter; De Cremer, Gert; Verstraeten, Natalie; Kint, Cyrielle; Michiels, Jan; Hofkens, Johan

2012-02-01

Venus is a recently developed, fast maturating, yellow fluorescent protein that has been used as a probe for in vivo applications. In the present work the photophysical characteristics of Venus were analyzed spectroscopically at the bulk and single molecule level. Through time-resolved single molecule measurements we found that single molecules of Venus display pronounced fluctuations in fluorescence emission, with clear fluorescence on- and off-times. These fluorescence intermittencies were found to occupy a broad range of time scales, ranging from milliseconds to several seconds. Such long off-times can complicate the analysis of single molecule counting experiments or single-molecule FRET experiments. This journal is © The Royal Society of Chemistry and Owner Societies 2012

Single molecule data under scrutiny. Comment on "Extracting physics of life at the molecular level: A review of single-molecule data analyses" by W. Colomb & S.K. Sarkar

NASA Astrophysics Data System (ADS)

Wohland, Thorsten

2015-06-01

Single Molecule Detection and Spectroscopy have grown from their first beginnings into mainstream, mature research areas that are widely applied in the biological sciences. However, despite the advances in technology and the application of many single molecule techniques even in in vivo settings, the data analysis of single molecule experiments is complicated by noise, systematic errors, and complex underlying processes that are only incompletely understood. Colomb and Sarkar provide in this issue an overview of single molecule experiments and the accompanying problems in data analysis, which have to be overcome for a proper interpretation of the experiments [1].

Patterns and conformations in molecularly thin films

NASA Astrophysics Data System (ADS)

Basnet, Prem B.

Molecularly thin films have been a subject of great interest for the last several years because of their large variety of industrial applications ranging from micro-electronics to bio-medicine. Additionally, molecularly thin films can be used as good models for biomembrane and other systems where surfaces are critical. Many different kinds of molecules can make stable films. My research has considered three such molecules: a polymerizable phospholipid, a bent-core molecules, and a polymer. One common theme of these three molecules is chirality. The phospolipid molecules studied here are strongly chiral, which can be due to intrinsically chiral centers on the molecules and also due to chiral conformations. We find that these molecules give rise to chiral patterns. Bent-core molecules are not intrinsically chiral, but individual molecules and groups of molecules can show chiral structures, which can be changed by surface interactions. One major, unconfirmed hypothesis for the polymer conformation at surface is that it forms helices, which would be chiral. Most experiments were carried out at the air/water interface, in what are called Langmuir films. Our major tools for studying these films are Brewster Angle Microscopy (BAM) coupled with the thermodynamic information that can be deduced from surface pressure isotherms. Phospholipids are one of the important constituents of liposomes -- a spherical vesicle com-posed of a bilayer membrane, typically composed of a phospholipid and cholesterol bilayer. The application of liposomes in drug delivery is well-known. Crumpling of vesicles of polymerizable phospholipids has been observed. With BAM, on Langmuir films of such phospholipids, we see novel spiral/target patterns during compression. We have found that both the patterns and the critical pressure at which they formed depend on temperature (below the transition to a i¬‘uid layer). Bent-core liquid crystals, sometimes knows as banana liquid crystals, have drawn increasing attention because of the richness in phases that they exhibit. Due to the unique coupling between dipole properties and the packing constraints placed by the bent shape, these molecules are emerging as strong candidates in electromechanical devices. However, most applications require that the molecules be aligned, which has proved difficult. Our group has tested such molecules both as Langmuir layers and, when transferred to a solid, as alignment layers with some limited success. However, these molecules do not behave well with the surfaces and the domains at the air/water interface tend to form ill-controlled multilayer structures since attraction with the surfaces is relatively weak. New bent-core molecules obtained from Prof. Dr. C. Tsehiemke from Department of Chemistry Institute of Organic Chemistry, Martin-Luther-University, Germany, have a hydrophilic group at one end. We expect this molecule to behave better on the surface because of the stronger attraction of the hydrophilic group towards the surface than for the bent-core molecules without the hydrophilic group. Polydimethylsiloxane (PDMS) is a polymer which finds many applications in modifying surface properties. It is used in manufacturing lubricants, protective coatings, hair conditioner and glass-coating. However its properties are not well understood. This polymer has been proposed to follow either helical or caterpillar conformations on a surface. The orientational order of CH3 side groups can test for these conformations (they would be predominantly up/down for the caterpillar conformation, but rotating through the entire 360 degree for the helical one). Thus previous work on the Langmuir polymer films at the air/water interface were complemented by deuterium NMR studies to probe their conformations at a surface. These experiments were performed using humid porous solids, in order to provide sufficient surface area for the technique. Previous tests in this group at room temperature were suggestive but inconclusive because of the rapid averaging motion of the molecules. Here, we attempt to freeze the molecules on the surface.

Intranucleus Single-Molecule Imaging in Living Cells.

PubMed

Shao, Shipeng; Xue, Boxin; Sun, Yujie

2018-06-01

Many critical processes occurring in mammalian cells are stochastic and can be directly observed at the single-molecule level within their physiological environment, which would otherwise be obscured in an ensemble measurement. There are various fundamental processes in the nucleus, such as transcription, replication, and DNA repair, the study of which can greatly benefit from intranuclear single-molecule imaging. However, the number of such studies is relatively small mainly because of lack of proper labeling and imaging methods. In the past decade, tremendous efforts have been devoted to developing tools for intranuclear imaging. Here, we mainly describe the recent methodological developments of single-molecule imaging and their emerging applications in the live nucleus. We also discuss the remaining issues and provide a perspective on future developments and applications of this field. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Revisiting the Central Dogma One Molecule at a Time

PubMed Central

Bustamante, Carlos; Cheng, Wei; Meija, Yara

2011-01-01

The faithful relay and timely expression of genetic information depend on specialized molecular machines, many of which function as nucleic acid translocases. The emergence over the last decade of single-molecule fluorescence detection and manipulation techniques with nm and Å resolution, and their application to the study of nucleic acid translocases are painting an increasingly sharp picture of the inner workings of these machines, the dynamics and coordination of their moving parts, their thermodynamic efficiency, and the nature of their transient intermediates. Here we present an overview of the main results arrived at by the application of single-molecule methods to the study of the main machines of the central dogma. PMID:21335233

Advantages and application of label-free detection assays in drug screening.

PubMed

Cunningham, Brian T; Laing, Lance G

2008-08-01

Adoption is accelerating for a new family of label-free optical biosensors incorporated into standard format microplates owing to their ability to enable highly sensitive detection of small molecules, proteins and cells for high-throughput drug discovery applications. Label-free approaches are displacing other detection technologies owing to their ability to provide simple assay procedures for hit finding/validation, accessing difficult target classes, screening the interaction of cells with drugs and analyzing the affinity of small molecule inhibitors to target proteins. This review describes several new drug discovery applications that are under development for microplate-based photonic crystal optical biosensors and the key issues that will drive adoption of the technology. Microplate-based optical biosensors are enabling a variety of cell-based assays, inhibition assays, protein-protein binding assays and protein-small molecule binding assays to be performed with high-throughput and high sensitivity.

Applications of Surface Plasmon Resonance for Characterization of Molecules Important in the Pathogenesis and Treatment of Neurodegenerative Diseases

PubMed Central

Wittenberg, Nathan J.; Wootla, Bharath; Jordan, Luke R.; Denic, Aleksandar; Warrington, Arthur E.; Oh, Sang-Hyun; Rodriguez, Moses

2014-01-01

Characterization of binding kinetics and affinity between a potential new drug and its receptor are key steps in the development of new drugs. Among the techniques available to determine binding affinities, surface plasmon resonance has emerged as the gold standard because it can measure binding and dissociation rates in real-time in a label-free fashion. Surface plasmon resonance is now finding applications in the characterization of molecules for treatment of neurodegenerative diseases, characterization of molecules associated with pathogenesis of neurodegenerative diseases and detection of neurodegenerative disease biomarkers. In addition it has been used in the characterization of a new class of natural autoantibodies that have therapeutic potential in a number of neurologic diseases. In this review we will introduce surface plasmon resonance and describe some applications of the technique that pertain to neurodegenerative disorders and their treatment. PMID:24625008

Second Moments (planar Moments) and Their Application in Spectroscopy

NASA Astrophysics Data System (ADS)

Bohn, Robert K.; Montgomery, John A., Jr.; Michels, H. Harvey; Byrd, Jason N.

2013-06-01

Second moments, also called planar moments (P_{ii} = Σ m_{i}^{} x_{i}^{2}), are the spectroscopic parameters used to determine substitution structures (r_{s}) ) by Kraitchman''s method from spectra of a molecule and its isotopologs. They are also useful for discussing other molecular structural properties. Just as bond lengths and angles are considered transferable among similar molecules, second moments of many common groups are also transferable. This paper discusses applications of second moments of methylene/methyl groups, singly or multiply, isopropyl/tert-butyl groups, phenyl groups, per{f}{l}uoro methylene/methyl groups, combinations of any of them, and planarity of molecules, the historically most common application of second moments. The inertial defect is Δ = (I_{c} - I_{a} - I_{b}) or -2P_{cc}. Some authors err by assuming each isotopolog provides three independent rotational constants, but in some cases they are not all independent. J. Kraitchman, Am. J. Phys. {21 (17), 1953.}

Defining RNA–Small Molecule Affinity Landscapes Enables Design of a Small Molecule Inhibitor of an Oncogenic Noncoding RNA

PubMed Central

2017-01-01

RNA drug targets are pervasive in cells, but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif–small molecule interactions identified via selection. Named High Throughput Structure–Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif–small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine/threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross-Linking and Isolation by Pull Down (Chem-CLIP), a covalent small molecule–RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of noncoding RNAs. PMID:28386598

Single-Molecule Fluorescence Imaging for Studying Organic, Organometallic, and Inorganic Reaction Mechanisms

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

Blum, Suzanne A.

2016-05-24

The reactive behavior of individual molecules is seldom observed, because we usually measure the average properties of billions of molecules. What we miss is important: the catalytic activity of less than 1% of the molecules under observation can dominate the outcome of a chemical reaction seen at a macroscopic level. Currently available techniques to examine reaction mechanisms (such as nuclear magnetic resonance spectroscopy and mass spectrometry) study molecules as an averaged ensemble. These ensemble techniques are unable to detect minor components (under ~1%) in mixtures or determine which components in the mixture are responsible for reactivity and catalysis. In themore » field of mechanistic chemistry, there is a resulting heuristic device that if an intermediate is very reactive in catalysis, it often cannot be observed (termed “Halpern’s Rule” ). Ultimately, the development of single-molecule imaging technology could be a powerful tool to observe these “unobservable” intermediates and active catalysts. Single-molecule techniques have already transformed biology and the understanding of biochemical processes. The potential of single-molecule fluorescence microscopy to address diverse chemical questions, such as the chemical reactivity of organometallic or inorganic systems with discrete metal complexes, however, has not yet been realized. In this respect, its application to chemical systems lags significantly behind its application to biophysical systems. This transformative imaging technique has broad, multidisciplinary impact with the potential to change the way the chemistry community studies reaction mechanisms and reactivity distributions, especially in the core area of catalysis.« less

Computational Prediction of the Immunomodulatory Potential of RNA Sequences.

PubMed

Nagpal, Gandharva; Chaudhary, Kumardeep; Dhanda, Sandeep Kumar; Raghava, Gajendra Pal Singh

2017-01-01

Advances in the knowledge of various roles played by non-coding RNAs have stimulated the application of RNA molecules as therapeutics. Among these molecules, miRNA, siRNA, and CRISPR-Cas9 associated gRNA have been identified as the most potent RNA molecule classes with diverse therapeutic applications. One of the major limitations of RNA-based therapeutics is immunotoxicity of RNA molecules as it may induce the innate immune system. In contrast, RNA molecules that are potent immunostimulators are strong candidates for use in vaccine adjuvants. Thus, it is important to understand the immunotoxic or immunostimulatory potential of these RNA molecules. The experimental techniques for determining immunostimulatory potential of siRNAs are time- and resource-consuming. To overcome this limitation, recently our group has developed a web-based server "imRNA" for predicting the immunomodulatory potential of RNA sequences. This server integrates a number of modules that allow users to perform various tasks including (1) generation of RNA analogs with reduced immunotoxicity, (2) identification of highly immunostimulatory regions in RNA sequence, and (3) virtual screening. This server may also assist users in the identification of minimum mutations required in a given RNA sequence to minimize its immunomodulatory potential that is required for designing RNA-based therapeutics. Besides, the server can be used for designing RNA-based vaccine adjuvants as it may assist users in the identification of mutations required for increasing immunomodulatory potential of a given RNA sequence. In summary, this chapter describes major applications of the "imRNA" server in designing RNA-based therapeutics and vaccine adjuvants (http://www.imtech.res.in/raghava/imrna/).

Ultracold Molecules in Optical Lattices: Efficient Production and Application to Molecular Clocks

DTIC Science & Technology

2015-05-03

near the intercombination- line threshold were measured for a variety of states, and explained by considering nonadiabatic effects ( Coriolis coupling) in...Moszynski, T. Zelevinsky. Nonadiabatic Effects in Ultracold Molecules via Anomalous Linear and Quadratic Zeeman Shifts, Physical Review Letters, (12...M. McDonald, G. Reinaudi, W. Skomorowski, R. Moszynski, T. Zelevinsky. Measurement of Nonadiabatic Effects in Ultracold Molecules via Anomalous

GREENER SYNTHETIC TRANSFORMATIONS USING MICROWAVES

EPA Science Inventory

Microwave irradiation has been used for a variety of organic transformations wherein chemical reactions are expedited because of selective adsorption of microwave (MW) energy by polar molecules, non-polar molecules being inert to the MW dielectric loss. The MW application under s...

Single molecule microscopy in 3D cell cultures and tissues.

PubMed

Lauer, Florian M; Kaemmerer, Elke; Meckel, Tobias

2014-12-15

From the onset of the first microscopic visualization of single fluorescent molecules in living cells at the beginning of this century, to the present, almost routine application of single molecule microscopy, the method has well-proven its ability to contribute unmatched detailed insight into the heterogeneous and dynamic molecular world life is composed of. Except for investigations on bacteria and yeast, almost the entire story of success is based on studies on adherent mammalian 2D cell cultures. However, despite this continuous progress, the technique was not able to keep pace with the move of the cell biology community to adapt 3D cell culture models for basic research, regenerative medicine, or drug development and screening. In this review, we will summarize the progress, which only recently allowed for the application of single molecule microscopy to 3D cell systems and give an overview of the technical advances that led to it. While initially posing a challenge, we finally conclude that relevant 3D cell models will become an integral part of the on-going success of single molecule microscopy. Copyright © 2014 Elsevier B.V. All rights reserved.

Insights into the sand fly saliva: Blood-feeding and immune interactions between sand flies, hosts, and Leishmania.

PubMed

Lestinova, Tereza; Rohousova, Iva; Sima, Michal; de Oliveira, Camila I; Volf, Petr

2017-07-01

Leishmaniases are parasitic diseases present worldwide that are transmitted to the vertebrate host by the bite of an infected sand fly during a blood feeding. Phlebotomine sand flies inoculate into the mammalian host Leishmania parasites embedded in promastigote secretory gel (PSG) with saliva, which is composed of a diverse group of molecules with pharmacological and immunomodulatory properties. In this review, we focus on 3 main aspects of sand fly salivary molecules: (1) structure and composition of salivary glands, including the properties of salivary molecules related to hemostasis and blood feeding, (2) immunomodulatory properties of salivary molecules and the diverse impacts of these molecules on leishmaniasis, ranging from disease exacerbation to vaccine development, and (3) use of salivary molecules for field applications, including monitoring host exposure to sand flies and the risk of Leishmania transmission. Studies showed interesting differences between salivary proteins of Phlebotomus and Lutzomyia species, however, no data were ever published on salivary proteins of Sergentomyia species. In the last 15 years, numerous studies have characterized sand fly salivary proteins and, in parallel, have addressed the impact of such molecules on the biology of the host-sand fly-parasite interaction. The results obtained shall pave the way for the development of field-application tools that could contribute to the management of leishmaniasis in endemic areas.

A scanning tunneling microscope break junction method with continuous bias modulation.

PubMed

Beall, Edward; Yin, Xing; Waldeck, David H; Wierzbinski, Emil

2015-09-28

Single molecule conductance measurements on 1,8-octanedithiol were performed using the scanning tunneling microscope break junction method with an externally controlled modulation of the bias voltage. Application of an AC voltage is shown to improve the signal to noise ratio of low current (low conductance) measurements as compared to the DC bias method. The experimental results show that the current response of the molecule(s) trapped in the junction and the solvent media to the bias modulation can be qualitatively different. A model RC circuit which accommodates both the molecule and the solvent is proposed to analyze the data and extract a conductance for the molecule.

Exchange-biased quantum tunnelling in a supramolecular dimer of single-molecule magnets.

PubMed

Wernsdorfer, Wolfgang; Aliaga-Alcalde, Núria; Hendrickson, David N; Christou, George

2002-03-28

Various present and future specialized applications of magnets require monodisperse, small magnetic particles, and the discovery of molecules that can function as nanoscale magnets was an important development in this regard. These molecules act as single-domain magnetic particles that, below their blocking temperature, exhibit magnetization hysteresis, a classical property of macroscopic magnets. Such 'single-molecule magnets' (SMMs) straddle the interface between classical and quantum mechanical behaviour because they also display quantum tunnelling of magnetization and quantum phase interference. Quantum tunnelling of magnetization can be advantageous for some potential applications of SMMs, for example, in providing the quantum superposition of states required for quantum computing. However, it is a disadvantage in other applications, such as information storage, where it would lead to information loss. Thus it is important to both understand and control the quantum properties of SMMs. Here we report a supramolecular SMM dimer in which antiferromagnetic coupling between the two components results in quantum behaviour different from that of the individual SMMs. Our experimental observations and theoretical analysis suggest a means of tuning the quantum tunnelling of magnetization in SMMs. This system may also prove useful for studying quantum tunnelling of relevance to mesoscopic antiferromagnets.

Observing and understanding the ultrafast photochemistry in small molecules: applications to sunscreens.

PubMed

Baker, Lewis A; Stavros, Vasilios G

2016-09-01

In this review, we discuss the importance of biological and artificial photoprotection against overexposure to harmful ultraviolet radiation. Transient electronic and transient vibrational absorption spectroscopies are highlighted as important tools in understanding the energy transfer in small molecules, with a focus on the application to commercial sunscreens with representative examples given. Oxybenzone, a common ingredient in commercial sunscreens and sinapoyl malate, a biological sunscreen in plant leaves are presented as case studies.

Advanced Applications of Vibrational Circular Dichroism: from Small Chiral Molecules to Fibrils

NASA Astrophysics Data System (ADS)

Dukor, Rina K.

2017-06-01

Vibrational Circular Dichroism (VCD), first discovered in the early 1970s, and commercialized in the late 1990's, is finally coming of age! No longer a curiosity of the few selected academic groups, it is now used by all major pharmaceutical companies, regulatory agencies, government labs and academic institutions. The main application for the technology has been determination of absolute configuration of small pharmaceutical molecules. In more recent years, this has extended to more complicated molecules such as natural products with many chiral centers and conformational flexibility. Other applications include determination of enantiomeric purity, chiral polymers, and characterization of other biological molecules such as proteins, carohydrates and nucleic acids. One of the most fascinating discoveries in the VCD field has been been unusual enhancement in intensity for proteins that form fibrils. We have demonstrated sensitivity of VCD to in situ solution-phase probe of the process of fibrillogenesis and subsequent development that currently can only be studied in detail with dried samples by such techniques as scanning electron microscopy or atomic force microscopy. We have further shown that several different proteins, that in their native state have different secondary structures, have a very similar unique signature of mature fibrils. In this presentation, we will discuss fundamentals of VCD, demonstrate a few examples of different applications and showcase the sensitivity to structure of fibrils, including new results on micro-sampling.

Open, Cross Platform Chemistry Application Unifying Structure Manipulation, External Tools, Databases and Visualization

DTIC Science & Technology

2014-05-30

mol.addBond(o1, h2, 1); Avogadro ::Core::Bond b2 = mol.addBond(o1, h3, 1); The QtGui::Molecule class inherits from Core::Molecule and Qt’s QObject...populated as an input (although they are all implemented in terms of the Core::Molecule class. The third is QtGui::RWMolecule which inherits from just...shown in Figure 16. The use of molecule fingerprinting techniques gives the database the ability to be searched by similarity to a desired structure, as

SOLVENT-FREE ALTERNATIVES TO ORGANIC SYNTHESES USING MICROWAVES

EPA Science Inventory

Microwave irradiation has been used for a variety of synthetic transformations wherein chemical reactions are accelerated because of selective adsorption of microwave (MW) energy by polar molecules, non-polar molecules being inert to the MW dielectric loss. The application of mic...

Recent Developments of Liposomes as Nanocarriers for Theranostic Applications

PubMed Central

Xing, Hang; Hwang, Kevin; Lu, Yi

2016-01-01

Liposomes are nanocarriers comprised of lipid bilayers encapsulating an aqueous core. The ability of liposomes to encapsulate a wide variety of diagnostic and therapeutic agents has led to significant interest in utilizing liposomes as nanocarriers for theranostic applications. In this review, we highlight recent progress in developing liposomes as nanocarriers for a) diagnostic applications to detect proteins, DNA, and small molecule targets using fluorescence, magnetic resonance, ultrasound, and nuclear imaging; b) therapeutic applications based on small molecule-based therapy, gene therapy and immunotherapy; and c) theranostic applications for simultaneous detection and treatment of heavy metal toxicity and cancers. In addition, we summarize recent studies towards understanding of interactions between liposomes and biological components. Finally, perspectives on future directions in advancing the field for clinical translations are also discussed. PMID:27375783

Acenes, Heteroacenes and Analogous Molecules for Organic Photovoltaic and Field Effect Transistor Applications

NASA Astrophysics Data System (ADS)

Granger, Devin Benjamin

Polycyclic aromatic hydrocarbons composed of benzenoid rings fused in a linear fashion comprise the class of compounds known as acenes. The structures containing three to six ring fusions are brightly colored and possess band gaps and charge transport efficiencies sufficient for semiconductor applications. These molecules have been investigated throughout the past several decades to assess their optoelectronic properties. The absorption, emission and charge transport properties of this series of molecules has been studied extensively to elucidate structure-property relationships. A wide variety of analogous molecules, incorporating heterocycles in place of benzenoid rings, demonstrate similar properties to the parent compounds and have likewise been investigated. Functionalization of acene compounds by placement of groups around the molecule affects the way in which molecules interact in the solid state, in addition to the energetics of the molecule. The use of electron donating or electron withdrawing groups affects the frontier molecular orbitals and thus affects the optical and electronic gaps of the molecules. The use of bulky side groups such as alkylsilylethynyl groups allows for crystal engineering of molecular aggregates, and changing the volume and dimensions of the alkylsilyl groups affects the intermolecular interactions and thus changes the packing motif. In chapter 2, a series of tetracene and pentacene molecules with strongly electron withdrawing groups is described. The investigation focuses on the change in energetics of the frontier molecular orbitals between the base acene and the nitrile and dicyanovinyl derivatives as well as the differences between the pentacene and tetracene molecules. The differences in close packing motifs through use of bulky alkylsilylethynyl groups is also discussed in relation to electron acceptor material design and bulk heterojunction organic photovoltaic characteristics. Chapter 3 focuses on molecular acceptor and donor molecules for bulk heterojunction organic photovoltaics based on anthrathiophene and benzo[1,2-b:4,5-b']dithiophene central units like literature molecules containing fluorene and dithieno[2,3-b:2',3'-d]silole cores. The synthetic strategies of developing reduced symmetry benzo[1,2-b:4,5-b']dithiophene to study the effect of substitution around the central unit is also described. The optical and electronic properties of the donors and acceptors are described along with the performance and characteristics of devices employing these molecules. The final two data chapters focus on new nitrogen containing polycyclic hydrocarbons containing indolizine and (2.2.2) cyclazine units. The optical, electronic and other physical properties of these molecules are explored, in addition to the synthetic strategies for incorporating the indolizine and cyclazine units. By use of alkylsilylethynyl groups, crystal engineering was investigated for the benzo[2,3-b:5,6-b']diindolizine chromophore described in chapter 4 to target the 2-D "brick-work" packing motif for application in field effect transistor devices. Optical and electronic properties of the cyclazine end-capped acene molecules described in chapter 5 were investigated and described in relation to the base acene molecules. In both cases, density functional theory calculations were conducted to better understand unexpected optical properties of these molecules, which are like the linear acene series despite the non-linear attachment.

Application of the generalized Euler series transformation for calculation of vibration-rotation energy levels of diatomic molecules

NASA Astrophysics Data System (ADS)

Kruglova, T. V.

2004-01-01

The detailed spectroscope information about highly excited molecules and radicals such us as H+3, H2, HI, H2O, CH2 is needed for a number of applications in the field of laser physics, astrophysics and chemistry. Studies of highly excited molecular vibration-rotation states face several problems connected with slowly convergence or even divergences of perturbation expansions. The physical reason for a perturbation expansion divergence is the large amplitude motion and strong vibration-rotation coupling. In this case one needs to use the special method of series summation. There were a number of papers devoted to this problem: papers 1-10 in the reference list are only example of studies on this topic. The present report is aimed at the application of GET method (Generalized Euler Transformation) to the diatomic molecule. Energy levels of a diatomic molecule is usually represented as Dunham series on rotational J(J+1) and vibrational (V+1/2) quantum numbers (within the perturbation approach). However, perturbation theory is not applicable for highly excited vibration-rotation states because the perturbation expansion in this case becomes divergent. As a consequence one need to use special method for the series summation. The Generalized Euler Transformation (GET) is known to be efficient method for summing of slowly convergent series, it was already used for solving of several quantum problems Refs.13 and 14. In this report the results of Euler transformation of diatomic molecule Dunham series are presented. It is shown that Dunham power series can be represented of functional series that is equivalent to its partial summation. It is also shown that transformed series has the butter convergent properties, than the initial series.

DNA confinement in nanochannels: physics and biological applications

NASA Astrophysics Data System (ADS)

Reisner, Walter; Pedersen, Jonas N.; Austin, Robert H.

2012-10-01

DNA is the central storage molecule of genetic information in the cell, and reading that information is a central problem in biology. While sequencing technology has made enormous advances over the past decade, there is growing interest in platforms that can readout genetic information directly from long single DNA molecules, with the ultimate goal of single-cell, single-genome analysis. Such a capability would obviate the need for ensemble averaging over heterogeneous cellular populations and eliminate uncertainties introduced by cloning and molecular amplification steps (thus enabling direct assessment of the genome in its native state). In this review, we will discuss how the information contained in genomic-length single DNA molecules can be accessed via physical confinement in nanochannels. Due to self-avoidance interactions, DNA molecules will stretch out when confined in nanochannels, creating a linear unscrolling of the genome along the channel for analysis. We will first review the fundamental physics of DNA nanochannel confinement—including the effect of varying ionic strength—and then discuss recent applications of these systems to genomic mapping. Apart from the intense biological interest in extracting linear sequence information from elongated DNA molecules, from a physics view these systems are fascinating as they enable probing of single-molecule conformation in environments with dimensions that intersect key physical length-scales in the 1 nm to 100 µm range.

Small Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways

PubMed Central

Al-Habib, Mey; Yu, Zongdong

2013-01-01

One fundamental issue regarding stem cells for regenerative medicine is the maintenance of stem cell stemness. The purpose of the study was to test whether small molecules can enhance stem cell properties of mesenchymal stem cells (MSCs) derived from human dental pulp (hDPSCs), which have potential for multiple clinical applications. We identified the effects of small molecules (Pluripotin (SC1), 6-bromoindirubin-3-oxime and rapamycin) on the maintenance of hDPSC properties in vitro and the mechanisms involved in exerting the effects. Primary cultures of hDPSCs were exposed to optimal concentrations of these small molecules. Treated hDPSCs were analyzed for their proliferation, the expression levels of pluripotent and MSC markers, differentiation capacities, and intracellular signaling activations. We found that small molecule treatments decreased cell proliferation and increased the expression of STRO-1, NANOG, OCT4, and SOX2, while diminishing cell differentiation into odonto/osteogenic, adipogenic, and neurogenic lineages in vitro. These effects involved Ras-GAP-, ERK1/2-, and mTOR-signaling pathways, which may preserve the cell self-renewal capacity, while suppressing differentiation. We conclude that small molecules appear to enhance the immature state of hDPSCs in culture, which may be used as a strategy for adult stem cell maintenance and extend their capacity for regenerative applications. PMID:23573877

DNA confinement in nanochannels: physics and biological applications.

PubMed

Reisner, Walter; Pedersen, Jonas N; Austin, Robert H

2012-10-01

DNA is the central storage molecule of genetic information in the cell, and reading that information is a central problem in biology. While sequencing technology has made enormous advances over the past decade, there is growing interest in platforms that can readout genetic information directly from long single DNA molecules, with the ultimate goal of single-cell, single-genome analysis. Such a capability would obviate the need for ensemble averaging over heterogeneous cellular populations and eliminate uncertainties introduced by cloning and molecular amplification steps (thus enabling direct assessment of the genome in its native state). In this review, we will discuss how the information contained in genomic-length single DNA molecules can be accessed via physical confinement in nanochannels. Due to self-avoidance interactions, DNA molecules will stretch out when confined in nanochannels, creating a linear unscrolling of the genome along the channel for analysis. We will first review the fundamental physics of DNA nanochannel confinement--including the effect of varying ionic strength--and then discuss recent applications of these systems to genomic mapping. Apart from the intense biological interest in extracting linear sequence information from elongated DNA molecules, from a physics view these systems are fascinating as they enable probing of single-molecule conformation in environments with dimensions that intersect key physical length-scales in the 1 nm to 100 µm range.

Individual Magnetic Molecules on Ultrathin Insulating Surfaces

NASA Astrophysics Data System (ADS)

El Hallak, Fadi; Warner, Ben; Hirjibehedin, Cyrus

2012-02-01

Single molecule magnets have attracted ample interest because of their exciting magnetic and quantum properties. Recent studies have demonstrated that some of these molecules can be evaporated on surfaces without losing their magnetic properties [M. Mannini et al., Nature 468, 417, (2010)]. This remarkable progress enhances the chances of real world applications for these molecules. We present STM imaging and spectroscopy data on iron phthalocyanine molecules deposited on Cu(100) and on a Cu2N ultrathin insulating surface. These molecules have been shown to display a large magnetic anisotropy on another thin insulating surface, oxidized Cu(110) [N. Tsukahara et al., Phys. Rev. Lett. 102, 167203 (2009)]. By using a combination of elastic and inelastic electron tunnelling spectroscopy, we investigate the binding of the molecules to the surface and the impact that the surface has on their electronic and magnetic properties.

Silk-based delivery systems of bioactive molecules

PubMed Central

Numata, Keiji; Kaplan, David L

2010-01-01

Silks are biodegradable, biocompatible, self-assemblying proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes are reviewed. PMID:20298729

Digital Microfluidics Assisted Sealing of Individual Magnetic Particles in Femtoliter-Sized Reaction Wells for Single-Molecule Detection.

PubMed

Decrop, Deborah; Ruiz, Elena Pérez; Kumar, Phalguni Tewari; Tripodi, Lisa; Kokalj, Tadej; Lammertyn, Jeroen

2017-01-01

Digital microfluidics has emerged in the last years as a promising liquid handling technology for a variety of applications. Here, we describe in detail how to build up an electrowetting-on-dielectric-based digital microfluidic chip with unique advantages for performing single-molecule detection. We illustrate how superparamagnetic particles can be printed with very high loading efficiency (over 98 %) and single-particle resolution in the microwell array patterned in the Teflon-AF ® surface of the grounding plate of the chip. Finally, the potential of the device for its application to single-molecule detection is demonstrated by the ultrasensitive detection of the biotinylated enzyme β-Galactosidase captured on streptavidin-coated particles in the described platform.

A Single-Molecule View of Genome Editing Proteins: Biophysical Mechanisms for TALEs and CRISPR/Cas9.

PubMed

Cuculis, Luke; Schroeder, Charles M

2017-06-07

Exciting new advances in genome engineering have unlocked the potential to radically alter the treatment of human disease. In this review, we discuss the application of single-molecule techniques to uncover the mechanisms behind two premier classes of genome editing proteins: transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas). These technologies have facilitated a striking number of gene editing applications in a variety of organisms; however, we are only beginning to understand the molecular mechanisms governing the DNA editing properties of these systems. Here, we discuss the DNA search and recognition process for TALEs and Cas9 that have been revealed by recent single-molecule experiments.

A reagent-assisted method in SERS detection of methyl salicylate

NASA Astrophysics Data System (ADS)

Li, Yali; Li, Qianwen; Wang, Yanan; Oh, Joohee; Jin, Sila; Park, Yeonju; Zhou, Tieli; Zhao, Bing; Ruan, Weidong; Jung, Young Mee

2018-04-01

With the explosive application of methyl salicylate (MS) molecules in food and cosmetics, the further detection of MS molecules becomes particularly important. Here we investigated the detection of MS molecules based on surface-enhanced Raman scattering (SERS) in a novel molecule/assistant/metal system constructed with MS, 4,4‧-(hexafluoroisopropylidene) bis (benzoic acid) and Ag nanoparticles (AgNPs). The minimum detection concentration is 10-4 M. To explore the function of assisted reagent, we also referred another system without assistant molecules. The result demonstrates that SERS signals were not acquired, which proves that the assistant molecules are critical for the capture of MS molecules. Two possible mechanisms of MS/assistant/AgNPs system were speculated through two patterns of hydrogen bonds. The linker molecules acted as the role of the bridge between metallic substrates and target molecules through the molecular recognition. This strategy is very beneficial to the expanding of MS detection techniques and other hydrogen bond based coupling detections with SERS.

ENVIRONMENTALLY FRIENDLIER ALTERNATIVES TO ORGANIC SYNTHESIS USING MICROWAVES

EPA Science Inventory

Microwave irradiation has been used for a variety of organic transformations wherein chemical reactions are expedited because of selective adsorption of microwave (MW) energy by polar molecules, non-polar molecules being inert to the MW dielectric loss. The MW application under s...

Chiroptical properties of an alternatingly functionalized cellotriose bearing two porphyrin groups

USDA-ARS?s Scientific Manuscript database

Alternatingly functionalized cellulose molecules have potential applications in optoelectronics and molecular receptors. For example, cellulose-based solar cells have been proposed. As a prototype for such molecules, the trisaccharide fragment of cellulose was modified by attachment of porphyrin gro...

The Three Forms of Molecular Oxygen.

ERIC Educational Resources Information Center

Laing, Michael

1989-01-01

Finds that a logical application of the simple rules of the molecular orbital bonding theory for diatomic molecules predicted the existence of three spin isomers of the oxygen molecule: one triplet form with two unpaired electrons and two singlet forms with all electrons paired. (MVL)

Algebraic theory of molecules

NASA Technical Reports Server (NTRS)

Iachello, Franco

1995-01-01

An algebraic formulation of quantum mechanics is presented. In this formulation, operators of interest are expanded onto elements of an algebra, G. For bound state problems in nu dimensions the algebra G is taken to be U(nu + 1). Applications to the structure of molecules are presented.

GREENER APPROACH TO EFFICIENT ORGANIC SYNTHESES USING MICROWAVES

EPA Science Inventory

Microwave irradiation has been used for a variety of organic transformations wherein chemical reactions are expedited because of selective adsorption of microwave (MW) energy by polar molecules, non-polar molecules being inert to the MW dielectric loss. The MW application under s...

Remote detection of explosives using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Fulton, Jack

2011-05-01

Stand-off detection of potentially hazardous small molecules at distances that allow the user to be safe has many applications, including explosives and chemical threats. The Naval Surface Warfare Center, Crane Division, with EYZtek, Inc. of Ohio, developed a prototype stand-off, eye-safe Raman spectrometer. With a stand-off distance greater than twenty meters and scanning optics, this system has the potential of addressing particularly difficult challenges in small molecule detection. An overview of the system design and desired application space is presented.

Enhancing the low frequency THz resonances (< 1 THz) of organic molecules via electronegative atom substitution

NASA Astrophysics Data System (ADS)

Dash, Jyotirmayee; Ray, Shaumik; Pesala, Bala

2015-03-01

Terahertz (THz) technology is an active area of research with various applications in non-intrusive imaging and spectroscopy. Very few organic molecules have significant resonances below 1 THz. Understanding the origin of low frequency THz modes in these molecules and their absence in other molecules could be extremely important in design and engineering molecules with low frequency THz resonances. These engineered molecules can be used as THz tags for anti-counterfeiting applications. Studies show that low frequency THz resonances are commonly observed in molecules having higher molecular mass and weak intermolecular hydrogen bonds. In this paper, we have explored the possibility of enhancing the strength of THz resonances below 1 THz through electronegative atom substitution. Adding an electronegative atom helps in achieving higher hydrogen bond strength to enhance the resonances below 1 THz. Here acetanilide has been used as a model system. THz-Time Domain Spectroscopy (THz-TDS) results show that acetanilide has a small peak observed below 1 THz. Acetanilide can be converted to 2-fluoroacetanilide by adding an electronegative atom, fluorine, which doesn't have any prominent peak below 1 THz. However, by optimally choosing the position of the electronegative atom as in 4-fluoroacetanilide, a significant THz resonance at 0.86 THz is observed. The origin of low frequency resonances can be understood by carrying out Density Functional Theory (DFT) simulations of full crystal structure. These studies show that adding an electronegative atom to the organic molecules at an optimized position can result in significantly enhanced resonances below 1 THz.

Docking and scoring in virtual screening for drug discovery: methods and applications.

PubMed

Kitchen, Douglas B; Decornez, Hélène; Furr, John R; Bajorath, Jürgen

2004-11-01

Computational approaches that 'dock' small molecules into the structures of macromolecular targets and 'score' their potential complementarity to binding sites are widely used in hit identification and lead optimization. Indeed, there are now a number of drugs whose development was heavily influenced by or based on structure-based design and screening strategies, such as HIV protease inhibitors. Nevertheless, there remain significant challenges in the application of these approaches, in particular in relation to current scoring schemes. Here, we review key concepts and specific features of small-molecule-protein docking methods, highlight selected applications and discuss recent advances that aim to address the acknowledged limitations of established approaches.

Molecular Imprinting: From Fundamentals to Applications

NASA Astrophysics Data System (ADS)

Komiyama, Makoto; Takeuchi, Toshifumi; Mukawa, Takashi; Asanuma, Hiroyuki

2003-03-01

Molecular imprinting, the polymerization of monomers in the presence of a template molecule which imprints structural information into the resulting polymers, is a scientific field which is rapidly gaining significance for a widening range of applications in biotechnology, biochemistry and pharmaceutical research. The methods and tools needed to distinguish target molecules from others by means of tailor-made receptors are constantly growing in importance and complexity. This book gives a concise and highly up-to-date overview of the remarkable progress made in this field in the last five years. The material is comprehensively presented by the authors, giving a thorough insight into fundamentals and applications for researchers in both industry and academy.

Simulating electric field interactions with polar molecules using spectroscopic databases

NASA Astrophysics Data System (ADS)

Owens, Alec; Zak, Emil J.; Chubb, Katy L.; Yurchenko, Sergei N.; Tennyson, Jonathan; Yachmenev, Andrey

2017-03-01

Ro-vibrational Stark-associated phenomena of small polyatomic molecules are modelled using extensive spectroscopic data generated as part of the ExoMol project. The external field Hamiltonian is built from the computed ro-vibrational line list of the molecule in question. The Hamiltonian we propose is general and suitable for any polar molecule in the presence of an electric field. By exploiting precomputed data, the often prohibitively expensive computations associated with high accuracy simulations of molecule-field interactions are avoided. Applications to strong terahertz field-induced ro-vibrational dynamics of PH3 and NH3, and spontaneous emission data for optoelectrical Sisyphus cooling of H2CO and CH3Cl are discussed.

Molecular matter waves - tools and applications

NASA Astrophysics Data System (ADS)

Juffmann, Thomas; Sclafani, Michele; Knobloch, Christian; Cheshnovsky, Ori; Arndt, Markus

2013-05-01

Fluorescence microscopy allows us to visualize the gradual emergence of a deterministic far-field matter-wave diffraction pattern from stochastically arriving single molecules. We create a slow beam of phthalocyanine molecules via laser desorption from a glass window. The small source size provides the transverse coherence required to observe an interference pattern in the far-field behind an ultra-thin nanomachined grating. There the molecules are deposited onto a quartz window and can be imaged in situ and in real time with single molecule sensitivity. This new setup not only allows for a textbook demonstration of quantum interference, but also enables quantitative explorations of the van der Waals interaction between molecules and material gratings.

Micro injector sample delivery system for charged molecules

DOEpatents

Davidson, James C.; Balch, Joseph W.

1999-11-09

A micro injector sample delivery system for charged molecules. The injector is used for collecting and delivering controlled amounts of charged molecule samples for subsequent analysis. The injector delivery system can be scaled to large numbers (>96) for sample delivery to massively parallel high throughput analysis systems. The essence of the injector system is an electric field controllable loading tip including a section of porous material. By applying the appropriate polarity bias potential to the injector tip, charged molecules will migrate into porous material, and by reversing the polarity bias potential the molecules are ejected or forced away from the tip. The invention has application for uptake of charged biological molecules (e.g. proteins, nucleic acids, polymers, etc.) for delivery to analytical systems, and can be used in automated sample delivery systems.

LASER APPLICATIONS AND OTHER TOPICS IN QUANTUM ELECTRONICS: Efficiency of passage of highly vibrationally excited CF3I molecules in a beam through a cooled converging hollow truncated cone

NASA Astrophysics Data System (ADS)

Makarov, Grigorii N.; Petin, A. N.

2006-09-01

The passage of CF3I molecules excited by high-intensity IR laser radiation to high vibrational states (with energy Ev >= 0.3-1.5 eV) and unexcited molecules in a pulsed beam through a converging truncated hollow metal cone cooled to Ts approx 80-85 K and mounted at an angle to the beam axis is studied. It is found that the excited molecules pass much more readily through the cone than the unexcited (vibrationally cold) molecules. This opens the possibility for studying the processes of energy transfer and redistribution over a cold surface covered by molecular (cluster) layers, and for separating excited and unexcited molecules in a beam.

SOLVENT-FREE APPROACH TO EXPEDITIOUS ORGANIC SYNTHESES USING MICROWAVE IRRADIATION

EPA Science Inventory

Microwave irradiation has been used for a variety of organic transformations wherein chemical reactions are accelerated because of selective adsorption of microwave (MW) energy by polar molecules, non-polar molecules being inert to the MW dielectric loss. The application of MW ir...

BRIEF COMMUNICATION: Calculation of a magnetic field effect on emission spectra of light diatomic molecules for diagnostic application to fusion edge plasmas

NASA Astrophysics Data System (ADS)

Shikama, T.; Fujii, K.; Mizushiri, K.; Hasuo, M.; Kado, S.; Zushi, H.

2009-12-01

A scheme for computation of emission spectra of light diatomic molecules under external magnetic and electric fields is presented. As model species in fusion edge plasmas, the scheme is applied to polarization-resolved emission spectra of H2, CH, C2, BH and BeH molecules. The possibility of performing spatially resolved measurements of these spectra is examined.

Resonant inelastic collisions of electrons with diatomic molecules

NASA Astrophysics Data System (ADS)

Houfek, Karel

2012-05-01

In this contribution we give a review of applications of the nonlocal resonance theory which has been successfully used for treating the nuclear dynamics of low-energy electron collisions with diatomic molecules over several decades. We give examples and brief explanations of various structures observed in the cross sections of vibrational excitation and dissociative electron attachment to diatomic molecules such as threshold peaks, boomerang oscillations below the dissociative attachment threshold, or outer-well resonances.

A-D-A small molecules for solution-processed organic photovoltaic cells.

PubMed

Ni, Wang; Wan, Xiangjian; Li, Miaomiao; Wang, Yunchuang; Chen, Yongsheng

2015-03-25

A-D-A small molecules have drawn more and more attention in solution-processed organic solar cells due to the advantages of a diversity of structures, easy control of energy levels, etc. Recently, a power conversion efficiency of nearly 10% has been achieved through careful material design and device optimization. This feature article reviews recent representative progress in the design and application of A-D-A small molecules in organic photovoltaic cells.

Multicomponent Gas Storage in Organic Cage Molecules

DOE PAGES

Zhang, Fei; He, Yadong; Huang, Jingsong; ...

2017-05-18

Porous liquids are a promising new class of materials featuring nanoscale cavity units dispersed in liquids that are suitable for applications such as gas storage and separation. In this work, we use molecular dynamics simulations to examine the multicomponent gas storage in a porous liquid consisting of crown-ether-substituted cage molecules dissolved in a 15-crown-5 solvent. We compute the storage of three prototypical small molecules including CO 2, CH 4, and N 2 and their binary mixtures in individual cage molecules. For porous liquids in equilibrium with a binary 1:1 gas mixture bath with partial gas pressure of 27.5 bar, amore » cage molecule shows a selectivity of 4.3 and 13.1 for the CO 2/CH 4 and CO 2/N 2 pairs, respectively. We provide a molecular perspective of how gas molecules are stored in the cage molecule and how the storage of one type of gas molecule is affected by other types of gas molecules. Finally, our results clarify the molecular mechanisms behind the selectivity of such cage molecules toward different gases.« less

Cell-Based Selection Expands the Utility of DNA-Encoded Small-Molecule Library Technology to Cell Surface Drug Targets: Identification of Novel Antagonists of the NK3 Tachykinin Receptor.

PubMed

Wu, Zining; Graybill, Todd L; Zeng, Xin; Platchek, Michael; Zhang, Jean; Bodmer, Vera Q; Wisnoski, David D; Deng, Jianghe; Coppo, Frank T; Yao, Gang; Tamburino, Alex; Scavello, Genaro; Franklin, G Joseph; Mataruse, Sibongile; Bedard, Katie L; Ding, Yun; Chai, Jing; Summerfield, Jennifer; Centrella, Paolo A; Messer, Jeffrey A; Pope, Andrew J; Israel, David I

2015-12-14

DNA-encoded small-molecule library technology has recently emerged as a new paradigm for identifying ligands against drug targets. To date, this technology has been used with soluble protein targets that are produced and used in a purified state. Here, we describe a cell-based method for identifying small-molecule ligands from DNA-encoded libraries against integral membrane protein targets. We use this method to identify novel, potent, and specific inhibitors of NK3, a member of the tachykinin family of G-protein coupled receptors (GPCRs). The method is simple and broadly applicable to other GPCRs and integral membrane proteins. We have extended the application of DNA-encoded library technology to membrane-associated targets and demonstrate the feasibility of selecting DNA-tagged, small-molecule ligands from complex combinatorial libraries against targets in a heterogeneous milieu, such as the surface of a cell.

Automatic Compound Annotation from Mass Spectrometry Data Using MAGMa

PubMed Central

Ridder, Lars; van der Hooft, Justin J. J.; Verhoeven, Stefan

2014-01-01

The MAGMa software for automatic annotation of mass spectrometry based fragmentation data was applied to 16 MS/MS datasets of the CASMI 2013 contest. Eight solutions were submitted in category 1 (molecular formula assignments) and twelve in category 2 (molecular structure assignment). The MS/MS peaks of each challenge were matched with in silico generated substructures of candidate molecules from PubChem, resulting in penalty scores that were used for candidate ranking. In 6 of the 12 submitted solutions in category 2, the correct chemical structure obtained the best score, whereas 3 molecules were ranked outside the top 5. All top ranked molecular formulas submitted in category 1 were correct. In addition, we present MAGMa results generated retrospectively for the remaining challenges. Successful application of the MAGMa algorithm required inclusion of the relevant candidate molecules, application of the appropriate mass tolerance and a sufficient degree of in silico fragmentation of the candidate molecules. Furthermore, the effect of the exhaustiveness of the candidate lists and limitations of substructure based scoring are discussed. PMID:26819876

Automatic Compound Annotation from Mass Spectrometry Data Using MAGMa.

PubMed

Ridder, Lars; van der Hooft, Justin J J; Verhoeven, Stefan

2014-01-01

The MAGMa software for automatic annotation of mass spectrometry based fragmentation data was applied to 16 MS/MS datasets of the CASMI 2013 contest. Eight solutions were submitted in category 1 (molecular formula assignments) and twelve in category 2 (molecular structure assignment). The MS/MS peaks of each challenge were matched with in silico generated substructures of candidate molecules from PubChem, resulting in penalty scores that were used for candidate ranking. In 6 of the 12 submitted solutions in category 2, the correct chemical structure obtained the best score, whereas 3 molecules were ranked outside the top 5. All top ranked molecular formulas submitted in category 1 were correct. In addition, we present MAGMa results generated retrospectively for the remaining challenges. Successful application of the MAGMa algorithm required inclusion of the relevant candidate molecules, application of the appropriate mass tolerance and a sufficient degree of in silico fragmentation of the candidate molecules. Furthermore, the effect of the exhaustiveness of the candidate lists and limitations of substructure based scoring are discussed.

Characterization of Low Pressure Cold Plasma in the Cleaning of Contaminated Surfaces

NASA Technical Reports Server (NTRS)

Lanz, Devin Garrett; Hintze, Paul E.

2016-01-01

The characterization of low pressure cold plasma is a broad topic which would benefit many different applications involving such plasma. The characterization described in this paper focuses on cold plasma used as a medium in cleaning and disinfection applications. Optical Emission Spectroscopy (OES) and Mass Spectrometry (MS) are the two analytical methods used in this paper to characterize the plasma. OES analyzes molecules in the plasma phase by displaying the light emitted by the plasma molecules on a graph of wavelength vs. intensity. OES was most useful in identifying species which may interact with other molecules in the plasma, such as atomic oxygen or hydroxide radicals. Extracting useful data from the MS is done by filtering out the peaks generated by expected molecules and looking for peaks caused by foreign ones leaving the plasma chamber. This paper describes the efforts at setting up and testing these methods in order to accurately and effectively characterize the plasma.

Imaging and sizing of single DNA molecules on a mobile phone.

PubMed

Wei, Qingshan; Luo, Wei; Chiang, Samuel; Kappel, Tara; Mejia, Crystal; Tseng, Derek; Chan, Raymond Yan Lok; Yan, Eddie; Qi, Hangfei; Shabbir, Faizan; Ozkan, Haydar; Feng, Steve; Ozcan, Aydogan

2014-12-23

DNA imaging techniques using optical microscopy have found numerous applications in biology, chemistry and physics and are based on relatively expensive, bulky and complicated set-ups that limit their use to advanced laboratory settings. Here we demonstrate imaging and length quantification of single molecule DNA strands using a compact, lightweight and cost-effective fluorescence microscope installed on a mobile phone. In addition to an optomechanical attachment that creates a high contrast dark-field imaging setup using an external lens, thin-film interference filters, a miniature dovetail stage and a laser-diode for oblique-angle excitation, we also created a computational framework and a mobile phone application connected to a server back-end for measurement of the lengths of individual DNA molecules that are labeled and stretched using disposable chips. Using this mobile phone platform, we imaged single DNA molecules of various lengths to demonstrate a sizing accuracy of <1 kilobase-pairs (kbp) for 10 kbp and longer DNA samples imaged over a field-of-view of ∼2 mm2.

Thermally activated delayed fluorescence organic dots for two-photon fluorescence lifetime imaging

NASA Astrophysics Data System (ADS)

He, Tingchao; Ren, Can; Li, Zhuohua; Xiao, Shuyu; Li, Junzi; Lin, Xiaodong; Ye, Chuanxiang; Zhang, Junmin; Guo, Lihong; Hu, Wenbo; Chen, Rui

2018-05-01

Autofluorescence is a major challenge in complex tissue imaging when molecules present in the biological tissue compete with the fluorophore. This issue may be resolved by designing organic molecules with long fluorescence lifetimes. The present work reports the two-photon absorption (TPA) properties of a thermally activated delayed fluorescence (TADF) molecule with carbazole as the electron donor and dicyanobenzene as the electron acceptor (i.e., 4CzIPN). The results indicate that 4CzIPN exhibits a moderate TPA cross-section (˜9 × 10-50 cm4 s photon-1), high fluorescence quantum yield, and a long fluorescence lifetime (˜1.47 μs). 4CzIPN was compactly encapsulated into an amphiphilic copolymer via nanoprecipitation to achieve water-soluble organic dots. Interestingly, 4CzIPN organic dots have been utilized in applications involving two-photon fluorescence lifetime imaging (FLIM). Our work aptly demonstrates that TADF molecules are promising candidates of nonlinear optical probes for developing next-generation multiphoton FLIM applications.

Electron scattering on molecules: search for semi-empirical indications

NASA Astrophysics Data System (ADS)

Fedus, Kamil; Karwasz, Grzegorz P.

2017-06-01

Reliable cross-sections for electron-molecule collisions are urgently needed for numerical modeling of various processes important from technological point of view. Unfortunately, a significant progress in theory and experiment over the last decade is not usually accompanied by the convergence of cross-sections measured at different laboratories and calculated with different methods. Moreover the most advanced contemporary theories involve such large basis sets and complicated equations that they are not easily applied to each specific molecule for which data are needed. For these reasons the search for semi-empirical indications in angular and energy dependencies of scattering cross-section becomes important. In this paper we make a brief review of the applicability of the Born-dipole approximation for elastic, rotational, vibrational and ionization processes that can occur during electron-molecule collisions. We take into account the most recent experimental findings as the reference points. Contribution to the Topical Issue "Atomic and Molecular Data and Their Applications", edited by Gordon W.F. Drake, Jung-Sik Yoon, Daiji Kato, and Grzegorz Karwasz.

Active molecular plasmonics: tuning surface plasmon resonances by exploiting molecular dimensions

NASA Astrophysics Data System (ADS)

Chen, Kai; Leong, Eunice Sok Ping; Rukavina, Michael; Nagao, Tadaaki; Liu, Yan Jun; Zheng, Yuebing

2015-06-01

Molecular plasmonics explores and exploits the molecule-plasmon interactions on metal nanostructures to harness light at the nanoscale for nanophotonic spectroscopy and devices. With the functional molecules and polymers that change their structural, electrical, and/or optical properties in response to external stimuli such as electric fields and light, one can dynamically tune the plasmonic properties for enhanced or new applications, leading to a new research area known as active molecular plasmonics (AMP). Recent progress in molecular design, tailored synthesis, and self-assembly has enabled a variety of scenarios of plasmonic tuning for a broad range of AMP applications. Dimension (i.e., zero-, two-, and threedimensional) of the molecules on metal nanostructures has proved to be an effective indicator for defining the specific scenarios. In this review article, we focus on structuring the field of AMP based on the dimension of molecules and discussing the state of the art of AMP. Our perspective on the upcoming challenges and opportunities in the emerging field of AMP is also included.

AFM visualization at a single-molecule level of denaturated states of proteins on graphite.

PubMed

Barinov, Nikolay A; Prokhorov, Valery V; Dubrovin, Evgeniy V; Klinov, Dmitry V

2016-10-01

Different graphitic materials are either already used or believed to be advantageous in biomedical and biotechnological applications, e.g., as biomaterials or substrates for sensors. Most of these applications or associated important issues, such as biocompatibility, address the problem of adsorption of protein molecules and, in particular the conformational state of the adsorbed protein molecule on graphite. High-resolution AFM demonstrates highly oriented pyrolytic graphite (HOPG) induced denaturation of four proteins of blood plasma, such as ferritin, fibrinogen, human serum albumin (HSA) and immunoglobulin G (IgG), at a single molecule level. Protein denaturation is accompanied by the decrease of the heights of protein globules and spreading of the denatured protein fraction on the surface. In contrast, the modification of HOPG with the amphiphilic oligoglycine-hydrocarbon derivative monolayer preserves the native-like conformation and provides even more mild conditions for the protein adsorption than typically used mica. Protein unfolding on HOPG may have universal character for "soft" globular proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical structure-nonlinear optical property relationships for a series of two-photon absorbing fluorene molecules

NASA Astrophysics Data System (ADS)

Hales, Joel Mccajah

This dissertation reports on the investigation of two-photon absorption (2PA) in a series of fluorenyl molecules. Several current and emerging technologies exploit this optical nonlinearity including two-photon fluorescence imaging, three-dimensional microfabrication, site-specific photodynamic cancer therapy and biological caging studies. The two key features of this nonlinearity which make it an ideal candidate for the above applications are its quadratic dependence on the incident irradiance and the improved penetration into absorbing media that it affords. As a consequence of the burgeoning field which exploits 2PA, it is a goal to find materials that exhibit strong two-photon absorbing capabilities. Organic materials are promising candidates for 2PA applications because their material properties can be tailored through molecular engineering thereby facilitating optimization of their nonlinear optical properties. Fluorene derivatives are particularly interesting since they possess high photochemical stability for organic molecules and are generally strongly fluorescent. By systematically altering the structural properties in a series of fluorenyl molecules, we have determined how these changes affect their two-photon absorbing capabilities. This was accomplished through characterization of both the strength and location of their 2PA spectra. In order to ensure the validity of these results, three separate nonlinear characterization techniques were employed: two-photon fluorescence spectroscopy, white-light continuum pump-probe spectroscopy, and the Z-scan technique. In addition, full linear spectroscopic characterization was performed on these molecules along with supplementary quantum chemical calculations to obtain certain molecular properties that might impact the nonlinearity. Different designs in chemical architecture allowed investigation of the effects of symmetry, solvism, donor-acceptor strengths, conjugation length, and multi-branched geometries on the two-photon absorbing properties of these molecules. In addition, the means to enhance 2PA via intermediate state resonances was investigated. To provide plausible explanations for the experimentally observed trends, a conceptually simple three level model was employed. The subsequent correlations found between chemical structure and the linear and nonlinear optical properties of these molecules provided definitive conclusions on how to properly optimize their two-photon absorbing capabilities. The resulting large nonlinearities found in these molecules have already shown promise in a variety of the aforementioned applications.

A RNA nanotechnology platform for a simultaneous two-in-one siRNA delivery and its application in synergistic RNAi therapy

PubMed Central

Jang, Mihue; Han, Hee Dong; Ahn, Hyung Jun

2016-01-01

Incorporating multiple copies of two RNAi molecules into a single nanostructure in a precisely controlled manner can provide an efficient delivery tool to regulate multiple gene pathways in the relation of mutual dependence. Here, we show a RNA nanotechnology platform for a two-in-one RNAi delivery system to contain polymeric two RNAi molecules within the same RNA nanoparticles, without the aid of polyelectrolyte condensation reagents. As our RNA nanoparticles lead to the simultaneous silencing of two targeted mRNAs, of which biological functions are highly interdependent, combination therapy for multi-drug resistance cancer cells, which was studied as a specific application of our two-in-one RNAi delivery system, demonstrates the efficient synergistic effects for cancer therapy. Therefore, this RNA nanoparticles approach has an efficient tool for a simultaneous co-delivery of RNAi molecules in the RNAi-based biomedical applications, and our current studies present an efficient strategy to overcome multi-drug resistance caused by malfunction of genes in chemotherapy. PMID:27562435

In Situ Oxidation Synthesis of p-Type Composite with Narrow-Bandgap Small Organic Molecule Coating on Single-Walled Carbon Nanotube: Flexible Film and Thermoelectric Performance.

PubMed

Gao, Caiyan; Chen, Guangming

2018-03-01

Although composites of organic polymers or n-type small molecule/carbon nanotube (CNT) have achieved significant advances in thermoelectric (TE) applications, p-type TE composites of small organic molecules as thick surface coating layers on the surfaces of inorganic nanoparticles still remain a great challenge. Taking advantage of in situ oxidation reaction of thieno[3,4-b]pyrazine (TP) into TP di-N-oxide (TPNO) on single-walled CNT (SWCNT) surface, a novel synthesis strategy is proposed to achieve flexible films of TE composites with narrow-bandgap (1.19 eV) small molecule coating on SWCNT surface. The TE performance can be effectively enhanced and conveniently tuned by poly(sodium-p-styrenesulfonate) content, TPNO/SWCNT mass ratio, and posttreatment by various polar solvents. The maximum of the composite power factor at room temperature is 29.4 ± 1.0 µW m -1 K -2 . The work presents a way to achieve flexible films of p-type small organic molecule/inorganic composites with clear surface coating morphology for TE application. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Toxicity evaluation of convection-enhanced delivery of small-molecule kinase inhibitors in naïve mouse brainstem.

PubMed

Zhou, Zhiping; Ho, Sharon L; Singh, Ranjodh; Pisapia, David J; Souweidane, Mark M

2015-04-01

Diffuse intrinsic pontine gliomas (DIPGs) are inoperable and lethal high-grade gliomas lacking definitive therapy. Platelet-derived growth factor receptor (PDGFR) and its downstream signaling molecules are the most commonly overexpressed oncogenes in DIPG. This study tested the effective concentration of PDGFR pathway inhibitors in cell culture and then toxicity of these small-molecule kinase inhibitors delivered to the mouse brainstem via convection-enhanced delivery (CED) for potential clinical application. Effective concentrations of small-molecule kinase inhibitors were first established in cell culture from a mouse brainstem glioma model. Sixteen mice underwent CED, a local drug delivery technique, of saline or of single and multidrug combinations of dasatinib (2 M), everolimus (20 M), and perifosine (0.63 mM) in the pons. Animals were kept alive for 3 days following the completion of infusion. No animals displayed any immediate or delayed neurological deficits postoperatively. Histological analysis revealed edema, microgliosis, acute inflammation, and/or axonal injury in the experimental animals consistent with mild acute drug toxicity. Brainstem CED of small-molecule kinase inhibitors in the mouse did not cause serious acute toxicities. Future studies will be necessary to evaluate longer-term safety to prepare for potential clinical application.

DFT Study of PH3 Physisorption and Chemisorptions on Boron Nitride Nanotubes

NASA Astrophysics Data System (ADS)

Rakhshi, Mahdi; Mohsennia, Mohsen; Rasa, Hossein

2018-03-01

The adsorption of PH3 molecules on the NiB,N-doped(4,4) and (5,5) BNNTS surfaces has been investigated using density functional theory (DFT). The adsorption energies, geometric and electronic structures of the adsorbed systems were studied to judge the possible application of NiB,N-doped BNNTS in PH3 monitoring systems. Our calculated results showed that NiB,N-doped BNNTS had much higher adsorption energy and shorter binding distances than pure BNNTS owning to chemisorptions of the PH3 molecule. The obtained density of states (DOS) and frontier orbitals demonstrated that the orbital hybridization was obvious between the PH3 molecule and NiB,N-doped BNNTS. However, due to weak physisorption according to the total electron density maps, there was no evidence for hybridization between PH3 molecule and pure BNNTS. It was shown that after doping of Ni atom, the primary symmetry of BNNTS decreased which enhanced the chemical activity of BNNTS towards PH3 molecules. According to the obtained results, we highlight the high potential application of NiB,N-doped BNNTS in the design and fabrication of PH3 sensing devices.

Structure-based analysis reveals hydration changes induced by arginine hydrochloride.

PubMed

Nakakido, Makoto; Tanaka, Yoshikazu; Mitsuhori, Mariko; Kudou, Motonori; Ejima, Daisuke; Arakawa, Tsutomu; Tsumoto, Kouhei

2008-10-01

Arginine hydrochloride has been used to suppress protein aggregation during refolding and in various other applications. We investigated the structure of hen egg-white lysozyme (HEL) and solvent molecules in arginine hydrochloride solution by X-ray crystallography. Neither the backbone nor side-chain structure of HEL was altered by the presence of arginine hydrochloride. In addition, no stably bound arginine molecules were observed. The number of hydration water molecules, however, changed with the arginine hydrochloride concentration. We suggest that arginine hydrochloride suppresses protein aggregation by altering the hydration structure and the transient binding of arginine molecules that could not be observed.

Silk-based delivery systems of bioactive molecules.

PubMed

Numata, Keiji; Kaplan, David L

2010-12-30

Silks are biodegradable, biocompatible, self-assembling proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes is reviewed. Copyright © 2010 Elsevier B.V. All rights reserved.

In singulo biochemistry: when less is more.

PubMed

Bustamante, Carlos

2008-01-01

It has been over one-and-a-half decades since methods of single-molecule detection and manipulation were first introduced in biochemical research. Since then, the application of these methods to an expanding variety of problems has grown at a vertiginous pace. While initially many of these experiments led more to confirmatory results than to new discoveries, today single-molecule methods are often the methods of choice to establish new mechanism-based results in biochemical research. Throughout this process, improvements in the sensitivity, versatility, and both spatial and temporal resolution of these techniques has occurred hand in hand with their applications. We discuss here some of the advantages of single-molecule methods over their bulk counterparts and argue that these advantages should help establish them as essential tools in the technical arsenal of the modern biochemist.

Using naturally occurring polysaccharides to align molecules with nonlinear optical activity

NASA Technical Reports Server (NTRS)

Prasthofer, Thomas

1996-01-01

The Biophysics and Advanced Materials Branch of the Microgravity Science and Applications Division at Marshall Space Flight Center has been investigating polymers with the potential for nonlinear optical (NLO) applications for a number of years. Some of the potential applications for NLO materials include optical communications, computing, and switching. To this point the branch's research has involved polydiacetylenes, phthalocyanins, and other synthetic polymers which have inherent NLO properties. The aim of the present research is to investigate the possibility of using naturally occurring polymers such as polysaccharides or proteins to trap and align small organic molecules with useful NLO properties. Ordering molecules with NLO properties enhances 3rd order nonlinear effects and is required for 2nd order nonlinear effects. Potential advantages of such a system are the flexibility to use different small molecules with varying chemical and optical properties, the stability and cost of the polymers, and the ability to form thin, optically transparent films. Since the quality of any polymer films depends on optimizing ordering and minimizing defects, this work is particularly well suited for microgravity experiments. Polysaccharide and protein polymers form microscopic crystallites which must align to form ordered arrays. The ordered association of crystallites is disrupted by gravity effects and NASA research on protein crystal growth has demonstrated that low gravity conditions can improve crystal quality.

Molecules in Living Systems: A Biochemistry Module. Teacher's Guide.

ERIC Educational Resources Information Center

Martin, David; Sampugna, Joseph; Sandoval, Amado

This teacher's guide provides information and resources for helping to familiarize students with chemistry and its everyday applications around the world using inquiry and investigations. Contents include: (1) "Introducing Molecules in Living Systems"; (2) "Considering Life Processes"; (3) "Understanding the Structure of Biomolecules"; (4)…

Application of Organometallic Catalysis to the Commercial Production of L-DOPA.

ERIC Educational Resources Information Center

Knowles, W. S.

1986-01-01

Shows how asymmetric organometallic catalysts can be used to make complex organic molecules with extremely high enantioselectivity. The molecule considered is l-3, 4-dihydroxyphenylalanine (L-DOPA), an amino acid which was found to be effective in the treatment of Parkinson's disease. (JN)

Conformal Electroplating of Azobenzene-Based Solar Thermal Fuels onto Large-Area and Fiber Geometries.

PubMed

Zhitomirsky, David; Grossman, Jeffrey C

2016-10-05

There is tremendous growth in fields where small functional molecules and colloidal nanomaterials are integrated into thin films for solid-state device applications. Many of these materials are synthesized in solution and there often exists a significant barrier to transition them into the solid state in an efficient manner. Here, we develop a methodology employing an electrodepositable copolymer consisting of small functional molecules for applications in solar energy harvesting and storage. We employ azobenzene solar thermal fuel polymers and functionalize them to enable deposition from low concentration solutions in methanol, resulting in uniform and large-area thin films. This approach enables conformal deposition on a variety of conducting substrates that can be either flat or structured depending on the application. Our approach further enables control over film growth via electrodepsition conditions and results in highly uniform films of hundreds of nanometers to microns in thickness. We demonstrate that this method enables superior retention of solar thermal fuel properties, with energy densities of ∼90 J/g, chargeability in the solid state, and exceptional materials utilization compared to other solid-state processing approaches. This novel approach is applicable to systems such as photon upconversion, photovoltaics, photosensing, light emission, and beyond, where small functional molecules enable solid-state applications.

The Molecule Pages database

PubMed Central

Saunders, Brian; Lyon, Stephen; Day, Matthew; Riley, Brenda; Chenette, Emily; Subramaniam, Shankar

2008-01-01

The UCSD-Nature Signaling Gateway Molecule Pages (http://www.signaling-gateway.org/molecule) provides essential information on more than 3800 mammalian proteins involved in cellular signaling. The Molecule Pages contain expert-authored and peer-reviewed information based on the published literature, complemented by regularly updated information derived from public data source references and sequence analysis. The expert-authored data includes both a full-text review about the molecule, with citations, and highly structured data for bioinformatics interrogation, including information on protein interactions and states, transitions between states and protein function. The expert-authored pages are anonymously peer reviewed by the Nature Publishing Group. The Molecule Pages data is present in an object-relational database format and is freely accessible to the authors, the reviewers and the public from a web browser that serves as a presentation layer. The Molecule Pages are supported by several applications that along with the database and the interfaces form a multi-tier architecture. The Molecule Pages and the Signaling Gateway are routinely accessed by a very large research community. PMID:17965093

The Molecule Pages database.

PubMed

Saunders, Brian; Lyon, Stephen; Day, Matthew; Riley, Brenda; Chenette, Emily; Subramaniam, Shankar; Vadivelu, Ilango

2008-01-01

The UCSD-Nature Signaling Gateway Molecule Pages (http://www.signaling-gateway.org/molecule) provides essential information on more than 3800 mammalian proteins involved in cellular signaling. The Molecule Pages contain expert-authored and peer-reviewed information based on the published literature, complemented by regularly updated information derived from public data source references and sequence analysis. The expert-authored data includes both a full-text review about the molecule, with citations, and highly structured data for bioinformatics interrogation, including information on protein interactions and states, transitions between states and protein function. The expert-authored pages are anonymously peer reviewed by the Nature Publishing Group. The Molecule Pages data is present in an object-relational database format and is freely accessible to the authors, the reviewers and the public from a web browser that serves as a presentation layer. The Molecule Pages are supported by several applications that along with the database and the interfaces form a multi-tier architecture. The Molecule Pages and the Signaling Gateway are routinely accessed by a very large research community.

In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

PubMed

Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

2013-11-26

Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

Biological Nanopores: Confined Spaces for Electrochemical Single-Molecule Analysis.

PubMed

Cao, Chan; Long, Yi-Tao

2018-02-20

Nanopore sensing is developing into a powerful single-molecule approach to investigate the features of biomolecules that are not accessible by studying ensemble systems. When a target molecule is transported through a nanopore, the ions occupying the pore are excluded, resulting in an electrical signal from the intermittent ionic blockade event. By statistical analysis of the amplitudes, duration, frequencies, and shapes of the blockade events, many properties of the target molecule can be obtained in real time at the single-molecule level, including its size, conformation, structure, charge, geometry, and interactions with other molecules. With the development of the use of α-hemolysin to characterize individual polynucleotides, nanopore technology has attracted a wide range of research interest in the fields of biology, physics, chemistry, and nanoscience. As a powerful single-molecule analytical method, nanopore technology has been applied for the detection of various biomolecules, including oligonucleotides, peptides, oligosaccharides, organic molecules, and disease-related proteins. In this Account, we highlight recent developments of biological nanopores in DNA-based sensing and in studying the conformational structures of DNA and RNA. Furthermore, we introduce the application of biological nanopores to investigate the conformations of peptides affected by charge, length, and dipole moment and to study disease-related proteins' structures and aggregation transitions influenced by an inhibitor, a promoter, or an applied voltage. To improve the sensing ability of biological nanopores and further extend their application to a wider range of molecular sensing, we focus on exploring novel biological nanopores, such as aerolysin and Stable Protein 1. Aerolysin exhibits an especially high sensitivity for the detection of single oligonucleotides both in current separation and duration. Finally, to facilitate the use of nanopore measurements and statistical analysis, we develop an integrated current measurement system and an accurate data processing method for nanopore sensing. The unique geometric structure of a biological nanopore offers a distinct advantage as a nanosensor for single-molecule sensing. The construction of the pore entrance is responsible for capturing the target molecule, while the lumen region determines the translocation process of the single molecule. Since the capture of the target molecule is predominantly diffusion-limited, it is expected that the capture ability of the nanopore toward the target analyte could be effectively enhanced by site-directed mutations of key amino acids with desirable groups. Additionally, changing the side chains inside the wall of the biological nanopore could optimize the geometry of the pore and realize an optimal interaction between the single-molecule interface and the analyte. These improvements would allow for high spatial and current resolution of nanopore sensors, which would ensure the possibility of dynamic study of single biomolecules, including their metastable conformations, charge distributions, and interactions. In the future, data analysis with powerful algorithms will make it possible to automatically and statistically extract detailed information while an analyte translocates through the pore. We conclude that these improvements could have tremendous potential applications for nanopore sensing in the near future.

Analyzing Single-Molecule Time Series via Nonparametric Bayesian Inference

PubMed Central

Hines, Keegan E.; Bankston, John R.; Aldrich, Richard W.

2015-01-01

The ability to measure the properties of proteins at the single-molecule level offers an unparalleled glimpse into biological systems at the molecular scale. The interpretation of single-molecule time series has often been rooted in statistical mechanics and the theory of Markov processes. While existing analysis methods have been useful, they are not without significant limitations including problems of model selection and parameter nonidentifiability. To address these challenges, we introduce the use of nonparametric Bayesian inference for the analysis of single-molecule time series. These methods provide a flexible way to extract structure from data instead of assuming models beforehand. We demonstrate these methods with applications to several diverse settings in single-molecule biophysics. This approach provides a well-constrained and rigorously grounded method for determining the number of biophysical states underlying single-molecule data. PMID:25650922

Superresolution Imaging using Single-Molecule Localization

PubMed Central

Patterson, George; Davidson, Michael; Manley, Suliana; Lippincott-Schwartz, Jennifer

2013-01-01

Superresolution imaging is a rapidly emerging new field of microscopy that dramatically improves the spatial resolution of light microscopy by over an order of magnitude (∼10–20-nm resolution), allowing biological processes to be described at the molecular scale. Here, we discuss a form of superresolution microscopy based on the controlled activation and sampling of sparse subsets of photoconvertible fluorescent molecules. In this single-molecule based imaging approach, a wide variety of probes have proved valuable, ranging from genetically encodable photoactivatable fluorescent proteins to photoswitchable cyanine dyes. These have been used in diverse applications of superresolution imaging: from three-dimensional, multicolor molecule localization to tracking of nanometric structures and molecules in living cells. Single-molecule-based superresolution imaging thus offers exciting possibilities for obtaining molecular-scale information on biological events occurring at variable timescales. PMID:20055680

Total internal partition sums for 166 isotopologues of 51 molecules important in planetary atmospheres: Application to HITRAN2016 and beyond

NASA Astrophysics Data System (ADS)

Gamache, Robert R.; Roller, Christopher; Lopes, Eldon; Gordon, Iouli E.; Rothman, Laurence S.; Polyansky, Oleg L.; Zobov, Nikolai F.; Kyuberis, Aleksandra A.; Tennyson, Jonathan; Yurchenko, Sergei N.; Császár, Attila G.; Furtenbacher, Tibor; Huang, Xinchuan; Schwenke, David W.; Lee, Timothy J.; Drouin, Brian J.; Tashkun, Sergei A.; Perevalov, Valery I.; Kochanov, Roman V.

2017-12-01

Total internal partition sums (TIPS) are reported for 166 isotopologues of 51 molecules important in planetary atmospheres. Molecules 1 to 50 are taken from the HITRAN2016 list, and, in some cases, additional isotopologues are considered for some of the molecules. Molecules 51-53 are C3H4, CH3, and CS2, respectively. TIPS are not reported for the O atom and CF4; thus, while there are 53 species in the list, data are reported for 51 molecules. The TIPS are determined by various methods from 1 K to a Tmax that ensures the TIPS reported have converged. These data are provided with HITRAN2016 and a new version of the TIPS code is available in both FORTRAN and python languages.

PHYSICAL MODEL FOR RECOGNITION TUNNELING

PubMed Central

Krstić, Predrag; Ashcroft, Brian; Lindsay, Stuart

2015-01-01

Recognition tunneling (RT) identifies target molecules trapped between tunneling electrodes functionalized with recognition molecules that serve as specific chemical linkages between the metal electrodes and the trapped target molecule. Possible applications include single molecule DNA and protein sequencing. This paper addresses several fundamental aspects of RT by multiscale theory, applying both all-atom and coarse-grained DNA models: (1) We show that the magnitude of the observed currents are consistent with the results of non-equilibrium Green's function calculations carried out on a solvated all-atom model. (2) Brownian fluctuations in hydrogen bond-lengths lead to current spikes that are similar to what is observed experimentally. (3) The frequency characteristics of these fluctuations can be used to identify the trapped molecules with a machine-learning algorithm, giving a theoretical underpinning to this new method of identifying single molecule signals. PMID:25650375

Expanding Biosensing Abilities through Computer-Aided Design of Metabolic Pathways.

PubMed

Libis, Vincent; Delépine, Baudoin; Faulon, Jean-Loup

2016-10-21

Detection of chemical signals is critical for cells in nature as well as in synthetic biology, where they serve as inputs for designer circuits. Important progress has been made in the design of signal processing circuits triggering complex biological behaviors, but the range of small molecules recognized by sensors as inputs is limited. The ability to detect new molecules will increase the number of synthetic biology applications, but direct engineering of tailor-made sensors takes time. Here we describe a way to immediately expand the range of biologically detectable molecules by systematically designing metabolic pathways that transform nondetectable molecules into molecules for which sensors already exist. We leveraged computer-aided design to predict such sensing-enabling metabolic pathways, and we built several new whole-cell biosensors for molecules such as cocaine, parathion, hippuric acid, and nitroglycerin.

p38 MAPK inhibitors: a patent review (2012 - 2013).

PubMed

Bühler, Stefanie; Laufer, Stefan A

2014-05-01

The p38 MAPK is a ubiquitous target in the research-based pharmaceutical industry. It plays a decisive role in the regulation of the production of proinflammatory cytokines. Since novel biological therapies have revolutionized the treatment of chronic inflammatory diseases, an intensive global search is underway for small molecules for the same application. Herein, the patents and the corresponding publications of international companies, which focus on the development and identification of a new generation of small-molecule p38 inhibitors, are summarized. The most promising approach is the development of linear binders, which induce a glycine flip at Gly110 of the kinase hinge region by a carbonyl oxygen atom of the respective ligand. The major focus of the patent works was the application of molecules in new indications. Previous applications were in the treatment of rheumatoid arthritis; currently, there are several new applications, including pulmonary diseases, cancer and Alzheimer's disease. Targeting p38 upstream kinases and downstream effectors has also proved to be a very promising step in the development of more effective inhibitors. A further trend is drug combination, applied to a wide range of indications, such as chronic obstructive pulmonary disease and cancer.

Quantitative analyses of bifunctional molecules.

PubMed

Braun, Patrick D; Wandless, Thomas J

2004-05-11

Small molecules can be discovered or engineered to bind tightly to biologically relevant proteins, and these molecules have proven to be powerful tools for both basic research and therapeutic applications. In many cases, detailed biophysical analyses of the intermolecular binding events are essential for improving the activity of the small molecules. These interactions can often be characterized as straightforward bimolecular binding events, and a variety of experimental and analytical techniques have been developed and refined to facilitate these analyses. Several investigators have recently synthesized heterodimeric molecules that are designed to bind simultaneously with two different proteins to form ternary complexes. These heterodimeric molecules often display compelling biological activity; however, they are difficult to characterize. The bimolecular interaction between one protein and the heterodimeric ligand (primary dissociation constant) can be determined by a number of methods. However, the interaction between that protein-ligand complex and the second protein (secondary dissociation constant) is more difficult to measure due to the noncovalent nature of the original protein-ligand complex. Consequently, these heterodimeric compounds are often characterized in terms of their activity, which is an experimentally dependent metric. We have developed a general quantitative mathematical model that can be used to measure both the primary (protein + ligand) and secondary (protein-ligand + protein) dissociation constants for heterodimeric small molecules. These values are largely independent of the experimental technique used and furthermore provide a direct measure of the thermodynamic stability of the ternary complexes that are formed. Fluorescence polarization and this model were used to characterize the heterodimeric molecule, SLFpYEEI, which binds to both FKBP12 and the Fyn SH2 domain, demonstrating that the model is useful for both predictive as well as ex post facto analytical applications.

Mass Spectrometry of Large, Fragile, and Involatile Molecules.

ERIC Educational Resources Information Center

Busch, Kenneth L.; Cooks, R. Graham

1982-01-01

Desorption ionization (DI) is used to obtain mass spectra of molecules whose vaporization by heating may lead to thermal degradation. Discusses DI techniques, characteristics of DI mass spectra, ion production, current applications of DI in mass spectroscopy, developments in DI, and prospects for future evolution of new DI techniques. (Author/JN)

Innovative application of metal-organic frameworks for encapsulation and controlled release of allyl isothiocyanate

USDA-ARS?s Scientific Manuscript database

This research investigated the technical feasibility of metal-organic frameworks (MOFs) as novel delivery systems for encapsulation and controlled release of volatile allyl isothiocyanate (AITC) molecules. We hypothesized that water vapor molecules could act as an external stimulus to trigger the re...

Research Update: Molecular electronics: The single-molecule switch and transistor

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

Sotthewes, Kai; Heimbuch, René, E-mail: r.heimbuch@utwente.nl; Kumar, Avijit

2014-01-01

In order to design and realize single-molecule devices it is essential to have a good understanding of the properties of an individual molecule. For electronic applications, the most important property of a molecule is its conductance. Here we show how a single octanethiol molecule can be connected to macroscopic leads and how the transport properties of the molecule can be measured. Based on this knowledge we have realized two single-molecule devices: a molecular switch and a molecular transistor. The switch can be opened and closed at will by carefully adjusting the separation between the electrical contacts and the voltage dropmore » across the contacts. This single-molecular switch operates in a broad temperature range from cryogenic temperatures all the way up to room temperature. Via mechanical gating, i.e., compressing or stretching of the octanethiol molecule, by varying the contact's interspace, we are able to systematically adjust the conductance of the electrode-octanethiol-electrode junction. This two-terminal single-molecule transistor is very robust, but the amplification factor is rather limited.« less

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

Zhang, Fei; He, Yadong; Huang, Jingsong

Porous liquids are a promising new class of materials featuring nanoscale cavity units dispersed in liquids that are suitable for applications such as gas storage and separation. In this work, we use molecular dynamics simulations to examine the multicomponent gas storage in a porous liquid consisting of crown-ether-substituted cage molecules dissolved in a 15-crown-5 solvent. We compute the storage of three prototypical small molecules including CO 2, CH 4, and N 2 and their binary mixtures in individual cage molecules. For porous liquids in equilibrium with a binary 1:1 gas mixture bath with partial gas pressure of 27.5 bar, amore » cage molecule shows a selectivity of 4.3 and 13.1 for the CO 2/CH 4 and CO 2/N 2 pairs, respectively. We provide a molecular perspective of how gas molecules are stored in the cage molecule and how the storage of one type of gas molecule is affected by other types of gas molecules. Finally, our results clarify the molecular mechanisms behind the selectivity of such cage molecules toward different gases.« less

Contactless experiments on individual DNA molecules show no evidence for molecular wire behavior.

PubMed

Gómez-Navarro, C; Moreno-Herrero, F; de Pablo, P J; Colchero, J; Gómez-Herrero, J; Baró, A M

2002-06-25

A fundamental requirement for a molecule to be considered a molecular wire (MW) is the ability to transport electrical charge with a reasonably low resistance. We have carried out two experiments that measure first, the charge transfer from an electrode to the molecule, and second, the dielectric response of the MW. The latter experiment requires no contacts to either end of the molecule. From our experiments we conclude that adsorbed individual DNA molecules have a resistivity similar to mica, glass, and silicon oxide substrates. Therefore adsorbed DNA is not a conductor, and it should not be considered as a viable candidate for MW applications. Parallel studies on other nanowires, including single-walled carbon nanotubes, showed conductivity as expected.

Monte-Carlo simulations of a coarse-grained model for α-oligothiophenes

NASA Astrophysics Data System (ADS)

Almutairi, Amani; Luettmer-Strathmann, Jutta

The interfacial layer of an organic semiconductor in contact with a metal electrode has important effects on the performance of thin-film devices. However, the structure of this layer is not easy to model. Oligothiophenes are small, π-conjugated molecules with applications in organic electronics that also serve as small-molecule models for polythiophenes. α-hexithiophene (6T) is a six-ring molecule, whose adsorption on noble metal surfaces has been studied extensively (see, e.g., Ref.). In this work, we develop a coarse-grained model for α-oligothiophenes. We describe the molecules as linear chains of bonded, discotic particles with Gay-Berne potential interactions between non-bonded ellipsoids. We perform Monte Carlo simulations to study the structure of isolated and adsorbed molecules

Adsorption of methanol molecule on graphene: Experimental results and first-principles calculations

NASA Astrophysics Data System (ADS)

Zhao, X. W.; Tian, Y. L.; Yue, W. W.; Chen, M. N.; Hu, G. C.; Ren, J. F.; Yuan, X. B.

2018-04-01

Adsorption properties of methanol molecule on graphene surface are studied both theoretically and experimentally. The adsorption geometrical structures, adsorption energies, band structures, density of states and the effective masses are obtained by means of first-principles calculations. It is found that the electronic characteristics and conductivity of graphene are sensitive to the methanol molecule adsorption. After adsorption of methanol molecule, bandgap appears. With the increasing of the adsorption distance, the bandgap, adsorption energy and effective mass of the adsorption system decreased, hence the resistivity of the system decreases gradually, these results are consistent with the experimental results. All these calculations and experiments indicate that the graphene-based sensors have a wide range of applications in detecting particular molecules.

Fluorescent aromatic sensors and their methods of use

NASA Technical Reports Server (NTRS)

Meador, Michael A. (Inventor); Tyson, Daniel S. (Inventor); Ilan, Ulvi F. (Inventor)

2012-01-01

Aromatic molecules that can be used as sensors are described. The aromatic sensors include a polycyclic aromatic hydrocarbon core with a five-membered imide rings fused to the core and at least two pendant aryl groups. The aromatic sensor molecules can detect target analytes or molecular strain as a result of changes in their fluorescence, in many cases with on-off behavior. Aromatic molecules that fluoresce at various frequencies can be prepared by altering the structure of the aromatic core or the substituents attached to it. The aromatic molecules can be used as sensors for various applications such as, for example, the detection of dangerous chemicals, biomedical diagnosis, and the detection of damage or strain in composite materials. Methods of preparing aromatic sensor molecules are also described.

Meeting report: SMART timing--principles of single molecule techniques course at the University of Michigan 2014.

PubMed

Bartke, Rebecca M; Cameron, Elizabeth L; Cristie-David, Ajitha S; Custer, Thomas C; Denies, Maxwell S; Daher, May; Dhakal, Soma; Ghosh, Soumi; Heinicke, Laurie A; Hoff, J Damon; Hou, Qian; Kahlscheuer, Matthew L; Karslake, Joshua; Krieger, Adam G; Li, Jieming; Li, Xiang; Lund, Paul E; Vo, Nguyen N; Park, Jun; Pitchiaya, Sethuramasundaram; Rai, Victoria; Smith, David J; Suddala, Krishna C; Wang, Jiarui; Widom, Julia R; Walter, Nils G

2015-05-01

Four days after the announcement of the 2014 Nobel Prize in Chemistry for "the development of super-resolved fluorescence microscopy" based on single molecule detection, the Single Molecule Analysis in Real-Time (SMART) Center at the University of Michigan hosted a "Principles of Single Molecule Techniques 2014" course. Through a combination of plenary lectures and an Open House at the SMART Center, the course took a snapshot of a technology with an especially broad and rapidly expanding range of applications in the biomedical and materials sciences. Highlighting the continued rapid emergence of technical and scientific advances, the course underscored just how brightly the future of the single molecule field shines. © 2014 Wiley Periodicals, Inc.

Application of chiral critical clusters to assymetric synthesis

DOEpatents

Ferrieri, Richard A.

2002-01-01

Disclosed is a composition, a method of making and a method of using critical clusters for asymmetric synthesis using substantially optically-pure chiral solvent molecules in a supercritical fluid. The solvent molecules are capable of forming a multipoint hydrogen bonded solvate as they encage at least one solute molecule. The encaged solute molecule is capable of reacting to form an optically active chiral center. In another aspect, there is disclosed a method of directing the position of bonding between a solute molecule and a ligand involving encaging the solute molecule and the ligand with polar solvent molecules in a supercritical fluid under conditions of temperature and pressure sufficient to change electric charge distribution in the solute molecule. In yet another aspect, disclosed is a method of making pharmaceutical compounds involving encaging a solute molecule, which is capable of forming a chiral center, and a ligand with polar solvent molecules in a supercritical fluid under conditions of temperature and pressure sufficient to change electric charge distribution of the solute molecule. The solute molecule and ligand are then reacted whereby the ligand bonds to the solute molecule forming a chiral center. Also disclosed is a method for racemic resolution using critical clusters involving encaging racemic mixtures of solute molecules with substantially optically-pure chiral solvent molecules in a supercritical fluid under conditions of temperature and pressure sufficient to form critical clusters. The solvent molecules are capable of multipoint hydrogen bonding with the solute molecules. The encaged solute molecules are then nonenzymatically reacted to enhance the optical purity of the solute molecules.

Nanoparticles functionalized with supramolecular host-guest systems for nanomedicine and healthcare.

PubMed

Wu, Zilong; Song, Nan; Menz, Ryan; Pingali, Bharadwaj; Yang, Ying-Wei; Zheng, Yuebing

2015-05-01

Synthetic macrocyclic host compounds can interact with suitable guest molecules via noncovalent interactions to form functional supramolecular systems. With the synergistic integration of the response of molecules and the unique properties at the nanoscale, nanoparticles functionalized with the host-guest supramolecular systems have shown great potentials for a broad range of applications in the fields of nanoscience and nanotechnology. In this review article, we focus on the applications of the nanoparticles functionalized with supramolecular host-guest systems in nanomedicine and healthcare, including therapeutic delivery, imaging, sensing and removal of harmful substances. A large number of examples are included to elucidate the working mechanisms, advantages, limitations and future developments of the nanoparticle-supramolecule systems in these applications.

Concepts and applications of "natural computing" techniques in de novo drug and peptide design.

PubMed

Hiss, Jan A; Hartenfeller, Markus; Schneider, Gisbert

2010-05-01

Evolutionary algorithms, particle swarm optimization, and ant colony optimization have emerged as robust optimization methods for molecular modeling and peptide design. Such algorithms mimic combinatorial molecule assembly by using molecular fragments as building-blocks for compound construction, and relying on adaptation and emergence of desired pharmacological properties in a population of virtual molecules. Nature-inspired algorithms might be particularly suited for bioisosteric replacement or scaffold-hopping from complex natural products to synthetically more easily accessible compounds that are amenable to optimization by medicinal chemistry. The theory and applications of selected nature-inspired algorithms for drug design are reviewed, together with practical applications and a discussion of their advantages and limitations.

Application of Aptamer-based hybrid molecules in Early Diagnosis and Treatment of Diabetes Mellitus: From the Concepts toward the Future.

PubMed

Ahmadi, Sepideh; Rabiee, Navid; Rabiee, Mohammad

2018-06-06

Aptamers have several positive advantages that made them eminent as a potential factor in diagnosing and treating diseases such as their application in prevention and treatment of diabetes. In this opinion-based mini review article, we aimed to investigate the DNA and RNA-based hybrid molecules specifically aptamers and had a logical conclusion as a promising future prospective in early diagnosis and treatment of diabetes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Monolayer coated gold nanoparticles for delivery applications

PubMed Central

Rana, Subinoy; Bajaj, Avinash; Mout, Rubul; Rotello, Vincent M.

2011-01-01

Gold nanoparticles (AuNPs) provide attractive vehicles for delivery of drugs, genetic materials, proteins, and small molecules. AuNPs feature low core toxicity coupled with the ability to parametrically control particle size and surface properties. In this review, we focus on engineering of the AuNP surface monolayer, highlighting recent advances in tuning monolayer structures for efficient delivery of drugs and biomolecules. This review covers two broad categories of particle functionalization, organic monolayers and biomolecule coatings, and discusses their applications in drug, DNA/RNA, protein and small molecule delivery. PMID:21925556

Multifunctional magnetic nanoparticles for targeted imaging and therapy

PubMed Central

McCarthy, Jason R.; Weissleder, Ralph

2008-01-01

Magnetic nanoparticles have become important tools for the imaging of prevalent diseases, such as cancer, atherosclerosis, diabetes, and others. While first generation nanoparticles were fairly nonspecific, newer generations have been targeted to specific cell types and molecular targets via affinity ligands. Commonly, these ligands emerge from phage or small molecule screens, or are based on antibodies or aptamers. Secondary reporters and combined therapeutic molecules have further opened potential clinical applications of these materials. This review summarizes some of the recent biomedical applications of these newer magnetic nanomaterials. PMID:18508157

Single-molecule experiments in biological physics: methods and applications.

PubMed

Ritort, F

2006-08-16

I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

TOPICAL REVIEW: Single-molecule experiments in biological physics: methods and applications

NASA Astrophysics Data System (ADS)

Ritort, F.

2006-08-01

I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

FlavorDB: a database of flavor molecules

PubMed Central

Garg, Neelansh; Sethupathy, Apuroop; Tuwani, Rudraksh; NK, Rakhi; Dokania, Shubham; Iyer, Arvind; Gupta, Ayushi; Agrawal, Shubhra; Singh, Navjot; Shukla, Shubham; Kathuria, Kriti; Badhwar, Rahul; Kanji, Rakesh; Jain, Anupam; Kaur, Avneet; Nagpal, Rashmi

2018-01-01

Abstract Flavor is an expression of olfactory and gustatory sensations experienced through a multitude of chemical processes triggered by molecules. Beyond their key role in defining taste and smell, flavor molecules also regulate metabolic processes with consequences to health. Such molecules present in natural sources have been an integral part of human history with limited success in attempts to create synthetic alternatives. Given their utility in various spheres of life such as food and fragrances, it is valuable to have a repository of flavor molecules, their natural sources, physicochemical properties, and sensory responses. FlavorDB (http://cosylab.iiitd.edu.in/flavordb) comprises of 25,595 flavor molecules representing an array of tastes and odors. Among these 2254 molecules are associated with 936 natural ingredients belonging to 34 categories. The dynamic, user-friendly interface of the resource facilitates exploration of flavor molecules for divergent applications: finding molecules matching a desired flavor or structure; exploring molecules of an ingredient; discovering novel food pairings; finding the molecular essence of food ingredients; associating chemical features with a flavor and more. Data-driven studies based on FlavorDB can pave the way for an improved understanding of flavor mechanisms. PMID:29059383

Optoelectrical Cooling of Polar Molecules to Submillikelvin Temperatures.

PubMed

Prehn, Alexander; Ibrügger, Martin; Glöckner, Rosa; Rempe, Gerhard; Zeppenfeld, Martin

2016-02-12

We demonstrate direct cooling of gaseous formaldehyde (H2CO) to the microkelvin regime. Our approach, optoelectrical Sisyphus cooling, provides a simple dissipative cooling method applicable to electrically trapped dipolar molecules. By reducing the temperature by 3 orders of magnitude and increasing the phase-space density by a factor of ∼10(4), we generate an ensemble of 3×10(5) molecules with a temperature of about 420  μK, populating a single rotational state with more than 80% purity.

A Comprehensive Analysis in Terms of Molecule-Intrinsic, Quasi-Atomic Orbitals. III. The Covalent Bonding Structure of Urea.

PubMed

West, Aaron C; Schmidt, Michael W; Gordon, Mark S; Ruedenberg, Klaus

2015-10-15

The analysis of molecular electron density matrices in terms of quasi-atomic orbitals, which was developed in previous investigations, is quantitatively exemplified by a detailed application to the urea molecule. The analysis is found to identify strong and weak covalent bonding interactions as well as intramolecular charge transfers. It yields a qualitative as well as quantitative ab initio description of the bonding structure of this molecule, which raises questions regarding some traditional rationalizations.

Spectroscopy and reactions of molecules important in chemical evolution

NASA Technical Reports Server (NTRS)

Becker, R. S.

1974-01-01

The research includes: (1) hot hydrogen atom reactions in terms of the nature of products produced, mechanism of the reactions and the implication and application of such reactions for molecules existing in interstellar clouds, in planetary atmospheres, and in chemical evolution; (2) photochemical reactions that can lead to molecules important in chemical evolution, interstellar clouds and as constituents in planetary atmospheres; and (3) spectroscopic and theoretical properties of biomolecules and their precursors and where possible, use these to understand their photochemical behavior.

Fullerene-free small molecule organic solar cells with a high open circuit voltage of 1.15 V.

PubMed

Ni, Wang; Li, Miaomiao; Kan, Bin; Liu, Feng; Wan, Xiangjian; Zhang, Qian; Zhang, Hongtao; Russell, Thomas P; Chen, Yongsheng

2016-01-11

A new small molecule named DTBTF with thiobarbituric acid as a terminal group was designed and synthesized as an acceptor for organic photovoltaic applications. DTBTF exhibits strong absorption in the visible region, and a relatively high lying LUMO energy level (-3.62 eV). All-small-molecule organic solar cells based on DR3TSBDT:DTBTF blend films show a considerable PCE of 3.84% with a high V(oc) of 1.15 V.

Optimizing the 391-nm lasing intensity from ionized nitrogen molecules in 800-nm femtosecond laser fields

NASA Astrophysics Data System (ADS)

Zhong, Xunqi; Miao, Zhiming; Zhang, Linlin; Jiang, Hongbing; Liu, Yunquan; Gong, Qihuang; Wu, Chengyin

2018-03-01

We investigate the 391-nm lasing dynamics from ionized nitrogen molecules in 800-nm femtosecond laser fields. By comparing the radiation intensity, spectrum shape, and temporal profile of the 391-nm lasing at various experimental conditions, we conclude that the lasing dynamics contains not only the generation and the decay of ionized nitrogen molecules, but also the seed-built coherence among emitters as well as the propagation effect in the plasma filamentation. These results provide reliable guidance for optimizing the 391-nm lasing from ionized nitrogen molecules in 800-nm femtosecond laser fields, which have potential applications for remote sensing in the atmosphere.

Single-Molecule Bioelectronics

PubMed Central

Rosenstein, Jacob K.; Lemay, Serge G.; Shepard, Kenneth L.

2014-01-01

Experimental techniques which interface single biomolecules directly with microelectronic systems are increasingly being used in a wide range of powerful applications, from fundamental studies of biomolecules to ultra-sensitive assays. Here we review several technologies which can perform electronic measurements of single molecules in solution: ion channels, nanopore sensors, carbon nanotube field-effect transistors, electron tunneling gaps, and redox cycling. We discuss the shared features among these techniques that enable them to resolve individual molecules, and discuss their limitations. Recordings from each of these methods all rely on similar electronic instrumentation, and we discuss the relevant circuit implementations and potential for scaling these single-molecule bioelectronic interfaces to high-throughput arrayed sensing platforms. PMID:25529538

Spectral properties from Matsubara Green's function approach: Application to molecules

NASA Astrophysics Data System (ADS)

Schüler, M.; Pavlyukh, Y.

2018-03-01

We present results for many-body perturbation theory for the one-body Green's function at finite temperatures using the Matsubara formalism. Our method relies on the accurate representation of the single-particle states in standard Gaussian basis sets, allowing to efficiently compute, among other observables, quasiparticle energies and Dyson orbitals of atoms and molecules. In particular, we challenge the second-order treatment of the Coulomb interaction by benchmarking its accuracy for a well-established test set of small molecules, which includes also systems where the usual Hartree-Fock treatment encounters difficulties. We discuss different schemes how to extract quasiparticle properties and assess their range of applicability. With an accurate solution and compact representation, our method is an ideal starting point to study electron dynamics in time-resolved experiments by the propagation of the Kadanoff-Baym equations.

An update on the application of physical technologies to enhance intradermal and transdermal drug delivery.

PubMed

Herwadkar, Anushree; Banga, Ajay K

2012-03-01

A large number of biopharmaceuticals and other macromolecules are being developed for therapeutic applications. Conventional oral delivery is not always possible due to first-pass metabolism and degradation in the GI tract. Parenteral delivery is invasive and has poor patient compliance. Transdermal delivery provides one attractive route of administration. Transdermal administration can achieve the continuous and non-invasive delivery of drugs. However, passive transdermal delivery is restricted to small lipophilic molecules. Active physical-enhancement technologies are being investigated to increase the scope of transdermal delivery to hydrophilic molecules and macromolecules. Recent developments in transdermal technologies, such as microporation, iontophoresis and sonophoresis can enable therapeutic delivery of many drug molecules, biopharmaceuticals, cosmeceuticals and vaccines. This review provides an update of recent developments in transdermal delivery focusing on physical-enhancement technologies.

Design, Optimization and Application of Small Molecule Biosensor in Metabolic Engineering.

PubMed

Liu, Yang; Liu, Ye; Wang, Meng

2017-01-01

The development of synthetic biology and metabolic engineering has painted a great future for the bio-based economy, including fuels, chemicals, and drugs produced from renewable feedstocks. With the rapid advance of genome-scale modeling, pathway assembling and genome engineering/editing, our ability to design and generate microbial cell factories with various phenotype becomes almost limitless. However, our lack of ability to measure and exert precise control over metabolite concentration related phenotypes becomes a bottleneck in metabolic engineering. Genetically encoded small molecule biosensors, which provide the means to couple metabolite concentration to measurable or actionable outputs, are highly promising solutions to the bottleneck. Here we review recent advances in the design, optimization and application of small molecule biosensor in metabolic engineering, with particular focus on optimization strategies for transcription factor (TF) based biosensors.

Binding Structures of Diatomic Molecules to Co-Porphyrins on Au(111) Studied by Scanning Tunneling Microscopy

NASA Astrophysics Data System (ADS)

Lee, Soon-Hyeong; Chang, Yun; Kim, Howon; Jang, Won; Kim, Yong-Hyun; Kahng, Se-Jong; Department Of Physics, Korea University. Collaboration; Graduate School Of Nanoscience; Technology (Wcu), Kaist Collaboration

2013-03-01

Axial bindings of diatomic molecules to metalloporphyrins involve in the dynamic processes of biological functions such as respiration, neurotransmission, and photosynthesis. The binding reactions are also useful in sensor applications and to control molecular spins in metalloporphyrins for spintronic applications. Here, we present the binding structures of diatomic molecules to surface-supported Co-porphyrins studied using scanning tunneling microscopy. Upon gas exposure, three-lobed structures of Co-porphyrins transformed to bright ring shapes on Au(111), whereas H2-porphyrins of dark rings remained intact. The bright rings are explained by the structures of reaction complexes where a diatomic ligand, tilted away from the axis normal to the porphyrin plane, is under precession. Our results are consistent with previous bulk experiments using X-ray diffraction and nuclear magnetic resonance spectroscopy.

Design, Optimization and Application of Small Molecule Biosensor in Metabolic Engineering

PubMed Central

Liu, Yang; Liu, Ye; Wang, Meng

2017-01-01

The development of synthetic biology and metabolic engineering has painted a great future for the bio-based economy, including fuels, chemicals, and drugs produced from renewable feedstocks. With the rapid advance of genome-scale modeling, pathway assembling and genome engineering/editing, our ability to design and generate microbial cell factories with various phenotype becomes almost limitless. However, our lack of ability to measure and exert precise control over metabolite concentration related phenotypes becomes a bottleneck in metabolic engineering. Genetically encoded small molecule biosensors, which provide the means to couple metabolite concentration to measurable or actionable outputs, are highly promising solutions to the bottleneck. Here we review recent advances in the design, optimization and application of small molecule biosensor in metabolic engineering, with particular focus on optimization strategies for transcription factor (TF) based biosensors. PMID:29089935

[Watching dance of the molecules - CARS microscopy].

PubMed

Korczyński, Jaroslaw; Kubiak, Katarzyna; Węgłowska, Edyta

2017-01-01

CARS (Coherent Anti-Stokes Raman Scattering) microscopy is an imaging method for living cells visualization as well as for food or cosmetics material analysis without the need for staining. The near infrared laser source generates the CARS signal - the characteristic intrinsic vibrational contrast of the molecules in a sample which is no longer caused by staining, but by the molecules themselves. It provides the benefit of a non-toxic, non-destructive and almost noninvasive method for sample imaging. CARS can easily be combined with fluorescence confocal microscopy so it is an excellent complementary imaging method. In this article we showed some of the applications for this technology: imaging of lipid droplets inside human HaCaT cells and analysis of the composition of cosmetic products. Moreover we believe, that soon new fields of application become accessible for this rapidly developing branch of microscopy.

Hydrogel Droplet Microfluidics for High-Throughput Single Molecule/Cell Analysis.

PubMed

Zhu, Zhi; Yang, Chaoyong James

2017-01-17

Heterogeneity among individual molecules and cells has posed significant challenges to traditional bulk assays, due to the assumption of average behavior, which would lose important biological information in heterogeneity and result in a misleading interpretation. Single molecule/cell analysis has become an important and emerging field in biological and biomedical research for insights into heterogeneity between large populations at high resolution. Compared with the ensemble bulk method, single molecule/cell analysis explores the information on time trajectories, conformational states, and interactions of individual molecules/cells, all key factors in the study of chemical and biological reaction pathways. Various powerful techniques have been developed for single molecule/cell analysis, including flow cytometry, atomic force microscopy, optical and magnetic tweezers, single-molecule fluorescence spectroscopy, and so forth. However, some of them have the low-throughput issue that has to analyze single molecules/cells one by one. Flow cytometry is a widely used high-throughput technique for single cell analysis but lacks the ability for intercellular interaction study and local environment control. Droplet microfluidics becomes attractive for single molecule/cell manipulation because single molecules/cells can be individually encased in monodisperse microdroplets, allowing high-throughput analysis and manipulation with precise control of the local environment. Moreover, hydrogels, cross-linked polymer networks that swell in the presence of water, have been introduced into droplet microfluidic systems as hydrogel droplet microfluidics. By replacing an aqueous phase with a monomer or polymer solution, hydrogel droplets can be generated on microfluidic chips for encapsulation of single molecules/cells according to the Poisson distribution. The sol-gel transition property endows the hydrogel droplets with new functionalities and diversified applications in single molecule/cell analysis. The hydrogel can act as a 3D cell culture matrix to mimic the extracellular environment for long-term single cell culture, which allows further heterogeneity study in proliferation, drug screening, and metastasis at the single-cell level. The sol-gel transition allows reactions in solution to be performed rapidly and efficiently with product storage in the gel for flexible downstream manipulation and analysis. More importantly, controllable sol-gel regulation provides a new way to maintain phenotype-genotype linkages in the hydrogel matrix for high throughput molecular evolution. In this Account, we will review the hydrogel droplet generation on microfluidics, single molecule/cell encapsulation in hydrogel droplets, as well as the progress made by our group and others in the application of hydrogel droplet microfluidics for single molecule/cell analysis, including single cell culture, single molecule/cell detection, single cell sequencing, and molecular evolution.

Magnetic amphiphilic hybrid carbon nanotubes containing N-doped and undoped sections: powerful tensioactive nanostructures

NASA Astrophysics Data System (ADS)

Purceno, Aluir D.; Machado, Bruno F.; Teixeira, Ana Paula C.; Medeiros, Tayline V.; Benyounes, Anas; Beausoleil, Julien; Menezes, Helvecio C.; Cardeal, Zenilda L.; Lago, Rochel M.; Serp, Philippe

2014-11-01

In this work, unique amphiphilic magnetic hybrid carbon nanotubes (CNTs) are synthesized and used as tensioactive nanostructures in different applications. These CNTs interact very well with aqueous media due to the hydrophilic N-doped section, whereas the undoped hydrophobic one has strong affinity for organic molecules. The amphiphilic character combined with the magnetic properties of these CNTs opens the door to completely new and exciting applications in adsorption science and catalysis. These amphiphilic N-doped CNTs can also be used as powerful tensioactive emulsification structures. They can emulsify water/organic mixtures and by a simple magnetic separation the emulsion can be easily broken. We demonstrate the application of these CNTs in the efficient adsorption of various molecules, in addition to promoting biphasic processes in three different reactions, i.e. transesterification of soybean oil, quinoline extractive oxidation with H2O2 and a metal-catalyzed aqueous oxidation of heptanol with molecular oxygen.In this work, unique amphiphilic magnetic hybrid carbon nanotubes (CNTs) are synthesized and used as tensioactive nanostructures in different applications. These CNTs interact very well with aqueous media due to the hydrophilic N-doped section, whereas the undoped hydrophobic one has strong affinity for organic molecules. The amphiphilic character combined with the magnetic properties of these CNTs opens the door to completely new and exciting applications in adsorption science and catalysis. These amphiphilic N-doped CNTs can also be used as powerful tensioactive emulsification structures. They can emulsify water/organic mixtures and by a simple magnetic separation the emulsion can be easily broken. We demonstrate the application of these CNTs in the efficient adsorption of various molecules, in addition to promoting biphasic processes in three different reactions, i.e. transesterification of soybean oil, quinoline extractive oxidation with H2O2 and a metal-catalyzed aqueous oxidation of heptanol with molecular oxygen. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr04005h

Counting and behavior of an individual fluorescent molecule without hydrodynamic flow, immobilization, or photon count statistics.

PubMed

Földes-Papp, Zeno; Baumann, Gerd; Demel, Ulrike; Tilz, Gernot P

2004-04-01

Many theoretical models of molecular interactions, biochemical and chemical reactions are described on the single-molecule level, although our knowledge about the biochemical/chemical structure and dynamics primarily originates from the investigation of many-molecule systems. At present, there are four experimental platforms to observe the movement and the behavior of single fluorescent molecules: wide-field epi-illumination, near-field optical scanning, and laser scanning confocal and multiphoton microscopy. The platforms are combined with analytical methods such as fluorescence resonance energy transfer (FRET), fluorescence auto-or two-color cross-correlation spectroscopy (FCS), fluorescence polarizing anisotropy, fluorescence quenching and fluorescence lifetime measurements. The original contribution focuses on counting and characterization of freely diffusing single molecules in a single-phase like a solution or a membrane without hydrodynamic flow, immobilization or burst size analysis of intensity traces. This can be achieved, for example, by Fluorescence auto- or two-color cross-Correlation Spectroscopy as demonstrated in this original article. Three criteria (Földes-Papp (2002) Pteridines, 13, 73-82; Földes-Papp et al. (2004a) J. Immunol. Meth., 286, 1-11; Földes-Papp et al. (2004b) J. Immunol. Meth., 286, 13-20) are discussed for performing continuous measurements with one and the same single (individual) molecule, freely diffusing in a solution or a membrane, from sub-milliseconds up to severals hours. The 'algorithms' developed for single-molecule fluorescence detection are called the 'selfsame single-fluorescent-molecule regime'. An interesting application of the results found is in the field of immunology. The application of the theory to experimental results shows that the theory is consistent with the experiments. The exposition of the novel ideas on Single (Solution)-Phase Single-Molecule Fluorescence auto- or two-color cross-Correlation Spectroscopy (SPSM-FCS) are comprehensively presented. As technology continues to improve, the limits of what FCS/FCCS is being asked to do are concomitantly pushed.

The Synthesis and Photophysical Characterization of Porphyrin Photoactive Materials for Use as Sensitizers in Organic Photovoltaics and Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Marin, Dawn Marie

Solar energy conversion and photodynamic therapy (PDT) are very different applications. However, both utilize very similar photoactive molecules called porphyrins. Porphyrins are structural analogs of chlorophyll and also function as prosthetic groups in some biological enzymes. Understanding the structure/function relationship of these molecules is crucial for enhancing the energy generation efficiency of molecular solar cells and improving chemotherapeutic activity in PDT. In this dissertation, two approaches were applied with the goal of increasing the efficiency of molecular semiconductors for these applications: the heavy atom effect and donor-acceptor molecules. We enhanced the efficiency of triplet excited state formation and singlet oxygen generation for porphyrin sensitizers using the heavy atom effect. The heavy atom effect induces spin-orbit coupling to promote intersystem crossing into the triplet state. In this study, a carbomethoxyphenyl substituent was replaced with either a bromophenyl or an iodophenyl substituent on 5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrin. The longer lifetimes obtained from the increase in the triplet excited state allow for longer exciton diffusion lengths and lower recombination rates in photovoltaics. Also, the enhanced intersystem crossing is beneficial for photodynamic therapy because it increases singlet oxygen generation, which destroys tumor cells. Optimizing photovoltaic performance and PDT efficacy can also be accomplished with donor-acceptor molecules because they have extended electronic pi bond delocalization across the molecule, which causes the molecule to absorb longer wavelengths of light. Donor-acceptor molecules should produce photovoltaic devices that absorb more of the solar spectrum and produce sensitizers that absorb wavelengths of light that can penetrate through tissues. Donor-acceptor molecules were synthesized using 5,15-bis(4-carbomethoxyphenyl)porphyrin as the acceptor and thiazolo[5,4-d]thiazole derivatives as the donor. The excited state dynamics of the heavy atom derivatives and donor-acceptor molecules were studied using UV-vis spectroscopy, steady-state emission, time-resolved and delayed photoluminescence.

Visualization of molecular structures using HoloLens-based augmented reality

PubMed Central

Hoffman, MA; Provance, JB

2017-01-01

Biological molecules and biologically active small molecules are complex three dimensional structures. Current flat screen monitors are limited in their ability to convey the full three dimensional characteristics of these molecules. Augmented reality devices, including the Microsoft HoloLens, offer an immersive platform to change how we interact with molecular visualizations. We describe a process to incorporate the three dimensional structures of small molecules and complex proteins into the Microsoft HoloLens using aspirin and the human leukocyte antigen (HLA) as examples. Small molecular structures can be introduced into the HoloStudio application, which provides native support for rotating, resizing and performing other interactions with these molecules. Larger molecules can be imported through the Unity gaming development platform and then Microsoft Visual Developer. The processes described here can be modified to import a wide variety of molecular structures into augmented reality systems and improve our comprehension of complex structural features. PMID:28815109

Roles of vacuum tunnelling and contact mechanics in single-molecule thermopower

NASA Astrophysics Data System (ADS)

Tsutsui, Makusu; Yokota, Kazumichi; Morikawa, Takanori; Taniguchi, Masateru

2017-03-01

Molecular junction is a chemically-defined nanostructure whose discrete electronic states are expected to render enhanced thermoelectric figure of merit suitable for energy-harvesting applications. Here, we report on geometrical dependence of thermoelectricity in metal-molecule-metal structures. We performed simultaneous measurements of the electrical conductance and thermovoltage of aromatic molecules having different anchoring groups at room temperature in vacuum. We elucidated the mutual contributions of vacuum tunnelling on thermoelectricity in the short molecular bridges. We also found stretching-induced thermoelectric voltage enhancement in thiol-linked single-molecule bridges along with absence of the pulling effects in diamine counterparts, thereby suggested that the electromechanical effect would be a rather universal phenomenon in Au-S anchored molecular junctions that undergo substantial metal-molecule contact elongation upon stretching. The present results provide a novel concept for molecular design to achieve high thermopower with single-molecule junctions.

Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory.

PubMed

Nicolaou, K C

2014-03-08

Synthetic organic chemists have the power to replicate some of the most intriguing molecules of living nature in the laboratory and apply their developed synthetic strategies and technologies to construct variations of them. Such molecules facilitate biology and medicine, as they often find uses as biological tools and drug candidates for clinical development. In addition, by employing sophisticated catalytic reactions and appropriately designed synthetic processes, they can synthesize not only the molecules of nature and their analogues, but also myriad other organic molecules for potential applications in many areas of science, technology and everyday life. After a short historical introduction, this article focuses on recent advances in the field of organic synthesis with demonstrative examples of total synthesis of complex bioactive molecules, natural or designed, from the author's laboratories, and their impact on chemistry, biology and medicine.

Single Molecule Enzymology via Nanoelectronic Circuits

NASA Astrophysics Data System (ADS)

Collins, Philip

Traditional single-molecule techniques rely on fluorescence or force transduction to monitor conformational changes and biochemical activity. Recent demonstrations of single-molecule monitoring with electronic transistors are poised to add to the single-molecule research toolkit. The transistor-based technique is sensitive to the motion of single charged side chain residues and can transduce those motions with microsecond resolution, opening the doors to single-molecule enzymology with unprecedented resolution. Furthermore, the solid-state platform provides opportunities for parallelization in arrays and long-duration monitoring of one molecule's activity or processivity, all without the limitations caused by photo-oxidation or mutagenic fluorophore incorporation. This presentation will review some of these advantages and their particular application to DNA polymerase I processing single-stranded DNA templates. This research was supported financially by the NIH NCI (R01 CA133592-01), the NIH NIGMS (1R01GM106957-01) and the NSF (DMR-1104629 and ECCS-1231910).

Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory

PubMed Central

Nicolaou, K. C.

2014-01-01

Synthetic organic chemists have the power to replicate some of the most intriguing molecules of living nature in the laboratory and apply their developed synthetic strategies and technologies to construct variations of them. Such molecules facilitate biology and medicine, as they often find uses as biological tools and drug candidates for clinical development. In addition, by employing sophisticated catalytic reactions and appropriately designed synthetic processes, they can synthesize not only the molecules of nature and their analogues, but also myriad other organic molecules for potential applications in many areas of science, technology and everyday life. After a short historical introduction, this article focuses on recent advances in the field of organic synthesis with demonstrative examples of total synthesis of complex bioactive molecules, natural or designed, from the author’s laboratories, and their impact on chemistry, biology and medicine. PMID:24611027

Physics with Cold Molecules Using Buffer Gas Cooling: Precision Measurement, Collisions, and Laser Cooling

NASA Astrophysics Data System (ADS)

Hutzler, Nicholas R.; Doyle, John M.

2014-06-01

Cryogenic buffer gas cooled beams and cells can be used to study many species, from atoms and polar molecules to biomolecules. We report on recent applications of this technique to improve the limit on the electron electric dipole moment [1], load polar molecules into a magnetic trap through optical pumping [2], perform chirally sensitive microwave spectroscopy on polyatomic molecules [3], progress towards magneto-optical trapping of polar molecules [4], and studies of atom-molecule sticking [5]. [1] The ACME Collaboration: J. Baron et al., Science 343, p. 269 (2014) [2] B. Hemmerling et al., arXiv:1310.2669, to appear in Phys. Rev. Lett. [3] D. Patterson, M. Schnell, & J. M. Doyle, Nature 497, p. 475 (2013) [4] H. Lu et al., arXiv:1310.3239, to appear in New. J. Phys. [5] J. Piskorski et al., under preparation

Intracellular delivery of peptide nucleic acid and organic molecules using zeolite-L nanocrystals.

PubMed

Bertucci, Alessandro; Lülf, Henning; Septiadi, Dedy; Manicardi, Alex; Corradini, Roberto; De Cola, Luisa

2014-11-01

The design and synthesis of smart nanomaterials can provide interesting potential applications for biomedical purposes from bioimaging to drug delivery. Manufacturing multifunctional systems in a way to carry bioactive molecules, like peptide nucleic acids able to recognize specific targets in living cells, represents an achievement towards the development of highly selective tools for both diagnosis and therapeutics. This work describes a very first example of the use of zeolite nanocrystals as multifunctional nanocarriers to deliver simultaneously PNA and organic molecules into living cells. Zeolite-L nanocrystals are functionalized by covalently attaching the PNA probes onto the surface, while the channel system is filled with fluorescent guest molecules. The cellular uptake of the PNA/Zeolite-L hybrid material is then significantly increased by coating the whole system with a thin layer of biodegradable poly-L-lysine. The delivery of DAPI as a model drug molecule, inserted into the zeolite pores, is also demonstrated to occur in the cells, proving the multifunctional ability of the system. Using this zeolite nanosystem carrying PNA probes designed to target specific RNA sequences of interest in living cells could open new possibilities for theranostic and gene therapy applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Förster-Induced Energy Transfer in Functionalized Graphene

PubMed Central

2014-01-01

Carbon nanostructures are ideal substrates for functionalization with molecules since they consist of a single atomic layer giving rise to an extraordinary sensitivity to changes in their surrounding. The functionalization opens a new research field of hybrid nanostructures with tailored properties. Here, we present a microscopic view on the substrate–molecule interaction in the exemplary hybrid material consisting of graphene functionalized with perylene molecules. First experiments on similar systems have been recently realized illustrating an extremely efficient transfer of excitation energy from adsorbed molecules to the carbon substrate, a process with a large application potential for high-efficiency photovoltaic devices and biomedical imaging and sensing. So far, there has been no microscopically founded explanation for the observed energy transfer. Based on first-principle calculations, we have explicitly investigated the different transfer mechanisms revealing the crucial importance of Förster coupling. Due to the efficient Coulomb interaction in graphene, we obtain strong Förster rates in the range of 1/fs. We investigate its dependence on the substrate–molecule distance R and describe the impact of the momentum transfer q for an efficient energy transfer. Furthermore, we find that the Dexter transfer mechanism is negligibly small due to the vanishing overlap between the involved strongly localized orbital functions. The gained insights are applicable to a variety of carbon-based hybrid nanostructures. PMID:24808936

Yeast-based biosensors: design and applications.

PubMed

Adeniran, Adebola; Sherer, Michael; Tyo, Keith E J

2015-02-01

Yeast-based biosensing (YBB) is an exciting research area, as many studies have demonstrated the use of yeasts to accurately detect specific molecules. Biosensors incorporating various yeasts have been reported to detect an incredibly large range of molecules including but not limited to odorants, metals, intracellular metabolites, carcinogens, lactate, alcohols, and sugars. We review the detection strategies available for different types of analytes, as well as the wide range of output methods that have been incorporated with yeast biosensors. We group biosensors into two categories: those that are dependent upon transcription of a gene to report the detection of a desired molecule and those that are independent of this reporting mechanism. Transcription-dependent biosensors frequently depend on heterologous expression of sensing elements from non-yeast organisms, a strategy that has greatly expanded the range of molecules available for detection by YBBs. Transcription-independent biosensors circumvent the problem of sensing difficult-to-detect analytes by instead relying on yeast metabolism to generate easily detected molecules when the analyte is present. The use of yeast as the sensing element in biosensors has proven to be successful and continues to hold great promise for a variety of applications. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Single molecule magnet behaviour in robust dysprosium-biradical complexes.

PubMed

Bernot, Kevin; Pointillart, Fabrice; Rosa, Patrick; Etienne, Mael; Sessoli, Roberta; Gatteschi, Dante

2010-09-21

A Dy-biradical complex was synthesized and characterized down to very low temperature. ac magnetic measurements reveal single molecule magnet behaviour visible without any application of dc field. The transition to the quantum tunneling regime is evidenced. Photophysical and EPR measurements provide evidence of the excellent stability of these complexes in solution.

A Direct, Competitive Enzyme-Linked Immunosorbent Assay (ELISA) as a Quantitative Technique for Small Molecules

ERIC Educational Resources Information Center

Powers, Jennifer L.; Rippe, Karen Duda; Imarhia, Kelly; Swift, Aileen; Scholten, Melanie; Islam, Naina

2012-01-01

ELISA (enzyme-linked immunosorbent assay) is a widely used technique with applications in disease diagnosis, detection of contaminated foods, and screening for drugs of abuse or environmental contaminants. However, published protocols with a focus on quantitative detection of small molecules designed for teaching laboratories are limited. A…

Advanced Analytical Methodologies Based on Raman Spectroscopy to Detect Prebiotic and Biotic Molecules: Applicability in the Study of the Martian Nakhlite NWA 6148 Meteorite

NASA Astrophysics Data System (ADS)

Madariaga, J. M.; Torre-Fdez, I.; Ruiz-Galende, P.; Aramendia, J.; Gomez-Nubla, L.; Fdez-Ortiz de Vallejuelo, S.; Maguregui, M.; Castro, K.; Arana, G.

2018-04-01

Advanced methodologies based on Raman spectroscopy are proposed to detect prebiotic and biotic molecules in returned samples from Mars: (a) optical microscopy with confocal micro-Raman, (b) the SCA instrument, (c) Raman Imaging. Examples for NWA 6148.

Adsorption of gas molecules on Cu impurities embedded monolayer MoS2: A first- principles study

NASA Astrophysics Data System (ADS)

Zhao, B.; Li, C. Y.; Liu, L. L.; Zhou, B.; Zhang, Q. K.; Chen, Z. Q.; Tang, Z.

2016-09-01

Adsorption of small gas molecules (O2, NO, NO2 and NH3) on transition-metal Cu atom embedded monolayer MoS2 was investigated by first-principles calculations based on the density-functional theory (DFT). The embedded Cu atom is strongly constrained on the sulfur vacancy of monolayer MoS2 with a high diffusion barrier. The stable adsorption geometry, charge transfer and electronic structures of these gas molecules on monolayer MoS2 embedded with transition-metal Cu atom are discussed in detail. It is found that the monolayer MoS2 with embedded Cu atom can effectively capture these gas molecules with high adsorption energy. The NH3 molecule acts as electron donor after adsorption, which is different from the other gas molecules (O2, NO, and NO2). The results suggest that MoS2-Cu system may be promising for future applications in gas molecules sensing and catalysis, which is similar to those of the transition-metal embedded graphene.

Theoretical study on adsorption and dissociation of NO2 molecules on BNNT surface

NASA Astrophysics Data System (ADS)

Singla, Preeti; Singhal, Sonal; Goel, Neetu

2013-10-01

The adsorption of NO2 molecules on (8,0) zigzag single-walled boron nitride nanotube surface is investigated using density functional theory calculations. Two interaction modes, nitro (interacting atom is N) and nitrite (O interacts with BNNT) have been studied with increase in number of NO2 molecules. The adsorption of single NO2 molecule in both configurations is observed to be exothermic and physical in nature. However, in nitrite configuration, NO2 molecules are chemisorbed on the surface leading to the dissociation of NO2 molecules into NO and O. The density of states, natural bond orbital analysis and frontier orbital pictures provide rational understanding of the charge transfer involved in the process and predict significant enhancement in the conductivity of the BNNT after NO2 adsorption. The DFT calculations show that NO2 adsorption introduces new impurity states in the band gap of bare BNNT and expand their applications as NO2 molecule gas sensor and catalytic surface for Nsbnd O dissociation depending upon the mode of adsorption.

Conductivity Modifications of Graphene by Electron Donative Organic Molecules

NASA Astrophysics Data System (ADS)

Masujima, Hiroaki; Mori, Takehiko; Hayamizu, Yuhei

2017-07-01

Graphene has been studied for the application of transparent electrodes in flexible electrical devices with semiconductor organics. Control of the charge carrier density in graphene is crucial to reduce the contact resistance between graphene and the active layer of organic semiconductor. Chemical doping of graphene is an approach to change the carrier density, where the adsorbed organic molecules donate or accept electrons form graphene. While various acceptor organic molecules have been demonstrated so far, investigation about donor molecules is still poor. In this work, we have investigated doping effect in graphene field-effect transistors functionalized by organic donor molecules such as dibenzotetrathiafulvalene (DBTTF), hexamethyltetrathiafulvalene (HMTTF), 1,5-diaminonaphthalene (DAN), and N, N, N', N'-tetramethyl- p-phenylenediamine (TMPD). Based on conductivity measurements of graphene transistors, the former three molecules do not have any significant effect to graphene transistors. However, TMPD shows effective n-type doping. The doping effect has a correlation with the level of highest occupied molecular orbital (HOMO) of each molecule, where TMPD has the highest HOMO level.

Self-assembled molecular magnets on patterned silicon substrates: bridging bio-molecules with nanoelectronics.

PubMed

Chang, Chia-Ching; Sun, Kien Wen; Lee, Shang-Fan; Kan, Lou-Sing

2007-04-01

The paper reports the methods of preparing molecular magnets and patterning of the molecules on a semiconductor surface. A highly magnetically aligned metallothionein containing Mn and Cd (Mn,Cd-MT-2) is first synthesized, and the molecules are then placed into nanopores prepared on silicon (001) surfaces using electron beam lithography and reactive ion-etching techniques. We have observed the self-assemble growth of the MT molecules on the patterned Si surface such that the MT molecules have grown into rod or ring type three-dimensional nanostructures, depending on the patterned nanostructures on the surface. We also provide scanning electron microscopy, atomic force microscopy, and magnetic force microscope studies of the molecular nanostructures. This engineered molecule shows molecular magnetization and is biocompatible with conventional semiconductors. These features make Mn,Cd-MT-2 a good candidate for biological applications and sensing sources of new nanodevices. Using molecular self-assembly and topographical patterning of the semiconductor substrate, we can close the gap between bio-molecules and nanoelectronics built into the semiconductor chip.

Proposal for a common nomenclature for fragment ions in mass spectra of lipids

PubMed Central

Hartler, Jürgen; Christiansen, Klaus; Gallego, Sandra F.; Peng, Bing; Ahrends, Robert

2017-01-01

Advances in mass spectrometry-based lipidomics have in recent years prompted efforts to standardize the annotation of the vast number of lipid molecules that can be detected in biological systems. These efforts have focused on cataloguing, naming and drawing chemical structures of intact lipid molecules, but have provided no guidelines for annotation of lipid fragment ions detected using tandem and multi-stage mass spectrometry, albeit these fragment ions are mandatory for structural elucidation and high confidence lipid identification, especially in high throughput lipidomics workflows. Here we propose a nomenclature for the annotation of lipid fragment ions, describe its implementation and present a freely available web application, termed ALEX123 lipid calculator, that can be used to query a comprehensive database featuring curated lipid fragmentation information for more than 430,000 potential lipid molecules from 47 lipid classes covering five lipid categories. We note that the nomenclature is generic, extendable to stable isotope-labeled lipid molecules and applicable to automated annotation of fragment ions detected by most contemporary lipidomics platforms, including LC-MS/MS-based routines. PMID:29161304

Proposal for a common nomenclature for fragment ions in mass spectra of lipids.

PubMed

Pauling, Josch K; Hermansson, Martin; Hartler, Jürgen; Christiansen, Klaus; Gallego, Sandra F; Peng, Bing; Ahrends, Robert; Ejsing, Christer S

2017-01-01

Advances in mass spectrometry-based lipidomics have in recent years prompted efforts to standardize the annotation of the vast number of lipid molecules that can be detected in biological systems. These efforts have focused on cataloguing, naming and drawing chemical structures of intact lipid molecules, but have provided no guidelines for annotation of lipid fragment ions detected using tandem and multi-stage mass spectrometry, albeit these fragment ions are mandatory for structural elucidation and high confidence lipid identification, especially in high throughput lipidomics workflows. Here we propose a nomenclature for the annotation of lipid fragment ions, describe its implementation and present a freely available web application, termed ALEX123 lipid calculator, that can be used to query a comprehensive database featuring curated lipid fragmentation information for more than 430,000 potential lipid molecules from 47 lipid classes covering five lipid categories. We note that the nomenclature is generic, extendable to stable isotope-labeled lipid molecules and applicable to automated annotation of fragment ions detected by most contemporary lipidomics platforms, including LC-MS/MS-based routines.

Internet Databases of the Properties, Enzymatic Reactions, and Metabolism of Small Molecules-Search Options and Applications in Food Science.

PubMed

Minkiewicz, Piotr; Darewicz, Małgorzata; Iwaniak, Anna; Bucholska, Justyna; Starowicz, Piotr; Czyrko, Emilia

2016-12-06

Internet databases of small molecules, their enzymatic reactions, and metabolism have emerged as useful tools in food science. Database searching is also introduced as part of chemistry or enzymology courses for food technology students. Such resources support the search for information about single compounds and facilitate the introduction of secondary analyses of large datasets. Information can be retrieved from databases by searching for the compound name or structure, annotating with the help of chemical codes or drawn using molecule editing software. Data mining options may be enhanced by navigating through a network of links and cross-links between databases. Exemplary databases reviewed in this article belong to two classes: tools concerning small molecules (including general and specialized databases annotating food components) and tools annotating enzymes and metabolism. Some problems associated with database application are also discussed. Data summarized in computer databases may be used for calculation of daily intake of bioactive compounds, prediction of metabolism of food components, and their biological activity as well as for prediction of interactions between food component and drugs.

Rational design of tetraphenylethylene-based luminescent down-shifting molecules: photophysical studies and photovoltaic applications in a CdTe solar cell from small to large units.

PubMed

Li, Yilin; Li, Zhipeng; Ablekim, Tursunjan; Ren, Tianhui; Dong, Wen-Ji

2014-12-21

A rational design strategy of novel fluorophores for luminescent down-shifting (LDS) application was proposed and tested in this paper. Three new fluorophores (1a-c) with specific intramolecular charge transfer (ICT) and aggregation-induced emission (AIE) characteristics were synthesized as LDS molecules for increasing the output short circuit current density (Jsc) of a CdTe solar cell. Photophysical studies of their solution and solid states, and photovoltaic measurements of their PMMA solid films applied on a CdTe solar cell suggested that the specific spectroscopic properties and Jsc enhancement effects of these molecules were highly related to their chemical structures. The Jsc enhancement effects of these fluorophores were measured on both a CdTe small cell and a large panel. An increase in the output Jsc by as high as 5.69% for a small cell and 8.88% for a large panel was observed. Compared to a traditional LDS molecule, Y083, these fluorophores exhibited more superior capabilities of LDS.

Report on the sixth blind test of organic crystal structure prediction methods

PubMed Central

Reilly, Anthony M.; Cooper, Richard I.; Adjiman, Claire S.; Bhattacharya, Saswata; Boese, A. Daniel; Brandenburg, Jan Gerit; Bygrave, Peter J.; Bylsma, Rita; Campbell, Josh E.; Car, Roberto; Case, David H.; Chadha, Renu; Cole, Jason C.; Cosburn, Katherine; Cuppen, Herma M.; Curtis, Farren; Day, Graeme M.; DiStasio Jr, Robert A.; Dzyabchenko, Alexander; van Eijck, Bouke P.; Elking, Dennis M.; van den Ende, Joost A.; Facelli, Julio C.; Ferraro, Marta B.; Fusti-Molnar, Laszlo; Gatsiou, Christina-Anna; Gee, Thomas S.; de Gelder, René; Ghiringhelli, Luca M.; Goto, Hitoshi; Grimme, Stefan; Guo, Rui; Hofmann, Detlef W. M.; Hoja, Johannes; Hylton, Rebecca K.; Iuzzolino, Luca; Jankiewicz, Wojciech; de Jong, Daniël T.; Kendrick, John; de Klerk, Niek J. J.; Ko, Hsin-Yu; Kuleshova, Liudmila N.; Li, Xiayue; Lohani, Sanjaya; Leusen, Frank J. J.; Lund, Albert M.; Lv, Jian; Ma, Yanming; Marom, Noa; Masunov, Artëm E.; McCabe, Patrick; McMahon, David P.; Meekes, Hugo; Metz, Michael P.; Misquitta, Alston J.; Mohamed, Sharmarke; Monserrat, Bartomeu; Needs, Richard J.; Neumann, Marcus A.; Nyman, Jonas; Obata, Shigeaki; Oberhofer, Harald; Oganov, Artem R.; Orendt, Anita M.; Pagola, Gabriel I.; Pantelides, Constantinos C.; Pickard, Chris J.; Podeszwa, Rafal; Price, Louise S.; Price, Sarah L.; Pulido, Angeles; Read, Murray G.; Reuter, Karsten; Schneider, Elia; Schober, Christoph; Shields, Gregory P.; Singh, Pawanpreet; Sugden, Isaac J.; Szalewicz, Krzysztof; Taylor, Christopher R.; Tkatchenko, Alexandre; Tuckerman, Mark E.; Vacarro, Francesca; Vasileiadis, Manolis; Vazquez-Mayagoitia, Alvaro; Vogt, Leslie; Wang, Yanchao; Watson, Rona E.; de Wijs, Gilles A.; Yang, Jack; Zhu, Qiang; Groom, Colin R.

2016-01-01

The sixth blind test of organic crystal structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible molecule. This blind test has seen substantial growth in the number of participants, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and ‘best practices’ for performing CSP calculations. All of the targets, apart from a single potentially disordered Z′ = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms. PMID:27484368

Ultralocalized thermal reactions in subnanoliter droplets-in-air.

PubMed

Salm, Eric; Guevara, Carlos Duarte; Dak, Piyush; Dorvel, Brian Ross; Reddy, Bobby; Alam, Muhammad Ashraf; Bashir, Rashid

2013-02-26

Miniaturized laboratory-on-chip systems promise rapid, sensitive, and multiplexed detection of biological samples for medical diagnostics, drug discovery, and high-throughput screening. Within miniaturized laboratory-on-chips, static and dynamic droplets of fluids in different immiscible media have been used as individual vessels to perform biochemical reactions and confine the products. Approaches to perform localized heating of these individual subnanoliter droplets can allow for new applications that require parallel, time-, and space-multiplex reactions on a single integrated circuit. Our method positions droplets on an array of individual silicon microwave heaters on chip to precisely control the temperature of droplets-in-air, allowing us to perform biochemical reactions, including DNA melting and detection of single base mismatches. We also demonstrate that ssDNA probe molecules can be placed on heaters in solution, dried, and then rehydrated by ssDNA target molecules in droplets for hybridization and detection. This platform enables many applications in droplets including hybridization of low copy number DNA molecules, lysing of single cells, interrogation of ligand-receptor interactions, and rapid temperature cycling for amplification of DNA molecules.

Applications of biological pores in nanomedicine, sensing, and nanoelectronics

PubMed Central

Majd, Sheereen; Yusko, Erik C; Billeh, Yazan N; Macrae, Michael X; Yang, Jerry; Mayer, Michael

2011-01-01

Biological protein pores and pore-forming peptides can generate a pathway for the flux of ions and other charged or polar molecules across cellular membranes. In nature, these nanopores have diverse and essential functions that range from maintaining cell homeostasis and participating in cell signaling to activating or killing cells. The combination of the nanoscale dimensions and sophisticated – often regulated – functionality of these biological pores make them particularly attractive for the growing field of nanobiotechnology. Applications range from single-molecule sensing to drug delivery and targeted killing of malignant cells. Potential future applications may include the use of nanopores for single strand DNA sequencing and for generating bio-inspired, and possibly, biocompatible visual detection systems and batteries. This article reviews the current state of applications of pore-forming peptides and proteins in nanomedicine, sensing, and nanoelectronics. PMID:20561776

On the existence of Rydberg nuclear molecules

NASA Astrophysics Data System (ADS)

Bertulani, C. A.; Frederico, T.; Hussein, M. S.

2017-11-01

Present nuclear detection techniques prevents us from determining if the analogue of a Rydberg molecule exists for the nuclear case. But nothing in nature disallows their existence. As in the atomic case, Rydberg nuclear molecules would be a laboratory for new aspects and applications of nuclear physics. We propose that Rydberg nuclear molecules, which represent the exotic, halo nuclei version, such as 11Be +11Be, of the well known quasimolecules observed in stable nuclei such as 12C +12C, might be common structures that could manifest their existence along the dripline. A study of possible candidates and the expected structure of such exotic clustering of two halo nuclei: the Rydberg nuclear molecules, is made on the basis of three different methods. It is shown that such cluster structures might be stable and unexpectedly common.

Identification of column edges of DNA fragments by using K-means clustering and mean algorithm on lane histograms of DNA agarose gel electrophoresis images

NASA Astrophysics Data System (ADS)

Turan, Muhammed K.; Sehirli, Eftal; Elen, Abdullah; Karas, Ismail R.

2015-07-01

Gel electrophoresis (GE) is one of the most used method to separate DNA, RNA, protein molecules according to size, weight and quantity parameters in many areas such as genetics, molecular biology, biochemistry, microbiology. The main way to separate each molecule is to find borders of each molecule fragment. This paper presents a software application that show columns edges of DNA fragments in 3 steps. In the first step the application obtains lane histograms of agarose gel electrophoresis images by doing projection based on x-axis. In the second step, it utilizes k-means clustering algorithm to classify point values of lane histogram such as left side values, right side values and undesired values. In the third step, column edges of DNA fragments is shown by using mean algorithm and mathematical processes to separate DNA fragments from the background in a fully automated way. In addition to this, the application presents locations of DNA fragments and how many DNA fragments exist on images captured by a scientific camera.

The spectroscopic characterization of newly developed emissive materials and the effects of environment on their photophysical properties

NASA Astrophysics Data System (ADS)

McNamara, Louis Edward, III

The development of new materials capable of efficient charge transfer and energy storage has become increasingly important in many areas of modern chemical research. This is especially true for the development of emissive optoelectronic devices and in the field of solar to electric energy conversion. The characterization of the photophysical properties of new molecular systems for these applications has become critical in the design and development of these materials. Many molecular building blocks have been developed and understanding the properties of these molecules at a fundamental level is essential for their successful implementation and future engineering. This dissertation focuses on the characterization of some of these newly-developed molecular systems. The spectroscopic studies focus on the characterization of newly-developed molecules based on perylene and indolizine derivatives for solar to electric energy conversion, thienopyrazine derivatives for near infrared (NIR) emissive applications, an SCS pincer complex for blue emissive materials and a fluorescent probe for medical applications. The effects of noncovalent interactions are also investigated on these systems and a benchmark biological molecule trimethylamine N-oxide (TMAO).

Peptide adsorption on the hydrophobic surface: A free energy perspective

NASA Astrophysics Data System (ADS)

Sheng, Yuebiao; Wang, Wei; Chen, P.

2011-05-01

Protein adsorption is a very attractive topic which relates to many novel applications in biomaterials, biotechnology and nanotechnology. Ionic complementary peptides are a group of novel nano-biomaterials with many biomedical applications. In this work, molecular dynamics simulations of the ionic-complementary peptide EAK16-II on a hydrophobic graphite surface were performed under neutral, acidic and basic solution conditions. Adsorption free energy contour maps were obtained by analyzing the dynamical trajectories. Hydrophobic interactions were found to govern the adsorption of the first peptide molecule, and both hydrophobic and electrostatic interactions contributed to the adsorption of the second peptide molecule. Especially under acidic and basic solution conditions, interplay existed among chain-chain hydrophobic, chain-surface hydrophobic and chain-chain electrostatic interactions during the adsorption of the second peptide molecule. Non-charged residues were found to lie on the graphite surface, while charged residue side-chains oriented towards the solution after the peptide deposited on the surface. These results provide a basis for understanding peptide adsorption on the hydrophobic surface under different solution conditions, which is useful for novel applications such as bioactive implant devices and drug delivery material design.

Safety of engineered allergen-specific immunotherapy vaccines

PubMed Central

Focke-Tejkl, Margarete; Valenta, Rudolf

2015-01-01

Purpose of review The purpose of the review is to summarize and comment on recent developments regarding the safety of engineered immunotherapy vaccines. Recent findings In the last 2 years, several studies were published in which allergy vaccines were developed on the basis of chemical modification of natural allergen extracts, the engineering of allergen molecules by recombinant DNA technology and synthetic peptide chemistry, allergen genes, new application routes and conjugation with immune modulatory molecules. Several studies exemplified the general applicability of hypoallergenic vaccines on the basis of recombinant fusion proteins consisting of nonallergenic allergen-derived peptides fused to allergen-unrelated carrier molecules. These vaccines are engineered to reduce both, immunoglobulin E (IgE) as well as allergen-specific T cell epitopes in the vaccines, and thus should provoke less IgE and T-cell-mediated side-effects. They are made to induce allergen-specific IgG antibodies against the IgE-binding sites of allergens with the T-cell help of the carrier molecule. Summary Several interesting examples of allergy vaccines with potentially increased safety profiles have been published. The concept of fusion proteins consisting of allergen-derived hypoallergenic peptides fused to allergen-unrelated proteins that seems to be broadly applicable for a variety of allergens appears to be of particular interest because it promises not only to reduce side-effects but also to increase efficacy and convenience of allergy vaccines. PMID:22885888

Novel alginate-based nanocarriers as a strategy to include high concentrations of hydrophobic compounds in hydrogels for topical application.

PubMed

Nguyen, H T P; Munnier, E; Souce, M; Perse, X; David, S; Bonnier, F; Vial, F; Yvergnaux, F; Perrier, T; Cohen-Jonathan, S; Chourpa, I

2015-01-26

The cutaneous penetration of hydrophobic active molecules is of foremost concern in the dermatology and cosmetic formulation fields. The poor solubility in water of those molecules limits their use in hydrophilic forms such as gels, which are favored by patients with chronic skin disease. The aim of this work is to design a novel nanocarrier of hydrophobic active molecules and to determine its potential as an ingredient of a topical form. The nanocarrier consists of an oily core surrounded by a protective shell of alginate, a natural polysaccharide isolated from brown algae. These calcium alginate-based nanocarriers (CaANCs) were prepared at room temperature and without the use of organic solvent by an accelerated nanoemulsification-polymer crosslinking method. The size (hydrodynamic diameter ~200 nm) and surface charge (zeta potential ~ - 30 mV) of the CaANCs are both compatible with their application on skin. CaANCs loaded with a fluorescent label were stable in model hydrophilic galenic forms under different storage conditions. Curcumin was encapsulated in CaANCs with an efficiency of ~95%, fully retaining its antioxidant activity. The application of the curcumin-loaded CaANCs on excised human skin led to a significant accumulation of the active molecules in the upper layers of the skin, asserting the potential of these nanocarriers in active pharmaceutical and cosmetic ingredients topical delivery.

Novel alginate-based nanocarriers as a strategy to include high concentrations of hydrophobic compounds in hydrogels for topical application

NASA Astrophysics Data System (ADS)

Nguyen, H. T. P.; Munnier, E.; Souce, M.; Perse, X.; David, S.; Bonnier, F.; Vial, F.; Yvergnaux, F.; Perrier, T.; Cohen-Jonathan, S.; Chourpa, I.

2015-06-01

The cutaneous penetration of hydrophobic active molecules is of foremost concern in the dermatology and cosmetic formulation fields. The poor solubility in water of those molecules limits their use in hydrophilic forms such as gels, which are favored by patients with chronic skin disease. The aim of this work is to design a novel nanocarrier of hydrophobic active molecules and to determine its potential as an ingredient of a topical form. The nanocarrier consists of an oily core surrounded by a protective shell of alginate, a natural polysaccharide isolated from brown algae. These calcium alginate-based nanocarriers (CaANCs) were prepared at room temperature and without the use of organic solvent by an accelerated nanoemulsification-polymer crosslinking method. The size (hydrodynamic diameter ˜200 nm) and surface charge (zeta potential ˜ - 30 mV) of the CaANCs are both compatible with their application on skin. CaANCs loaded with a fluorescent label were stable in model hydrophilic galenic forms under different storage conditions. Curcumin was encapsulated in CaANCs with an efficiency of ˜95%, fully retaining its antioxidant activity. The application of the curcumin-loaded CaANCs on excised human skin led to a significant accumulation of the active molecules in the upper layers of the skin, asserting the potential of these nanocarriers in active pharmaceutical and cosmetic ingredients topical delivery.

Alcohol molecules adsorption on graphane nanosheets - A first-principles investigation

NASA Astrophysics Data System (ADS)

Nagarajan, V.; Chandiramouli, R.

2018-05-01

The geometric structure, electronic and adsorption properties of methanol, ethanol and 1-propanol molecules on hydrogenated graphene (graphane) were investigated using first-principles calculations. The stability of graphane base material is confirmed using formation energy and phonon band structures. The adsorption of alcohol molecules on bare graphane and hydrogen vacant graphane nanosheet is found to be prominent and the selectivity of alcohol molecules can be achieved using bare or hydrogen vacant graphane nanosheet. Moreover, the interaction of alcohol molecules on bare and hydrogen vacant graphane nanosheets is studied using the adsorption energy, energy band gap variation, Bader charge transfer and average energy band gap variation. The adsorption energy ranges from -0.149 to -0.383 eV upon alcohol adsorption. The energy gap varies from 4.71 to 2.62 eV for bare graphane and from 4.02 to 3.60 eV for hydrogen vacant graphane nanosheets upon adsorption of alcohol molecules. The adsorption properties of alcohol molecules provide useful information for the possible application of graphane nanosheet as a base material for the detection of alcohol molecules.

Chemozart: a web-based 3D molecular structure editor and visualizer platform.

PubMed

Mohebifar, Mohamad; Sajadi, Fatemehsadat

2015-01-01

Chemozart is a 3D Molecule editor and visualizer built on top of native web components. It offers an easy to access service, user-friendly graphical interface and modular design. It is a client centric web application which communicates with the server via a representational state transfer style web service. Both client-side and server-side application are written in JavaScript. A combination of JavaScript and HTML is used to draw three-dimensional structures of molecules. With the help of WebGL, three-dimensional visualization tool is provided. Using CSS3 and HTML5, a user-friendly interface is composed. More than 30 packages are used to compose this application which adds enough flexibility to it to be extended. Molecule structures can be drawn on all types of platforms and is compatible with mobile devices. No installation is required in order to use this application and it can be accessed through the internet. This application can be extended on both server-side and client-side by implementing modules in JavaScript. Molecular compounds are drawn on the HTML5 Canvas element using WebGL context. Chemozart is a chemical platform which is powerful, flexible, and easy to access. It provides an online web-based tool used for chemical visualization along with result oriented optimization for cloud based API (application programming interface). JavaScript libraries which allow creation of web pages containing interactive three-dimensional molecular structures has also been made available. The application has been released under Apache 2 License and is available from the project website https://chemozart.com.

Smart surface coating of drug nanoparticles with cross-linkable polyethylene glycol for bio-responsive and highly efficient drug delivery

NASA Astrophysics Data System (ADS)

Wei, Weijia; Zhang, Xiujuan; Chen, Xianfeng; Zhou, Mengjiao; Xu, Ruirui; Zhang, Xiaohong

2016-04-01

Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability and minimal premature release of therapeutic molecules during circulation in the blood stream. To meet this requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG molecules can be cross-linked on the surface of the NPs to endow them with greater stability and the cross-link is sensitive to intracellular environment for bio-responsive drug release. With this elegant design, our experimental results show that the liberation of DOX from DOX-cross-linked PEG NPs is dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX release profile can be controlled by tuning the concentration of the reducing agent to break the cross-link between PEG molecules. More importantly, in vivo studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood circulation half-life (>4 h) and intense accumulation in tumor areas, enabling effective anti-cancer therapy. We expect this work will provide a powerful strategy for stabilizing carrier-free nanomedicines and pave the way to their successful clinical applications in the future.Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability and minimal premature release of therapeutic molecules during circulation in the blood stream. To meet this requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG molecules can be cross-linked on the surface of the NPs to endow them with greater stability and the cross-link is sensitive to intracellular environment for bio-responsive drug release. With this elegant design, our experimental results show that the liberation of DOX from DOX-cross-linked PEG NPs is dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX release profile can be controlled by tuning the concentration of the reducing agent to break the cross-link between PEG molecules. More importantly, in vivo studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood circulation half-life (>4 h) and intense accumulation in tumor areas, enabling effective anti-cancer therapy. We expect this work will provide a powerful strategy for stabilizing carrier-free nanomedicines and pave the way to their successful clinical applications in the future. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr09167e

Applications of Fermi-Lowdin-Orbital Self-Interaction Correction Scheme to Organic Systems

NASA Astrophysics Data System (ADS)

Baruah, Tunna; Kao, Der-You; Yamamoto, Yoh

Recent progress in treating the self-interaction errors by means of local, Lowdin-orthogonalized Fermi Orbitals offers a promising route to study the effect of self-interaction errors in the electronic structure of molecules. The Fermi orbitals depend on the location of the electronic positions, called as Fermi orbital descriptors. One advantage of using the Fermi orbitals is that the corrected Hamiltonian is unitarily invariant. Minimization of the corrected energies leads to an optimized set of centroid positions. Here we discuss the applications of this method to various systems from constituent atoms to several medium size molecules such as Mg-porphyrin, C60, pentacene etc. The applications to the ionic systems will also be discussed. De-SC0002168, NSF-DMR 125302.

Electrochemical Detection of the Molecules of Life

NASA Technical Reports Server (NTRS)

Thomson, Seamus; Quinn, Richard; Koehne, Jessica

2017-01-01

All forms of life on Earth contain cellular machinery that can transform and regulate chemical energy through metabolic pathways. These processes are oxidation-reduction reactions that are performed by four key classes of molecules: flavins, nicotinamaides, porphyrins, and quinones. By detecting the electrochemical interaction of these redox-active molecules with an electrode, a method of differentiating them by their class could be established and incorporated into future life-detecting missions. This body of work investigates the electrochemistry of ubiquitous molecules found in life and how they may be detected. Molecules can oxidise or reduce the surface of an electrode - giving or receiving electrons - and these interactions are represented by changes in current with respect to an applied voltage. This relationship varies with: electrolyte type and concentration, working electrode material, the redox-active molecule itself, and scan rate. Flavin adenine dinucleotide (FAD), riboflavin, nicotinamide adenine dinucleotide (NADH), and anthraquinone are all molecules found intracellularly in almost all living organisms. An organism-synthesised extracellular redox-active molecule, Plumbagin, was also selected as part of this study. The goal of this work is to detect these molecules in seawater and assess its application in searching for life on Ocean Worlds.

Surface Biology of DNA by Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Hansma, Helen G.

2001-10-01

The atomic force microscope operates on surfaces. Since surfaces occupy much of the space in living organisms, surface biology is a valid and valuable form of biology that has been difficult to investigate in the past owing to a lack of good technology. Atomic force microscopy (AFM) of DNA has been used to investigate DNA condensation for gene therapy, DNA mapping and sizing, and a few applications to cancer research and to nanotechnology. Some of the most exciting new applications for atomic force microscopy of DNA involve pulling on single DNA molecules to obtain measurements of single-molecule mechanics and thermodynamics.

Polyethylene Glycol Propionaldehydes

NASA Technical Reports Server (NTRS)

Harris, Joe M.; Sedaghat-Herati, Mohammad R.; Karr, Laurel J.

1992-01-01

New class of compounds derived from polyethylene glycol (PEG's) namely, PEG-propionaldehydes, offers two important advantages over other classes of PEG aldehyde derivatives: compounds exhibit selective chemical reactivity toward amino groups and are stable in aqueous environment. PEG's and derivatives used to couple variety of other molecules, such as, to tether protein molecules to surfaces. Biotechnical and biomedical applications include partitioning of two phases in aqueous media; immobilization of such proteins as enzymes, antibodies, and antigens; modification of drugs; and preparation of protein-rejecting surfaces. In addition, surfaces coated with PEG's and derivatives used to control wetting and electroosmosis. Another potential application, coupling to aminated surfaces.

Organic fluorescent dye-based nanomaterials: Advances in the rational design for imaging and sensing applications.

PubMed

Svechkarev, Denis; Mohs, Aaron M

2018-02-25

Self-assembled fluorescent nanomaterials based on small-molecule organic dyes are gaining increasing popularity in imaging and sensing applications over the past decade. This is primarily due to their ability to combine spectral property tunability and biocompatibility of small molecule organic fluorophores with brightness, chemical, and colloidal stability of inorganic materials. Such a unique combination of features comes with rich versatility of dye-based nanomaterials: from aggregates of small molecules to sophisticated core-shell nanoarchitectures involving hyperbranched polymers. Along with the ongoing discovery of new materials and better ways of their synthesis, it is very important to continue systematic studies of fundamental factors that regulate the key properties of fluorescent nanomaterials: their size, polydispersity, colloidal stability, chemical stability, absorption and emission maxima, biocompatibility, and interactions with biological interfaces. In this review, we focus on the systematic description of various types of organic fluorescent nanomaterials, approaches to their synthesis, and ways to optimize and control their characteristics. The discussion is built on examples from reports on recent advances in design and applications of such materials. Conclusions made from this analysis allow a perspective on future development of fluorescent nanomaterials design for biomedical and related applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Application of chemical biology in target identification and drug discovery.

PubMed

Zhu, Yue; Xiao, Ting; Lei, Saifei; Zhou, Fulai; Wang, Ming-Wei

2015-09-01

Drug discovery and development is vital to the well-being of mankind and sustainability of the pharmaceutical industry. Using chemical biology approaches to discover drug leads has become a widely accepted path partially because of the completion of the Human Genome Project. Chemical biology mainly solves biological problems through searching previously unknown targets for pharmacologically active small molecules or finding ligands for well-defined drug targets. It is a powerful tool to study how these small molecules interact with their respective targets, as well as their roles in signal transduction, molecular recognition and cell functions. There have been an increasing number of new therapeutic targets being identified and subsequently validated as a result of advances in functional genomics, which in turn led to the discovery of numerous active small molecules via a variety of high-throughput screening initiatives. In this review, we highlight some applications of chemical biology in the context of drug discovery.

Organic Nanocrystals with Bright Red Persistent Room-Temperature Phosphorescence for Biological Applications.

PubMed

Fateminia, S M Ali; Mao, Zhu; Xu, Shidang; Yang, Zhiyong; Chi, Zhenguo; Liu, Bin

2017-09-25

Persistent room-temperature phosphorescence (RTP) in pure organic materials has attracted great attention because of their unique optical properties. The design of organic materials with bright red persistent RTP remains challenging. Herein, we report a new design strategy for realizing high brightness and long lifetime of red-emissive RTP molecules, which is based on introducing an alkoxy spacer between the hybrid units in the molecule. The spacer offers easy Br-H bond formation during crystallization, which also facilitates intermolecular electron coupling to favor persistent RTP. As the majority of RTP compounds have to be confined in a rigid environment to quench nonradiative relaxation pathways for bright phosphorescence emission, nanocrystallization is used to not only rigidify the molecules but also offer the desirable size and water-dispersity for biomedical applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Molecular Rotation on Charge Transport Phenomena

NASA Astrophysics Data System (ADS)

Garg, O. P.; Lamba, Vijay Kr; Kaushik, D. K.

2015-12-01

The study of electron transport properties of molecular systems could be explained on the basis of the Landauer formalism. Unfortunately, due to the complexity of the experimental setup, most of these measurements have no control over the details of the electrode geometry, rotation of molecules, variation in angle of contacts, effect of fano resonances associated with side groups attached to rigid backbones, which results in a spectrum of IV-characteristics. Theoretical models can therefore help to understand and helps to develop new applications such as molecular sensors, etc. Thus we used simulation methods that generate the required structural ensemble, which is then analyzed with Green’s function methods to characterize the electronic transport properties. In present work we had discussed applications of this approach to understand the conductance in molecular system in the direction of controlling electron transport through molecules and studied the effect of rotation of sandwiched molecule.

Protein Detection via Direct Enzymatic Amplification of Short DNA Aptamers

PubMed Central

Fischer, Nicholas O.; Tarasow, Theodore M.; Tok, Jeffrey B.-H.

2008-01-01

Aptamers are single-stranded nucleic acids that fold into defined tertiary structures to bind target molecules with high specificities and affinities. DNA aptamers have garnered much interest as recognition elements for biodetection and diagnostic applications due to their small size, ease of discovery and synthesis, and chemical and thermal stability. Herein, we describe the design and application of a short DNA molecule capable of both protein target binding and amplifiable bioreadout processes. As both recognition and readout capabilities are incorporated into a single DNA molecule, tedious conjugation procedures required for protein-DNA hybrids can be omitted. The DNA aptamer is designed to be amplified directly by either the polymerase chain reaction (PCR) or rolling circle amplification (RCA) processes, taking advantage of real-time amplification monitoring techniques for target detection. A combination of both RCA and PCR provides a wide protein target dynamic range (1 μM to 10 pM). PMID:17980857

Interaction of Nanostructured Calcium Silicate Hydrate with Ibuprofen Drug Molecules: X-ray Absorption Near Edge Structure (XANES) Study at the Ca, Si and O K-edge

NASA Astrophysics Data System (ADS)

Guo, X. X.; Sham, T. K.; Zhu, Y. J.; Hu, Y. F.

2013-04-01

Mesoporous calcium silicate hydrate (CSH) nanostructure has been proven to be bioactive and biocompatible, and has a bright future in the application of bone treatment among other applications. X-ray absorption near edge structure (XANES) is a powerful tool for the study of the interactions of calcium silicate hydrates with drug molecules because it is element specific and it probes the unoccupied electronic states. Herein, we report the use of the calcium, silicon and oxygen K-edge XANES spectroscopy to identify how drug molecules interact with different groups in calcium silicate hydrate mesoporous nano-carriers with different morphologies. Significant changes are observed in XANES spectra after drug loading into the calcium silicate hydrate system, especially at the Si and O K-edge. The implications of these findings are discussed.

Estimating the domain of applicability for machine learning QSAR models: a study on aqueous solubility of drug discovery molecules.

PubMed

Schroeter, Timon Sebastian; Schwaighofer, Anton; Mika, Sebastian; Ter Laak, Antonius; Suelzle, Detlev; Ganzer, Ursula; Heinrich, Nikolaus; Müller, Klaus-Robert

2007-12-01

We investigate the use of different Machine Learning methods to construct models for aqueous solubility. Models are based on about 4000 compounds, including an in-house set of 632 drug discovery molecules of Bayer Schering Pharma. For each method, we also consider an appropriate method to obtain error bars, in order to estimate the domain of applicability (DOA) for each model. Here, we investigate error bars from a Bayesian model (Gaussian Process (GP)), an ensemble based approach (Random Forest), and approaches based on the Mahalanobis distance to training data (for Support Vector Machine and Ridge Regression models). We evaluate all approaches in terms of their prediction accuracy (in cross-validation, and on an external validation set of 536 molecules) and in how far the individual error bars can faithfully represent the actual prediction error.

Estimating the domain of applicability for machine learning QSAR models: a study on aqueous solubility of drug discovery molecules.

PubMed

Schroeter, Timon Sebastian; Schwaighofer, Anton; Mika, Sebastian; Ter Laak, Antonius; Suelzle, Detlev; Ganzer, Ursula; Heinrich, Nikolaus; Müller, Klaus-Robert

2007-09-01

We investigate the use of different Machine Learning methods to construct models for aqueous solubility. Models are based on about 4000 compounds, including an in-house set of 632 drug discovery molecules of Bayer Schering Pharma. For each method, we also consider an appropriate method to obtain error bars, in order to estimate the domain of applicability (DOA) for each model. Here, we investigate error bars from a Bayesian model (Gaussian Process (GP)), an ensemble based approach (Random Forest), and approaches based on the Mahalanobis distance to training data (for Support Vector Machine and Ridge Regression models). We evaluate all approaches in terms of their prediction accuracy (in cross-validation, and on an external validation set of 536 molecules) and in how far the individual error bars can faithfully represent the actual prediction error.

Drawing the PDB: Protein-Ligand Complexes in Two Dimensions.

PubMed

Stierand, Katrin; Rarey, Matthias

2010-12-09

The two-dimensional representation of molecules is a popular communication medium in chemistry and the associated scientific fields. Computational methods for drawing small molecules with and without manual investigation are well-established and widely spread in terms of numerous software tools. Concerning the planar depiction of molecular complexes, there is considerably less choice. We developed the software PoseView, which automatically generates two-dimensional diagrams of macromolecular complexes, showing the ligand, the interactions, and the interacting residues. All depicted molecules are drawn on an atomic level as structure diagrams; thus, the output plots are clearly structured and easily readable for the scientist. We tested the performance of PoseView in a large-scale application on nearly all druglike complexes of the PDB (approximately 200000 complexes); for more than 92% of the complexes considered for drawing, a layout could be computed. In the following, we will present the results of this application study.

Polyamidoamine Dendrimers for Enhanced Solubility of Small Molecules and Other Desirable Properties for Site Specific Delivery: Insights from Experimental and Computational Studies.

PubMed

Shadrack, Daniel M; Swai, Hulda S; Munissi, Joan J E; Mubofu, Egid B; Nyandoro, Stephen S

2018-06-12

Clinical applications of many small molecules are limited due to poor solubility and lack of controlled release besides lack of other desirable properties. Experimental and computational studies have reported on the therapeutic potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers in pre-clinical and clinical settings. Besides formulation strategies, factors such as pH, PAMAM dendrimer generation, PAMAM dendrimer concentration, nature of the PAMAM core, special ligand and surface modifications of PAMAM dendrimer have an influence on drug solubility and other recommendable pharmacological properties. This review, therefore, compiles the recently reported applications of PAMAM dendrimers in pre-clinical and clinical uses as enhancers of solubility and other desirable properties such as sustained and controlled release, bioavailability, bio-distribution, toxicity reduction or enhancement, and targeted delivery of small molecules with emphasis on cancer treatment.

Estimating the domain of applicability for machine learning QSAR models: a study on aqueous solubility of drug discovery molecules

NASA Astrophysics Data System (ADS)

Schroeter, Timon Sebastian; Schwaighofer, Anton; Mika, Sebastian; Ter Laak, Antonius; Suelzle, Detlev; Ganzer, Ursula; Heinrich, Nikolaus; Müller, Klaus-Robert

2007-12-01

We investigate the use of different Machine Learning methods to construct models for aqueous solubility. Models are based on about 4000 compounds, including an in-house set of 632 drug discovery molecules of Bayer Schering Pharma. For each method, we also consider an appropriate method to obtain error bars, in order to estimate the domain of applicability (DOA) for each model. Here, we investigate error bars from a Bayesian model (Gaussian Process (GP)), an ensemble based approach (Random Forest), and approaches based on the Mahalanobis distance to training data (for Support Vector Machine and Ridge Regression models). We evaluate all approaches in terms of their prediction accuracy (in cross-validation, and on an external validation set of 536 molecules) and in how far the individual error bars can faithfully represent the actual prediction error.

Estimating the domain of applicability for machine learning QSAR models: a study on aqueous solubility of drug discovery molecules

NASA Astrophysics Data System (ADS)

Schroeter, Timon Sebastian; Schwaighofer, Anton; Mika, Sebastian; Ter Laak, Antonius; Suelzle, Detlev; Ganzer, Ursula; Heinrich, Nikolaus; Müller, Klaus-Robert

2007-09-01

We investigate the use of different Machine Learning methods to construct models for aqueous solubility. Models are based on about 4000 compounds, including an in-house set of 632 drug discovery molecules of Bayer Schering Pharma. For each method, we also consider an appropriate method to obtain error bars, in order to estimate the domain of applicability (DOA) for each model. Here, we investigate error bars from a Bayesian model (Gaussian Process (GP)), an ensemble based approach (Random Forest), and approaches based on the Mahalanobis distance to training data (for Support Vector Machine and Ridge Regression models). We evaluate all approaches in terms of their prediction accuracy (in cross-validation, and on an external validation set of 536 molecules) and in how far the individual error bars can faithfully represent the actual prediction error.

PhAST: pharmacophore alignment search tool.

PubMed

Hähnke, Volker; Hofmann, Bettina; Grgat, Tomislav; Proschak, Ewgenij; Steinhilber, Dieter; Schneider, Gisbert

2009-04-15

We present a ligand-based virtual screening technique (PhAST) for rapid hit and lead structure searching in large compound databases. Molecules are represented as strings encoding the distribution of pharmacophoric features on the molecular graph. In contrast to other text-based methods using SMILES strings, we introduce a new form of text representation that describes the pharmacophore of molecules. This string representation opens the opportunity for revealing functional similarity between molecules by sequence alignment techniques in analogy to homology searching in protein or nucleic acid sequence databases. We favorably compared PhAST with other current ligand-based virtual screening methods in a retrospective analysis using the BEDROC metric. In a prospective application, PhAST identified two novel inhibitors of 5-lipoxygenase product formation with minimal experimental effort. This outcome demonstrates the applicability of PhAST to drug discovery projects and provides an innovative concept of sequence-based compound screening with substantial scaffold hopping potential. 2008 Wiley Periodicals, Inc.

Distinguishing Individual DNA Bases in a Network by Non-Resonant Tip-Enhanced Raman Scattering.

PubMed

Zhang, Rui; Zhang, Xianbiao; Wang, Huifang; Zhang, Yao; Jiang, Song; Hu, Chunrui; Zhang, Yang; Luo, Yi; Dong, Zhenchao

2017-05-08

The importance of identifying DNA bases at the single-molecule level is well recognized for many biological applications. Although such identification can be achieved by electrical measurements using special setups, it is still not possible to identify single bases in real space by optical means owing to the diffraction limit. Herein, we demonstrate the outstanding ability of scanning tunneling microscope (STM)-controlled non-resonant tip-enhanced Raman scattering (TERS) to unambiguously distinguish two individual complementary DNA bases (adenine and thymine) with a spatial resolution down to 0.9 nm. The distinct Raman fingerprints identified for the two molecules allow to differentiate in real space individual DNA bases in coupled base pairs. The demonstrated ability of non-resonant Raman scattering with super-high spatial resolution will significantly extend the applicability of TERS, opening up new routes for single-molecule DNA sequencing. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Graphene-based nanoprobes for molecular diagnostics.

PubMed

Chen, Shixing; Li, Fuwu; Fan, Chunhai; Song, Shiping

2015-10-07

In recent years, graphene has received widespread attention owing to its extraordinary electrical, chemical, optical, mechanical and structural properties. Lately, considerable interest has been focused on exploring the potential applications of graphene in life sciences, particularly in disease-related molecular diagnostics. In particular, the coupling of functional molecules with graphene as a nanoprobe offers an excellent platform to realize the detection of biomarkers, such as nucleic acids, proteins and other bioactive molecules, with high performance. This article reviews emerging graphene-based nanoprobes in electrical, optical and other assay methods and their application in various strategies of molecular diagnostics. In particular, this review focuses on the construction of graphene-based nanoprobes and their special advantages for the detection of various bioactive molecules. Properties of graphene-based materials and their functionalization are also comprehensively discussed in view of the development of nanoprobes. Finally, future challenges and perspectives of graphene-based nanoprobes are discussed.

Interstellar molecules and dense clouds.

NASA Technical Reports Server (NTRS)

Rank, D. M.; Townes, C. H.; Welch, W. J.

1971-01-01

Current knowledge of the interstellar medium is discussed on the basis of recent published studies. The subjects considered include optical identification of interstellar molecules, radio molecular lines, interstellar clouds, isotopic abundances, formation and disappearance of interstellar molecules, and interstellar probing techniques. Diagrams are plotted for the distribution of galactic sources exhibiting molecular lines, for hydrogen molecule, hydrogen atom and electron abundances due to ionization, for the densities, velocities and temperature of NH3 in the direction of Sagitarius B2, for the lower rotational energy levels of H2CO, and for temporal spectral variations in masing H2O clouds of the radio source W49. Future applications of the maser and of molecular microscopy in this field are visualized.

DNA-Based Single-Molecule Electronics: From Concept to Function.

PubMed

Wang, Kun

2018-01-17

Beyond being the repository of genetic information, DNA is playing an increasingly important role as a building block for molecular electronics. Its inherent structural and molecular recognition properties render it a leading candidate for molecular electronics applications. The structural stability, diversity and programmability of DNA provide overwhelming freedom for the design and fabrication of molecular-scale devices. In the past two decades DNA has therefore attracted inordinate amounts of attention in molecular electronics. This review gives a brief survey of recent experimental progress in DNA-based single-molecule electronics with special focus on single-molecule conductance and I-V characteristics of individual DNA molecules. Existing challenges and exciting future opportunities are also discussed.

Profiling protein function with small molecule microarrays

PubMed Central

Winssinger, Nicolas; Ficarro, Scott; Schultz, Peter G.; Harris, Jennifer L.

2002-01-01

The regulation of protein function through posttranslational modification, local environment, and protein–protein interaction is critical to cellular function. The ability to analyze on a genome-wide scale protein functional activity rather than changes in protein abundance or structure would provide important new insights into complex biological processes. Herein, we report the application of a spatially addressable small molecule microarray to an activity-based profile of proteases in crude cell lysates. The potential of this small molecule-based profiling technology is demonstrated by the detection of caspase activation upon induction of apoptosis, characterization of the activated caspase, and inhibition of the caspase-executed apoptotic phenotype using the small molecule inhibitor identified in the microarray-based profile. PMID:12167675

DNA-Based Single-Molecule Electronics: From Concept to Function

PubMed Central

2018-01-01

Beyond being the repository of genetic information, DNA is playing an increasingly important role as a building block for molecular electronics. Its inherent structural and molecular recognition properties render it a leading candidate for molecular electronics applications. The structural stability, diversity and programmability of DNA provide overwhelming freedom for the design and fabrication of molecular-scale devices. In the past two decades DNA has therefore attracted inordinate amounts of attention in molecular electronics. This review gives a brief survey of recent experimental progress in DNA-based single-molecule electronics with special focus on single-molecule conductance and I–V characteristics of individual DNA molecules. Existing challenges and exciting future opportunities are also discussed. PMID:29342091

Morphogen Electrochemically Triggered Self-Construction of Polymeric Films Based on Mussel-Inspired Chemistry.

PubMed

Maerten, Clément; Garnier, Tony; Lupattelli, Paolo; Chau, Nguyet Trang Thanh; Schaaf, Pierre; Jierry, Loïc; Boulmedais, Fouzia

2015-12-15

Inspired by the strong chemical adhesion mechanism of mussels, we designed a catechol-based electrochemically triggered self-assembly of films based on ethylene glycol molecules bearing catechol groups on both sides and denoted as bis-catechol molecules. These molecules play the role of morphogens and, in contrast to previously investigated systems, they are also one of the constituents, after reaction, of the film. Unable to interact together, commercially available poly(allylamine hydrochloride) (PAH) chains and bis-catechol molecules are mixed in an aqueous solution and brought in contact with an electrode. By application of defined potential cycles, bis-catechol molecules undergo oxidation leading to molecules bearing "reactive" quinone groups which diffuse toward the solution. In this active state, the quinones react with amino groups of PAH through Michael addition and Schiff's base condensation reaction. The application of cyclic voltammetry (CV) between 0 and 500 mV (vs Ag/AgCl, scan rate of 50 mV/s) of a PAH/bis-catechol solution results in a fast self-construction of a film that reaches a thickness of 40 nm after 60 min. The films present a spiky structure which is attributed to the use of bis-functionalized molecules as one component of the films. XPS measurements show the presence of both PAH and bis-catechol cross-linked together in a covalent way. We show that the amine/catechol ratio is an important parameter which governs the film buildup. For a given amine/catechol ratio, it does exist an optimum CV scan rate leading to a maximum of the film thickness as a function of the scan rate.

FlavorDB: a database of flavor molecules.

PubMed

Garg, Neelansh; Sethupathy, Apuroop; Tuwani, Rudraksh; Nk, Rakhi; Dokania, Shubham; Iyer, Arvind; Gupta, Ayushi; Agrawal, Shubhra; Singh, Navjot; Shukla, Shubham; Kathuria, Kriti; Badhwar, Rahul; Kanji, Rakesh; Jain, Anupam; Kaur, Avneet; Nagpal, Rashmi; Bagler, Ganesh

2018-01-04

Flavor is an expression of olfactory and gustatory sensations experienced through a multitude of chemical processes triggered by molecules. Beyond their key role in defining taste and smell, flavor molecules also regulate metabolic processes with consequences to health. Such molecules present in natural sources have been an integral part of human history with limited success in attempts to create synthetic alternatives. Given their utility in various spheres of life such as food and fragrances, it is valuable to have a repository of flavor molecules, their natural sources, physicochemical properties, and sensory responses. FlavorDB (http://cosylab.iiitd.edu.in/flavordb) comprises of 25,595 flavor molecules representing an array of tastes and odors. Among these 2254 molecules are associated with 936 natural ingredients belonging to 34 categories. The dynamic, user-friendly interface of the resource facilitates exploration of flavor molecules for divergent applications: finding molecules matching a desired flavor or structure; exploring molecules of an ingredient; discovering novel food pairings; finding the molecular essence of food ingredients; associating chemical features with a flavor and more. Data-driven studies based on FlavorDB can pave the way for an improved understanding of flavor mechanisms. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Two Case Studies in the Scientific Method: Antisense Experiments and HIV Vaccination Studies.

ERIC Educational Resources Information Center

Guilfoile, Patrick

1999-01-01

Presents two recent cases that can be used in the classroom to illustrate the application of scientific methods in biological research: (1) the use of a complementary RNA or DNA molecule to block the production or translation of an mRNA molecule; and (2) the development of HIV trial vaccines. Contains 20 references. (WRM)

TNF superfamily: costimulation and clinical applications

PubMed Central

Vinay, Dass S; Kwon, Byoung S

2009-01-01

The molecules concerned with costimulation belong either to the immunoglobulin (Ig) or tumor necrosis factor (TNF) superfamilies. The tumor necrosis superfamily comprises molecules capable of providing both costimulation and cell death. In this review we briefly summarize certain TNF superfamily receptor-ligand pairs that are endowed with costimulatory properties and their importance in health and disease. PMID:19230849

Raman Optical Activity of Biological Molecules

NASA Astrophysics Data System (ADS)

Blanch, Ewan W.; Barron, Laurence D.

Now an incisive probe of biomolecular structure, Raman optical activity (ROA) measures a small difference in Raman scattering from chiral molecules in right- and left-circularly polarized light. As ROA spectra measure vibrational optical activity, they contain highly informative band structures sensitive to the secondary and tertiary structures of proteins, nucleic acids, viruses and carbohydrates as well as the absolute configurations of small molecules. In this review we present a survey of recent studies on biomolecular structure and dynamics using ROA and also a discussion of future applications of this powerful new technique in biomedical research.

Single wall carbon nanotubes dispersion study of different dye molecules and chitosan

NASA Astrophysics Data System (ADS)

Ramli, Muhammad M.; Isa, Siti S. Mat; Abdullah, M. M. A. B.; Murad, S. A. Z.

2017-09-01

Carbon Nanotubes (CNTs) is known for their hydrophobicity ability. However, this ability can become the bottleneck for the application of CNTs where a highly dispersion of materials are needed. In this project, different dispersing agents were investigated namely dye molecules and chitosan. Three different dyes are studied with different concentration, including 0.05 % of chitosan. The dispersion quality is determined by examining through UV-Vis-NIR. The best dispersion quality investigated here is when the concentration of dye molecules is higher, which is around 2.5 mM.

A structural biology perspective on bioactive small molecules and their plant targets.

PubMed

Kumari, Selva; van der Hoorn, Renier A L

2011-10-01

Structural biology efforts in recent years have generated numerous co-crystal structures of bioactive small molecules interacting with their plant targets. These studies include the targets of various phytohormones, pathogen-derived effectors, herbicides and other bioactive compounds. Here we discuss that this collection of structures contains excellent examples of nine collective observations: molecular glues, allostery, inhibitors, molecular mimicry, promiscuous binding sites, unexpected electron densities, natural selection at atomic resolution, and applications in structure-guided mutagenesis and small molecule design. Copyright © 2011 Elsevier Ltd. All rights reserved.

High-Resolution Photoionization, Photoelectron and Photodissociation Studies. Determination of Accurate Energetic and Spectroscopic Database for Combustion Radicals and Molecules

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

Ng, Cheuk-Yiu

2016-04-25

The main goal of this research program was to obtain accurate thermochemical and spectroscopic data, such as ionization energies (IEs), 0 K bond dissociation energies, 0 K heats of formation, and spectroscopic constants for radicals and molecules and their ions of relevance to combustion chemistry. Two unique, generally applicable vacuum ultraviolet (VUV) laser photoion-photoelectron apparatuses have been developed in our group, which have used for high-resolution photoionization, photoelectron, and photodissociation studies for many small molecules of combustion relevance.

Development and Characterization of Liquid Crystal-Gold Nanoparticle Hybrid Materials for Optical Applications

NASA Astrophysics Data System (ADS)

Quint, Makiko T.

Hybrid material, mixtures of two or more materials with new properties, represents an exciting class of new materials for a variety of potential applications such as displays, optoelectronics, and sensors due to their unique physical and optical properties. The scope of this dissertation is to produce two new plasmonic applications by combining liquid crystals with gold nanoparticles. The first application is gold nanoparticle coated liquid crystal thin film. Most liquid crystal (LC) thin films require external voltage to reorient LC molecules. Recent advances in optical controlling technology of LC molecule behavior, resulting in the reduction of energy consumption, have stimulated research and development of new LC thin films. In order to re-orient LC molecules by just using light, the common approach is to include either a photo-responsive LC host, one that require high power light and severely narrows the range of usable materials, or add photo-active dye or polymer layer, photodegradation over time. Our work designing an all-optical method for LC re-orientation that overcomes all the limitations mentioned above. We have successfully both in- and out-of-plane spatial orientation of nematic liquid crystal (LC) molecules by leveraging the highly localized electric fields produced in the near-field regime of a gold nanoparticle (AuNP) layer. This re-orientation of LC molecules in thin LC-AuNP film is all-optical, driven by a small resonance excitation power with the localized surface plasmon absorption of the AuNPs at room temperature. The second application is LC mediated nano-assembled gold microcapsules. This application has a potential in controlled-release cargo-style delivery system. Targeted delivery systems with controlled release mechanisms have been the subject of extensive research more than fifty years. One is to control the release process remotely by using optical excitation. Optical actuation of delivery capsules, which plasmonic nanoparticle such as gold, allows rapid release at specific locations and uses the photothermal effect to unload contents. Almost all gold-based delivery applications including Au coated nanocrystals or AuNPs with soft materials like gels and polymers are not suitable for control release applications in real life since these applications do not provide robust leakage-free containment lower than the American National Standards Institute (ANSI) maximum permissible light exposure limit. We have successfully managed the difficulties mentioned above and produced a new gold-based delivery application. The application is spherical capsules with a densely packed wall of AuNPs. The rigid capsule wall allows encapsulation of cargo that can be contained, virtually leakage-free, over several months. Further, by leveraging LSPR of AuNPs, we can rupture the microshells using optical excitation with ultralow power (< 2 mW), controllably and rapidly releasing the encapsulated contents in less than 5 seconds. Our results exhibiting the capture and optically regulated release of encapsulated substances are a novel platform that combines controlled-release cargo-style delivery and photothermal therapy in one versatile and multifunctional unit. Both our applications are overcoming current limitations and promising future research directions towards the next generation of LC-AuNPs hybrid material research and developments.

Gibbs Free Energy of Hydrolytic Water Molecule in Acyl-Enzyme Intermediates of a Serine Protease: A Potential Application for Computer-Aided Discovery of Mechanism-Based Reversible Covalent Inhibitors.

PubMed

Masuda, Yosuke; Yamaotsu, Noriyuki; Hirono, Shuichi

2017-01-01

In order to predict the potencies of mechanism-based reversible covalent inhibitors, the relationships between calculated Gibbs free energy of hydrolytic water molecule in acyl-trypsin intermediates and experimentally measured catalytic rate constants (k cat ) were investigated. After obtaining representative solution structures by molecular dynamics (MD) simulations, hydration thermodynamics analyses using WaterMap™ were conducted. Consequently, we found for the first time that when Gibbs free energy of the hydrolytic water molecule was lower, logarithms of k cat were also lower. The hydrolytic water molecule with favorable Gibbs free energy may hydrolyze acylated serine slowly. Gibbs free energy of hydrolytic water molecule might be a useful descriptor for computer-aided discovery of mechanism-based reversible covalent inhibitors of hydrolytic enzymes.

Application of the dressed-bound-state molecular strong-field approximation to above-threshold ionization of heteronuclear molecules: NO vs. CO.

PubMed

Busuladžić, M; Hasović, E; Becker, W; Milošević, D B

2012-10-07

We theoretically investigate high-order above-threshold ionization (HATI) of heteronuclear diatomic molecules applying the molecular strong-field approximation which includes dressing of the molecular bound state. We consider HATI of nitrogen monoxide molecules, which are characterized by the π symmetry of their highest occupied molecular orbital. We show that the HATI spectra of NO exhibit characteristic interference structures. We analyze the differences and similarities of the HATI spectra of NO molecules and the spectra of CO (σ symmetry) and O(2) (π(g) symmetry) molecules. The symmetry properties of the molecular HATI spectra governed by linearly and elliptically polarized fields are considered in detail. The yields of high-energy electrons, contributing to the plateau region of the photoelectron spectra, strongly depend on the employed ellipticity.

Quantitative single-molecule imaging by confocal laser scanning microscopy.

PubMed

Vukojevic, Vladana; Heidkamp, Marcus; Ming, Yu; Johansson, Björn; Terenius, Lars; Rigler, Rudolf

2008-11-25

A new approach to quantitative single-molecule imaging by confocal laser scanning microscopy (CLSM) is presented. It relies on fluorescence intensity distribution to analyze the molecular occurrence statistics captured by digital imaging and enables direct determination of the number of fluorescent molecules and their diffusion rates without resorting to temporal or spatial autocorrelation analyses. Digital images of fluorescent molecules were recorded by using fast scanning and avalanche photodiode detectors. In this way the signal-to-background ratio was significantly improved, enabling direct quantitative imaging by CLSM. The potential of the proposed approach is demonstrated by using standard solutions of fluorescent dyes, fluorescently labeled DNA molecules, quantum dots, and the Enhanced Green Fluorescent Protein in solution and in live cells. The method was verified by using fluorescence correlation spectroscopy. The relevance for biological applications, in particular, for live cell imaging, is discussed.

Chirality-dependent cellular uptake of chiral nanocarriers and intracellular delivery of different amounts of guest molecules

NASA Astrophysics Data System (ADS)

Kehr, Nermin Seda; Jose, Joachim

2017-12-01

We demonstrate the organic molecules loaded and chiral polymers coated periodic mesoporous organosilica (PMO) to generate chiral nanocarriers that we used to study chirality-dependent cellular uptake in serum and serum-free media and the subsequent delivery of different amounts of organic molecules into cells. Our results show that the amount of internalized PMO and thus the transported amount of organic molecules by nanocarrier PMO into cells was chirality dependent and controlled by hard/soft protein corona formation on the PMO surfaces. Therefore, this study demonstrate that chiral porous nanocarriers could potentially be used as advanced drug delivery systems which are able to use the specific chiral surface-protein interactions to influence/control the amount of (bio)active molecules delivered to cells in drug delivery and/or imaging applications.

From single-molecule spectroscopy to super-resolution imaging of the neuron: a review

PubMed Central

Laine, Romain F; Kaminski Schierle, Gabriele S; van de Linde, Sebastian; Kaminski, Clemens F

2016-01-01

Abstract For more than 20 years, single-molecule spectroscopy has been providing invaluable insights into nature at the molecular level. The field has received a powerful boost with the development of the technique into super-resolution imaging methods, ca. 10 years ago, which overcome the limitations imposed by optical diffraction. Today, single molecule super-resolution imaging is routinely used in the study of macromolecular function and structure in the cell. Concomitantly, computational methods have been developed that provide information on numbers and positions of molecules at the nanometer-scale. In this overview, we outline the technical developments that have led to the emergence of localization microscopy techniques from single-molecule spectroscopy. We then provide a comprehensive review on the application of the technique in the field of neuroscience research. PMID:28809165

Nanobiodevices for Biomolecule Analysis and Imaging

NASA Astrophysics Data System (ADS)

Yasui, Takao; Kaji, Noritada; Baba, Yoshinobu

2013-06-01

Nanobiodevices have been developed to analyze biomolecules and cells for biomedical applications. In this review, we discuss several nanobiodevices used for disease-diagnostic devices, molecular imaging devices, regenerative medicine, and drug-delivery systems and describe the numerous advantages of nanobiodevices, especially in biological, medical, and clinical applications. This review also outlines the fabrication technologies for nanostructures and nanomaterials, including top-down nanofabrication and bottom-up molecular self-assembly approaches. We describe nanopillar arrays and nanowall arrays for the ultrafast separation of DNA or protein molecules and nanoball materials for the fast separation of a wide range of DNA molecules, and we present examples of applications of functionalized carbon nanotubes to obtain information about subcellular localization on the basis of mobility differences between free fluorophores and fluorophore-labeled carbon nanotubes. Finally, we discuss applications of newly synthesized quantum dots to the screening of small interfering RNA, highly sensitive detection of disease-related proteins, and development of cancer therapeutics and diagnostics.

Applications of biological pores in nanomedicine, sensing, and nanoelectronics.

PubMed

Majd, Sheereen; Yusko, Erik C; Billeh, Yazan N; Macrae, Michael X; Yang, Jerry; Mayer, Michael

2010-08-01

Biological protein pores and pore-forming peptides can generate a pathway for the flux of ions and other charged or polar molecules across cellular membranes. In nature, these nanopores have diverse and essential functions that range from maintaining cell homeostasis and participating in cell signaling to activating or killing cells. The combination of the nanoscale dimensions and sophisticated - often regulated - functionality of these biological pores make them particularly attractive for the growing field of nanobiotechnology. Applications range from single-molecule sensing to drug delivery and targeted killing of malignant cells. Potential future applications may include the use of nanopores for single strand DNA sequencing and for generating bio-inspired, and possibly, biocompatible visual detection systems and batteries. This article reviews the current state of applications of pore-forming peptides and proteins in nanomedicine, sensing, and nanoelectronics. Copyright © 2010 Elsevier Ltd. All rights reserved.

Indium tin oxide with zwitterionic interfacial design for biosensing applications in complex matrices

NASA Astrophysics Data System (ADS)

Darwish, Nadia T.; Alias, Yatimah; Khor, Sook Mei

2015-01-01

Biosensing interfaces consisting of linker molecules (COOH or NH2) and charged, antifouling moieties ((sbnd SO3- and N+(Me)3) for biosensing applications were prepared for the first time by the in situ deposition of mixtures of aryl diazonium cations on indium tin oxide (ITO) electrodes. A linker molecule is required for the attachment of biorecognition molecules (e.g., antibodies, enzymes, DNA chains, and aptamers) close to the transducer surface. The attached molecules improve the biosensing sensitivity and also provide a short response time for analyte detection. Thus, the incorporation of a linker and antifouling molecules is an important interfacial design for both affinity and enzymatic biosensors. The reductive adsorption behavior and electrochemical measurement were studied for (1) an individual compound and (2) a mixture of antifouling zwitterionic molecules together with linker molecules [combination 1: 4-sulfophenyl (SP), 4-trimethylammoniophenyl (TMAP), and 1,4-phenylenediamine (PPD); combination 2: 4-sulfophenyl (SP), 4-trimethylammoniophenyl (TMAP), and 4-aminobenzoic acid (PABA)] of aryl diazonium cations grafted onto an ITO electrode. The mixture ratios of SP:TMAP:PPD and SP:TMAP:PABA that provided the greatest resistance to non-specific protein adsorptions of bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC) and cytochrome c labeled with rhodamine B isothiocyanate (RBITC-Cyt c) were determined by confocal laser scanning microscopy (CLSM). For the surface antifouling study, we used 2-[2-(2-methoxyethoxy) ethoxy]acetic acid (OEG) as a standard control because of its prominent antifouling properties. Surface compositions of combinations 1 and 2 were characterized using X-ray photoelectron spectroscopy (XPS). Field-emission scanning electron microscopy (FE-SEM) was used to characterize the morphology of the grafted films to confirm the even distribution between linker and antifouling molecules grafted onto the ITO surfaces. Combination 1 (SP:TMAP:PPD) with a ratio of 0.5:1.5:0.37 exhibited the best antifouling capability with respect to resisting the nonspecific adsorption of proteins.

Chip-based microtrap arrays for cold polar molecules

NASA Astrophysics Data System (ADS)

Hou, Shunyong; Wei, Bin; Deng, Lianzhong; Yin, Jianping

2017-12-01

Compared to the atomic chip, which has been a powerful platform to perform an astonishing range of applications from rapid Bose-Einstein condensate (BEC) production to the atomic clock, the molecular chip is only in its infant stages. Recently a one-dimensional electric lattice was demonstrated to trap polar molecules on a chip. This excellent work opens up the way to building a molecular chip laboratory. Here we propose a two-dimensional (2D) electric lattice on a chip with concise and robust structure, which is formed by arrays of squared gold wires. Arrays of microtraps that originate in the microsize electrodes offer a steep gradient and thus allow for confining both light and heavy polar molecules. Theoretical analysis and numerical calculations are performed using two types of sample molecules, N D3 and SrF, to justify the possibility of our proposal. The height of the minima of the potential wells is about 10 μm above the surface of the chip and can be easily adjusted in a wide range by changing the voltages applied on the electrodes. These microtraps offer intriguing perspectives for investigating cold molecules in periodic potentials, such as quantum computing science, low-dimensional physics, and some other possible applications amenable to magnetic or optical lattice. The 2D adjustable electric lattice is expected to act as a building block for a future gas-phase molecular chip laboratory.

Nanofabricated Racks of Aligned and Anchored DNA Substrates for Single-Molecule Imaging

PubMed Central

2009-01-01

Single-molecule studies of biological macromolecules can benefit from new experimental platforms that facilitate experimental design and data acquisition. Here we develop new strategies to construct curtains of DNA in which the molecules are aligned with respect to one another and maintained in an extended configuration by anchoring both ends of the DNA to the surface of a microfluidic sample chamber that is otherwise coated with an inert lipid bilayer. This “double-tethered” DNA substrate configuration is established through the use of nanofabricated rack patterns comprised of two distinct functional elements: linear barriers to lipid diffusion that align DNA molecules anchored by one end to the bilayer and antibody-coated pentagons that provide immobile anchor points for the opposite ends of the DNA. These devices enable the alignment and anchoring of thousands of individual DNA molecules, which can then be visualized using total internal reflection fluorescence microscopy under conditions that do not require continuous application of buffer flow to stretch the DNA. This unique strategy offers the potential for studying protein−DNA interactions on large DNA substrates without compromising measurements through application of hydrodynamic force. We provide a proof-of-principle demonstration that double-tethered DNA curtains made with nanofabricated rack patterns can be used in a one-dimensional diffusion assay that monitors the motion of quantum dot-tagged proteins along DNA. PMID:19736980

Nanofabricated racks of aligned and anchored DNA substrates for single-molecule imaging.

PubMed

Gorman, Jason; Fazio, Teresa; Wang, Feng; Wind, Shalom; Greene, Eric C

2010-01-19

Single-molecule studies of biological macromolecules can benefit from new experimental platforms that facilitate experimental design and data acquisition. Here we develop new strategies to construct curtains of DNA in which the molecules are aligned with respect to one another and maintained in an extended configuration by anchoring both ends of the DNA to the surface of a microfluidic sample chamber that is otherwise coated with an inert lipid bilayer. This "double-tethered" DNA substrate configuration is established through the use of nanofabricated rack patterns comprised of two distinct functional elements: linear barriers to lipid diffusion that align DNA molecules anchored by one end to the bilayer and antibody-coated pentagons that provide immobile anchor points for the opposite ends of the DNA. These devices enable the alignment and anchoring of thousands of individual DNA molecules, which can then be visualized using total internal reflection fluorescence microscopy under conditions that do not require continuous application of buffer flow to stretch the DNA. This unique strategy offers the potential for studying protein-DNA interactions on large DNA substrates without compromising measurements through application of hydrodynamic force. We provide a proof-of-principle demonstration that double-tethered DNA curtains made with nanofabricated rack patterns can be used in a one-dimensional diffusion assay that monitors the motion of quantum dot-tagged proteins along DNA.

Surface charge sensing by altering the phase transition in VO2

NASA Astrophysics Data System (ADS)

Kumar, S.; Esfandyarpour, R.; Davis, R.; Nishi, Y.

2014-08-01

Detection of surface charges has various applications in medicine, electronics, biotechnology, etc. The source of surface charge induction may range from simple charge-polarized molecules like water to complicated proteins. It was recently discovered that surface charge accumulation can alter the temperature at which VO2 undergoes a Mott transition. Here, we deposited polar molecules onto the surface of two-terminal thin-film VO2 lateral devices and monitored the joule-heating-driven Mott transition, or conductance switching. We observed that the power required to induce the conductance switching reduced upon treatment with polar molecules and, using in-situ blackbody-emission direct measurement of local temperature, we show that this reduction in power was accompanied by reduction in the Mott transition temperature. Further evidence suggested that this effect has specificity to the nature of the species used to induce surface charges. Using x-ray absorption spectroscopy, we also show that there is no detectable change in oxidation state of vanadium or structural phase in the bulk of the 40 nm VO2 thin-film even as the phase transition temperature is reduced by up to 20 K by the polar molecules. The ability to alter the phase transition parameters by depositing polar molecules suggests a potential application in sensing surface charges of different origins and this set of results also highlights interesting aspects of the phase transition in VO2.

Antimicrobial Activity of Lactoferrin-Related Peptides and Applications in Human and Veterinary Medicine.

PubMed

Bruni, Natascia; Capucchio, Maria Teresa; Biasibetti, Elena; Pessione, Enrica; Cirrincione, Simona; Giraudo, Leonardo; Corona, Antonio; Dosio, Franco

2016-06-11

Antimicrobial peptides (AMPs) represent a vast array of molecules produced by virtually all living organisms as natural barriers against infection. Among AMP sources, an interesting class regards the food-derived bioactive agents. The whey protein lactoferrin (Lf) is an iron-binding glycoprotein that plays a significant role in the innate immune system, and is considered as an important host defense molecule. In search for novel antimicrobial agents, Lf offers a new source with potential pharmaceutical applications. The Lf-derived peptides Lf(1-11), lactoferricin (Lfcin) and lactoferrampin exhibit interesting and more potent antimicrobial actions than intact protein. Particularly, Lfcin has demonstrated strong antibacterial, anti-fungal and antiparasitic activity with promising applications both in human and veterinary diseases (from ocular infections to osteo-articular, gastrointestinal and dermatological diseases).

Molecular structure, functionality and applications of oxidized starches: A review.

PubMed

Vanier, Nathan Levien; El Halal, Shanise Lisie Mello; Dias, Alvaro Renato Guerra; da Rosa Zavareze, Elessandra

2017-04-15

During oxidation, the hydroxyl groups of starch molecules are first oxidized to carbonyl groups, then to carboxyl groups. The contents of the carbonyl and carboxyl groups in a starch molecule therefore indicate the extent of starch oxidation. The mechanisms of starch oxidation with different oxidizing agents, including sodium hypochlorite, hydrogen peroxide, ozone and sodium periodate, are described in this review. The effects of these oxidizing agents on the molecular, physicochemical, thermal, pasting and morphological properties of starch are described as well. In addition, the main industrial applications of oxidized starches are presented. The present review is important for understanding the effects of oxidation on starch properties, and this information may facilitate the development of novel oxidized starches for both food and non-food applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Method of Continuous Variations: Applications of Job Plots to the Study of Molecular Associations in Organometallic Chemistry[**

PubMed Central

Renny, Joseph S.; Tomasevich, Laura L.; Tallmadge, Evan H.; Collum, David B.

2014-01-01

Applications of the method of continuous variations—MCV or the Method of Job—to problems of interest to organometallic chemists are described. MCV provides qualitative and quantitative insights into the stoichiometries underlying association of m molecules of A and n molecules of B to form AmBn. Applications to complex ensembles probe associations that form metal clusters and aggregates. Job plots in which reaction rates are monitored provide relative stoichiometries in rate-limiting transition structures. In a specialized variant, ligand- or solvent-dependent reaction rates are dissected into contributions in both the ground states and transition states, which affords insights into the full reaction coordinate from a single Job plot. Gaps in the literature are identified and critiqued. PMID:24166797

Multilayer Choline Phosphate Molecule Modified Surface with Enhanced Cell Adhesion but Resistance to Protein Adsorption.

PubMed

Chen, Xingyu; Yang, Ming; Liu, Botao; Li, Zhiqiang; Tan, Hong; Li, Jianshu

2017-08-22

Choline phosphate (CP), which is a new zwitterionic molecule, and has the reverse order of phosphate choline (PC) and could bind to the cell membrane though the unique CP-PC interaction. Here we modified a glass surface with multilayer CP molecules using surface-initiated atom-transfer radical polymerization (SI-ATRP) and the ring-opening method. Polymeric brushes of (dimethylamino)ethyl methacrylate (DMAEMA) were synthesized by SI-ATRP from the glass surface. Then the grafted PDMAEMA brushes were used to introduce CP groups to fabricate the multilayer CP molecule modified surface. The protein adsorption experiment and cell culture test were used to evaluate the biocompatibility of the modified surfaces by using human umbilical veinendothelial cells (HUVECs). The protein adsorption results demonstrated that the multilayer CP molecule decorated surface could prevent the adsorption of fibrinogen and serum protein. The adhesion and proliferation of cells were improved significantly on the multilayer CP molecule modified surface. Therefore, the biocompatibility of the material surface could be improved by the modified multilayer CP molecule, which exhibits great potential for biomedical applications, e.g., scaffolds in tissue engineering.

Porous materials with pre-designed single-molecule traps for CO2 selective adsorption

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

Li, JR; Yu, JM; Lu, WG

2013-02-26

Despite tremendous efforts, precise control in the synthesis of porous materials with pre-designed pore properties for desired applications remains challenging. Newly emerged porous metal-organic materials, such as metal-organic polyhedra and metal-organic frameworks, are amenable to design and property tuning, enabling precise control of functionality by accurate design of structures at the molecular level. Here we propose and validate, both experimentally and computationally, a precisely designed cavity, termed a 'single-molecule trap', with the desired size and properties suitable for trapping target CO2 molecules. Such a single-molecule trap can strengthen CO2-host interactions without evoking chemical bonding, thus showing potential for CO2 capture.more » Molecular single-molecule traps in the form of metal-organic polyhedra are designed, synthesised and tested for selective adsorption of CO2 over N-2 and CH4, demonstrating the trapping effect. Building these pre-designed single-molecule traps into extended frameworks yields metal-organic frameworks with efficient mass transfer, whereas the CO2 selective adsorption nature of single-molecule traps is preserved.« less

Quantitative Aspects of Single Molecule Microscopy

PubMed Central

Ober, Raimund J.; Tahmasbi, Amir; Ram, Sripad; Lin, Zhiping; Ward, E. Sally

2015-01-01

Single molecule microscopy is a relatively new optical microscopy technique that allows the detection of individual molecules such as proteins in a cellular context. This technique has generated significant interest among biologists, biophysicists and biochemists, as it holds the promise to provide novel insights into subcellular processes and structures that otherwise cannot be gained through traditional experimental approaches. Single molecule experiments place stringent demands on experimental and algorithmic tools due to the low signal levels and the presence of significant extraneous noise sources. Consequently, this has necessitated the use of advanced statistical signal and image processing techniques for the design and analysis of single molecule experiments. In this tutorial paper, we provide an overview of single molecule microscopy from early works to current applications and challenges. Specific emphasis will be on the quantitative aspects of this imaging modality, in particular single molecule localization and resolvability, which will be discussed from an information theoretic perspective. We review the stochastic framework for image formation, different types of estimation techniques and expressions for the Fisher information matrix. We also discuss several open problems in the field that demand highly non-trivial signal processing algorithms. PMID:26167102

Statistical Mechanical Theory of Coupled Slow Dynamics in Glassy Polymer-Molecule Mixtures

NASA Astrophysics Data System (ADS)

Zhang, Rui; Schweizer, Kenneth

The microscopic Elastically Collective Nonlinear Langevin Equation theory of activated relaxation in one-component supercooled liquids and glasses is generalized to polymer-molecule mixtures. The key idea is to account for dynamic coupling between molecule and polymer segment motion. For describing the molecule hopping event, a temporal casuality condition is formulated to self-consistently determine a dimensionless degree of matrix distortion relative to the molecule jump distance based on the concept of coupled dynamic free energies. Implementation for real materials employs an established Kuhn sphere model of the polymer liquid and a quantitative mapping to a hard particle reference system guided by the experimental equation-of-state. The theory makes predictions for the mixture dynamic shear modulus, activated relaxation time and diffusivity of both species, and mixture glass transition temperature as a function of molecule-Kuhn segment size ratio and attraction strength, composition and temperature. Model calculations illustrate the dynamical behavior in three distinct mixture regimes (fully miscible, bridging, clustering) controlled by the molecule-polymer interaction or chi-parameter. Applications to specific experimental systems will be discussed.

Estimation of boiling points using density functional theory with polarized continuum model solvent corrections.

PubMed

Chan, Poh Yin; Tong, Chi Ming; Durrant, Marcus C

2011-09-01

An empirical method for estimation of the boiling points of organic molecules based on density functional theory (DFT) calculations with polarized continuum model (PCM) solvent corrections has been developed. The boiling points are calculated as the sum of three contributions. The first term is calculated directly from the structural formula of the molecule, and is related to its effective surface area. The second is a measure of the electronic interactions between molecules, based on the DFT-PCM solvation energy, and the third is employed only for planar aromatic molecules. The method is applicable to a very diverse range of organic molecules, with normal boiling points in the range of -50 to 500 °C, and includes ten different elements (C, H, Br, Cl, F, N, O, P, S and Si). Plots of observed versus calculated boiling points gave R²=0.980 for a training set of 317 molecules, and R²=0.979 for a test set of 74 molecules. The role of intramolecular hydrogen bonding in lowering the boiling points of certain molecules is quantitatively discussed. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Ultracold molecules for the masses: Evaporative cooling and magneto-optical trapping

NASA Astrophysics Data System (ADS)

Stuhl, B. K.

While cold molecule experiments are rapidly moving towards their promised benefits of precision spectroscopy, controllable chemistry, and novel condensed phases, heretofore the field has been greatly limited by a lack of methods to cool and compress chemically diverse species to temperatures below ten millikelvin. While in atomic physics these needs are fulfilled by laser cooling, magneto-optical trapping, and evaporative cooling, until now none of these techniques have been applicable to molecules. In this thesis, two major breakthroughs are reported. The first is the observation of evaporative cooling in magnetically trapped hydroxyl (OH) radicals, which potentially opens a path all the way to Bose-Einstein condensation of dipolar radicals, as well as allowing cold- and ultracold-chemistry studies of fundamental reaction mechanisms. Through the combination of an extremely high gradient magnetic quadrupole trap and the use of the OH Λ-doublet transition to enable highly selective forced evaporation, cooling by an order of magnitude in temperature was achieved and yielded a final temperature no higher than 5mK. The second breakthrough is the successful application of laser cooling and magneto-optical trapping to molecules. Motivated by a proposal in this thesis, laser cooling of molecules is now known to be technically feasible in a select but substantial pool of diatomic molecules. The demonstration of not only Doppler cooling but also two-dimensional magneto-optical trapping in yttrium (II) oxide, YO, is expected to enable rapid growth in the availability of ultracold molecules—just as the invention of the atomic magneto-optical trap stimulated atomic physics twenty-five years ago.

Advances in the treatment of explicit water molecules in docking and binding free energy calculations.

PubMed

Hu, Xiao; Maffucci, Irene; Contini, Alessandro

2018-05-13

The inclusion of direct effects mediated by water during the ligand-receptor recognition is a hot-topic of modern computational chemistry applied to drug discovery and development. Docking or virtual screening with explicit hydration is still debatable, despite the successful cases that have been presented in the last years. Indeed, how to select the water molecules that will be included in the docking process or how the included waters should be treated remain open questions. In this review, we will discuss some of the most recent methods that can be used in computational drug discovery and drug development when the effect of a single water, or of a small network of interacting waters, needs to be explicitly considered. Here, we analyse software to aid the selection, or to predict the position, of water molecules that are going to be explicitly considered in later docking studies. We also present software and protocols able to efficiently treat flexible water molecules during docking, including examples of applications. Finally, we discuss methods based on molecular dynamics simulations that can be used to integrate docking studies or to reliably and efficiently compute binding energies of ligands in presence of interfacial or bridging water molecules. Software applications aiding the design of new drugs that exploit water molecules, either as displaceable residues or as bridges to the receptor, are constantly being developed. Although further validation is needed, workflows that explicitly consider water will probably become a standard for computational drug discovery soon. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Molecular Mechanics: Illustrations of Its Application.

ERIC Educational Resources Information Center

Cox, Philip J.

1982-01-01

The application of molecular mechanics (a nonquantum mechanical method for solving problems concerning molecular geometries) to calculate force fields for n-butane and cyclohexane is discussed. Implications regarding the stable conformations of the example molecules are also discussed. (Author/SK)

Supramolecular Systems and Chemical Reactions in Single-Molecule Break Junctions.

PubMed

Li, Xiaohui; Hu, Duan; Tan, Zhibing; Bai, Jie; Xiao, Zongyuan; Yang, Yang; Shi, Jia; Hong, Wenjing

2017-04-01

The major challenges of molecular electronics are the understanding and manipulation of the electron transport through the single-molecule junction. With the single-molecule break junction techniques, including scanning tunneling microscope break junction technique and mechanically controllable break junction technique, the charge transport through various single-molecule and supramolecular junctions has been studied during the dynamic fabrication and continuous characterization of molecular junctions. This review starts from the charge transport characterization of supramolecular junctions through a variety of noncovalent interactions, such as hydrogen bond, π-π interaction, and electrostatic force. We further review the recent progress in constructing highly conductive molecular junctions via chemical reactions, the response of molecular junctions to external stimuli, as well as the application of break junction techniques in controlling and monitoring chemical reactions in situ. We suggest that beyond the measurement of single molecular conductance, the single-molecule break junction techniques provide a promising access to study molecular assembly and chemical reactions at the single-molecule scale.

Controlling Plasmon-Enhanced Fluorescence via Intersystem Crossing in Photoswitchable Molecules.

PubMed

Wang, Mingsong; Hartmann, Gregory; Wu, Zilong; Scarabelli, Leonardo; Rajeeva, Bharath Bangalore; Jarrett, Jeremy W; Perillo, Evan P; Dunn, Andrew K; Liz-Marzán, Luis M; Hwang, Gyeong S; Zheng, Yuebing

2017-10-01

By harnessing photoswitchable intersystem crossing (ISC) in spiropyran (SP) molecules, active control of plasmon-enhanced fluorescence in the hybrid systems of SP molecules and plasmonic nanostructures is achieved. Specifically, SP-derived merocyanine (MC) molecules formed by photochemical ring-opening reaction display efficient ISC due to their zwitterionic character. In contrast, ISC in quinoidal MC molecules formed by thermal ring-opening reaction is negligible. The high ISC rate can improve fluorescence quantum yield of the plasmon-modified spontaneous emission, only when the plasmonic electromagnetic field enhancement is sufficiently high. Along this line, extensive photomodulation of fluorescence is demonstrated by switching the ISC in MC molecules at Au nanoparticle aggregates, where strongly enhanced plasmonic hot spots exist. The ISC-mediated plasmon-enhanced fluorescence represents a new approach toward controlling the spontaneous emission of fluorophores near plasmonic nanostructures, which expands the applications of active molecular plasmonics in information processing, biosensing, and bioimaging. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design and engineering of organic molecules for customizable Terahertz tags

NASA Astrophysics Data System (ADS)

Ray, Shaumik; Dash, Jyotirmayee; Nallappan, Kathirvel; Kaware, Vaibhav; Basutkar, Nitin; Ambade, Ashootosh; Joshi, Kavita; Pesala, Bala

2014-03-01

Terahertz (THz) frequency band lies between the microwave and infrared region of the electromagnetic spectrum. Molecules having strong resonances in this frequency range are ideal for realizing "Terahertz tags" which can be easily incorporated into various materials. THz spectroscopy of molecules, especially at frequencies below 10 THz, provides valuable information on the low frequency vibrational modes, viz. intermolecular vibrational modes, hydrogen bond stretching, torsional vibrations in several chemical and biological compounds. So far there have been very few attempts to engineer molecules which can demonstrate customizable resonances in the THz frequency region. In this paper, Diamidopyridine (DAP) based molecules are used as a model system to demonstrate engineering of THz resonances (< 10 THz) by fine-tuning the molecular mass and bond strengths. Density Functional Theory (DFT) simulations have been carried out to explain the origin of THz resonances and factors contributing to the shift in resonances due to the addition of various functional groups. The design approach presented here can be easily extended to engineer various organic molecules suitable for THz tags application.

Chitosugar translocation by an unexpressed monomeric protein channel

NASA Astrophysics Data System (ADS)

Soysa, H. Sasimali M.; Suginta, Wipa; Moonsap, Watcharaporn; Smith, M. F.

2018-05-01

The outer membrane protein channel Ec ChiP , associated with a silent gene in E . coli, is a monomeric chitoporin. In a glucose-deficient environment, E . coli can express the ChiP gene to exploit chitin degradation products. Single-channel small ion current measurements, which reveal the dynamics of single sugar molecules trapped in channel, are used here to study the exotic transport of chitosugars by E . coli. Molecules escape from the channel on multiple timescales. Voltage-dependent trapping rates observed for charged chitosan molecules, as well as model calculations, indicate that the rapid escape processes are those in which the molecule escapes back to the side of the membrane from which it originated. The probability that a sugar molecule is translocated through the membrane is thus estimated from the current data and the dependence of this translocation probability on the length of the chitosugar molecule and the applied voltage analyzed. The described method for obtaining the translocation probability and related molecular translocation current is applicable to other transport channels.

Effect of different substitution position on the switching behavior in single-molecule device with carbon nanotube electrodes

NASA Astrophysics Data System (ADS)

Yang, Jingjuan; Han, Xiaoxiao; Yuan, Peipei; Bian, Baoan; Wang, Yixiang

2018-01-01

We investigate the electronic transport properties of dihydroazulene (DHA) and vinylheptafulvene (VHF) molecule sandwiched between two carbon nanotubes using density functional theory and non-equilibrium Green's function. The device displays significantly switching behavior between DHA and VHF isomerizations. It is found the different substitution position of F in the molecule influences the switching ratio of device, which is analyzed by transmission spectra and molecular projected self-consistent Hamiltonian. The observed negative differential resistance effect is explained by transmission spectra and transmission eigenstates of transmission peak in the bias window. The observed reverse of current in VHF form in which two H atoms on the right side of the benzene ring of the molecule are replaced by F is explained by transmission spectra and molecule-electrode coupling with the varied bias. The results suggest that the reasonable substitution position of molecule may improve the switching ratio, displaying a potential application in future molecular circuit.

Covalent modification of a ten-residue cationic antimicrobial peptide with levofloxacin

NASA Astrophysics Data System (ADS)

Rodriguez, Carlos; Papanastasiou, Emilios; Juba, Melanie; Bishop, Barney

2014-09-01

The rampant spread of antibiotic resistant bacteria has spurred interest in alternative strategies for developing next-generation antibacterial therapies. As such, there has been growing interest in cationic antimicrobial peptides (CAMPs) and their therapeutic applications. Modification of CAMPs via conjugation to auxiliary compounds, including small molecule drugs, is a new approach to developing effective, broad-spectrum antibacterial agents with novel physicochemical properties and versatile antibacterial mechanisms. Here, we’ve explored design parameters for engineering CAMPs conjugated to small molecules with favorable physicochemical and antibacterial properties by covalently affixing a fluoroquinolone antibiotic, levofloxacin, to the ten-residue CAMP Pep-4. Relative to the unmodified Pep-4, the conjugate was found to demonstrate substantially increased antibacterial potency under high salt concentrations. Historically, it has been observed that most CAMPs lose antibacterial effectiveness in such high ionic strength environments, a fact that has presented a challenge to their development as therapeutics. Physicochemical studies revealed that P4LC was more hydrophobic than Pep-4, while mechanistic findings indicated that the conjugate was more effective at disrupting bacterial membrane integrity. Although the inherent antibacterial effect of the incorporated levofloxacin molecules did not appear to be substantially realized in this conjugate, these findings nevertheless suggest that covalent attachment of small molecule antibiotics with favorable physicochemical properties to CAMPs could be a promising strategy for enhancing peptide performance and overall therapeutic potential. These results have broader applicability to the development of future CAMP-antibiotic conjugates for potential therapeutic applications.

Molecular imprinted polymers for separation science: a review of reviews.

PubMed

Cheong, Won Jo; Yang, Song Hee; Ali, Faiz

2013-02-01

Molecular imprinted polymer is an artificial receptor made by imprinting molecules of a template in a polymer matrix followed by removing the template molecules via thorough washing to give the permanent template grooves. They show favored affinity to the template molecule compared to other molecules, and this property is the basic driving force for such diverse application of this techniques. Such techniques have been increasingly employed in a wide scope of applications such as chromatography, sample pretreatment, purification, catalysts, sensors, and drug delivery, etc., mostly in bioanalytical areas. A major part of them is related to development of new stationary phases and their application in chromatography and sample pretreatment. Embodiments of molecular imprinted polymer materials have been carried out in a variety of forms such as irregularly ground particles, regular spherical particles, nanoparticles, monoliths in a stainless steel or capillary column, open tubular layers in capillaries, surface attached thin layers, membranes, and composites, etc. There have been numerous review articles on molecular imprinted polymer issues. In this special review, the reviews in recent ca. 10 years will be categorized into several subgroups according to specified topics in separation science, and each review in each subgroup will be introduced in the order of date with brief summaries and comments on new developments and different scopes of prospects. Brief summaries of each categories and conclusive future perspectives are also given. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Simple Method to Determine the "R" or "S" Configuration of Molecules with an Axis of Chirality

ERIC Educational Resources Information Center

Wang, Cunde; Wu, Weiming

2011-01-01

A simple method for the "R" or "S" designation of molecules with an axis of chirality is described. The method involves projection of the substituents along the chiral axis, utilizes the Cahn-Ingold-Prelog sequence rules in assigning priority to the substituents, is easy to use, and has broad applicability. (Contains 5 figures.)

Interactively Applying the Variational Method to the Dihydrogen Molecule: Exploring Bonding and Antibonding

ERIC Educational Resources Information Center

Cruzeiro, Vinícius Wilian D.; Roitberg, Adrian; Polfer, Nicolas C.

2016-01-01

In this work we are going to present how an interactive platform can be used as a powerful tool to allow students to better explore a foundational problem in quantum chemistry: the application of the variational method to the dihydrogen molecule using simple Gaussian trial functions. The theoretical approach for the hydrogen atom is quite…

A Review: Fundamental Aspects of Silicate Mesoporous Materials

PubMed Central

ALOthman, Zeid A.

2012-01-01

Silicate mesoporous materials have received widespread interest because of their potential applications as supports for catalysis, separation, selective adsorption, novel functional materials, and use as hosts to confine guest molecules, due to their extremely high surface areas combined with large and uniform pore sizes. Over time a constant demand has developed for larger pores with well-defined pore structures. Silicate materials, with well-defined pore sizes of about 2.0–10.0 nm, surpass the pore-size constraint (<2.0 nm) of microporous zeolites. They also possess extremely high surface areas (>700 m2 g−1) and narrow pore size distributions. Instead of using small organic molecules as templating compounds, as in the case of zeolites, long chain surfactant molecules were employed as the structure-directing agent during the synthesis of these highly ordered materials. The structure, composition, and pore size of these materials can be tailored during synthesis by variation of the reactant stoichiometry, the nature of the surfactant molecule, the auxiliary chemicals, the reaction conditions, or by post-synthesis functionalization techniques. This review focuses mainly on a concise overview of silicate mesoporous materials together with their applications. Perusal of the review will enable researchers to obtain succinct information about microporous and mesoporous materials.

Automated insertion of sequences into a ribosomal RNA alignment: An application of computational linguistics in molecular biology

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

Taylor, R.C.

This thesis involved the construction of (1) a grammar that incorporates knowledge on base invariancy and secondary structure in a molecule and (2) a parser engine that uses the grammar to position bases into the structural subunits of the molecule. These concepts were combined with a novel pinning technique to form a tool that semi-automates insertion of a new species into the alignment for the 16S rRNA molecule (a component of the ribosome) maintained by Dr. Carl Woese's group at the University of Illinois at Urbana. The tool was tested on species extracted from the alignment and on a groupmore » of entirely new species. The results were very encouraging, and the tool should be substantial aid to the curators of the 16S alignment. The construction of the grammar was itself automated, allowing application of the tool to alignments for other molecules. The logic programming language Prolog was used to construct all programs involved. The computational linguistics approach used here was found to be a useful way to attach the problem of insertion into an alignment.« less

Automated insertion of sequences into a ribosomal RNA alignment: An application of computational linguistics in molecular biology

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

Taylor, Ronald C.

This thesis involved the construction of (1) a grammar that incorporates knowledge on base invariancy and secondary structure in a molecule and (2) a parser engine that uses the grammar to position bases into the structural subunits of the molecule. These concepts were combined with a novel pinning technique to form a tool that semi-automates insertion of a new species into the alignment for the 16S rRNA molecule (a component of the ribosome) maintained by Dr. Carl Woese`s group at the University of Illinois at Urbana. The tool was tested on species extracted from the alignment and on a groupmore » of entirely new species. The results were very encouraging, and the tool should be substantial aid to the curators of the 16S alignment. The construction of the grammar was itself automated, allowing application of the tool to alignments for other molecules. The logic programming language Prolog was used to construct all programs involved. The computational linguistics approach used here was found to be a useful way to attach the problem of insertion into an alignment.« less

Peptide-based ambidextrous bifunctional gelator: applications in oil spill recovery and removal of toxic organic dyes for waste water management.

PubMed

Basu, Kingshuk; Nandi, Nibedita; Mondal, Biplab; Dehsorkhi, Ashkan; Hamley, Ian W; Banerjee, Arindam

2017-12-06

A low molecular weight peptide-based ambidextrous gelator molecule has been discovered for efficient control of water pollution. The gelator molecules can gel various organic solvents with diverse polarity, e.g. n -hexane, n -octane, petroleum ether, petrol, diesel, aromatic solvents like chlorobenzene, toluene, benzene, o -xylene and even aqueous phosphate buffer of pH 7.5. These gels have been thoroughly characterized using various techniques including field emission scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray powder diffraction analysis, small angle X-ray scattering and rheological experiments. Interestingly, hydrogel obtained from the gelator molecule has been found to absorb toxic organic dyes (both cationic and anionic dyes) from dye-contaminated water. The gelator molecule can be reused for several cycles, indicating its possible future use in waste water management. Moreover, this gelator can selectively gel petrol, diesel, pump oil from an oil-water mixture in the presence of a carrier solvent, ethyl acetate, suggesting its efficient application for oil spill recovery. These results indicate that the peptide-based ambidextrous gelator produces soft materials (gels) with dual function: (i) removal of toxic organic dyes in waste water treatment and (ii) oil spill recovery.

Remote excitation fluorescence correlation spectroscopy using silver nanowires

NASA Astrophysics Data System (ADS)

Su, Liang; Yuan, Haifeng; Lu, Gang; Hofkens, Johan; Roeffaers, Maarten; Uji-i, Hiroshi

2014-11-01

Fluorescence correlation spectroscopy (FCS), a powerful tool to resolve local properties, dynamical process of molecules, rotational and translational diffusion motions, relies on the fluctuations of florescence observables in the observation volume. In the case of rare transition events or small dynamical fluctuations, FCS requires few molecules or even single molecules in the observation volume at a time to minimize the background signals. Metal nanoparticle which possess unique localized surface plasmon resonance (LSPR) have been used to reduce the observation volume down to sub-diffraction limited scale while maintain at high analyst concentration up to tens of micromolar. Nevertheless, the applications of functionalized nanoparticles in living cell are limited due to the continuous diffusion after cell uptake, which makes it difficult to target the region of interests in the cell. In this work, we demonstrate the use of silver nanowires for remote excitation FCS on fluorescent molecules in solution. By using propagation surface plasmon polaritons (SPPs) which supported by the silver nanowire to excite the fluorescence, both illumination and observation volume can be reduced simultaneously. In such a way, less perturbation is induced to the target region, and this will broaden the application scope of silver nanowire as tip in single cell endoscopy.

Design of an ectoine-responsive AraC mutant and its application in metabolic engineering of ectoine biosynthesis.

PubMed

Chen, Wei; Zhang, Shan; Jiang, Peixia; Yao, Jun; He, Yongzhi; Chen, Lincai; Gui, Xiwu; Dong, Zhiyang; Tang, Shuang-Yan

2015-07-01

Advanced high-throughput screening methods for small molecules may have important applications in the metabolic engineering of the biosynthetic pathways of these molecules. Ectoine is an excellent osmoprotectant that has been widely used in cosmetics. In this study, the Escherichia coli regulatory protein AraC was engineered to recognize ectoine as its non-natural effector and to activate transcription upon ectoine binding. As an endogenous reporter of ectoine, the mutated AraC protein was successfully incorporated into high-throughput screening of ectoine hyper-producing strains. The ectoine biosynthetic cluster from Halomonas elongata was cloned into E. coli. By engineering the rate-limiting enzyme L-2,4-diaminobutyric acid (DABA) aminotransferase (EctB), ectoine production and the specific activity of the EctB mutant were increased. Thus, these results demonstrated the effectiveness of engineering regulatory proteins into sensitive and rapid screening tools for small molecules and highlighted the importance and efficacy of directed evolution strategies applied to the engineering of genetic components for yield improvement in the biosynthesis of small molecules. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Lipase immobilization for catalytic applications obtained using fumed silica deposited with MAPLE technique

NASA Astrophysics Data System (ADS)

Bloisi, Francesco; Califano, Valeria; Perretta, Giuseppe; Nasti, Libera; Aronne, Antonio; Di Girolamo, Rocco; Auriemma, Finizia; De Rosa, Claudio; Vicari, Luciano R. M.

2016-06-01

Lipases are enzymes used for catalyzing reactions of acylglycerides in biodiesel production from lipids, where enzyme immobilization on a substrate is required. Silica nanoparticles in different morphologies and configurations are currently used in conjunction with biological molecules for drug delivery and catalysis applications, but up to date their use for triglycerides has been limited by the large size of long-chain lipid molecules. Matrix assisted pulsed laser evaporation (MAPLE), a laser deposition technique using a frozen solution/suspension as a target, is widely used for deposition of biomaterials and other delicate molecules. We have carried out a MAPLE deposition starting from a frozen mixture containing fumed silica and lipase in water. Deposition parameters were chosen in order to increase surface roughness and to promote the formation of complex structures. Both the target (a frozen thickened mixture of nanoparticles/catalyst in water) and the deposition configuration (a small target to substrate distance) are unusual and have been adopted in order to increase surface contact of catalyst and to facilitate access to long-chain molecules. The resulting innovative film morphology (fumed silica/lipase cluster level aggregation) and the lipase functionality (for catalytic biodiesel production) have been studied by FESEM, FTIR and transesterification tests.

Dynamic Colloidal Molecules Maneuvered by Light-Controlled Janus Micromotors.

PubMed

Gao, Yirong; Mou, Fangzhi; Feng, Yizheng; Che, Shengping; Li, Wei; Xu, Leilei; Guan, Jianguo

2017-07-12

In this work, we propose and demonstrate a dynamic colloidal molecule that is capable of moving autonomously and performing swift, reversible, and in-place assembly dissociation in a high accuracy by manipulating a TiO 2 /Pt Janus micromotor with light irradiation. Due to the efficient motion of the TiO 2 /Pt Janus motor and the light-switchable electrostatic interactions between the micromotor and colloidal particles, the colloidal particles can be captured and assembled one by one on the fly, subsequently forming into swimming colloidal molecules by mimicking space-filling models of simple molecules with central atoms. The as-demonstrated dynamic colloidal molecules have a configuration accurately controlled and stabilized by regulating the time-dependent intensity of UV light, which controls the stop-and-go motion of the colloidal molecules. The dynamic colloidal molecules are dissociated when the light irradiation is turned off due to the disappearance of light-switchable electrostatic interaction between the motor and the colloidal particles. The strategy for the assembly of dynamic colloidal molecules is applicable to various charged colloidal particles. The simulated optical properties of a dynamic colloidal molecule imply that the results here may provide a novel approach for in-place building functional microdevices, such as microlens arrays, in a swift and reversible manner.

A DFT investigation on group 8B transition metal-doped silicon carbide nanotubes for hydrogen storage application

NASA Astrophysics Data System (ADS)

Tabtimsai, Chanukorn; Ruangpornvisuti, Vithaya; Tontapha, Sarawut; Wanno, Banchob

2018-05-01

The binding of group 8B transition metal (TMs) on silicon carbide nanotubes (SiCNT) hydrogenated edges and the adsorption of hydrogen molecule on the pristine and TM-doped SiCNTs were investigated using the density functional theory method. The B3LYP/LanL2DZ method was employed in all calculations for the considered structural, adsorption, and electronic properties. The Os atom doping on the SiCNT is found to be the strongest binding. The hydrogen molecule displays a weak interaction with pristine SiCNT, whereas it has a strong interaction with TM-doped SiCNTs in which the Os-doped SiCNT shows the strongest interaction with the hydrogen molecule. The improvement in the adsorption abilities of hydrogen molecule onto TM-doped SiCNTs is due to the protruding structure and the induced charge transfer between TM-doped SiCNT and hydrogen molecule. These observations point out that TM-doped SiCNTs are highly sensitive toward hydrogen molecule. Moreover, the adsorptions of 2-5 hydrogen molecules on TM-doped SiCNT were also investigated. The maximum storage number of hydrogen molecules adsorbed on the first layer of TM-doped SiCNTs is 3 hydrogen molecules. Therefore, TM-doped SiCNTs are suitable to be sensing and storage materials for hydrogen gas.

Detection of magnetic dipolar coupling of water molecules at the nanoscale using quantum magnetometry

NASA Astrophysics Data System (ADS)

Yang, Zhiping; Shi, Fazhan; Wang, Pengfei; Raatz, Nicole; Li, Rui; Qin, Xi; Meijer, Jan; Duan, Changkui; Ju, Chenyong; Kong, Xi; Du, Jiangfeng

2018-05-01

It is a crucial issue to study interactions among water molecules and hydrophobic interfacial water at the nanoscale. Here we succeed in measuring the nuclear magnetic resonance spectrum of a diamond-water interfacial ice with a detection volume of about 2.2 ×10-22 L. More importantly, the magnetic dipolar coupling between the two protons of a water molecule is resolved by measuring the signal contributed from about 7000 water molecules at the nanoscale. The resolved intramolecule magnetic dipolar interactions are about 15 and 33 kHz with spectral resolution of 5 kHz. This work provides a platform for hydrophobic interfacial water study under ambient conditions, with further applications in more general nanoscale structural analysis.

Method for determining surface properties of microparticles

DOEpatents

Eisenthal, Kenneth B.

2000-01-01

Second harmonic generation (SHG), sum frequency generation (SFG) and difference frequency generation (DFG) can be used for surface analysis or characterization of microparticles having a non-metallic surface feature. The microparticles can be centrosymmetric or such that non-metallic molecules of interest are centrosymmetrically distributed inside and outside the microparticles but not at the surface of the microparticles where the asymmetry aligns the molecules. The signal is quadratic in incident laser intensity or proportional to the product of two incident laser intensities for SFG, it is sharply peaked at the second harmonic wavelength, quadratic in the density of molecules adsorbed onto the microparticle surface, and linear in microparticles density. In medical or pharmacological applications, molecules of interest may be of drugs or toxins, for example.

Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications

PubMed Central

Laurencin, Cato T.; Ashe, Keshia M.; Henry, Nicole; Kan, Ho Man; Lo, Kevin W-H.

2014-01-01

Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. Common limitations with protein growth factors are high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host. New strategies for bone regeneration that obviate these problems can have a significant impact on the treatment of skeletal injury and diseases. Over the past decade, a large number of small molecules with the potential of regenerating skeletal tissue have been reported in the literature. Here, we review this literature, paying specific attention to the prospects for small molecule-based bone-regenerative engineering. We also review the preclinical study of small molecules associated with bone regeneration. PMID:24508820

Cyclodextrin-supported organic matrix for application of MALDI-MS for forensics. Soft-ionization to obtain protonated molecules of low molecular weight compounds

NASA Astrophysics Data System (ADS)

Yonezawa, Tetsu; Asano, Takashi; Fujino, Tatsuya; Nishihara, Hiroshi

2013-06-01

A mass measurement technique for detecting low-molecular-weight drugs with a cyclodextrin-supported organic matrix was investigated. By using cyclodextrin-supported 2,4,6-trihydroxyacetophenone (THAP), the matrix-related peaks of drugs were suppressed. The peaks of protonated molecules of the sample and THAP were mainly observed, and small fragments were detected in a few cases. Despite the Na+ and K+ peaks were observed in the spectrum, Na+ or K+ adduct sample molecules were undetected, owing to the sugar units of cyclodextrin. The advantages of MALDI-MS with cyclodextrin-supported matrices as an analytical tool for forensic samples are discussed. The suppression of alkali adducted molecules and desorption process are also discussed.

Single molecule real-time (SMRT) sequencing comes of age: applications and utilities for medical diagnostics

PubMed Central

Ardui, Simon; Ameur, Adam; Vermeesch, Joris R; Hestand, Matthew S

2018-01-01

Abstract Short read massive parallel sequencing has emerged as a standard diagnostic tool in the medical setting. However, short read technologies have inherent limitations such as GC bias, difficulties mapping to repetitive elements, trouble discriminating paralogous sequences, and difficulties in phasing alleles. Long read single molecule sequencers resolve these obstacles. Moreover, they offer higher consensus accuracies and can detect epigenetic modifications from native DNA. The first commercially available long read single molecule platform was the RS system based on PacBio's single molecule real-time (SMRT) sequencing technology, which has since evolved into their RSII and Sequel systems. Here we capsulize how SMRT sequencing is revolutionizing constitutional, reproductive, cancer, microbial and viral genetic testing. PMID:29401301

Frequency-domain photoacoustic and fluorescence microscopy: application on labeled and unlabeled cells

NASA Astrophysics Data System (ADS)

Langer, Gregor; Buchegger, Bianca; Jacak, Jaroslaw; Pfeffer, Karoline; Wohlfarth, Sven; Hannesschläger, Günther; Klar, Thomas A.; Berer, Thomas

2018-02-01

In this paper, multimodal optical-resolution frequency-domain photoacoustic and fluorescence scanning microscopy is presented on labeled and unlabeled cells. In many molecules, excited electrons relax radiatively and non-radiatively, leading to fluorescence and photoacoustic signals, respectively. Both signals can then be detected simultaneously. There also exist molecules, e.g. hemoglobin, which do not exhibit fluorescence, but provide photoacoustic signals solely. Other molecules, especially fluorescent dyes, preferentially exhibit fluorescence. The fluorescence quantum yield of a molecule and with it the strength of photoacoustic and fluorescence signals depends on the local environment, e.g. on the pH. Therefore, the local distribution of the simultaneously recorded photoacoustic and fluorescence signals may be used in order to obtain information about the local chemistry.

Water dynamics in rigid ionomer networks.

PubMed

Osti, N C; Etampawala, T N; Shrestha, U M; Aryal, D; Tyagi, M; Diallo, S O; Mamontov, E; Cornelius, C J; Perahia, D

2016-12-14

The dynamics of water within ionic polymer networks formed by sulfonated poly(phenylene) (SPP), as revealed by quasi-elastic neutron scattering (QENS), is presented. These polymers are distinguished from other ionic macromolecules by their rigidity and therefore in their network structure. QENS measurements as a function of temperature as the fraction of ionic groups and humidity were varied have shown that the polymer molecules are immobile while absorbed water molecules remain dynamic. The water molecules occupy multiple sites, either bound or loosely constrained, and bounce between the two. With increasing temperature and hydration levels, the system becomes more dynamic. Water molecules remain mobile even at subzero temperatures, illustrating the applicability of the SPP membrane for selective transport over a broad temperature range.

Molecular magnetism, status and perspectives

NASA Astrophysics Data System (ADS)

Gatteschi, Dante; Bogani, Lapo; Cornia, Andrea; Mannini, Matteo; Sorace, Lorenzo; Sessoli, Roberta

2008-12-01

A short review is made of molecular magnetism, trying to discuss what is alive and well, with perspectives for the future. All the main fields of activity are mentioned, ranging from the so-called spin cross-over systems to the quest for organic (molecular) ferromagnets. Particular attention is devoted to some of the recent advances in these fields, highlighting also the opportunities for the development of applications. Low dimensional magnets are perhaps the best opportunity to use molecules, and the status of single-molecule and single chain magnets is discussed. The last part is devoted to the organization of magnetic molecules and to the development of techniques which allow to measure the magnetic properties of thin layers and, in perspective, of single molecules.

Exciton confinement in organic dendrimer quantum wells for opto-electronic applications

NASA Astrophysics Data System (ADS)

Lupton, J. M.; Samuel, I. D. W.; Burn, P. L.; Mukamel, S.

2002-01-01

Organic dendrimers are a fascinating new class of materials for opto-electronic applications. We present coupled electronic oscillator calculations on novel nanoscale conjugated dendrimers for use in organic light-emitting diodes. Strong confinement of excitations at the center of the dendrimers is observed, which accounts for the dependence of intermolecular interactions and charge transport on the degree of branching of the dendrimer. The calculated absorption spectra are in excellent agreement with the measured data and show that benzene rings are shared between excitations on the linear segments of the hyperbranched molecules. The coupled electronic oscillator approach is ideally suited to treat large dendritic molecules.

Advances in aptamer screening and small molecule aptasensors.

PubMed

Kim, Yeon Seok; Gu, Man Bock

2014-01-01

It has been 20 years since aptamer and SELEX (systematic evolution of ligands by exponential enrichment) were described independently by Andrew Ellington and Larry Gold. Based on the great advantages of aptamers, there have been numerous isolated aptamers for various targets that have actively been applied as therapeutic and analytical tools. Over 2,000 papers related to aptamers or SELEX have been published, attesting to their wide usefulness and the applicability of aptamers. SELEX methods have been modified or re-created over the years to enable aptamer isolation with higher affinity and selectivity in more labor- and time-efficient manners, including automation. Initially, most of the studies about aptamers have focused on the protein targets, which have physiological functions in the body, and their applications as therapeutic agents or receptors for diagnostics. However, aptamers for small molecules such as organic or inorganic compounds, drugs, antibiotics, or metabolites have not been studied sufficiently, despite the ever-increasing need for rapid and simple analytical methods for various chemical targets in the fields of medical diagnostics, environmental monitoring, food safety, and national defense against targets including chemical warfare. This review focuses on not only recent advances in aptamer screening methods but also its analytical application for small molecules.

First principles investigations of vinazene molecule and molecular crystal: a prospective candidate for organic photovoltaic applications.

PubMed

Mohamad, Mazmira; Ahmed, Rashid; Shaari, Amirudin; Goumri-Said, Souraya

2015-02-01

Escalating demand for sustainable energy resources, because of the rapid exhaustion of conventional energy resources as well as to maintain the environmental level of carbon dioxide (CO2) to avoid its adverse effect on the climate, has led to the exploitation of photovoltaic technology manifold more than ever. In this regard organic materials have attracted great attention on account of demonstrating their potential to harvest solar energy at an affordable rate for photovoltaic technology. 2-vinyl-4,5-dicyanoimidazole (vinazene) is considered as a suitable material over the fullerenes for photovoltaic applications because of its particular chemical and physical nature. In the present study, DFT approaches are employed to provide an exposition of optoelectronic properties of vinazene molecule and molecular crystal. To gain insight into its properties, different forms of exchange correlation energy functional/potential such as LDA, GGA, BLYP, and BL3YP are used. Calculated electronic structure of vinazene molecule has been displayed via HOMO-LUMO isosurfaces, whereas electronic structure of the vinazene molecular crystal, via electronic band structure, is presented. The calculated electronic and optical properties were analyzed and compared as well. Our results endorse vinazene as a suitable material for organic photovoltaic applications.

Modeling of Sheath Ion-Molecule Reactions in Plasma Enhanced Chemical Vapor Deposition of Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Hash, David B.; Govindan, T. R.; Meyyappan, M.

2004-01-01

In many plasma simulations, ion-molecule reactions are modeled using ion energy independent reaction rate coefficients that are taken from low temperature selected-ion flow tube experiments. Only exothermic or nearly thermoneutral reactions are considered. This is appropriate for plasma applications such as high-density plasma sources in which sheaths are collisionless and ion temperatures 111 the bulk p!asma do not deviate significantly from the gas temperature. However, for applications at high pressure and large sheath voltages, this assumption does not hold as the sheaths are collisional and ions gain significant energy in the sheaths from Joule heating. Ion temperatures and thus reaction rates vary significantly across the discharge, and endothermic reactions become important in the sheaths. One such application is plasma enhanced chemical vapor deposition of carbon nanotubes in which dc discharges are struck at pressures between 1-20 Torr with applied voltages in the range of 500-700 V. The present work investigates The importance of the inclusion of ion energy dependent ion-molecule reaction rates and the role of collision induced dissociation in generating radicals from the feedstock used in carbon nanotube growth.

Twinning, Epitaxy and Domain Switching in Ferroelastic Inclusion Compounds

NASA Technical Reports Server (NTRS)

Hollingsworth, Mark D.; Peterson, Matthew L.

2003-01-01

Our research is in the area of solid-state organic chemistry, which lies at the interface between physical organic chemistry and materials science. We use crystalline solids as models to probe fundamental issues about physical processes, molecular interactions and chemical reactions that are important for fabrication, stabilization and application of technological materials. Much of our most recent work has focused on the phenomena of ferroelastic and ferroelectric domain switching, in which application of an external force or electric field to a crystal causes the molecules inside the crystal to reorient, in tandem, to a new orientational state. To better understand and control the domain switching process, we have designed and synthesized over twenty closely related, ferroelastic organic crystals. Our approach has been to use crystalline inclusion compounds, in which one molecule (the guest) is trapped within the crystalline framework of a second molecule (the host). By keeping the host constant and varying the proportions and kinds of guests, it has been possible to tailor these materials so that domain switching is rapid and reversible (which is desirable for high technology applications). Inclusion compounds therefore serve as powerful systems for understanding the specific molecular mechanisms that control domain switching.

Quantum Electric Dipole Lattice - Water Molecules Confined to Nanocavities in Beryl

NASA Astrophysics Data System (ADS)

Dressel, Martin; Zhukova, Elena S.; Thomas, Victor G.; Gorshunov, Boris P.

2018-02-01

Water is subject to intense investigations due to its importance in biological matter but keeps many of its secrets. Here, we unveil an even other aspect by confining H2O molecules to nanosize cages. Our THz and infrared spectra of water in the gemstone beryl evidence quantum tunneling of H2O molecules in the crystal lattice. The water molecules are spread out when confined in a nanocage. In combination with low-frequency dielectric measurements, we were also able to show that dipolar coupling among the H2O molecules leads towards a ferroelectric state at low temperatures. Upon cooling, a ferroelectric soft mode shifts through the THz range. Only quantum fluctuations prevent perfect macroscopic order to be fully achieved. Beside the significance to life science and possible application, nanoconfined water may become the prime example of a quantum electric dipolar lattice.

High thermopower of mechanically stretched single-molecule junctions

PubMed Central

Tsutsui, Makusu; Morikawa, Takanori; He, Yuhui; Arima, Akihide

2015-01-01

Metal-molecule-metal junction is a promising candidate for thermoelectric applications that utilizes quantum confinement effects in the chemically defined zero-dimensional atomic structure to achieve enhanced dimensionless figure of merit ZT. A key issue in this new class of thermoelectric nanomaterials is to clarify the sensitivity of thermoelectricity on the molecular junction configurations. Here we report simultaneous measurements of the thermoelectric voltage and conductance on Au-1,4-benzenedithiol (BDT)-Au junctions mechanically-stretched in-situ at sub-nanoscale. We obtained the average single-molecule conductance and thermopower of 0.01 G0 and 15 μV/K, respectively, suggesting charge transport through the highest occupied molecular orbital. Meanwhile, we found the single-molecule thermoelectric transport properties extremely-sensitive to the BDT bridge configurations, whereby manifesting the importance to design the electrode-molecule contact motifs for optimizing the thermoelectric performance of molecular junctions. PMID:26112999

Electronic Structure of Small Lanthanide Containing Molecules

NASA Astrophysics Data System (ADS)

Kafader, Jared O.; Ray, Manisha; Topolski, Josey E.; Chick Jarrold, Caroline

2016-06-01

Lanthanide-based materials have unusual electronic properties because of the high number of electronic degrees of freedom arising from partial occupation of 4f orbitals, which make these materials optimal for their utilization in many applications including electronics and catalysis. Electronic spectroscopy of small lanthanide molecules helps us understand the role of these 4f electrons, which are generally considered core-like because of orbital contraction, but are energetically similar to valence electrons. The spectroscopy of small lanthanide-containing molecules is relatively unexplored and to broaden this understanding we have completed the characterization of small cerium, praseodymium, and europium molecules using photoelectron spectroscopy coupled with DFT calculations. The characterization of PrO, EuH, EuO/EuOH, and CexOy molecules have allowed for the determination of their electron affinity, the assignment of numerous anion to neutral state transitions, modeling of anion/neutral structures and electron orbital occupation.

Single molecule characterization of DNA binding and strand displacement reactions on lithographic DNA origami microarrays.

PubMed

Scheible, Max B; Pardatscher, Günther; Kuzyk, Anton; Simmel, Friedrich C

2014-03-12

The combination of molecular self-assembly based on the DNA origami technique with lithographic patterning enables the creation of hierarchically ordered nanosystems, in which single molecules are positioned at precise locations on multiple length scales. Based on a hybrid assembly protocol utilizing DNA self-assembly and electron-beam lithography on transparent glass substrates, we here demonstrate a DNA origami microarray, which is compatible with the requirements of single molecule fluorescence and super-resolution microscopy. The spatial arrangement allows for a simple and reliable identification of single molecule events and facilitates automated read-out and data analysis. As a specific application, we utilize the microarray to characterize the performance of DNA strand displacement reactions localized on the DNA origami structures. We find considerable variability within the array, which results both from structural variations and stochastic reaction dynamics prevalent at the single molecule level.

Photoswitchable Molecular Rings for Solar-Thermal Energy Storage.

PubMed

Durgun, E; Grossman, Jeffrey C

2013-03-21

Solar-thermal fuels reversibly store solar energy in the chemical bonds of molecules by photoconversion, and can release this stored energy in the form of heat upon activation. Many conventional photoswichable molecules could be considered as solar thermal fuels, although they suffer from low energy density or short lifetime in the photoinduced high-energy metastable state, rendering their practical use unfeasible. We present a new approach to the design of chemistries for solar thermal fuel applications, wherein well-known photoswitchable molecules are connected by different linker agents to form molecular rings. This approach allows for a significant increase in both the amount of stored energy per molecule and the stability of the fuels. Our results suggest a range of possibilities for tuning the energy density and thermal stability as a function of the type of the photoswitchable molecule, the ring size, or the type of linkers.

Deep-UV biological imaging by lanthanide ion molecular protection

PubMed Central

Kumamoto, Yasuaki; Fujita, Katsumasa; Smith, Nicholas Isaac; Kawata, Satoshi

2015-01-01

Deep-UV (DUV) light is a sensitive probe for biological molecules such as nucleobases and aromatic amino acids due to specific absorption. However, the use of DUV light for imaging is limited because DUV can destroy or denature target molecules in a sample. Here we show that trivalent ions in the lanthanide group can suppress molecular photodegradation under DUV exposure, enabling a high signal-to-noise ratio and repetitive DUV imaging of nucleobases in cells. Underlying mechanisms of the photodegradation suppression can be excitation relaxation of the DUV-absorptive molecules due to energy transfer to the lanthanide ions, and/or avoiding ionization and reactions with surrounding molecules, including generation of reactive oxygen species, which can modify molecules that are otherwise transparent to DUV light. This approach, directly removing excited energy at the fundamental origin of cellular photodegradation, indicates an important first step towards the practical use of DUV imaging in a variety of biological applications. PMID:26819825

Cold molecules: Progress in quantum engineering of chemistry and quantum matter

NASA Astrophysics Data System (ADS)

Bohn, John L.; Rey, Ana Maria; Ye, Jun

2017-09-01

Cooling atoms to ultralow temperatures has produced a wealth of opportunities in fundamental physics, precision metrology, and quantum science. The more recent application of sophisticated cooling techniques to molecules, which has been more challenging to implement owing to the complexity of molecular structures, has now opened the door to the longstanding goal of precisely controlling molecular internal and external degrees of freedom and the resulting interaction processes. This line of research can leverage fundamental insights into how molecules interact and evolve to enable the control of reaction chemistry and the design and realization of a range of advanced quantum materials.

Image processing for optical mapping.

PubMed

Ravindran, Prabu; Gupta, Aditya

2015-01-01

Optical Mapping is an established single-molecule, whole-genome analysis system, which has been used to gain a comprehensive understanding of genomic structure and to study structural variation of complex genomes. A critical component of Optical Mapping system is the image processing module, which extracts single molecule restriction maps from image datasets of immobilized, restriction digested and fluorescently stained large DNA molecules. In this review, we describe robust and efficient image processing techniques to process these massive datasets and extract accurate restriction maps in the presence of noise, ambiguity and confounding artifacts. We also highlight a few applications of the Optical Mapping system.

Towards the mass production of slow, trappable molecules

NASA Astrophysics Data System (ADS)

McCarron, Daniel J.

2018-05-01

The Fast Track Communication by Petzold et al (2018 New J. Phys. 20 042001) demonstrates the first Zeeman slowing scheme for species with type-II optical cycling transitions. This new approach is directly applicable to those 2Σ molecules that have recently been captured and cooled in molecular magneto-optical traps (MOTs) and has the potential to efficiently and continuously load these traps for the first time. This advance could produce molecular MOTs with populations comparable to their atomic counterparts and realize an ideal platform for a wide range of studies using large, dense samples of ultracold molecules.

One-Shot Determination of Residual Dipolar Couplings: Application to the Structural Discrimination of Small Molecules Containing Multiple Stereocenters.

PubMed

Castañar, Laura; Garcia, Manuela; Hellemann, Erich; Nolis, Pau; Gil, Roberto R; Parella, Teodor

2016-11-18

A novel approach for the fast and efficient structural discrimination of molecules containing multiple stereochemical centers is described. A robust J-resolved HSQC experiment affording highly resolved 1 J CH / 1 T CH splittings along the indirect dimension and homodecoupled 1 H signals in the detected dimension is proposed. The experiment enables in situ distinction of both isotropic and anisotropic components of molecules dissolved in compressed PMMA gels, allowing a rapid and direct one-shot determination of accurate residual dipolar coupling constants from a single NMR spectrum.

Further efforts in optimizing nonlinear optical molecules

NASA Astrophysics Data System (ADS)

Dirk, Carl W.; Caballero, Noel; Tan, Alarice; Kuzyk, Mark G.; Cheng, Lap-Tak A.; Katz, Howard E.; Shilling, Marcia; King, Lori A.

1993-02-01

We summarize some of our past work in the field on optimizing molecules for second order and third order nonlinear optical applications. We also present some previously unpublished results suggesting a particular optimization of the popular cyano- and nitrovinyl acceptor groups. In addition we provide some new quadratic electro-optic results which serve to further verify our choice of a restricted three-level model suitable for optimizing third order nonlinearities in molecules. Finally we present a new squarylium dye with a large third order optical nonlinearity (-9.5 X 10-34 cm7/esu2; EFISH (gamma) at 1906 nm).

Molecular spintronics using single-molecule magnets

NASA Astrophysics Data System (ADS)

Bogani, Lapo; Wernsdorfer, Wolfgang

2008-03-01

A revolution in electronics is in view, with the contemporary evolution of the two novel disciplines of spintronics and molecular electronics. A fundamental link between these two fields can be established using molecular magnetic materials and, in particular, single-molecule magnets. Here, we review the first progress in the resulting field, molecular spintronics, which will enable the manipulation of spin and charges in electronic devices containing one or more molecules. We discuss the advantages over more conventional materials, and the potential applications in information storage and processing. We also outline current challenges in the field, and propose convenient schemes to overcome them.

Nanotechnology applications and approaches for neuroregeneration and drug delivery to the central nervous system.

PubMed

Silva, Gabriel A

2010-06-01

Nanotechnology is the science and engineering concerned with the design, synthesis, and characterization of materials and devices that have a functional organization in at least one dimension on the nanometer (i.e., one billionth of a meter) scale. The potential impact of bottom up self-assembling nanotechnology, custom made molecules that self-assemble or self-organize into higher ordered structures in response to a defined chemical or physical cue, and top down lithographic type technologies where detail is engineered at smaller scales starting from bulk materials, stems from the fact that these nanoengineered materials and devices exhibit emergent mesocale and macroscale chemical and physical properties that are often different than their constituent nanoscale building block molecules or materials. As such, applications of nanotechnology to medicine and biology allow the interaction and integration of cells and tissues with nanoengineered substrates at a molecular (i.e., subcellular) level with a very high degree of functional specificity and control. This review considers applications of nanotechnology aimed at the neuroprotection and functional regeneration of the central nervous system (CNS) following traumatic or degenerative insults, and nanotechnology approaches for delivering drugs and other small molecules across the blood-brain barrier. It also discusses developing platform technologies that may prove to have broad applications to medicine and physiology, including some being developed for rescuing or replacing anatomical and/or functional CNS structures.

sscMap: an extensible Java application for connecting small-molecule drugs using gene-expression signatures.

PubMed

Zhang, Shu-Dong; Gant, Timothy W

2009-07-31

Connectivity mapping is a process to recognize novel pharmacological and toxicological properties in small molecules by comparing their gene expression signatures with others in a database. A simple and robust method for connectivity mapping with increased specificity and sensitivity was recently developed, and its utility demonstrated using experimentally derived gene signatures. This paper introduces sscMap (statistically significant connections' map), a Java application designed to undertake connectivity mapping tasks using the recently published method. The software is bundled with a default collection of reference gene-expression profiles based on the publicly available dataset from the Broad Institute Connectivity Map 02, which includes data from over 7000 Affymetrix microarrays, for over 1000 small-molecule compounds, and 6100 treatment instances in 5 human cell lines. In addition, the application allows users to add their custom collections of reference profiles and is applicable to a wide range of other 'omics technologies. The utility of sscMap is two fold. First, it serves to make statistically significant connections between a user-supplied gene signature and the 6100 core reference profiles based on the Broad Institute expanded dataset. Second, it allows users to apply the same improved method to custom-built reference profiles which can be added to the database for future referencing. The software can be freely downloaded from http://purl.oclc.org/NET/sscMap.

Molecular targets for small-molecule modulators of circadian clocks

PubMed Central

He, Baokun; Chen, Zheng

2016-01-01

Background Circadian clocks are endogenous timing systems that regulate various aspects of mammalian metabolism, physiology and behavior. Traditional chronotherapy refers to the administration of drugs in a defined circadian time window to achieve optimal pharmacokinetic and therapeutic efficacies. In recent years, substantial efforts have been dedicated to developing novel small-molecule modulators of circadian clocks. Methods Here, we review the recent progress in the identification of molecular targets of small-molecule clock modulators and their efficacies in clock-related disorders. Specifically, we examine the clock components and regulatory factors as possible molecular targets of small molecules, and we review several key clock-related disorders as promising venues for testing the preventive/therapeutic efficacies of these small molecules. Finally, we also discuss circadian regulation of drug metabolism. Results Small molecules can modulate the period, phase and/or amplitude of the circadian cycle. Core clock proteins, nuclear hormone receptors, and clock-related kinases and other epigenetic regulators are promising molecular targets for small molecules. Through these targets small molecules exert protective effects against clock-related disorders including the metabolic syndrome, immune disorders, sleep disorders and cancer. Small molecules can also modulate circadian drug metabolism and response to existing therapeutics. Conclusion Small-molecule clock modulators target clock components or diverse cellular pathways that functionally impinge upon the clock. Target identification of new small-molecule modulators will deepen our understanding of key regulatory nodes in the circadian network. Studies of clock modulators will facilitate their therapeutic applications, alone or in combination, for clock-related diseases. PMID:26750111

Pot economy and one-pot synthesis.

PubMed

Hayashi, Yujiro

2016-02-01

The one-pot synthesis of a target molecule in the same reaction vessel is widely considered to be an efficient approach in synthetic organic chemistry. In this review, the characteristics and limitations of various one-pot syntheses of biologically active molecules are explained, primarily involving organocatalytic methods as key tactics. Besides catalysis, the pot-economy concepts presented herein are also applicable to organometallic and organic reaction methods in general.

Synthesis of polycyclic molecules by double C(sp2)-H/C(sp3)-H arylations with a single palladium catalyst.

PubMed

Pierre, Cathleen; Baudoin, Olivier

2011-04-01

Polycyclic molecules were obtained in good yields by double C(sp(2))-H/C(sp(3))-H arylations mediated by a single palladium/phosphine catalyst. Both double intermolecular/intramolecular and intramolecular/intramolecular C-C couplings were performed successfully, which indicates that this concept has a broad applicability for the rapid construction of molecular complexity.

Electrondriven processes in polyatomic molecules

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

McKoy, Vincent

2017-03-20

This project developed and applied scalable computational methods to obtain information about low-energy electron collisions with larger polyatomic molecules. Such collisions are important in modeling radiation damage to living systems, in spark ignition and combustion, and in plasma processing of materials. The focus of the project was to develop efficient methods that could be used to obtain both fundamental scientific insights and data of practical value to applications.

Water-soluble carbon nanotube compositions for drug delivery and medicinal applications

DOEpatents

Tour, James M.; Lucente-Schultz, Rebecca; Leonard, Ashley; Kosynkin, Dmitry V.; Price, Brandi Katherine; Hudson, Jared L.; Conyers, Jr., Jodie L.; Moore, Valerie C.; Casscells, S. Ward; Myers, Jeffrey N.; Milas, Zvonimir L.; Mason, Kathy A.; Milas, Luka

2014-07-22

Compositions comprising a plurality of functionalized carbon nanotubes and at least one type of payload molecule are provided herein. The compositions are soluble in water and PBS in some embodiments. In certain embodiments, the payload molecules are insoluble in water. Methods are described for making the compositions and administering the compositions. An extended release formulation for paclitaxel utilizing functionalized carbon nanotubes is also described.

Vibrational Energy in Molecules and Nanoparticles: Applications to Energetic Materials

DTIC Science & Technology

2009-01-30

of vibrational energy in a polyatomic molecule, nitromethane . Work on water and amino acids partially supported by AFOSR are developmental in nature...have characterized the surface vibrations of HMX explosive and their interaction with polymer binders. We have introduced a major improvement in SFG...Vibrational energy in nitromethane and benzene E. Time resolved spectroscopy of chemistry in flash-heated nanoenergetic materials F. Complete

Isotope separation by photochromatography

DOEpatents

Suslick, Kenneth S.

1977-01-01

An isotope separation method which comprises physically adsorbing an isotopically mixed molecular species on an adsorptive surface and irradiating the adsorbed molecules with radiation of a predetermined wavelength which will selectively excite a desired isotopic species. Sufficient energy is transferred to the excited molecules to desorb them from the surface and thereby separate them from the unexcited undesired isotopic species. The method is particularly applicable to the separation of hydrogen isotopes.

Effect of Atmospheric-Pressure Plasma Jet of Neon on 7-Acetoxy-6-(2,3-Dibromopropyl)-4,8-Dimethylcoumarin Molecule

NASA Astrophysics Data System (ADS)

Tanışlı, Murat; Taşal, Erol

2017-06-01

Atmospheric-pressure low-temperature plasma jets and their applications are a topic of great interest in the fields of physics, technology, and medicine. In this study, the used self-made plasma jet is based on a dielectric barrier discharge (DBD) in neon (Ne) with typical processing parameters, such as frequency in the kHz range and voltage in the kV range. The plasma is characterized by optical emission spectroscopy (OES). These types of plasma can be used in various applications such as surface modification, inactivation of microorganisms, and chemical decomposition. This study is concerned with the Fourier transform infrared spectrum (FT-IR) and ultraviolet-visible (UV-vis) absorption spectroscopy of the large 7-acetoxy-6-(2,3-dibromopropyl)-4,8-dimethylcoumarin molecule (abbreviated as 7AC) dissolved in ethanol and methanol solvents and their modification after atmospheric-pressure plasma treatment (APPT) with the DBD. The research is motivated by the significance of this molecule in different fields of application. Also the changes in the structure are recorded. After APPT, the peak corresponding to the carbonyl bond at a wavenumber of 1715 cm-1 disappears in the IR spectrum of the ethanol solution, and when splitting at a wavenumber of 1405 cm-1 is observed, the peak at 1224 cm-1 is found to disappear after plasma is applied. It is seen new peaks at frequencies of 432 and 655 cm-1 are formed. When the same situation is analyzed for the 7AC molecule dissolved in methanol, a new peak is observed at 1634 cm-1. The intensities of the peaks at 3433 and 2075 cm-1 also increase and there is a large change in the wavenumber at 600 cm-1. In the UV spectra, a significant increase in the absorbance of the 7AC molecule dissolved in ethanol is observed after APPT, whereas a small decrease in the absorbance of the 7AC molecule dissolved in methanol is obtained. Owing to the lack of symmetry, many normal bands of vibrations are mixed.

General Dialdehyde Click Chemistry for Amine Bioconjugation.

PubMed

Elahipanah, Sina; O'Brien, Paul J; Rogozhnikov, Dmitry; Yousaf, Muhammad N

2017-05-17

The development of methods for conjugating a range of molecules to primary amine functional groups has revolutionized the fields of chemistry, biology, and material science. The primary amine is a key functional group and one of the most important nucleophiles and bases used in all of synthetic chemistry. Therefore, tremendous interest in the synthesis of molecules containing primary amines and strategies to devise chemical reactions to react with primary amines has been at the core of chemical research. In particular, primary amines are a ubiquitous functional group found in biological systems as free amino acids, as key side chain lysines in proteins, and in signaling molecules and metabolites and are also present in many natural product classes. Due to its abundance, the primary amine is the most convenient functional group handle in molecules for ligation to other molecules for a broad range of applications that impact all scientific fields. Because of the primary amine's central importance in synthetic chemistry, acid-base chemistry, redox chemistry, and biology, many methods have been developed to efficiently react with primary amines, including activated carboxylic acids, isothiocyanates, Michael addition type systems, and reaction with ketones or aldehydes followed by in situ reductive amination. Herein, we introduce a new traceless, high-yield, fast click-chemistry method based on the rapid and efficient trapping of amine groups via a functionalized dialdehyde group. The click reaction occurs in mild conditions in organic solvents or aqueous media and proceeds in high yield, and the starting dialdehyde reagent and resulting dialdehyde click conjugates are stable. Moreover, no catalyst or dialdehyde-activating group is required, and the only byproduct is water. The initial dialdehyde and the resulting conjugate are both straightforward to characterize, and the reaction proceeds with high atom economy. To demonstrate the broad scope of this new click-conjugation strategy, we designed a straightforward scheme to synthesize a suite of dialdehyde reagents. The dialdehyde molecules were used for applications in cell-surface engineering and for tailoring surfaces for material science applications. We anticipate the broad utility of the general dialdehyde click chemistry to primary amines in all areas of chemical research, ranging from polymers and bioconjugation to material science and nanoscience.

Capillary electrophoresis application in metal speciation and complexation characterization

USDA-ARS?s Scientific Manuscript database

Capillary electrophoresis is amenable to the separation of metal ionic species and the characterization of metal-ligand interactions. This book chapter reviews and discusses three representative case studies in applications of CE technology in speciation and reactions of metal with organic molecules...

Stem cells as delivery vehicles for regenerative medicine-challenges and perspectives

PubMed Central

Labusca, Luminita; Herea, Dumitru Daniel; Mashayekhi, Kaveh

2018-01-01

The use of stem cells as carriers for therapeutic agents is an appealing modality for targeting tissues or organs of interest. Combined delivery of cells together with various information molecules as therapeutic agents has the potential to enhance, modulate or even initiate local or systemic repair processes, increasing stem cell efficiency for regenerative medicine applications. Stem-cell-mediated delivery of genes, proteins or small molecules takes advantage of the innate capability of stem cells to migrate and home to injury sites. As the native migratory properties are affected by in vitro expansion, the existent methods for enhancing stem cell targeting capabilities (modified culture methods, genetic modification, cell surface engineering) are described. The role of various nanoparticles in equipping stem cells with therapeutic small molecules is revised together with their class-specific advantages and shortcomings. Modalities to circumvent common challenges when designing a stem-cell-mediated targeted delivery system are described as well as future prospects in using this approach for regenerative medicine applications. PMID:29849930

N-(2-Ethylhexyl)carbazole: A New Fluorophore Highly Suitable as a Monomolecular Liquid Scintillator.

PubMed

Montbarbon, Eva; Sguerra, Fabien; Bertrand, Guillaume H V; Magnier, Élodie; Coulon, Romain; Pansu, Robert B; Hamel, Matthieu

2016-08-16

The synthesis, photophysical properties, and applications in scintillation counting of N-(2-ethylhexyl)carbazole (EHCz) are reported. This molecule displays all of the required characteristics for an efficient liquid scintillator (emission wavelength, scintillation yield), and can be used without any extra fluorophores. Thus, its scintillation properties are discussed, as well as its fast neutron/gamma discrimination. For the latter application, the material is compared with the traditional liquid scintillator BC-501 A, and other liquid fluorescent molecules classically used as scintillation solvents, such as xylene, pseudocumene (PC), linear alkylbenzenes (LAB), diisopropylnaphthalene (DIN), 1-methylnaphthalene (1-MeNapht), and 4-isopropylbiphenyl (iPrBiph). For the first time, an excimeric form of a molecule has been advantageously used in scintillation counting. A moderate discrimination between fast neutrons and gamma rays was observed in bulk EHCz, with an apparent neutron/gamma discrimination potential half of that of BC-501 A. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New strategy for protein interactions and application to structure-based drug design

NASA Astrophysics Data System (ADS)

Zou, Xiaoqin

One of the greatest challenges in computational biophysics is to predict interactions between biological molecules, which play critical roles in biological processes and rational design of therapeutic drugs. Biomolecular interactions involve delicate interplay between multiple interactions, including electrostatic interactions, van der Waals interactions, solvent effect, and conformational entropic effect. Accurate determination of these complex and subtle interactions is challenging. Moreover, a biological molecule such as a protein usually consists of thousands of atoms, and thus occupies a huge conformational space. The large degrees of freedom pose further challenges for accurate prediction of biomolecular interactions. Here, I will present our development of physics-based theory and computational modeling on protein interactions with other molecules. The major strategy is to extract microscopic energetics from the information embedded in the experimentally-determined structures of protein complexes. I will also present applications of the methods to structure-based therapeutic design. Supported by NSF CAREER Award DBI-0953839, NIH R01GM109980, and the American Heart Association (Midwest Affiliate) [13GRNT16990076].

Nanomaterials as Assisted Matrix of Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for the Analysis of Small Molecules.

PubMed

Lu, Minghua; Yang, Xueqing; Yang, Yixin; Qin, Peige; Wu, Xiuru; Cai, Zongwei

2017-04-21

Matrix-assisted laser desorption/ionization (MALDI), a soft ionization method, coupling with time-of-flight mass spectrometry (TOF MS) has become an indispensible tool for analyzing macromolecules, such as peptides, proteins, nucleic acids and polymers. However, the application of MALDI for the analysis of small molecules (<700 Da) has become the great challenge because of the interference from the conventional matrix in low mass region. To overcome this drawback, more attention has been paid to explore interference-free methods in the past decade. The technique of applying nanomaterials as matrix of laser desorption/ionization (LDI), also called nanomaterial-assisted laser desorption/ionization (nanomaterial-assisted LDI), has attracted considerable attention in the analysis of low-molecular weight compounds in TOF MS. This review mainly summarized the applications of different types of nanomaterials including carbon-based, metal-based and metal-organic frameworks as assisted matrices for LDI in the analysis of small biological molecules, environmental pollutants and other low-molecular weight compounds.

Blue emitting 1,8-naphthalimides with electron transport properties for organic light emitting diode applications

NASA Astrophysics Data System (ADS)

Ulla, Hidayath; Kiran, M. Raveendra; Garudachari, B.; Ahipa, T. N.; Tarafder, Kartick; Adhikari, Airody Vasudeva; Umesh, G.; Satyanarayan, M. N.

2017-09-01

In this article, the synthesis, characterization and use of two novel naphthalimides as electron-transporting emitter materials for organic light emitting diode (OLED) applications are reported. The molecules were obtained by substituting electron donating chloro-phenoxy group at the C-4 position. A detailed optical, thermal, electrochemical and related properties were systematically studied. Furthermore, theoretical calculations (DFT) were performed to get a better understanding of the electronic structures. The synthesized molecules were used as electron transporters and emitters in OLEDs with three different device configurations. The devices with the molecules showed blue emission with efficiencies of 1.89 cdA-1, 0.98 lmW-1, 0.71% at 100 cdm-2. The phosphorescent devices with naphthalimides as electron transport materials displayed better performance in comparison to the device without any electron transporting material and were analogous with the device using standard electron transporting material, Alq3. The results demonstrate that the naphthalimides could play a significant part in the progress of OLEDs.

Nanomaterials as Assisted Matrix of Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for the Analysis of Small Molecules

PubMed Central

Lu, Minghua; Yang, Xueqing; Yang, Yixin; Qin, Peige; Wu, Xiuru; Cai, Zongwei

2017-01-01

Matrix-assisted laser desorption/ionization (MALDI), a soft ionization method, coupling with time-of-flight mass spectrometry (TOF MS) has become an indispensible tool for analyzing macromolecules, such as peptides, proteins, nucleic acids and polymers. However, the application of MALDI for the analysis of small molecules (<700 Da) has become the great challenge because of the interference from the conventional matrix in low mass region. To overcome this drawback, more attention has been paid to explore interference-free methods in the past decade. The technique of applying nanomaterials as matrix of laser desorption/ionization (LDI), also called nanomaterial-assisted laser desorption/ionization (nanomaterial-assisted LDI), has attracted considerable attention in the analysis of low-molecular weight compounds in TOF MS. This review mainly summarized the applications of different types of nanomaterials including carbon-based, metal-based and metal-organic frameworks as assisted matrices for LDI in the analysis of small biological molecules, environmental pollutants and other low-molecular weight compounds. PMID:28430138

Expansion microscopy: development and neuroscience applications.

PubMed

Karagiannis, Emmanouil D; Boyden, Edward S

2018-06-01

Many neuroscience questions center around understanding how the molecules and wiring in neural circuits mechanistically yield behavioral functions, or go awry in disease states. However, mapping the molecules and wiring of neurons across the large scales of neural circuits has posed a great challenge. We recently developed expansion microscopy (ExM), a process in which we physically magnify biological specimens such as brain circuits. We synthesize throughout preserved brain specimens a dense, even mesh of a swellable polymer such as sodium polyacrylate, anchoring key biomolecules such as proteins and nucleic acids to the polymer. After mechanical homogenization of the specimen-polymer composite, we add water, and the polymer swells, pulling biomolecules apart. Due to the larger separation between molecules, ordinary microscopes can then perform nanoscale resolution imaging. We here review the ExM technology as well as applications to the mapping of synapses, cells, and circuits, including deployment in species such as Drosophila, mouse, non-human primate, and human. Copyright © 2017 Elsevier Ltd. All rights reserved.

Application of cabin atmosphere monitors to rapid screening of breath samples for the early detection of disease states

NASA Technical Reports Server (NTRS)

Valentine, J. L.; Bryant, P. J.

1975-01-01

Analysis of human breath is a nonintrusive method to monitor both endogenous and exogenous chemicals found in the body. Several technologies were investigated and developed which are applicable to monitoring some organic molecules important in both physiological and pathological states. Two methods were developed for enriching the organic molecules exhaled in the breath of humans. One device is based on a respiratory face mask fitted with a polyethylene foam wafer; while the other device is a cryogenic trap utilizing an organic solvent. Using laboratory workers as controls, two organic molecules which occurred in the enriched breath of all subjects were tentatively identified as lactic acid and contisol. Both of these substances occurred in breath in sufficient amounts that the conventional method of gas-liquid chromatography was adequate for detection and quantification. To detect and quantitate trace amounts of chemicals in breath, another type of technology was developed in which analysis was conducted using high pressure liquid chromatography and mass spectrometry.

The CRISPR/Cas revolution reaches the RNA world: Cas13, a new Swiss Army knife for plant biologists.

PubMed

Wolter, Felix; Puchta, Holger

2018-06-01

Application of the bacterial CRISPR/Cas systems to eukaryotes is revolutionizing biology. Cas9 and Cas12 (previously called Cpf1) are widely used as DNA nucleases for inducing site-specific DNA breaks for different kinds of genome engineering applications, and in their mutated forms as DNA-binding proteins to modify gene expression. Moreover, histone modifications, as well as cytosine methylation or base editing, were achieved with these systems in plants. Recently, with the discovery of the nuclease Cas13a (previously called C2c2), molecular biologists have obtained a system that enables sequence-specific cleavage of single-stranded RNA molecules. The latest experiments with this and also the alternative Cas13b system demonstrate that these proteins can be used in a similar manner in eukaryotes for RNA manipulation as Cas9 and Cas12 for DNA manipulations. The first application of Cas13a for post-transcriptional regulation of gene expression in plants has been reported. Recent results show that the system is also applicable for combating viral infection in plants. As single-stranded RNA viruses are by far the most abundant class of viruses in plants, the application of this system is of special promise for crops. More interesting applications are imminent for plant biologists, with nuclease dead versions of Cas13 enabling the ability to visualize RNA molecules in vivo, as well as to edit different kinds of RNA molecules at specific bases by deamination or to modify them by conjugation. Moreover, by combining DNA- and RNA-directed systems, the most complex of changes in plant metabolism might be achievable. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Tunable electronic and optical properties of gas molecules adsorbed monolayer graphitic ZnO: Implications for gas sensor and environment monitoring

NASA Astrophysics Data System (ADS)

Zhang, Wei; Du, Qikui; Zhang, Lifa

2017-12-01

Due to the large surface area and the peculiar electronic characters, great attention has been paid to 2D materials for the gas sensing applications. Here, using the hybrid density functional calculations, we systematically study the adsorptions of gas molecules on the monolayer graphitic ZnO (g-ZnO), including CO, H2, H2O, H2S, NH3, NO, NO2, O2, and SO2. For most of the molecules, g-ZnO shows superior sensing performance to the well-known MoS2, black phosphorus, blue phosphorus, antimonene, and germanene. H2S, NO, NO2, and SO2 act as charge acceptors, and CO, H2, H2O, and NH3 serve as charge donors. These molecules also induce distinct modifications to the electronic structures, work functions, and optical adsorptions. NO, NO2, and O2 form flat bands in the bandgaps of the spin-up or spin-down states, whereas other molecules mainly tune the bandgaps and the orbital couplings. In particular, g-ZnO is most likely to adsorb the atmospheric pollutant SO2, which has the strongest interaction through hybridizing its widely broadened 2p orbitals with the 3d orbitals of g-ZnO. Moreover, the improved visible light absorption is demonstrated in the NO2 adsorbed g-ZnO. Our results not only confirm that the electronic and optical properties of g-ZnO can be effectively tuned by the selective adsorption of gas molecules but also provide insightful guidance for the potential application of g-ZnO in the field of gas sensors.

Probing the Properties of the Molecular Adlayers on Metal Substrates: Scanning Tunneling Microscopy Study of Amine Adsorption on Gold(111) and Graphene Nanoislands on Cobalt(0001)

NASA Astrophysics Data System (ADS)

Zhou, Hui

In this thesis, we present our findings on two major topics, both of which are studies of molecules on metal surfaces by scanning tunneling microscopy (STM). The first topic is on adsorption of a model amine compound, 1,4-benzenediamine (BDA), on the reconstructed Au(111) surface, chosen for its potential application as a molecular electronic device. The molecules were deposited in the gas phase onto the substrate in the vacuum chamber. Five different patterns of BDA molecules on the surface at different coverages, and the preferred adsorption sites of BDA molecules on reconstructed Au(111) surface, were observed. In addition, BDA molecules were susceptible to tip-induced movement, suggesting that BDA molecules on metal surfaces can be a potential candidate in STM molecular manipulations. We also studied graphene nanoislands on Co(0001) in the hope of understanding interaction of expitaxially grown graphene and metal substrates. This topic can shed a light on the potential application of graphene as an electronic device, especially in spintronics. The graphene nanoislands were formed by annealing contorted hexabenzocoronene (HBC) on the Co(0001) surface. In our experiments, we have determined atop registry of graphene atoms with respect to the underlying Co surface. We also investigated the low-energy electronic structures of graphene nanoislands by scanning tunneling spectroscopy. The result was compared with a first-principle calculation using density functional theory (DFT) which suggested strong coupling between graphene pi-bands and cobalt d-electrons. We also observed that the islands exhibit zigzag edges, which exhibits unique electronic structures compared with the center areas of the islands.

Detection of creatinine enriched on a surface imprinted polystyrene film using FT-ATR-IR.

PubMed

Sreenivasan, K

2006-01-01

The surface of polystyrene (PS) was chemically modified by coating a thin layer of polyaniline (PANI) by oxidizing aniline using ammonium persulfate. Affinity sites for creatinine, a clinically relevant molecule, were created in the coated layer by adding creatinine as print molecules during the oxidation. The imprinted layer adsorbed creatinine was compared to non-imprinted surface reflecting the creation of creatinine-specific sites on the surface. The equilibrium was attained rapidly, indicating that a material of this kind is suitable for sensing applications. The adsorbed creatinine on the surface was detected using the technique of Fourier transform attenuated total internal reflection infra red spectroscopy (FT-ATR-IR). The results show that molecularly imprinted surface can enrich molecules of interest and the enriched molecules can be detected using FT-IR.

Current-induced switching of magnetic molecules on topological insulator surfaces

NASA Astrophysics Data System (ADS)

Locane, Elina; Brouwer, Piet W.

2017-03-01

Electrical currents at the surface or edge of a topological insulator are intrinsically spin polarized. We show that such surface or edge currents can be used to switch the orientation of a molecular magnet weakly coupled to the surface or edge of a topological insulator. For the edge of a two-dimensional topological insulator as well as for the surface of a three-dimensional topological insulator the application of a well-chosen surface or edge current can lead to a complete polarization of the molecule if the molecule's magnetic anisotropy axis is appropriately aligned with the current direction. For a generic orientation of the molecule a nonzero but incomplete polarization is obtained. We calculate the probability distribution of the magnetic states and the switching rates as a function of the applied current.

Rolling Circle Amplification For Spatially Directed Synthesis Of A Solid Phase Anchored Single-Stranded DNA Molecule

NASA Astrophysics Data System (ADS)

Reiß, Edda; Hölzel, Ralph; von Nickisch-Rosenegk, Markus; Bier, Frank F.

2006-09-01

In this article the usefulness of the enzyme phi29 DNA polymerase and the principle of rolling circle amplification (RCA) for creating single-stranded DNA (ssDNA) nanostructures is described. Currently we are working on the spatial orientation of a growing ssDNA molecule during its RCA-based synthesis by the application of a hydrodynamic force. Starting at an immobilized primer at single molecule level, the aim is to construct a nanostructure of known location and orientation, providing multiple repeating binding sites that can be addressed via complementary base-pairing. Proof-of-principle experiments demonstrate the potential of the enzymatic reaction. ssDNA molecules of more than 20 μm length were created at an immobilized primer and detected by means of fluorescence microscopy.

Size, weight and position: ion mobility spectrometry and imaging MS combined.

PubMed

Kiss, András; Heeren, Ron M A

2011-03-01

Size, weight and position are three of the most important parameters that describe a molecule in a biological system. Ion mobility spectrometry is capable of separating molecules on the basis of their size or shape, whereas imaging mass spectrometry is an effective tool to measure the molecular weight and spatial distribution of molecules. Recent developments in both fields enabled the combination of the two technologies. As a result, ion-mobility-based imaging mass spectrometry is gaining more and more popularity as a (bio-)analytical tool enabling the determination of the size, weight and position of several molecules simultaneously on biological surfaces. This paper reviews the evolution of ion-mobility-based imaging mass spectrometry and provides examples of its application in analytical studies of biological surfaces.

Molecular Diode Studies Based on a Highly Sensitive Molecular Measurement Technique.

PubMed

Iwane, Madoka; Fujii, Shintaro; Kiguchi, Manabu

2017-04-26

In 1974, molecular electronics pioneers Mark Ratner and Arieh Aviram predicted that a single molecule could act as a diode, in which electronic current can be rectified. The electronic rectification property of the diode is one of basic functions of electronic components and since then, the molecular diode has been investigated as a first single-molecule device that would have a practical application. In this review, we first describe the experimental fabrication and electronic characterization techniques of molecular diodes consisting of a small number of molecules or a single molecule. Then, two main mechanisms of the rectification property of the molecular diode are discussed. Finally, representative results for the molecular diode are reviewed and a brief outlook on crucial issues that need to be addressed in future research is discussed.

Molecular Diode Studies Based on a Highly Sensitive Molecular Measurement Technique

PubMed Central

Iwane, Madoka; Fujii, Shintaro; Kiguchi, Manabu

2017-01-01

In 1974, molecular electronics pioneers Mark Ratner and Arieh Aviram predicted that a single molecule could act as a diode, in which electronic current can be rectified. The electronic rectification property of the diode is one of basic functions of electronic components and since then, the molecular diode has been investigated as a first single-molecule device that would have a practical application. In this review, we first describe the experimental fabrication and electronic characterization techniques of molecular diodes consisting of a small number of molecules or a single molecule. Then, two main mechanisms of the rectification property of the molecular diode are discussed. Finally, representative results for the molecular diode are reviewed and a brief outlook on crucial issues that need to be addressed in future research is discussed. PMID:28445393

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

Stavis, Samuel M; Edel, Joshua B; Samiee, Kevan T

A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidicmore » channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.« less

Biosensors and Bio-Bar Code Assays Based on Biofunctionalized Magnetic Microbeads

PubMed Central

Jaffrezic-Renault, Nicole; Martelet, Claude; Chevolot, Yann; Cloarec, Jean-Pierre

2007-01-01

This review paper reports the applications of magnetic microbeads in biosensors and bio-bar code assays. Affinity biosensors are presented through different types of transducing systems: electrochemical, piezo electric or magnetic ones, applied to immunodetection and genodetection. Enzymatic biosensors are based on biofunctionalization through magnetic microbeads of a transducer, more often amperometric, potentiometric or conductimetric. The bio-bar code assays relie on a sandwich structure based on specific biological interaction of a magnetic microbead and a nanoparticle with a defined biological molecule. The magnetic particle allows the separation of the reacted target molecules from unreacted ones. The nanoparticles aim at the amplification and the detection of the target molecule. The bio-bar code assays allow the detection at very low concentration of biological molecules, similar to PCR sensitivity.

Quantitative gene expression analysis in Caenorhabditis elegans using single molecule RNA FISH.

PubMed

Bolková, Jitka; Lanctôt, Christian

2016-04-01

Advances in fluorescent probe design and synthesis have allowed the uniform in situ labeling of individual RNA molecules. In a technique referred to as single molecule RNA FISH (smRNA FISH), the labeled RNA molecules can be imaged as diffraction-limited spots and counted using image analysis algorithms. Single RNA counting has provided valuable insights into the process of gene regulation. This microscopy-based method has often revealed a high cell-to-cell variability in expression levels, which has in turn led to a growing interest in investigating the biological significance of gene expression noise. Here we describe the application of the smRNA FISH technique to samples of Caenorhabditis elegans, a well-characterized model organism. Copyright © 2015 Elsevier Inc. All rights reserved.

Advances in Quantum Mechanochemistry: Electronic Structure Methods and Force Analysis.

PubMed

Stauch, Tim; Dreuw, Andreas

2016-11-23

In quantum mechanochemistry, quantum chemical methods are used to describe molecules under the influence of an external force. The calculation of geometries, energies, transition states, reaction rates, and spectroscopic properties of molecules on the force-modified potential energy surfaces is the key to gain an in-depth understanding of mechanochemical processes at the molecular level. In this review, we present recent advances in the field of quantum mechanochemistry and introduce the quantum chemical methods used to calculate the properties of molecules under an external force. We place special emphasis on quantum chemical force analysis tools, which can be used to identify the mechanochemically relevant degrees of freedom in a deformed molecule, and spotlight selected applications of quantum mechanochemical methods to point out their synergistic relationship with experiments.

LASER APPLICATIONS AND OTHER TOPICS IN QUANTUM ELECTRONICS: Influence of the layer thickness and concentration of dye molecules on the emission amplification in cholesteric liquid crystals

NASA Astrophysics Data System (ADS)

Alaverdyan, R. B.; Gevorgyan, A. A.; Chilingaryan, A. D.; Chilingaryan, Yu S.

2008-05-01

The propagation of light through a planar layer of a cholesteric liquid crystal doped with dye molecules is considered. The features of the emission spectra of the crystal are studied both in the absence and presence of dielectric boundaries. The increase in the emission intensity is investigated for different layer thicknesses and different concentrations of dye molecules. It is shown that an anomalously strong increase in the emission intensity with the diffraction intrinsic polarisation takes place in the case of a comparatively small crystal thickness and a relatively low concentration of dye molecules. The obtained results can be used for the development of miniature lasers with the circular polarisation of the fundamental radiation mode.

Experimental evidence of pharmacological management of anchorage in Orthodontics: A systematic review

PubMed Central

Fernández-González, Felipe José; Cañigral, Aránzazu; Balbontín-Ayala, Felipe; Gonzalo-Orden, José Manuel; de Carlos, Felix; Cobo, Teresa; Fernández-Vázquez, Jose Pedro; Sánchez-Lasheras, Fernando; Vega, José Antonio

2015-01-01

Introduction: Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed. Objectives: The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage. Methods: The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed. Results: Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs). Conclusions: Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements. PMID:26560822

Experimental evidence of pharmacological management of anchorage in Orthodontics: A systematic review.

PubMed

Fernández-González, Felipe José; Cañigral, Aránzazu; Balbontín-Ayala, Felipe; Gonzalo-Orden, José Manuel; Carlos, Felix de; Cobo, Teresa; Fernández-Vázquez, Jose Pedro; Sánchez-Lasheras, Fernando; Vega, José Antonio

2015-10-01

Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed. The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage. The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed. Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs). Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements.

Graphene via Molecule-Assisted Ultrasound-Induced Liquid-Phase Exfoliation: A Supramolecular Approach

NASA Astrophysics Data System (ADS)

Eredia, Matilde; Ciesielski, Artur; Samorì, Paolo

2016-12-01

Graphene is a two-dimensional (2D) material holding unique optical, mechanical, thermal and electrical properties. The combination of these exceptional characteristics makes graphene an ideal model system for fundamental physical and chemical studies as well as technologically ground breaking material for a large range of applications. Graphene can be produced either following a bottom-up or top-down method. The former is based on the formation of covalent networks suitably engineered molecular building blocks undergoing chemical reaction. The latter takes place through the exfoliation of bulk graphite into individual graphene sheets. Among them, ultrasound-induced liquid-phase exfoliation (UILPE) is an appealing method, being very versatile and applicable to different environments and on various substrate types. In this chapter, we describe the recently reported methods to produce graphene via molecule-assisted UILPE of graphite, aiming at the generation of high-quality graphene. In particular, we will focus on the supramolecular approach, which consists in the use of suitably designed organic molecules during the UILPE of graphite. These molecules act as graphene dispersion-stabilizing agents during the exfoliation. This method relying on the joint effect of a solvent and ad hoc molecules to foster the exfoliation of graphite into graphene in liquid environment represents a promising and modular method toward the improvement of the process of UILPE in terms of the concentration and quality of the exfoliated material. Furthermore, exfoliations in aqueous and organic solutions are presented and discussed separately.

Smart surface coating of drug nanoparticles with cross-linkable polyethylene glycol for bio-responsive and highly efficient drug delivery.

PubMed

Wei, Weijia; Zhang, Xiujuan; Chen, Xianfeng; Zhou, Mengjiao; Xu, Ruirui; Zhang, Xiaohong

2016-04-21

Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability and minimal premature release of therapeutic molecules during circulation in the blood stream. To meet this requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG molecules can be cross-linked on the surface of the NPs to endow them with greater stability and the cross-link is sensitive to intracellular environment for bio-responsive drug release. With this elegant design, our experimental results show that the liberation of DOX from DOX-cross-linked PEG NPs is dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX release profile can be controlled by tuning the concentration of the reducing agent to break the cross-link between PEG molecules. More importantly, in vivo studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood circulation half-life (>4 h) and intense accumulation in tumor areas, enabling effective anti-cancer therapy. We expect this work will provide a powerful strategy for stabilizing carrier-free nanomedicines and pave the way to their successful clinical applications in the future.

A DFT and QTAIM study of the adsorption of organic molecules over the copper-doped coronene and circumcoronene

NASA Astrophysics Data System (ADS)

Malček, Michal; Cordeiro, M. Natalia D. S.

2018-01-01

Graphene based materials are nowadays extensively studied because of their potential applications as gas sensors, biosensors or adsorbents. Doping the graphene surface with heteroatoms or transition metals can improve its electronic properties and chemical reactivity. Polyaromatic hydrocarbons coronene and circumcoronene can be used as models of tiny graphene quantum dots. The adsorption of a set of organic molecules (water, hydrogen peroxide, hydrogen sulfide, methanol, ethanol and oxygen molecule) over the copper-doped coronene and circumcoronene was theoretically studied using density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM). In the case of coronene, only one site was considered for the Cu-doping, whereas in the case of circumcoronene being a polyaromatic hydrocarbon composed of 54 carbon atoms, three different sites for Cu-doping were considered. For the systems under study, the adsorption of O2 was found energetically the most favorable, with energetic outcome ranging from -3.1 to -3.7 eV related to the position of dopant Cu atom. Changes in the topology of charge densities at Cu and in its vicinity after the adsorption of studied molecules were investigated in the framework of QTAIM. In addition, QTAIM analysis of bond critical points (BCP) was employed to study the character of the newly formed chemical bonds. The results of this study point out the suitability of Cu-doped graphene materials as sensors and/or adsorbents in practical applications.

An integrated optics microfluidic device for detecting single DNA molecules.

PubMed

Krogmeier, Jeffrey R; Schaefer, Ian; Seward, George; Yantz, Gregory R; Larson, Jonathan W

2007-12-01

A fluorescence-based integrated optics microfluidic device is presented, capable of detecting single DNA molecules in a high throughput and reproducible manner. The device integrates microfluidics for DNA stretching with two optical elements for single molecule detection (SMD): a plano-aspheric refractive lens for fluorescence excitation (illuminator) and a solid parabolic reflective mirror for fluorescence collection (collector). Although miniaturized in size, both optical components were produced and assembled onto the microfluidic device by readily manufacturable fabrication techniques. The optical resolution of the device is determined by the small and relatively low numerical aperture (NA) illuminator lens (0.10 effective NA, 4.0 mm diameter) that delivers excitation light to a diffraction limited 2.0 microm diameter spot at full width half maximum within the microfluidic channel. The collector (0.82 annular NA, 15 mm diameter) reflects the fluorescence over a large collection angle, representing 71% of a hemisphere, toward a single photon counting module in an infinity-corrected scheme. As a proof-of-principle experiment for this simple integrated device, individual intercalated lambda-phage DNA molecules (48.5 kb) were stretched in a mixed elongational-shear microflow, detected, and sized with a fluorescence signal to noise ratio of 9.9 +/-1.0. We have demonstrated that SMD does not require traditional high numerical aperture objective lenses and sub-micron positioning systems conventionally used in many applications. Rather, standard manufacturing processes can be combined in a novel way that promises greater accessibility and affordability for microfluidic-based single molecule applications.

A multi-emitter fitting algorithm for potential live cell super-resolution imaging over a wide range of molecular densities.

PubMed

Takeshima, T; Takahashi, T; Yamashita, J; Okada, Y; Watanabe, S

2018-05-25

Multi-emitter fitting algorithms have been developed to improve the temporal resolution of single-molecule switching nanoscopy, but the molecular density range they can analyse is narrow and the computation required is intensive, significantly limiting their practical application. Here, we propose a computationally fast method, wedged template matching (WTM), an algorithm that uses a template matching technique to localise molecules at any overlapping molecular density from sparse to ultrahigh density with subdiffraction resolution. WTM achieves the localization of overlapping molecules at densities up to 600 molecules μm -2 with a high detection sensitivity and fast computational speed. WTM also shows localization precision comparable with that of DAOSTORM (an algorithm for high-density super-resolution microscopy), at densities up to 20 molecules μm -2 , and better than DAOSTORM at higher molecular densities. The application of WTM to a high-density biological sample image demonstrated that it resolved protein dynamics from live cell images with subdiffraction resolution and a temporal resolution of several hundred milliseconds or less through a significant reduction in the number of camera images required for a high-density reconstruction. WTM algorithm is a computationally fast, multi-emitter fitting algorithm that can analyse over a wide range of molecular densities. The algorithm is available through the website. https://doi.org/10.17632/bf3z6xpn5j.1. © 2018 The Authors. Journal of Microscopy published by JohnWiley & Sons Ltd on behalf of Royal Microscopical Society.

Dynamics of bound water molecules in fullerenol at different hydration levels

NASA Astrophysics Data System (ADS)

Wang, Yilin; Robey, Steven; Reutt-Robey, Janice

Fullerenols, polyhydroxylated fullerenes, are of great interest as promising materials in medical application because of their high water solubility and biocompatibility. Fullerenols are highly responsive to their environment, for example, they readily undergo hydration under ambient conditions. Understanding the dynamics of water molecules bound to fullerenols, and the interplay between water molecules and fullerenols is important in realizing biological function. Here, broadband dielectric spectroscopy (BDS), was performed on a fullerenol with 44 hydroxyl groups, C60(OH)44, between 300 K and 340 K. At room temperature and under ambient conditions, C60(OH)44 is hydrated, releasing bound water molecules with increasing temperature, as quantified by thermal gravimetric analysis (TGA) measurements. At room temperature, a dielectric band due to collective bulk-like dynamics of the bound water molecules is observed. The relaxation peak of the water molecules shifts to higher frequency with increasing of temperature, reflecting the dynamics of bound water. Upon loss of water molecules, either thermally induced or vacuum induced, the relaxation peak shifts to lower frequency. The stoichiometric relationship between the dielectric properties of the hydrated fullerenol and the interplay between the bound water molecules and C60(OH)44 will be discussed. This work was supported by the National Science Foundation (NSF) under Award Number 1310380.

Simple method of DNA stretching on glass substrate for fluorescence image and spectroscopy

NASA Astrophysics Data System (ADS)

Neupane, Guru P.; Dhakal, Krishna P.; Lee, Hyunsoo; Guthold, Martin; Joseph, Vincent S.; Hong, Jong-Dal; Kim, Jeongyong

2013-05-01

Study of biological molecule DNA has contributed to developing many breaking thoughts and wide applications in multidisciplinary fields, such as genomic, medical, sensing and forensic fields. Stretching of DNA molecules is an important supportive tool for AFM or spectroscopic studies of DNA in a single molecular level. In this article, we established a simple method of DNA stretching (to its full length) that occurred on a rotating negatively-charged surface of glass substrate. The isolation of a single DNA molecule was attained by the two competitive forces on DNA molecules, that is, the electrostatic attraction developed between the positively charged YOYO-1 stained DNA and the negatively charged substrate, and the centrifugal force of the rotating substrate, which separates the DNA aggregates into the single molecule. Density of stretched DNA molecules was controlled by selecting the specific parameters such as spinning time and rates, loading volume of DNA-dye complex solution etc. The atomic force microscopy image exhibited a single DNA molecule on the negatively-charged substrate in an isolated state. Further, the photoluminescence spectra of a single DNA molecule stained with YOYO-1 were achieved using the method developed in the present study, which is strongly believed to effectively support the spectroscopic analysis of DNA in a single molecular level.

Selectivity of Glycine for Facets on Gold Nanoparticles.

PubMed

Shao, Qing; Hall, Carol K

2018-04-05

The performance of nanoparticles in medical applications depends on their interactions with various molecules. Despite extensive research on this subject, it remains unclear where on an inhomogeneous nanoparticle molecules prefer to adsorb. Here we investigate the selectivity of glycine molecules for facets on five bare gold nanoparticles with diameters from 1.0 to 5.0 nm. Well-tempered metadynamics simulations are conducted to calculate the adsorption free-energy landscapes of a glycine molecule on various locations for the five gold nanoparticles in explicit water. We also calculate the glycine molecule's adsorption free energies on the five gold nanoparticles in vacuum and on three flat gold surfaces as a reference. The simulation results show that glycine molecules prefer to adsorb on the (110) facet for the 1.0 and 2.0 nm nanoparticles, the edges for the 3.0 nm nanoparticle, and the (111) facet for the 4.0 and 5.0 nm nanoparticles in water. The effect of water solvent on the selectivity is investigated through comparing the adsorption free-energy landscapes for glycine molecules on the nanoparticles in water and in vacuum. The area of the facet plays a key role in determining the selectivity of glycine molecules for the different facets, especially the shift of the selectivity as the nanoparticle diameter changes. Our simulations suggest that nanoparticle size and shape can be engineered to control the preferred adsorption location of molecules.

Measurement of the orientation of buffer-gas-cooled, electrostatically-guided ammonia molecules

NASA Astrophysics Data System (ADS)

Steer, Edward W.; Petralia, Lorenzo S.; Western, Colin M.; Heazlewood, Brianna R.; Softley, Timothy P.

2017-02-01

The extent to which the spatial orientation of internally and translationally cold ammonia molecules can be controlled as molecules pass out of a quadrupole guide and through different electric field regions is examined. Ammonia molecules are collisionally cooled in a buffer gas cell, and are subsequently guided by a three-bend electrostatic quadrupole into a detection chamber. The orientation of ammonia molecules is probed using (2 + 1) resonance-enhanced multiphoton ionisation (REMPI), with the laser polarisation axis aligned both parallel and perpendicular to the time-of-flight axis. Even with the presence of a near-zero field region, the ammonia REMPI spectra indicate some retention of orientation. Monte Carlo simulations propagating the time-dependent Schrödinger equation in a full basis set including the hyperfine interaction enable the orientation of ammonia molecules to be calculated - with respect to both the local field direction and a space-fixed axis - as the molecules pass through different electric field regions. The simulations indicate that the orientation of ∼95% of ammonia molecules in JK =11 could be achieved with the application of a small bias voltage (17 V) to the mesh separating the quadrupole and detection regions. Following the recent combination of the buffer gas cell and quadrupole guide apparatus with a linear Paul ion trap, this result could enable one to examine the influence of molecular orientation on ion-molecule reaction dynamics and kinetics.

The effect of pressure on the hydration structure around hydrophobic solute: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Sarma, Rahul; Paul, Sandip

2012-03-01

Molecular dynamics simulations are performed to study the effects of pressure on the hydrophobic interactions between neopentane molecules immersed in water. Simulations are carried out for five different pressure values ranging from 1 atm to 8000 atm. From potential of mean force calculations, we find that with enhancement of pressure, there is decrease in the well depth of contact minimum (CM) and the relative stability of solvent separated minimum over CM increases. Lower clustering of neopentane at high pressure is also observed in association constant and cluster-structure analysis. Selected site-site radial distribution functions suggest efficient packing of water molecules around neopentane molecules at elevated pressure. The orientational profile calculations of water molecules show that the orientation of water molecules in the vicinity of solute molecule is anisotropic and this distribution becomes flatter as we move away from the solute. Increasing pressure slightly changes the water distribution. Our hydrogen bond properties and dynamics calculations reveal pressure-induced formation of more and more number of water molecules with five and four hydrogen bond at the expense of breaking of two and three hydrogen bonded water molecules. We also find lowering of water-water continuous hydrogen bond lifetime on application of pressure. Implication of these results for relative dispersion of hydrophobic molecules at high pressure are discussed.

Controlled Bioactive Molecules Delivery Strategies for Tendon and Ligament Tissue Engineering using Polymeric Nanofibers.

PubMed

Hiong Teh, Thomas Kok; Hong Goh, James Cho; Toh, Siew Lok

2015-01-01

The interest in polymeric nanofibers has escalated over the past decade given its promise as tissue engineering scaffolds that can mimic the nanoscale structure of the native extracellular matrix. With functionalization of the polymeric nanofibers using bioactive molecules, localized signaling moieties can be established for the attached cells, to stimulate desired biological effects and direct cellular or tissue response. The inherently high surface area per unit mass of polymeric nanofibers can enhance cell adhesion, bioactive molecules loading and release efficiencies, and mass transfer properties. In this review article, the application of polymeric nanofibers for controlled bioactive molecules delivery will be discussed, with a focus on tendon and ligament tissue engineering. Various polymeric materials of different mechanical and degradation properties will be presented along with the nanofiber fabrication techniques explored. The bioactive molecules of interest for tendon and ligament tissue engineering, including growth factors and small molecules, will also be reviewed and compared in terms of their nanofiber incorporation strategies and release profiles. This article will also highlight and compare various innovative strategies to control the release of bioactive molecules spatiotemporally and explore an emerging tissue engineering strategy involving controlled multiple bioactive molecules sequential release. Finally, the review article concludes with challenges and future trends in the innovation and development of bioactive molecules delivery using polymeric nanofibers for tendon and ligament tissue engineering.

Local delivery of molecules from a nanopipette for quantitative receptor mapping on live cells.

PubMed

Babakinejad, Babak; Jönsson, Peter; López Córdoba, Ainara; Actis, Paolo; Novak, Pavel; Takahashi, Yasufumi; Shevchuk, Andrew; Anand, Uma; Anand, Praveen; Drews, Anna; Ferrer-Montiel, Antonio; Klenerman, David; Korchev, Yuri E

2013-10-01

Using nanopipettes to locally deliver molecules to the surface of living cells could potentially open up studies of biological processes down to the level of single molecules. However, in order to achieve precise and quantitative local delivery it is essential to be able to determine the amount and distribution of the molecules being delivered. In this work, we investigate how the size of the nanopipette, the magnitude of the applied pressure or voltage, which drives the delivery, and the distance to the underlying surface influences the number and spatial distribution of the delivered molecules. Analytical expressions describing the delivery are derived and compared with the results from finite element simulations and experiments on delivery from a 100 nm nanopipette in bulk solution and to the surface of sensory neurons. We then developed a setup for rapid and quantitative delivery to multiple subcellular areas, delivering the molecule capsaicin to stimulate opening of Transient Receptor Potential Vanilloid subfamily member 1 (TRPV1) channels, membrane receptors involved in pain sensation. Overall, precise and quantitative delivery of molecules from nanopipettes has been demonstrated, opening up many applications in biology such as locally stimulating and mapping receptors on the surface of live cells.

Erythrocyte interactions - Comparison of the aggregation power of polymer molecules used in medicine - Not only size does matter.

PubMed

Jovtchev, S; Alexandrov, S; Hristova-Avakumova, N; Miteva, S; Traikov, L; Gerasimova, D; Stoeff, S

2016-01-01

Different colloids are used as a part of solutions for fluid resuscitation and organ preservation: hydroxyethyl starches (HES), dextran (Dx), polyethylene glycols (PEG), polyvinyl pyrrolidone (PVP). Some of the problems associated with their application are addressed to alteration in erythrocyte (ERY) rheology. We intended to estimate in vitro and compare the aggregation power (AP) of these molecules related to ERY interactions. Washed human ERY are used during the study. The zeta sedimentation technique is used to quantify the cell aggregation. Zeta sedimentation ratio (ZSR) based indices (AI) are calculated. The hydrodynamic radius (Rh) of the polymer molecules is determined using viscometry. For all polymers tested a linear range in the relationship AI - concentration was found. The slope of the calculated line was interpreted as measure of the molecule's AP. The following ranking was obtained: PEG >PVP >DX >HES. Within the same chemical type of polymer, increasing Rh of the molecules leads to elevated AI. Comparison of the AP of molecules with similar Rh reveals a significant dependence on their chemical nature. Our results show that molecule's AP is significantly dependent on their chemical nature - i.e. not only molecular size does matter.

Decomposition of 2-((2-methoxyphenyl)diazenyl)benzene-1,3,5-triol molecule by an argon plasma jet

NASA Astrophysics Data System (ADS)

Tanışlı, Murat; Taşal, Erol

2018-05-01

In this study, we have presented the effects of the argon plasma on a 2-((2-methoxyphenyl)diazenyl)benzene-1,3,5-triol molecule—AZO compound (abbreviated as 2MDB)—under atmospheric pressure. In order to do this, the validated molecule has been considered and plasma has been used to modify it. The atmospheric pressure plasma jet system was specially designed for performing decomposing processes of the 2MDB molecule. The characterizations before and after the application of plasma—which takes only 3 minutes under atmospheric pressure conditions, to dissolve the 2MDB molecule in ethanol and methanol solutions—were examined using the Fourier transform infrared and Ultraviolet-Visible (UV-Vis) spectroscopies. After the plasma treatment, the molecule was broken at -C-N=N-C-C bond. Accurate and important changes are seen clearly from the results. In addition, according to UV-Vis spectra, π-π* electronic transitions related to -N=N- AZO bridge for the 2MDB molecule in polar-aprotic solvents such as ethanol and methanol were recorded as strong transitions. The new photoproducts such as -C-N-N=C and C=O were obtained from the 2MDB molecule.

Directional rolling of positively charged nanoparticles along a flexibility gradient on long DNA molecules.

PubMed

Park, Suehyun; Joo, Heesun; Kim, Jun Soo

2018-01-31

Directing the motion of molecules/colloids in any specific direction is of great interest in many applications of chemistry, physics, and biological sciences, where regulated positioning or transportation of materials is highly desired. Using Brownian dynamics simulations of coarse-grained models of a long, double-stranded DNA molecule and positively charged nanoparticles, we observed that the motion of a single nanoparticle bound to and wrapped by the DNA molecule can be directed along a gradient of DNA local flexibility. The flexibility gradient is constructed along a 0.8 kilobase-pair DNA molecule such that local persistence length decreases gradually from 50 nm to 40 nm, mimicking a gradual change in sequence-dependent flexibility. Nanoparticles roll over a long DNA molecule from less flexible regions towards more flexible ones as a result of the decreasing energetic cost of DNA bending and wrapping. In addition, the rolling becomes slightly accelerated as the positive charge of nanoparticles decreases due to a lower free energy barrier of DNA detachment from charged nanoparticle for processive rolling. This study suggests that the variation in DNA local flexibility can be utilized in constructing and manipulating supramolecular assemblies of DNA molecules and nanoparticles in structural DNA nanotechnology.

Single-molecule techniques in biophysics: a review of the progress in methods and applications.

PubMed

Miller, Helen; Zhou, Zhaokun; Shepherd, Jack; Wollman, Adam J M; Leake, Mark C

2018-02-01

Single-molecule biophysics has transformed our understanding of biology, but also of the physics of life. More exotic than simple soft matter, biomatter lives far from thermal equilibrium, covering multiple lengths from the nanoscale of single molecules to up to several orders of magnitude higher in cells, tissues and organisms. Biomolecules are often characterized by underlying instability: multiple metastable free energy states exist, separated by levels of just a few multiples of the thermal energy scale k B T, where k B is the Boltzmann constant and T absolute temperature, implying complex inter-conversion kinetics in the relatively hot, wet environment of active biological matter. A key benefit of single-molecule biophysics techniques is their ability to probe heterogeneity of free energy states across a molecular population, too challenging in general for conventional ensemble average approaches. Parallel developments in experimental and computational techniques have catalysed the birth of multiplexed, correlative techniques to tackle previously intractable biological questions. Experimentally, progress has been driven by improvements in sensitivity and speed of detectors, and the stability and efficiency of light sources, probes and microfluidics. We discuss the motivation and requirements for these recent experiments, including the underpinning mathematics. These methods are broadly divided into tools which detect molecules and those which manipulate them. For the former we discuss the progress of super-resolution microscopy, transformative for addressing many longstanding questions in the life sciences, and for the latter we include progress in 'force spectroscopy' techniques that mechanically perturb molecules. We also consider in silico progress of single-molecule computational physics, and how simulation and experimentation may be drawn together to give a more complete understanding. Increasingly, combinatorial techniques are now used, including correlative atomic force microscopy and fluorescence imaging, to probe questions closer to native physiological behaviour. We identify the trade-offs, limitations and applications of these techniques, and discuss exciting new directions.

Single-molecule techniques in biophysics: a review of the progress in methods and applications

NASA Astrophysics Data System (ADS)

Miller, Helen; Zhou, Zhaokun; Shepherd, Jack; Wollman, Adam J. M.; Leake, Mark C.

2018-02-01

Single-molecule biophysics has transformed our understanding of biology, but also of the physics of life. More exotic than simple soft matter, biomatter lives far from thermal equilibrium, covering multiple lengths from the nanoscale of single molecules to up to several orders of magnitude higher in cells, tissues and organisms. Biomolecules are often characterized by underlying instability: multiple metastable free energy states exist, separated by levels of just a few multiples of the thermal energy scale k B T, where k B is the Boltzmann constant and T absolute temperature, implying complex inter-conversion kinetics in the relatively hot, wet environment of active biological matter. A key benefit of single-molecule biophysics techniques is their ability to probe heterogeneity of free energy states across a molecular population, too challenging in general for conventional ensemble average approaches. Parallel developments in experimental and computational techniques have catalysed the birth of multiplexed, correlative techniques to tackle previously intractable biological questions. Experimentally, progress has been driven by improvements in sensitivity and speed of detectors, and the stability and efficiency of light sources, probes and microfluidics. We discuss the motivation and requirements for these recent experiments, including the underpinning mathematics. These methods are broadly divided into tools which detect molecules and those which manipulate them. For the former we discuss the progress of super-resolution microscopy, transformative for addressing many longstanding questions in the life sciences, and for the latter we include progress in ‘force spectroscopy’ techniques that mechanically perturb molecules. We also consider in silico progress of single-molecule computational physics, and how simulation and experimentation may be drawn together to give a more complete understanding. Increasingly, combinatorial techniques are now used, including correlative atomic force microscopy and fluorescence imaging, to probe questions closer to native physiological behaviour. We identify the trade-offs, limitations and applications of these techniques, and discuss exciting new directions.

Design and Applications of Noncanonical DNA Base Pairs.

PubMed

Jissy, A K; Datta, Ayan

2014-01-02

While the Watson-Crick base pairs are known to stabilize the DNA double helix and play a vital role in storage/replication of genetic information, their replacement with non-Watson-Crick base pairs has recently been shown to have interesting practical applications. Nowadays, theoretical calculations are routinely performed on very complex systems to gain a better understanding of how molecules interact with each other. We not only bring together some of the basic concepts of how mispaired or unnatural nucleobases interact with each other but also look at how such an understanding influences the prediction of novel properties and development of new materials. We highlight the recent developments in this field of research. In this Perspective, we discuss the success of DFT methods, particularly, dispersion-corrected DFT, for applications such as pH-controlled molecular switching, electric-field-induced stacking of disk-like molecules with guanine quartets, and optical birefringence of alkali-metal-coordinated guanine quartets. The synergy between theoretical models and real applications is highlighted.

Molecular engineering of two-photon fluorescent probes for bioimaging applications

NASA Astrophysics Data System (ADS)

Liu, Hong-Wen; Liu, Yongchao; Wang, Peng; Zhang, Xiao-Bing

2017-03-01

During the past two decades, two-photon microscopy (TPM), which utilizes two near-infrared photons as the excitation source, has emerged as a novel, attractive imaging tool for biological research. Compared with one-photon microscopy, TPM offers several advantages, such as lowering background fluorescence in living cells and tissues, reducing photodamage to biosamples, and a photobleaching phenomenon, offering better 3D spatial localization, and increasing penetration depth. Small-molecule-based two-photon fluorescent probes have been well developed for the detection and imaging of various analytes in biological systems. In this review, we will give a general introduction of molecular engineering of two-photon fluorescent probes based on different fluorescence response mechanisms for bioimaging applications during the past decade. Inspired by the desired advantages of small-molecule two-photon fluorescent probes in biological imaging applications, we expect that more attention will be devoted to the development of new two-photon fluorophores and applications of TPM in areas of bioanalysis and disease diagnosis.

Triarylborane-Based Materials for OLED Applications.

PubMed

Turkoglu, Gulsen; Cinar, M Emin; Ozturk, Turan

2017-09-13

Multidisciplinary research on organic fluorescent molecules has been attracting great interest owing to their potential applications in biomedical and material sciences. In recent years, electron deficient systems have been increasingly incorporated into fluorescent materials. Triarylboranes with the empty p orbital of their boron centres are electron deficient and can be used as strong electron acceptors in conjugated organic fluorescent materials. Moreover, their applications in optoelectronic devices, energy harvesting materials and anion sensing, due to their natural Lewis acidity and remarkable solid-state fluorescence properties, have also been investigated. Furthermore, fluorescent triarylborane-based materials have been commonly utilized as emitters and electron transporters in organic light emitting diode (OLED) applications. In this review, triarylborane-based small molecules and polymers will be surveyed, covering their structure-property relationships, intramolecular charge transfer properties and solid-state fluorescence quantum yields as functional emissive materials in OLEDs. Also, the importance of the boron atom in triarylborane compounds is emphasized to address the key issues of both fluorescent emitters and their host materials for the construction of high-performance OLEDs.

NUTS and BOLTS: Applications of Fluorescence Detected Sedimentation

PubMed Central

Kroe, Rachel R.; Laue, Thomas M.

2008-01-01

Analytical ultracentrifugation is a widely used method for characterizing the solution behavior of macromolecules. However, the two commonly used detectors (absorbance and interference) impose some fundamental restrictions on the concentrations and complexity of the solutions that can be analyzed. The recent addition of a fluorescence detector for the XL-I analytical ultracentrifuge (AU-FDS) enables two different types of sedimentation experiments. First, the AU-FDS can detect picomolar concentrations of labeled solutes allowing the characterization of very dilute solutions of macromolecules, applications we call Normal Use Tracer Sedimentation (NUTS). The great sensitivity of NUTS analysis allows the characterization of small quantities of materials and high affinity interactions. Second, AU-FDS allows characterization of trace quantities of labeled molecules in solutions containing high concentrations and complex mixtures of unlabeled molecules, applications we call Biological On Line Tracer Sedimentation (BOLTS). The discrimination of BOLTS enables the size distribution of a labeled macromolecule to be determined in biological milieu such as cell lysates and serum. Examples are presented that embody features of both NUTS and BOLTS applications, along with our observations on these applications. PMID:19103145

Development of Functional Fluorescent Molecular Probes for the Detection of Biological Substances

PubMed Central

Suzuki, Yoshio; Yokoyama, Kenji

2015-01-01

This review is confined to sensors that use fluorescence to transmit biochemical information. Fluorescence is, by far, the most frequently exploited phenomenon for chemical sensors and biosensors. Parameters that define the application of such sensors include intensity, decay time, anisotropy, quenching efficiency, and luminescence energy transfer. To achieve selective (bio)molecular recognition based on these fluorescence phenomena, various fluorescent elements such as small organic molecules, enzymes, antibodies, and oligonucleotides have been designed and synthesized over the past decades. This review describes the immense variety of fluorescent probes that have been designed for the recognitions of ions, small and large molecules, and their biological applications in terms of intracellular fluorescent imaging techniques. PMID:26095660

Chapter 7: Total internal reflection fluorescence microscopy.

PubMed

Axelrod, Daniel

2008-01-01

Total internal reflection fluorescence microscopy (TIRFM), also known as evanescent wave microscopy, is used in a wide range of applications, particularly to view single molecules attached to planar surfaces and to study the position and dynamics of molecules and organelles in living culture cells near the contact regions with the glass coverslip. TIRFM selectively illuminates fluorophores only in a very thin (less than 100 nm deep) layer near the substrate, thereby avoiding excitation of fluorophores outside this subresolution optical section. This chapter reviews the history, current applications in cell biology and biochemistry, basic optical theory, combinations with numerous other optical and spectroscopic approaches, and a range of setup methods, both commercial and custom.

Virosome, a hybrid vehicle for efficient and safe drug delivery and its emerging application in cancer treatment.

PubMed

Liu, Hanqing; Tu, Zhigang; Feng, Fan; Shi, Haifeng; Chen, Keping; Xu, Ximing

2015-06-01

A virosome is an innovative hybrid drug delivery system with advantages of both viral and non-viral vectors. Studies have shown that a virosome can carry various biologically active molecules, such as nucleic acids, peptides, proteins and small organic molecules. Targeted drug delivery using virosome-based systems can be achieved through surface modifications of virosomes. A number of virosome-based prophylactic and therapeutic products with high safety profiles are currently available in the market. Cancer treatment is a big battlefield for virosome-based drug delivery systems. This review provides an overview of the general concept, preparation procedures, working mechanisms, preclinical studies and clinical applications of virosomes in cancer treatment.

2D nanomaterials assembled from sequence-defined molecules

DOE PAGES

Mu, Peng; Zhou, Guangwen; Chen, Chun-Long

2017-10-21

Two dimensional (2D) nanomaterials have attracted broad interest owing to their unique physical and chemical properties with potential applications in electronics, chemistry, biology, medicine and pharmaceutics. Due to the current limitations of traditional 2D nanomaterials (e.g., graphene and graphene oxide) in tuning surface chemistry and compositions, 2D nanomaterials assembled from sequence-defined molecules (e.g., DNAs, proteins, peptides and peptoids) have recently been developed. They represent an emerging class of 2D nanomaterials with attractive physical and chemical properties. Here, we summarize the recent progress in the synthesis and applications of this type of sequence-defined 2D nanomaterials. We also discuss the challenges andmore » opportunities in this new field.« less

2D nanomaterials assembled from sequence-defined molecules

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

Mu, Peng; Zhou, Guangwen; Chen, Chun-Long

Two dimensional (2D) nanomaterials have attracted broad interest owing to their unique physical and chemical properties with potential applications in electronics, chemistry, biology, medicine and pharmaceutics. Due to the current limitations of traditional 2D nanomaterials (e.g., graphene and graphene oxide) in tuning surface chemistry and compositions, 2D nanomaterials assembled from sequence-defined molecules (e.g., DNAs, proteins, peptides and peptoids) have recently been developed. They represent an emerging class of 2D nanomaterials with attractive physical and chemical properties. Here, we summarize the recent progress in the synthesis and applications of this type of sequence-defined 2D nanomaterials. We also discuss the challenges andmore » opportunities in this new field.« less

Capacitive Biosensors and Molecularly Imprinted Electrodes.

PubMed

Ertürk, Gizem; Mattiasson, Bo

2017-02-17

Capacitive biosensors belong to the group of affinity biosensors that operate by registering direct binding between the sensor surface and the target molecule. This type of biosensors measures the changes in dielectric properties and/or thickness of the dielectric layer at the electrolyte/electrode interface. Capacitive biosensors have so far been successfully used for detection of proteins, nucleotides, heavy metals, saccharides, small organic molecules and microbial cells. In recent years, the microcontact imprinting method has been used to create very sensitive and selective biorecognition cavities on surfaces of capacitive electrodes. This chapter summarizes the principle and different applications of capacitive biosensors with an emphasis on microcontact imprinting method with its recent capacitive biosensor applications.

Nanomanipulation of Single RNA Molecules by Optical Tweezers

PubMed Central

Stephenson, William; Wan, Gorby; Tenenbaum, Scott A.; Li, Pan T. X.

2014-01-01

A large portion of the human genome is transcribed but not translated. In this post genomic era, regulatory functions of RNA have been shown to be increasingly important. As RNA function often depends on its ability to adopt alternative structures, it is difficult to predict RNA three-dimensional structures directly from sequence. Single-molecule approaches show potentials to solve the problem of RNA structural polymorphism by monitoring molecular structures one molecule at a time. This work presents a method to precisely manipulate the folding and structure of single RNA molecules using optical tweezers. First, methods to synthesize molecules suitable for single-molecule mechanical work are described. Next, various calibration procedures to ensure the proper operations of the optical tweezers are discussed. Next, various experiments are explained. To demonstrate the utility of the technique, results of mechanically unfolding RNA hairpins and a single RNA kissing complex are used as evidence. In these examples, the nanomanipulation technique was used to study folding of each structural domain, including secondary and tertiary, independently. Lastly, the limitations and future applications of the method are discussed. PMID:25177917

Molecule-specific determination of atomic polarizabilities with the polarizable atomic multipole model.

PubMed

Woo Kim, Hyun; Rhee, Young Min

2012-07-30

Recently, many polarizable force fields have been devised to describe induction effects between molecules. In popular polarizable models based on induced dipole moments, atomic polarizabilities are the essential parameters and should be derived carefully. Here, we present a parameterization scheme for atomic polarizabilities using a minimization target function containing both molecular and atomic information. The main idea is to adopt reference data only from quantum chemical calculations, to perform atomic polarizability parameterizations even when relevant experimental data are scarce as in the case of electronically excited molecules. Specifically, our scheme assigns the atomic polarizabilities of any given molecule in such a way that its molecular polarizability tensor is well reproduced. We show that our scheme successfully works for various molecules in mimicking dipole responses not only in ground states but also in valence excited states. The electrostatic potential around a molecule with an externally perturbing nearby charge also exhibits a near-quantitative agreement with the reference data from quantum chemical calculations. The limitation of the model with isotropic atoms is also discussed to examine the scope of its applicability. Copyright © 2012 Wiley Periodicals, Inc.

Figuration and detection of single molecules

NASA Astrophysics Data System (ADS)

Nevels, R.; Welch, G. R.; Cremer, P. S.; Hemmer, P.; Phillips, T.; Scully, S.; Sokolov, A. V.; Svidzinsky, A. A.; Xia, H.; Zheltikov, A.; Scully, M. O.

2012-08-01

Recent advances in the description of atoms and molecules based on Dimensional scaling analysis, developed by Dudley Herschbach and co-workers, provided new insights into visualization of molecular structure and chemical bonding. Prof. Herschbach is also a giant in the field of single molecule scattering. We here report on the engineering of molecular detectors. Such systems have a wide range of application from medical diagnostics to the monitoring of chemical, biological and environmental hazards. We discuss ways to identify preselected molecules, in particular, mycotoxin contaminants using coherent laser spectroscopy. Mycotoxin contaminants, e.g. aflatoxin B1 which is present in corn and peanuts, are usually analysed by time-consuming microscopic, chemical and biological assays. We present a new approach that derives from recent experiments in which molecules are prepared by one (or more) femtosecond laser(s) and probed by another set. We call this technique FAST CARS (femto second adaptive spectroscopic technique for coherent anti-Stokes Raman spectroscopy). We propose and analyse ways in which FAST CARS can be used to identify preselected molecules, e.g. aflatoxin, rapidly and economically.

DFT computational analysis of piracetam

NASA Astrophysics Data System (ADS)

Rajesh, P.; Gunasekaran, S.; Seshadri, S.; Gnanasambandan, T.

2014-11-01

Density functional theory calculation with B3LYP using 6-31G(d,p) and 6-31++G(d,p) basis set have been used to determine ground state molecular geometries. The first order hyperpolarizability (β0) and related properties (β, α0 and Δα) of piracetam is calculated using B3LYP/6-31G(d,p) method on the finite-field approach. The stability of molecule has been analyzed by using NBO/NLMO analysis. The calculation of first hyperpolarizability shows that the molecule is an attractive molecule for future applications in non-linear optics. Molecular electrostatic potential (MEP) at a point in the space around a molecule gives an indication of the net electrostatic effect produced at that point by the total charge distribution of the molecule. The calculated HOMO and LUMO energies show that charge transfer occurs within these molecules. Mulliken population analysis on atomic charge is also calculated. Because of vibrational analysis, the thermodynamic properties of the title compound at different temperatures have been calculated. Finally, the UV-Vis spectra and electronic absorption properties are explained and illustrated from the frontier molecular orbitals.

Triphenylamine-Based Push–Pull Molecule for Photovoltaic Applications: From Synthesis to Ultrafast Device Photophysics

PubMed Central

2017-01-01

Small push–pull molecules attract much attention as prospective donor materials for organic solar cells (OSCs). By chemical engineering, it is possible to combine a number of attractive properties such as broad absorption, efficient charge separation, and vacuum and solution processabilities in a single molecule. Here we report the synthesis and early time photophysics of such a molecule, TPA-2T-DCV-Me, based on the triphenylamine (TPA) donor core and dicyanovinyl (DCV) acceptor end group connected by a thiophene bridge. Using time-resolved photoinduced absorption and photoluminescence, we demonstrate that in blends with [70]PCBM the molecule works both as an electron donor and hole acceptor, thereby allowing for two independent channels of charge generation. The charge-generation process is followed by the recombination of interfacial charge transfer states that takes place on the subnanosecond time scale as revealed by time-resolved photoluminescence and nongeminate recombination as follows from the OSC performance. Our findings demonstrate the potential of TPA-DCV-based molecules as donor materials for both solution-processed and vacuum-deposited OSCs. PMID:28413568

C60 fullerene binding to DNA

NASA Astrophysics Data System (ADS)

Alshehri, Mansoor H.; Cox, Barry J.; Hill, James M.

2014-09-01

Fullerenes have attracted considerable attention in various areas of science and technology. Owing to their exceptional physical, chemical, and biological properties, they have many applications, particularly in cosmetic and medical products. Using the Lennard-Jones 6-12 potential function and the continuum approximation, which assumes that intermolecular interactions can be approximated by average atomic surface densities, we determine the binding energies of a C60 fullerene with respect to both single-strand and double-strand DNA molecules. We assume that all configurations are in a vacuum and that the C60 fullerene is initially at rest. Double integrals are performed to determine the interaction energy of the system. We find that the C60 fullerene binds to the double-strand DNA molecule, at either the major or minor grooves, with binding energies of -4.7 eV or -2.3 eV, respectively, and that the C60 molecule binds to the single-strand DNA molecule with a binding energy of -1.6 eV. Our results suggest that the C60 molecule is most likely to be linked to the major groove of the dsDNA molecule.

Theory of diatomic molecules in an external electromagnetic field from first quantum mechanical principles.

PubMed

Sindelka, Milan; Moiseyev, Nimrod

2006-04-27

We study a general problem of the translational/rotational/vibrational/electronic dynamics of a diatomic molecule exposed to an interaction with an arbitrary external electromagnetic field. The theory developed in this paper is relevant to a variety of specific applications, such as alignment or orientation of molecules by lasers, trapping of ultracold molecules in optical traps, molecular optics and interferometry, rovibrational spectroscopy of molecules in the presence of intense laser light, or generation of high order harmonics from molecules. Starting from the first quantum mechanical principles, we derive an appropriate molecular Hamiltonian suitable for description of the center of mass, rotational, vibrational, and electronic molecular motions driven by the field within the electric dipole approximation. Consequently, the concept of the Born-Oppenheimer separation between the electronic and the nuclear degrees of freedom in the presence of an electromagnetic field is introduced. Special cases of the dc/ac-field limits are then discussed separately. Finally, we consider a perturbative regime of a weak dc/ac field, and obtain simple analytic formulas for the associated Born-Oppenheimer translational/rotational/vibrational molecular Hamiltonian.

Probing Buffer-Gas Cooled Molecules with Direct Frequency Comb Spectroscopy in the Mid-Infrrared

NASA Astrophysics Data System (ADS)

Spaun, Ben; Changala, Bryan; Bjork, Bryce J.; Heckl, Oliver H.; Patterson, David; Doyle, John M.; Ye, Jun

2015-06-01

We present the first demonstration of cavity-enhanced direct frequency comb spectroscopy on buffer-gas cooled molecules.By coupling a mid-infrared frequency comb to a high-finesse cavity surrounding a helium buffer-gas chamber, we can gather rotationally resolved absorption spectra with high sensitivity over a broad wavelength region. The measured ˜10 K rotational and translational temperatures of buffer-gas cooled molecules drastically simplify the observed spectra, compared to those of room temperature molecules, and allow for high spectral resolution limited only by Doppler broadening (10-100 MHz). Our system allows for the extension of high-resolution spectroscopy to larger molecules, enabling detailed analysis of molecular structure and dynamics, while taking full advantage of the powerful optical properties of frequency combs. A. Foltynowicz et al. Cavity-enhanced optical frequency comb spectroscopy in the mid-infrared application to trace detection of hydrogen peroxide. Applied Physics B, vol. 110, pp. 163-175, 2013. {D. Patterson and J. M. Doyle. Cooling molecules in a cell for FTMW spectroscopy. Molecular Physics 110, 1757-1766, 2012

Isotope separation by photochromatography

DOEpatents

Suslick, K.S.

1975-10-03

A photochromatographic method for isotope separation is described. An isotopically mixed molecular species is adsorbed on an adsorptive surface, and the adsorbed molecules are irradiated with radiation of a predetermined wavelength which will selectively excite desired isotopic species. Sufficient energy is transferred to the excited molecules to desorb them from the surface and thus separate them from the undesired isotopic species. The method is particularly applicable to the separation of hydrogen isotopes. (BLM)

Next Generation Highly Conducting Organic Films Using Novel Donor-Acceptor Molecules for Opto-electronic Applications

DTIC Science & Technology

2010-06-01

addition, a new class of donor molecules was invented in the course of the DRI program. 2.1 Polymer Based Donor-acceptor Material The following work by...average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data...information, including suggestions for reducing the burden, to Department of Defense, Washington Headquarters Services, Directorate for Information

Selective high-affinity polydentate ligands and methods of making such

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

Denardo, Sally J.; Denardo, Gerald L.; Balhorn, Rodney L.

This invention provides novel polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each bind different region son the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

Selective high-affinity polydentate ligands and methods of making such

DOEpatents

DeNardo, Sally; DeNardo, Gerald; Balhorn, Rodney

2013-09-17

This invention provides polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each binds different regions on the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

Selective high affinity polydentate ligands and methods of making such

DOEpatents

DeNardo, Sally; DeNardo, Gerald; Balhorn, Rodney

2010-02-16

This invention provides novel polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each bind different region son the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

Molecular-beam Studies of Primary Photochemical Processes

DOE R&D Accomplishments Database

Lee, Y. T.

1982-12-01

Application of the method of molecular-beam photofragmentation translational spectroscopy to the investigation of primary photochemical processes of polyatomic molecules is described. Examples will be given to illustrate how information concerning the energetics, dynamics, and mechanism of dissociation processes can be obtained from the precise measurements of angular and velocity distributions of products in an experiment in which a well-defined beam of molecules is crossed with a laser.

Small Molecule Injection into Single-Cell C. elegans Embryos via Carbon-Reinforced Nanopipettes

PubMed Central

Morton, Diane G.; Fellman, Shanna M.; Chung, SueYeon; Soltani, Mohammad; Kevek, Joshua W.; McEuen, Paul M.; Kemphues, Kenneth J.; Wang, Michelle D.

2013-01-01

The introduction of chemical inhibitors into living cells at specific times in development is a useful method for investigating the roles of specific proteins or cytoskeletal components in developmental processes. Some embryos, such as those of Caenorhabditis elegans, however, possess a tough eggshell that makes introducing drugs and other molecules into embryonic cells challenging. We have developed a procedure using carbon-reinforced nanopipettes (CRNPs) to deliver molecules into C. elegans embryos with high temporal control. The use of CRNPs allows for cellular manipulation to occur just subsequent to meiosis II with minimal damage to the embryo. We have used our technique to replicate classical experiments using latrunculin A to inhibit microfilaments and assess its effects on early polarity establishment. Our injections of latrunculin A confirm the necessity of microfilaments in establishing anterior-posterior polarity at this early stage, even when microtubules remain intact. Further, we find that latrunculin A treatment does not prevent association of PAR-2 or PAR-6 with the cell cortex. Our experiments demonstrate the application of carbon-reinforced nanopipettes to the study of one temporally-confined developmental event. The use of CRNPs to introduce molecules into the embryo should be applicable to investigations at later developmental stages as well as other cells with tough outer coverings. PMID:24086620

Small molecule injection into single-cell C. elegans embryos via carbon-reinforced nanopipettes.

PubMed

Brennan, Lucy D; Roland, Thibault; Morton, Diane G; Fellman, Shanna M; Chung, SueYeon; Soltani, Mohammad; Kevek, Joshua W; McEuen, Paul M; Kemphues, Kenneth J; Wang, Michelle D

2013-01-01

The introduction of chemical inhibitors into living cells at specific times in development is a useful method for investigating the roles of specific proteins or cytoskeletal components in developmental processes. Some embryos, such as those of Caenorhabditis elegans, however, possess a tough eggshell that makes introducing drugs and other molecules into embryonic cells challenging. We have developed a procedure using carbon-reinforced nanopipettes (CRNPs) to deliver molecules into C. elegans embryos with high temporal control. The use of CRNPs allows for cellular manipulation to occur just subsequent to meiosis II with minimal damage to the embryo. We have used our technique to replicate classical experiments using latrunculin A to inhibit microfilaments and assess its effects on early polarity establishment. Our injections of latrunculin A confirm the necessity of microfilaments in establishing anterior-posterior polarity at this early stage, even when microtubules remain intact. Further, we find that latrunculin A treatment does not prevent association of PAR-2 or PAR-6 with the cell cortex. Our experiments demonstrate the application of carbon-reinforced nanopipettes to the study of one temporally-confined developmental event. The use of CRNPs to introduce molecules into the embryo should be applicable to investigations at later developmental stages as well as other cells with tough outer coverings.

3D Oxidized Graphene Frameworks: An Efficient Adsorbent for Methylene Blue

NASA Astrophysics Data System (ADS)

Pandey, Abhishek; Deb, Madhurima; Tiwari, Shreya; Pawar, Pranav Bhagwan; Saxena, Sumit; Shukla, Shobha

2018-04-01

Extraordinary properties of graphene and its derivatives have found application in varied areas such as energy, electronics, optical devices and sensors, to name a few. Large surface area along with specialized functional groups make these materials attractive for removal of dye molecules in solution via adsorption. Industrial effluents contain large amounts of toxic chemicals resulting in pollution of water bodies, which pose environmental hazards in general. Here we report application of 3D oxidized graphene frameworks in the efficient removal of cationic dye molecules such as methylene blue via adsorption. Systematic parametric studies investigating the effect of the initial dye concentration, pH and contact time have been performed. Spectroscopic analysis of the filtrate suggests that tortuous paths in 3D oxidized graphene frameworks result in efficient removal of dye molecules due to enhanced interaction. The hydroxyl groups retained in these 3D oxidized graphene frameworks facilitate adsorption of the dye molecules while passing through the adsorbent. pH studies suggest that maximum removal efficiency for methylene blue was achieved at pH value of 9. The results suggest that these 3D oxidized graphene frameworks can be used for purification of large volumes of contaminated water from cationic dyes in waste water treatment plants.

Electrotunable artificial molecules based on van der Waals heterostructures

PubMed Central

Zhang, Zhuo-Zhi; Song, Xiang-Xiang; Luo, Gang; Deng, Guang-Wei; Mosallanejad, Vahid; Taniguchi, Takashi; Watanabe, Kenji; Li, Hai-Ou; Cao, Gang; Guo, Guang-Can; Nori, Franco; Guo, Guo-Ping

2017-01-01

Quantum confinement has made it possible to detect and manipulate single-electron charge and spin states. The recent focus on two-dimensional (2D) materials has attracted significant interests on possible applications to quantum devices, including detecting and manipulating either single-electron charging behavior or spin and valley degrees of freedom. However, the most popular model systems, consisting of tunable double-quantum-dot molecules, are still extremely difficult to realize in these materials. We show that an artificial molecule can be reversibly formed in atomically thin MoS2 sandwiched in hexagonal boron nitride, with each artificial atom controlled separately by electrostatic gating. The extracted values for coupling energies at different regimes indicate a single-electron transport behavior, with the coupling strength between the quantum dots tuned monotonically. Moreover, in the low-density regime, we observe a decrease of the conductance with magnetic field, suggesting the observation of Coulomb blockade weak anti-localization. Our experiments demonstrate for the first time the realization of an artificial quantum-dot molecule in a gated MoS2 van der Waals heterostructure, which could be used to investigate spin-valley physics. The compatibility with large-scale production, gate controllability, electron-hole bipolarity, and new quantum degrees of freedom in the family of 2D materials opens new possibilities for quantum electronics and its applications. PMID:29062893

Theoretical research program to study chemical reactions in AOTV bow shock tubes

NASA Technical Reports Server (NTRS)

Taylor, Peter R.

1993-01-01

The main focus was the development, implementation, and calibration of methods for performing molecular electronic structure calculations to high accuracy. These various methods were then applied to a number of chemical reactions and species of interest to NASA, notably in the area of combustion chemistry. Among the development work undertaken was a collaborative effort to develop a program to efficiently predict molecular structures and vibrational frequencies using energy derivatives. Another major development effort involved the design of new atomic basis sets for use in chemical studies: these sets were considerably more accurate than those previously in use. Much effort was also devoted to calibrating methods for computing accurate molecular wave functions, including the first reliable calibrations for realistic molecules using full CI results. A wide variety of application calculations were undertaken. One area of interest was the spectroscopy and thermochemistry of small molecules, including establishing small molecule binding energies to an accuracy rivaling, or even on occasion surpassing, the experiment. Such binding energies are essential input to modeling chemical reaction processes, such as combustion. Studies of large molecules and processes important in both hydrogen and hydrocarbon combustion chemistry were also carried out. Finally, some effort was devoted to the structure and spectroscopy of small metal clusters, with applications to materials science problems.

Imaging of conformational changes

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

Michl, Josef

2016-03-13

Control of intramolecular conformational change in a small number of molecules or even a single one by an application of an outside electric field defined by potentials on nearby metal or dielectric surfaces has potential applications in both 3-D and 2-D nanotechnology. Specifically, the synthesis, characterization, and understanding of designed solids with controlled built-in internal rotational motion of a dipole promises a new class of materials with intrinsic dielectric, ferroelectric, optical and optoelectronic properties not found in nature. Controlled rotational motion is of great interest due to its expected utility in phenomena as diverse as transport, current flow in molecularmore » junctions, diffusion in microfluidic channels, and rotary motion in molecular machines. A direct time-resolved observation of the dynamics of motion on ps or ns time scale in a single molecule would be highly interesting but is also very difficult and has yet to be accomplished. Much can be learned from an easier but still challenging comparison of directly observed initial and final orientational states of a single molecule, which is the basis of this project. The project also impacts the understanding of surface-enhanced Raman spectroscopy (SERS) and single-molecule spectroscopic detection, as well as the synthesis of solid-state materials with tailored properties from designed precursors.« less

Phthalo-carbonitride: an ab initio prediction of a stable two-dimensional material

NASA Astrophysics Data System (ADS)

Tsetseris, Leonidas

2016-06-01

Using density-functional theory calculations, we identify a stable two-dimensional carbonitride polymorph which resembles the core of phthalocyanine molecules. This so-called phthalo-carbonitride is found to be the lowest-energy polymer made of tetracyanoethylene molecules. It is a two-dimensional metal in its pristine form. Functionalization of the phthalo-cores with copper or iron atoms retains the metallic character of the material, but also adds magnetization to the system. Based on these properties and the established use of phthalocyanine molecules in various applications, the growth of phthalo-carbonitride sheets can add another multi-functional building block to the research and technology of two-dimensional materials.

Combinatorial structures to modeling simple games and applications

NASA Astrophysics Data System (ADS)

Molinero, Xavier

2017-09-01

We connect three different topics: combinatorial structures, game theory and chemistry. In particular, we establish the bases to represent some simple games, defined as influence games, and molecules, defined from atoms, by using combinatorial structures. First, we characterize simple games as influence games using influence graphs. It let us to modeling simple games as combinatorial structures (from the viewpoint of structures or graphs). Second, we formally define molecules as combinations of atoms. It let us to modeling molecules as combinatorial structures (from the viewpoint of combinations). It is open to generate such combinatorial structures using some specific techniques as genetic algorithms, (meta-)heuristics algorithms and parallel programming, among others.

Indistinguishable near-infrared single photons from an individual organic molecule

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

Trebbia, Jean-Baptiste; Tamarat, Philippe; Lounis, Brahim

2010-12-15

By using the zero-phonon line emission of an individual organic molecule, we realized a source of indistinguishable single photons in the near infrared. A Hong-Ou-Mandel interference experiment is performed and a two-photon coalescence probability higher than 50% at 2 K is obtained. The contribution of the temperature-dependent dephasing processes to the two-photon interference contrast is studied. We show that the molecule delivers nearly ideal indistinguishable single photons at the lowest temperatures when the dephasing is nearly lifetime limited. This source is used to generate postselected polarization-entangled photon pairs as a test bench for applications in quantum information.

Dual band metamaterial perfect absorber based on artificial dielectric "molecules".

PubMed

Liu, Xiaoming; Lan, Chuwen; Li, Bo; Zhao, Qian; Zhou, Ji

2016-07-13

Dual band metamaterial perfect absorbers with two absorption bands are highly desirable because of their potential application areas such as detectors, transceiver system, and spectroscopic imagers. However, most of these dual band metamaterial absorbers proposed were based on resonances of metal patterns. Here, we numerically and experimentally demonstrate a dual band metamaterial perfect absorber composed of artificial dielectric "molecules" with high symmetry. The artificial dielectric "molecule" consists of four "atoms" of two different sizes corresponding to two absorption bands with near unity absorptivity. Numerical and experimental absorptivity verify that the dual-band metamaterial absorber is polarization insensitive and can operate in wide-angle incidence.

Thermoelectronic transport through spin-crossover single molecule Fe[(H2Bpz2)2bipy

NASA Astrophysics Data System (ADS)

Liu, N.; Zhu, L.; Yao, K. L.

2018-04-01

By means of density functional theory combined with the method of Keldysh nonequilibrium Green’s function, the thermal transport properties of high- and low-spin states of mononuclear FeII molecules with spin-crossover characteristics are studied. It is found that the high-spin molecular junction has a larger current than the low-spin one, producing thermally-induced switching effect. Furthermore, for high spin state molecule, the spin-up thermo-current is strongly blocked, thus achieving a pure thermo spin current. The enhanced Seebeck coefficient and the figure of merit value of high-spin state indicate that it is an ideal candidate for thermoelectric applications.

Photodetachment and Doppler laser cooling of anionic molecules

NASA Astrophysics Data System (ADS)

Gerber, Sebastian; Fesel, Julian; Doser, Michael; Comparat, Daniel

2018-02-01

We propose to extend laser-cooling techniques, so far only achieved for neutral molecules, to molecular anions. A detailed computational study is performed for {{{C}}}2- molecules stored in Penning traps using GPU based Monte Carlo simulations. Two cooling schemes—Doppler laser cooling and photodetachment cooling—are investigated. The sympathetic cooling of antiprotons is studied for the Doppler cooling scheme, where it is shown that cooling of antiprotons to subKelvin temperatures could becomes feasible, with impacts on the field of antimatter physics. The presented cooling schemes also have applications for the generation of cold, negatively charged particle sources and for the sympathetic cooling of other molecular anions.

Ultrafast electron dynamics in phenylalanine initiated by attosecond pulses.

PubMed

Calegari, F; Ayuso, D; Trabattoni, A; Belshaw, L; De Camillis, S; Anumula, S; Frassetto, F; Poletto, L; Palacios, A; Decleva, P; Greenwood, J B; Martín, F; Nisoli, M

2014-10-17

In the past decade, attosecond technology has opened up the investigation of ultrafast electronic processes in atoms, simple molecules, and solids. Here, we report the application of isolated attosecond pulses to prompt ionization of the amino acid phenylalanine and the subsequent detection of ultrafast dynamics on a sub-4.5-femtosecond temporal scale, which is shorter than the vibrational response of the molecule. The ability to initiate and observe such electronic dynamics in polyatomic molecules represents a crucial step forward in attosecond science, which is progressively moving toward the investigation of more and more complex systems. Copyright © 2014, American Association for the Advancement of Science.

Porous silicon ring resonator for compact, high sensitivity biosensing applications

DOE PAGES

Rodriguez, Gilberto A.; Hu, Shuren; Weiss, Sharon M.

2015-01-01

A ring resonator is patterned on a porous silicon slab waveguide to produce a compact, high quality factor biosensor with a large internal surface area available for enhanced recognition of biological and chemical molecules. The porous nature of the ring resonator allows molecules to directly interact with the guided mode. Quality factors near 10,000 were measured for porous silicon ring resonators with a radius of 25 μm. A bulk detection sensitivity of 380 nm/RIU was measured upon exposure to salt water solutions. Specific detection of nucleic acid molecules was demonstrated with a surface detection sensitivity of 4 pm/nM.

The electron-spin--nuclear-spin interaction studied by polarized neutron scattering.

PubMed

Stuhrmann, Heinrich B

2007-11-01

Dynamic nuclear spin polarization (DNP) is mediated by the dipolar interaction of paramagnetic centres with nuclear spins. This process is most likely to occur near paramagnetic centres at an angle close to 45 degrees with respect to the direction of the external magnetic field. The resulting distribution of polarized nuclear spins leads to an anisotropy of the polarized neutron scattering pattern, even with randomly oriented radical molecules. The corresponding cross section of polarized coherent neutron scattering in terms of a multipole expansion is derived for radical molecules in solution. An application using data of time-resolved polarized neutron scattering from an organic chromium(V) molecule is tested.

A review on nanomechanical resonators and their applications in sensors and molecular transportation

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

Arash, Behrouz; Rabczuk, Timon, E-mail: timon.rabczuk@uni-weimar.de; Jiang, Jin-Wu

2015-06-15

Nanotechnology has opened a new area in science and engineering, leading to the development of novel nano-electromechanical systems such as nanoresonators with ultra-high resonant frequencies. The ultra-high-frequency resonators facilitate wide-ranging applications such as ultra-high sensitive sensing, molecular transportation, molecular separation, high-frequency signal processing, and biological imaging. This paper reviews recent studies on dynamic characteristics of nanoresonators. A variety of theoretical approaches, i.e., continuum modeling, molecular simulations, and multiscale methods, in modeling of nanoresonators are reviewed. The potential application of nanoresonators in design of sensor devices and molecular transportation systems is introduced. The essence of nanoresonator sensors for detection of atomsmore » and molecules with vibration and wave propagation analyses is outlined. The sensitivity of the resonator sensors and their feasibility in detecting different atoms and molecules are particularly discussed. Furthermore, the applicability of molecular transportation using the propagation of mechanical waves in nanoresonators is presented. An extended application of the transportation methods for building nanofiltering systems with ultra-high selectivity is surveyed. The article aims to provide an up-to-date review on the mechanical properties and applications of nanoresonators, and inspire additional potential of the resonators.« less

Levulinic acid: a valuable platform chemical for fermentative syntheses

USDA-ARS?s Scientific Manuscript database

In 2004 the DOE included levulinic acid (LA) as a top platform molecule because of its production from renewable resources in large yields and its broad application potential as a precursor for many valuable chemical derivatives. While LA and its chemical derivatives have high application potential,...

A Biomedical Application of Activated Carbon Adsorption: An Experiment Using Acetaminophen and N-Acetylcysteine.

ERIC Educational Resources Information Center

Rybolt, Thomas R.; And Others

1988-01-01

Illustrates an interesting biomedical application of adsorption from solution and demonstrates some of the factors that influence the in vivo adsorption of drug molecules onto activated charcoal. Uses acetaminophen and N-acetylcysteine for the determination. Suggests several related experiments. (MVL)

Towards a unified model of passive drug permeation I: origins of the unstirred water layer with applications to ionic permeation.

PubMed

Ghosh, Avijit; Scott, Dennis O; Maurer, Tristan S

2014-02-14

In this work, we provide a unified theoretical framework describing how drug molecules can permeate across membranes in neutral and ionized forms for unstirred in vitro systems. The analysis provides a self-consistent basis for the origin of the unstirred water layer (UWL) within the Nernst-Planck framework in the fully unstirred limit and further provides an accounting mechanism based simply on the bulk aqueous solvent diffusion constant of the drug molecule. Our framework makes no new assumptions about the underlying physics of molecular permeation. We hold simply that Nernst-Planck is a reasonable approximation at low concentrations and all physical systems must conserve mass. The applicability of the derived framework has been examined both with respect to the effect of stirring and externally applied voltages to measured permeability. The analysis contains data for 9 compounds extracted from the literature representing a range of permeabilities and aqueous diffusion coefficients. Applicability with respect to ionized permeation is examined using literature data for the permanently charged cation, crystal violet, providing a basis for the underlying mechanism for ionized drug permeation for this molecule as being due to mobile counter-current flow. Copyright © 2013 Elsevier B.V. All rights reserved.

Crown ethers in graphene

DOE PAGES

Guo, Junjie; Lee, Jaekwang; Contescu, Cristian I.; ...

2014-11-13

Crown ethers, introduced by Pedersen1, are at their most basic level neutral rings constructed of oxygen atoms linked by two- or three-carbon chains. They have attracted special attention for their ability to selectively incorporate various atoms2 or molecules within the cavity formed by the ring3-6. This property has led to the use of crown ethers and their compounds in a wide range of chemical and biological applications7,8. However, crown ethers are typically highly flexible, frustrating efforts to rigidify them for many uses that demand higher binding affinity and selectivity9,10. In this Letter, we report atomic-resolution images of the same basicmore » structures of the original crown ethers embedded in graphene. This arrangement constrains the crown ethers to be rigid and planar and thus uniquely suited for the many applications that crown ethers are known for. First-principles calculations show that the close similarity of the structures seen in graphene with those of crown ether molecules also extends to their selectivity towards specific metal cations depending on the ring size. Atoms (or molecules) incorporated within the crown ethers in graphene offer a simple environment that can be easily and systematically probed and modeled. Thus, we expect that this discovery will introduce a new wave of investigations and applications of chemically functionalized graphene.« less

Biosurfactants, bioemulsifiers and exopolysaccharides from marine microorganisms.

PubMed

Satpute, Surekha K; Banat, Ibrahim M; Dhakephalkar, Prashant K; Banpurkar, Arun G; Chopade, Balu A

2010-01-01

Marine biosphere offers wealthy flora and fauna, which represents a vast natural resource of imperative functional commercial grade products. Among the various bioactive compounds, biosurfactant (BS)/bioemulsifiers (BE) are attracting major interest and attention due to their structural and functional diversity. The versatile properties of surface active molecules find numerous applications in various industries. Marine microorganisms such as Acinetobacter, Arthrobacter, Pseudomonas, Halomonas, Myroides, Corynebacteria, Bacillus, Alteromonas sp. have been studied for production of BS/BE and exopolysaccharides (EPS). Due to the enormity of marine biosphere, most of the marine microbial world remains unexplored. The discovery of potent BS/BE producing marine microorganism would enhance the use of environmental biodegradable surface active molecule and hopefully reduce total dependence or number of new application oriented towards the chemical synthetic surfactant industry. Our present review gives comprehensive information on BS/BE which has been reported to be produced by marine microorganisms and their possible potential future applications.

SERS microscopy: plasmonic nanoparticle probes and biomedical applications

NASA Astrophysics Data System (ADS)

Gellner, M.; Schütz, M.; Salehi, M.; Packeisen, J.; Ströbel, P.; Marx, A.; Schmuck, C.; Schlücker, S.

2010-08-01

Nanoparticle probes for use in targeted detection schemes and readout by surface-enhanced Raman scattering (SERS) comprise a metal core, Raman reporter molecules and a protective shell. One design of SERS labels specifically optimized for biomedical applications in conjunction with red laser excitation is based on tunable gold/silver nanoshells, which are completely covered by a self-assembled monolayer (SAM) of Raman reporters. A shell around the SAM-coated metal core stabilizes the colloid and prevents particle aggregation. The optical properties and SERS efficiencies of these plasmonic nanostructures are characterized both experimentally and theoretically. Subsequent bioconjugation of SERS probes to ligands such as antibodies is a prerequisite for the selective detection of the corresponding target molecule via the characteristic Raman signature of the label. Biomedical imaging applications of SERS-labeled antibodies for tumor diagnostics by SERS microscopy are presented, using the localization of the tumor suppressor p63 in prostate tissue sections as an example.

Stable Radical Materials for Energy Applications.

PubMed

Wilcox, Daniel A; Agarkar, Varad; Mukherjee, Sanjoy; Boudouris, Bryan W

2018-06-07

Although less studied than their closed-shell counterparts, materials containing stable open-shell chemistries have played a key role in many energy storage and energy conversion devices. In particular, the oxidation-reduction (redox) properties of these stable radicals have made them a substantial contributor to the progress of organic batteries. Moreover, the use of radical-based materials in photovoltaic devices and thermoelectric systems has allowed for these emerging molecules to have impacts in the energy conversion realm. Additionally, the unique doublet states of radical-based materials provide access to otherwise inaccessible spin states in optoelectronic devices, offering many new opportunities for efficient usage of energy in light-emitting devices. Here, we review the current state of the art regarding the molecular design, synthesis, and application of stable radicals in these energy-related applications. Finally, we point to fundamental and applied arenas of future promise for these designer open-shell molecules, which have only just begun to be evaluated in full.

Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design.

PubMed

Meanwell, Nicholas A

2018-02-05

The electronic properties and relatively small size of fluorine endow it with considerable versatility as a bioisostere and it has found application as a substitute for lone pairs of electrons, the hydrogen atom, and the methyl group while also acting as a functional mimetic of the carbonyl, carbinol, and nitrile moieties. In this context, fluorine substitution can influence the potency, conformation, metabolism, membrane permeability, and P-gp recognition of a molecule and temper inhibition of the hERG channel by basic amines. However, as a consequence of the unique properties of fluorine, it features prominently in the design of higher order structural metaphors that are more esoteric in their conception and which reflect a more sophisticated molecular construction that broadens biological mimesis. In this Perspective, applications of fluorine in the construction of bioisosteric elements designed to enhance the in vitro and in vivo properties of a molecule are summarized.

Generic strategies for chemical space exploration.

PubMed

Andersen, Jakob L; Flamm, Christoph; Merkle, Daniel; Stadler, Peter F

2014-01-01

The chemical universe of molecules reachable from a set of start compounds by iterative application of a finite number of reactions is usually so vast, that sophisticated and efficient exploration strategies are required to cope with the combinatorial complexity. A stringent analysis of (bio)chemical reaction networks, as approximations of these complex chemical spaces, forms the foundation for the understanding of functional relations in Chemistry and Biology. Graphs and graph rewriting are natural models for molecules and reactions. Borrowing the idea of partial evaluation from functional programming, we introduce partial applications of rewrite rules. A framework for the specification of exploration strategies in graph-rewriting systems is presented. Using key examples of complex reaction networks from carbohydrate chemistry we demonstrate the feasibility of this high-level strategy framework. While being designed for chemical applications, the framework can also be used to emulate higher-level transformation models such as illustrated in a small puzzle game.

Antimicrobial peptides and proteins of the horse - insights into a well-armed organism

PubMed Central

2011-01-01

Antimicrobial peptides play a pivotal role as key effectors of the innate immune system in plants and animals and act as endogenous antibiotics. The molecules exhibit an antimicrobial activity against bacteria, viruses, and eukaryotic pathogens with different specificities and potencies depending on the structure and amino-acid composition of the peptides. Several antimicrobial peptides were comprehensively investigated in the last three decades and some molecules with remarkable antimicrobial properties have reached the third phase of clinical studies. Next to the peptides themselves, numerous organisms were examined and analyzed regarding their repertoire of antimicrobial peptides revealing a huge number of candidates with potencies and properties for future medical applications. One of these organisms is the horse, which possesses numerous peptides that are interesting candidates for therapeutical applications in veterinary medicine. Here we summarize investigations and knowledge on equine antimicrobial peptides, point to interesting candidates, and discuss prospects for therapeutical applications. PMID:21888650

Growth and modelling of spherical crystalline morphologies of molecular materials

NASA Astrophysics Data System (ADS)

Shalev, O.; Biswas, S.; Yang, Y.; Eddir, T.; Lu, W.; Clarke, R.; Shtein, M.

2014-10-01

Crystalline, yet smooth, sphere-like morphologies of small molecular compounds are desirable in a wide range of applications but are very challenging to obtain using common growth techniques, where either amorphous films or faceted crystallites are the norm. Here we show solvent-free, guard flow-assisted organic vapour jet printing of non-faceted, crystalline microspheroids of archetypal small molecular materials used in organic electronic applications. We demonstrate how process parameters control the size distribution of the spheroids and propose an analytical model and a phase diagram predicting the surface morphology evolution of different molecules based on processing conditions, coupled with the thermophysical and mechanical properties of the molecules. This experimental approach opens a path for exciting applications of small molecular organic compounds in optical coatings, textured surfaces with controlled wettability, pharmaceutical and food substance printing and others, where thick organic films and particles with high surface area are needed.

Transforming MOFs for energy applications using the guest@MOF concept

DOE PAGES

Ullman, Andrew M.; Brown, Jonathan W.; Foster, Michael E.; ...

2016-07-11

As the world transitions from fossil fuels to clean energy sources in the coming decades, many technological challenges will require chemists and material scientists to develop new materials for applications related to energy conversion, storage, and efficiency. Because of their unprecedented adaptability, metal–organic frameworks (MOFs) will factor strongly in this portfolio. By utilizing the broad synthetic toolkit provided by the fields of organic and inorganic chemistry, MOF pores can be customized to suit a particular application. Of particular importance is the ability to tune the strength of the interaction between the MOF pores and guest molecules. By cleverly controlling thesemore » MOF–guest interactions, the chemist may impart new function into the Guest@MOF materials otherwise lacking in vacant MOF. Herein, we highlight the concept of the Guest@MOF as it relates to our efforts to develop these materials for energy-related applicatons. Additionally, our work in the areas of H 2 and noble gas storage, hydrogenolysis of biomass, light-harvesting, and conductive materials will be discussed. Of relevance to light-harvesting applications, we report for the first time a postsynthetic modification strategy for increasing the loading of a light-sensitive electron-donor molecule in the pores of a functionalized MIL-101 structure. Through the demonstrated versatility of these approaches, we show that, by treating guest molecules as integral design elements for new MOF constructs, MOF science can have a significant impact on the advancement of clean energy technologies.« less

Transforming MOFs for Energy Applications Using the Guest@MOF Concept.

PubMed

Ullman, Andrew M; Brown, Jonathan W; Foster, Michael E; Léonard, François; Leong, Kirsty; Stavila, Vitalie; Allendorf, Mark D

2016-08-01

As the world transitions from fossil fuels to clean energy sources in the coming decades, many technological challenges will require chemists and material scientists to develop new materials for applications related to energy conversion, storage, and efficiency. Because of their unprecedented adaptability, metal-organic frameworks (MOFs) will factor strongly in this portfolio. By utilizing the broad synthetic toolkit provided by the fields of organic and inorganic chemistry, MOF pores can be customized to suit a particular application. Of particular importance is the ability to tune the strength of the interaction between the MOF pores and guest molecules. By cleverly controlling these MOF-guest interactions, the chemist may impart new function into the Guest@MOF materials otherwise lacking in vacant MOF. Herein, we highlight the concept of the Guest@MOF as it relates to our efforts to develop these materials for energy-related applicatons. Our work in the areas of H2 and noble gas storage, hydrogenolysis of biomass, light-harvesting, and conductive materials will be discussed. Of relevance to light-harvesting applications, we report for the first time a postsynthetic modification strategy for increasing the loading of a light-sensitive electron-donor molecule in the pores of a functionalized MIL-101 structure. Through the demonstrated versatility of these approaches, we show that, by treating guest molecules as integral design elements for new MOF constructs, MOF science can have a significant impact on the advancement of clean energy technologies.

Quantitative Connection Between Ensemble Thermodynamics and Single-Molecule Kinetics: A Case Study Using Cryo-EM and smFRET Investigations of the Ribosome

PubMed Central

Frank, Joachim; Gonzalez, Ruben L.

2015-01-01

At equilibrium, thermodynamic and kinetic information can be extracted from biomolecular energy landscapes by many techniques. However, while static, ensemble techniques yield thermodynamic data, often only dynamic, single-molecule techniques can yield the kinetic data that describes transition-state energy barriers. Here we present a generalized framework based upon dwell-time distributions that can be used to connect such static, ensemble techniques with dynamic, single-molecule techniques, and thus characterize energy landscapes to greater resolutions. We demonstrate the utility of this framework by applying it to cryogenic electron microscopy and single-molecule fluorescence resonance energy transfer studies of the bacterial ribosomal pretranslocation complex. Among other benefits, application of this framework to these data explains why two transient, intermediate conformations of the pretranslocation complex, which are observed in a cryogenic electron microscopy study, may not be observed in several single-molecule fluorescence resonance energy transfer studies. PMID:25785884

Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10.

PubMed

Yang, Wang-Yong; Gao, Rui; Southern, Mark; Sarkar, Partha S; Disney, Matthew D

2016-06-01

RNA is an important target for chemical probes of function and lead therapeutics; however, it is difficult to target with small molecules. One approach to tackle this problem is to identify compounds that target RNA structures and utilize them to multivalently target RNA. Here we show that small molecules can be identified to selectively bind RNA base pairs by probing a library of RNA-focused small molecules. A small molecule that selectively binds AU base pairs informed design of a dimeric compound (2AU-2) that targets the pathogenic RNA, expanded r(AUUCU) repeats, that causes spinocerebellar ataxia type 10 (SCA10) in patient-derived cells. Indeed, 2AU-2 (50 nM) ameliorates various aspects of SCA10 pathology including improvement of mitochondrial dysfunction, reduced activation of caspase 3, and reduction of nuclear foci. These studies provide a first-in-class chemical probe to study SCA10 RNA toxicity and potentially define broadly applicable compounds targeting RNA AU base pairs in cells.

A photo-driven dual-frequency addressable optical device of banana-shaped molecules

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

Krishna Prasad, S., E-mail: skpras@gmail.com; Lakshmi Madhuri, P.; Hiremath, Uma S.

We propose a photonic switch employing a blend of host banana-shaped liquid crystalline molecules and guest photoisomerizable calamitic molecules. The material exhibits a change in the sign of the dielectric anisotropy switching from positive to negative, at a certain crossover frequency of the probing field. The consequent change in electric torque can be used to alter the orientation of the molecules between surface-determined and field-driven optical states resulting in a large change in the optical transmission characteristics. Here, we demonstrate the realization of this feature by an unpolarized UV beam, the first of its kind for banana-shaped molecules. The underlyingmore » principle of photoisomerization eliminates the need for a second driving frequency. The device also acts as a reversible conductance switch with an order of magnitude increase of conductivity brought about by light. Possible usage of this for optically driven display devices and image storage applications is suggested.« less

Reverse engineering of an affinity-switchable molecular interaction characterized by atomic force microscopy single-molecule force spectroscopy.

PubMed

Anselmetti, Dario; Bartels, Frank Wilco; Becker, Anke; Decker, Björn; Eckel, Rainer; McIntosh, Matthew; Mattay, Jochen; Plattner, Patrik; Ros, Robert; Schäfer, Christian; Sewald, Norbert

2008-02-19

Tunable and switchable interaction between molecules is a key for regulation and control of cellular processes. The translation of the underlying physicochemical principles to synthetic and switchable functional entities and molecules that can mimic the corresponding molecular functions is called reverse molecular engineering. We quantitatively investigated autoinducer-regulated DNA-protein interaction in bacterial gene regulation processes with single atomic force microscopy (AFM) molecule force spectroscopy in vitro, and developed an artificial bistable molecular host-guest system that can be controlled and regulated by external signals (UV light exposure and thermal energy). The intermolecular binding functionality (affinity) and its reproducible and reversible switching has been proven by AFM force spectroscopy at the single-molecule level. This affinity-tunable optomechanical switch will allow novel applications with respect to molecular manipulation, nanoscale rewritable molecular memories, and/or artificial ion channels, which will serve for the controlled transport and release of ions and neutral compounds in the future.

Dissipation dynamics of field-free molecular alignment for symmetric-top molecules: Ethane (C2H6)

NASA Astrophysics Data System (ADS)

Zhang, H.; Billard, F.; Yu, X.; Faucher, O.; Lavorel, B.

2018-03-01

The field-free molecular alignment of symmetric-top molecules, ethane, induced by intense non-resonant linearly polarized femtosecond laser pulses is investigated experimentally in the presence of collisional relaxation. The dissipation dynamics of field-free molecular alignment are measured by the balanced detection of ultrafast molecular birefringence of ethane gas samples at high pressures. By separating the molecular alignment into the permanent alignment and the transient alignment, the decay time-constants of both components are quantified at the same pressure. It is observed that the permanent alignment always decays slower compared to the transient alignment within the measured pressure range. This demonstrates that the propensity of molecules to conserve the orientation of angular momentum during collisions, previously observed for linear species, is also applicable to symmetric-top molecules. The results of this work provide valuable information for further theoretical understanding of collisional relaxation within nonlinear polyatomic molecules, which are expected to present interesting and nontrivial features due to an extra rotational degree of freedom.

Solving the Schroedinger Equation of Atoms and Molecules without Analytical Integration Based on the Free Iterative-Complement-Interaction Wave Function

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

Nakatsuji, H.; Nakashima, H.; Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510

2007-12-14

A local Schroedinger equation (LSE) method is proposed for solving the Schroedinger equation (SE) of general atoms and molecules without doing analytic integrations over the complement functions of the free ICI (iterative-complement-interaction) wave functions. Since the free ICI wave function is potentially exact, we can assume a flatness of its local energy. The variational principle is not applicable because the analytic integrations over the free ICI complement functions are very difficult for general atoms and molecules. The LSE method is applied to several 2 to 5 electron atoms and molecules, giving an accuracy of 10{sup -5} Hartree in total energy.more » The potential energy curves of H{sub 2} and LiH molecules are calculated precisely with the free ICI LSE method. The results show the high potentiality of the free ICI LSE method for developing accurate predictive quantum chemistry with the solutions of the SE.« less

Exploring Charge Transport in Guest Molecule Infiltrated Cu 3(BTC) 2 Metal Organic Framework

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

Leonard, Francois Leonard; Stavila, Vitalie; Allendorf, Mark D.

2014-09-01

The goal of this Exploratory Express project was to expand the understanding of the physical properties of our recently discovered class of materials consisting of metal-organic frameworks with electroactive ‘guest’ molecules that together form an electrically conducting charge-transfer complex (molecule@MOF). Thin films of Cu 3(BTC) 2 were grown on fused silica using solution step-by-step growth and were infiltrated with the molecule tetracyanoquinodimethane (TCNQ). The infiltrated MOF films were extensively characterized using optical microscopy, scanning electron microscopy, Raman spectroscopy, electrical conductivity, and thermoelectric properties. Thermopower measurements on TCNQ@Cu 3(BTC) 2 revealed a positive Seebeck coefficient of ~400 μV/k, indicating that holesmore » are the primary carriers in this material. The high value of the Seebeck coefficient and the expected low thermal conductivity suggest that molecule@MOF materials may be attractive for thermoelectric power conversion applications requiring low cost, solution-processable, and non-toxic active materials.« less

9,10-Azaboraphenanthrene-containing small molecules and conjugated polymers: synthesis and their application in chemodosimeters for the ratiometric detection of fluoride ions.

PubMed

Zhang, Weidong; Li, Guoping; Xu, Letian; Zhuo, Yue; Wan, Wenming; Yan, Ni; He, Gang

2018-05-21

The introduction of main group elements into conjugated scaffolds is emerging as a key route to novel optoelectronic materials. Herein, an efficient and versatile way to synthesize polymerizable 9,10-azaboraphenanthrene ( BNP )-containing monomers by aromaticity-driven ring expansion reactions between highly antiaromatic borafluorene and azides is reported, and the corresponding conjugated small molecules and polymers are developed as well. The BNP -containing small molecules and conjugated polymers showed good air/moisture stability and notable fluorescence properties. Addition of fluoride ions to the BNP -based small molecules and polymers induced a rapid change in the emission color from blue to green/yellow, respectively, accompanied by strong intensity changes. The conjugated polymers showed better ratiometric sensing performance than small molecules due to the exciton migration along the conjugated chains. Further experiments showed that the sensing process is fully reversible. The films prepared by solution-deposition of BNP -based compounds in the presence of polycaprolactone also showed good ratiometric sensing for fluoride ions.

High-Frequency Electron Paramagnetic Resonance Spectroscopy of Nitroxide-Functionalized Nanodiamonds in Aqueous Solution.

PubMed

Akiel, R D; Stepanov, V; Takahashi, S

2017-06-01

Nanodiamond (ND) is an attractive class of nanomaterial for fluorescent labeling, magnetic sensing of biological molecules, and targeted drug delivery. Many of those applications require tethering of target biological molecules on the ND surface. Even though many approaches have been developed to attach macromolecules to the ND surface, it remains challenging to characterize dynamics of tethered molecule. Here, we show high-frequency electron paramagnetic resonance (HF EPR) spectroscopy of nitroxide-functionalized NDs. Nitroxide radical is a commonly used spin label to investigate dynamics of biological molecules. In the investigation, we developed a sample holder to overcome water absorption of HF microwave. Then, we demonstrated HF EPR spectroscopy of nitroxide-functionalized NDs in aqueous solution and showed clear spectral distinction of ND and nitroxide EPR signals. Moreover, through EPR spectral analysis, we investigate dynamics of nitroxide radicals on the ND surface. The demonstration sheds light on the use of HF EPR spectroscopy to investigate biological molecule-functionalized nanoparticles.

1,3,5-trinitro-1,3,5-triazine decomposition and chemisorption on Al(111) surface: first-principles molecular dynamics study.

PubMed

Umezawa, Naoto; Kalia, Rajiv K; Nakano, Aiichiro; Vashista, Priya; Shimojo, Fuyuki

2007-06-21

We have investigated the decomposition and chemisorption of a 1,3,5-trinitro-1,3,5-triazine (RDX) molecule on Al(111) surface using molecular dynamics simulations, in which interatomic forces are computed quantum mechanically in the framework of the density functional theory (DFT). The real-space DFT calculations are based on higher-order finite difference and norm-conserving pseudopotential methods. Strong attractive forces between oxygen and aluminum atoms break N-O and N-N bonds in the RDX and, subsequently, the dissociated oxygen atoms and NO molecules oxidize the Al surface. In addition to these Al surface-assisted decompositions, ring cleavage of the RDX molecule is also observed. These reactions occur spontaneously without potential barriers and result in the attachment of the rest of the RDX molecule to the surface. This opens up the possibility of coating Al nanoparticles with RDX molecules to avoid the detrimental effect of oxidation in high energy density material applications.

Small molecules enhance CRISPR genome editing in pluripotent stem cells.

PubMed

Yu, Chen; Liu, Yanxia; Ma, Tianhua; Liu, Kai; Xu, Shaohua; Zhang, Yu; Liu, Honglei; La Russa, Marie; Xie, Min; Ding, Sheng; Qi, Lei S

2015-02-05

The bacterial CRISPR-Cas9 system has emerged as an effective tool for sequence-specific gene knockout through non-homologous end joining (NHEJ), but it remains inefficient for precise editing of genome sequences. Here we develop a reporter-based screening approach for high-throughput identification of chemical compounds that can modulate precise genome editing through homology-directed repair (HDR). Using our screening method, we have identified small molecules that can enhance CRISPR-mediated HDR efficiency, 3-fold for large fragment insertions and 9-fold for point mutations. Interestingly, we have also observed that a small molecule that inhibits HDR can enhance frame shift insertion and deletion (indel) mutations mediated by NHEJ. The identified small molecules function robustly in diverse cell types with minimal toxicity. The use of small molecules provides a simple and effective strategy to enhance precise genome engineering applications and facilitates the study of DNA repair mechanisms in mammalian cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Vibrational spectroscopic and structural investigations on fullerene: A DFT approach

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

Christy, P. Anto; Premkumar, S.; Asath, R. Mohamed

2016-05-06

The molecular structure of fullerene (C{sub 60}) molecule was optimized by the DFT/B3LYP method with 6-31G and 6-31G(d,p) basis sets using Gaussian 09 program. The vibrational frequencies were calculated for the optimized molecular structure of the molecule. The calculated vibrational frequencies confirm that the molecular structure of the molecule was located at the minimum energy potential energy surface. The calculated vibrational frequencies were assigned on the basis of functional group analysis and also confirmed using the GaussView 05 software. The frontier molecular orbitals analysis was carried out. The FMOs related molecular properties were predicted. The higher ionization potential, higher electronmore » affinity, higher softness, lower band gap energy and lower hardness values were obtained, which confirm that the fullerene molecule has a higher molecular reactivity. The Mulliken atomic charge distribution of the molecule was also calculated. Hence, these results play an important role due to its potential applications as drug delivery devices.« less

Quantitative Connection between Ensemble Thermodynamics and Single-Molecule Kinetics: A Case Study Using Cryogenic Electron Microscopy and Single-Molecule Fluorescence Resonance Energy Transfer Investigations of the Ribosome.

PubMed

Thompson, Colin D Kinz; Sharma, Ajeet K; Frank, Joachim; Gonzalez, Ruben L; Chowdhury, Debashish

2015-08-27

At equilibrium, thermodynamic and kinetic information can be extracted from biomolecular energy landscapes by many techniques. However, while static, ensemble techniques yield thermodynamic data, often only dynamic, single-molecule techniques can yield the kinetic data that describe transition-state energy barriers. Here we present a generalized framework based upon dwell-time distributions that can be used to connect such static, ensemble techniques with dynamic, single-molecule techniques, and thus characterize energy landscapes to greater resolutions. We demonstrate the utility of this framework by applying it to cryogenic electron microscopy (cryo-EM) and single-molecule fluorescence resonance energy transfer (smFRET) studies of the bacterial ribosomal pre-translocation complex. Among other benefits, application of this framework to these data explains why two transient, intermediate conformations of the pre-translocation complex, which are observed in a cryo-EM study, may not be observed in several smFRET studies.

Controlled enzymatic cutting of DNA molecules adsorbed on surfaces using soft lithography

NASA Astrophysics Data System (ADS)

Auerbach, Alyssa; Budassi, Julia; Shea, Emily; Zhu, Ke; Sokolov, Jonathan

2013-03-01

The enzyme DNase I was applied to adsorbed and aligned DNA molecules (Lamda, 48.5 kilobase pairs (kbp), and T4, 165.6 kbp), stretched linearly on a surface, by stamping with a polydimethylsiloxane (PDMS) grating. The DNAs were cut by the enzyme into separated, micron-sized segments along the length of the molecules at positions determined by the grating dimensions (3-20 microns). Ozone-treated PDMS stamps were coated with DNase I solutions and placed in contact with surface-adsorbed DNA molecules deposited on a 750 polymethylmethacrylate (PMMA) film spun-cast onto a silicon substrate. The stamps were applied under pressure for times up to 15 minutes at 37 C. The cutting was observed by fluorescence microscopy imaging of DNA labeled with YOYO dye. Cutting was found to be efficient despite the steric hindrance due to surface attachment of the molecules. Methods for detaching and separating the cut segments for sequencing applications will be discussed. Supported by NSF-DMR program.

A Computational Study of the Rheology and Structure of Surfactant Covered Droplets

NASA Astrophysics Data System (ADS)

Maia, Joao; Boromand, Arman; Jamali, Safa

2015-11-01

The use of different types of surface-active agents is ubiquitous practice in different industrial applications ranging from cosmetic and food industries to polymeric nano-composite and blends. This allows stable multiphasic systems like foams and emulsions to be produced. Stability and shelf-life of those products are directly determined by the efficiency of the surfactant molecules. Although the effect of molecular configuration of the surface-active molecules on the planar interfaces has been studied both experimentally and computationally, it remains challenging to track the efficiency and effectiveness of different surfactant molecules on curved interfaces. In this study we address this gap by using Dissipative Particle Dynamics, to study the effectiveness and efficiency of different surfactant molecules (linear vs. branched) on a curved interface in equilibrium and far from equilibrium. In particular, we are interested to relate interfacial properties of the surface covered droplets and its dynamics to the molecular configuration of the surface active molecules under equilibrium and far from equilibrium condition.

Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists.

PubMed

Kollmann, Christopher S; Bai, Xiaopeng; Tsai, Ching-Hsuan; Yang, Hongfang; Lind, Kenneth E; Skinner, Steven R; Zhu, Zhengrong; Israel, David I; Cuozzo, John W; Morgan, Barry A; Yuki, Koichi; Xie, Can; Springer, Timothy A; Shimaoka, Motomu; Evindar, Ghotas

2014-04-01

The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Innovative application of small molecules to influence -pathogenicity of dental plaque].

PubMed

Janus, M M; Volgenant, C M C; Krom, B P

2018-05-01

Current preventive measures against infectious oral diseases are mainly focussed on plaque removal and promoting a healthy lifestyle. This in vitro study investigated a third preventive method: maintaining healthy dental plaque with the use of small molecules. As a model of dental plaque, in vitro biofilms were cultivated under conditions that induce pathogenic characteristics. The effect of erythritol and other small molecules on the pathogenic characteristics and bacterial composition of the biofilm was evaluated. The artificial sweetener erythritol and the molecule 3-Oxo-N-(2-oxycyclohexyl)dodecanamide (3-Oxo-N) had no clinically relevant effect on total biofilm formation. Erythritol did, however, lower the gingivitis related protease activity of the biofilm, while 3-Oxo-N blocked the caries related lactic acid accumulation. Furthermore, both substances ensured the biofilm maintained a young, non-pathogenic microbial composition. This shows it is possible to influence the dental plaque in a positive manner in vitro with the help of small molecules. Further research is necessary before this manipulation of dental plaque can be applied.

Wafer-scale metasurface for total power absorption, local field enhancement and single molecule Raman spectroscopy

PubMed Central

Wang, Dongxing; Zhu, Wenqi; Best, Michael D.; Camden, Jon P.; Crozier, Kenneth B.

2013-01-01

The ability to detect molecules at low concentrations is highly desired for applications that range from basic science to healthcare. Considerable interest also exists for ultrathin materials with high optical absorption, e.g. for microbolometers and thermal emitters. Metal nanostructures present opportunities to achieve both purposes. Metal nanoparticles can generate gigantic field enhancements, sufficient for the Raman spectroscopy of single molecules. Thin layers containing metal nanostructures (“metasurfaces”) can achieve near-total power absorption at visible and near-infrared wavelengths. Thus far, however, both aims (i.e. single molecule Raman and total power absorption) have only been achieved using metal nanostructures produced by techniques (high resolution lithography or colloidal synthesis) that are complex and/or difficult to implement over large areas. Here, we demonstrate a metasurface that achieves the near-perfect absorption of visible-wavelength light and enables the Raman spectroscopy of single molecules. Our metasurface is fabricated using thin film depositions, and is of unprecedented (wafer-scale) extent. PMID:24091825

Bioinspired nanovalves with selective permeability and pH sensitivity

NASA Astrophysics Data System (ADS)

Zheng, Z.; Huang, X.; Schenderlein, M.; Moehwald, H.; Xu, G.-K.; Shchukin, D. G.

2015-01-01

Biological systems with controlled permeability and release functionality, which are among the successful examples of living beings to survive in evolution, have attracted intensive investigation and have been mimicked due to their broad spectrum of applications. We present in this work, for the first time, an example of nuclear pore complexes (NPCs)-inspired controlled release system that exhibits on-demand release of angstrom-sized molecules. We do so in a cost-effective way by stabilizing porous cobalt basic carbonates as nanovalves and realizing pH-sensitive release of entrapped subnano cargo. The proof-of-concept work also consists of the establishment of two mathematical models to explain the selective permeability of the nanovalves. Finally, gram-sized (or larger) quantities of the bio-inspired controlled release system can be synthesized through a scaling-up strategy, which opens up opportunities for controlled release of functional molecules in wider practical applications.Biological systems with controlled permeability and release functionality, which are among the successful examples of living beings to survive in evolution, have attracted intensive investigation and have been mimicked due to their broad spectrum of applications. We present in this work, for the first time, an example of nuclear pore complexes (NPCs)-inspired controlled release system that exhibits on-demand release of angstrom-sized molecules. We do so in a cost-effective way by stabilizing porous cobalt basic carbonates as nanovalves and realizing pH-sensitive release of entrapped subnano cargo. The proof-of-concept work also consists of the establishment of two mathematical models to explain the selective permeability of the nanovalves. Finally, gram-sized (or larger) quantities of the bio-inspired controlled release system can be synthesized through a scaling-up strategy, which opens up opportunities for controlled release of functional molecules in wider practical applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06378c

Accelerator mass spectrometry in the biomedical sciences: applications in low-exposure biomedical and environmental dosimetry

NASA Astrophysics Data System (ADS)

Felton, J. S.; Turteltaub, K. W.; Vogel, J. S.; Balhorn, R.; Gledhill, B. L.; Southon, J. R.; Caffee, M. W.; Finkel, R. C.; Nelson, D. E.; Proctor, I. D.; Davis, J. C.

1990-12-01

We are utilizing accelerator mass spectrometry as a sensitive detector for tracking the disposition of radioisotopically labeled molecules in the biomedical sciences. These applications have shown the effectiveness of AMS as a tool to quantify biologically important molecules at extremely low levels. For example, AMS is being used to determine the amount of carcinogen covalently bound to animal DNA (DNA adduct) at levels relevent to human exposure. Detection sensitivities are 1 carcinogen molecule bound in 1011 to 1012 DNA bases, depending on the specific activity of the radiolabeled carcinogen. Studies have been undertaken in our laboratory utilizing heterocyclic amine food-borne carcinogens and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent environmental carcinogen, to study the metabolism of carcinogens at low doses. In addition, AMS is being used to detect the presence of rare proteins (mutant forms of protamine) in human sperm. Approximately l per 106 sperm analyzed contain the rare form of the protamine. Protamine isolated from this small number of cells is being analyzed by AMS, following 14C labeling. Thus, AMS can be used to verify the identity of an extremely small amount of biological material. Furthermore, an additional improvement of 2 orders of magnitude in the sensitivity of biomédical tracer studies is suggested by preliminary work with bacterial hosts depleted in radiocarbon. Other problems in the life sciences where detection sensitivity or sample sizes are limitations should also benefit from AMS. Studies are underway to measure the molecular targeting of cancer chemotherapeutics in human tissue and to pursue applications for receptor biology. We are also applying other candidate isotopes, such as 3H (double labeling with 14C) and 41Ca (bone absorption) to problems in biology. The detection of 36Cl and 26Al have applications for determination of human neutron exposure and understanding neurological toxicity, respectively. The results described here with 14C-labeled molecules coupled with new isotope applications clearly show AMS technology to be an important new tool for the biomedical sciences community.

Coherent Control of Ground State NaK Molecules

NASA Astrophysics Data System (ADS)

Yan, Zoe; Park, Jee Woo; Loh, Huanqian; Will, Sebastian; Zwierlein, Martin

2016-05-01

Ultracold dipolar molecules exhibit anisotropic, tunable, long-range interactions, making them attractive for the study of novel states of matter and quantum information processing. We demonstrate the creation and control of 23 Na40 K molecules in their rovibronic and hyperfine ground state. By applying microwaves, we drive coherent Rabi oscillations of spin-polarized molecules between the rotational ground state (J=0) and J=1. The control afforded by microwave manipulation allows us to pursue engineered dipolar interactions via microwave dressing. By driving a two-photon transition, we are also able to observe Ramsey fringes between different J=0 hyperfine states, with coherence times as long as 0.5s. The realization of long coherence times between different molecular states is crucial for applications in quantum information processing. NSF, AFOSR- MURI, Alfred P. Sloan Foundation, DARPA-OLE

Symmetry numbers for rigid, flexible, and fluxional molecules: theory and applications.

PubMed

Gilson, Michael K; Irikura, Karl K

2010-12-16

The use of molecular simulations and ab initio calculations to predict thermodynamic properties of molecules has become routine. Such methods rely upon an accurate representation of the molecular partition function or configurational integral, which in turn often includes a rotational symmetry number. However, the reason for including the symmetry number is unclear to many practitioners, and there is also a need for a general prescription for evaluating the symmetry numbers of flexible molecules, i.e., for molecules with thermally active internal degrees of freedom, such as internal rotors. Surprisingly, we have been unable to find any complete and convincing explanations of these important issues in textbooks or the journal literature. The present paper aims to explain why symmetry numbers are needed and how their values should be determined. Both classical and quantum approaches are provided.

[Imaging Mass Spectrometry in Histopathologic Analysis].

PubMed

Yamazaki, Fumiyoshi; Seto, Mitsutoshi

2015-04-01

Matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) enables visualization of the distribution of a range of biomolecules by integrating biochemical information from mass spectrometry with positional information from microscopy. IMS identifies a target molecule. In addition, IMS enables global analysis of biomolecules containing unknown molecules by detecting the ratio of the molecular weight to electric charge without any target, which makes it possible to identify novel molecules. IMS generates data on the distribution of lipids and small molecules in tissues, which is difficult to visualize with either conventional counter-staining or immunohistochemistry. In this review, we firstly introduce the principle of imaging mass spectrometry and recent advances in the sample preparation method. Secondly, we present findings regarding biological samples, especially pathological ones. Finally, we discuss the limitations and problems of the IMS technique and clinical application, such as in drug development.

Microscopie de fluorescence de protéines autofluorescentes uniques pour la biologie cellulaire

NASA Astrophysics Data System (ADS)

Cognet, Laurent; Coussen, Françoise; Choquet, Daniel; Lounis, Brahim

In this paper we review the applicability of autofluorescent proteins for single-molecule imaging in biology. The photophysical characteristics of several mutants of the Green Fluorescent Protein (GFP) and those of DsRed are compared and critically discussed for their use in cellular biology. The alternative use of two-photon excitation at the single-molecule level or Fluorescence Correlation Spectroscopy is envisaged for the study of individual autofluorescent proteins. Single-molecule experiments performed in live cells using eGFP and preferably eYFP fusion proteins are reviewed. Finally, the first use at the single-molecule level of citrine, a more photostable variant of the eYFP is reported when fused to a receptor for neurotransmitter in live cells. To cite this article: L. Cognet et al., C. R. Physique 3 (2002) 645-656.

Imaging single spin probes embedded in a conductive diamagnetic layer.

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

Messina, P.; Fradin, F.

2009-01-01

The detection of spin noise by means of scanning tunneling microscopy (STM) has recently been substantially improved by the work presented by Komeda and Manassen (Komeda, T.; Manassen, Y. Appl. Phys. Lett. 2008, 92, 212506). The application of this technique to molecular paramagnets requires the positioning and anchoring of paramagnetic molecules at surfaces. It also requires the possibility of tunneling high current densities into the STM-molecule-substrate tunneling junction. In this letter, we exploit the self-assembly of 1,10-phenantroline on the Au(111) surface to form a diamagnetic matrix that hosts individual molecules and dimers of diphenyl-2-picryl-hydrazyl (DPPH). STM measurements are used tomore » characterize the molecular layer. Electron spin resonance (ESR) measurements elucidate the role of thermal annealing in the preservation of the paramagnetic nature of the DPPH molecules.« less

Quantum dot conjugates in a sub-micrometer fluidic channel

DOEpatents

Stavis, Samuel M.; Edel, Joshua B.; Samiee, Kevan T.; Craighead, Harold G.

2010-04-13

A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

Quantum dot conjugates in a sub-micrometer fluidic channel

DOEpatents

Stavis, Samuel M [Ithaca, NY; Edel, Joshua B [Brookline, MA; Samiee, Kevan T [Ithaca, NY; Craighead, Harold G [Ithaca, NY

2008-07-29

A nanofluidic channel fabricated in fused silica with an approximately 500 nm square cross section was used to isolate, detect and identify individual quantum dot conjugates. The channel enables the rapid detection of every fluorescent entity in solution. A laser of selected wavelength was used to excite multiple species of quantum dots and organic molecules, and the emission spectra were resolved without significant signal rejection. Quantum dots were then conjugated with organic molecules and detected to demonstrate efficient multicolor detection. PCH was used to analyze coincident detection and to characterize the degree of binding. The use of a small fluidic channel to detect quantum dots as fluorescent labels was shown to be an efficient technique for multiplexed single molecule studies. Detection of single molecule binding events has a variety of applications including high throughput immunoassays.

A COMPUTER MODELING STUDY OF BINDING PROPERTIES OF CHIRAL NUCLEOPEPTIDE FOR BIOMEDICAL APPLICATIONS.

PubMed

Pirtskhalava, M; Egoyan, A; Mirtskhulava, M; Roviello, G

2017-12-01

Nucleopeptides often show interesting properties of molecular binding that render them good candidates for development of innovative drugs for anticancer and antiviral therapies. In this work we present results of computer modeling of interactions between the molecules of hexathymine nucleopeptide (T6) and poly rA RNA (A18). The results of geometry optimization calculated using Hyperchem software and our own computer program for molecular docking show that molecules establish stable complexes due to the complementary-nucleobase interaction and the electrostatic interaction between the negative phosphate group of poly rA and the positively-charged residues present in the cationic nucleopeptide structure. Computer modeling makes it possible to find the optimal binding configuration of the molecules of a nucleopeptide and poly rA RNA and to estimate the binding energy between the molecules.

Antioxidants, mechanisms, and recovery by membrane processes.

PubMed

Bazinet, Laurent; Doyen, Alain

2017-03-04

Antioxidants molecules have a great interest for bio-food and nutraceutical industries since they play a vital role for their capacity to reduce oxidative processes. Consequently, these molecules, generally present in complex matrices, have to be fractionated and purified to characterize them and to test their antioxidant activity. However, as natural or synthetics antioxidant molecules differ in terms of structural composition and physico-chemical properties, appropriate separation technologies must be selected. Different fractionation technologies are available but the most commonly used are filtration processes. Indeed, these technologies allow fractionation according to molecular size (pressure-driven processes), charge, or both size and charge (electrically driven processes). In this context, and after summarizing the reaction mechanisms of the different classes and nature of antioxidants as well as membrane fractionation technologies, this manuscript presents the specific applications of these membranes processes for the recovery of antioxidant molecules.

Two-dimensional description of surface-bounded exospheres with application to the migration of water molecules on the Moon

NASA Astrophysics Data System (ADS)

Schorghofer, Norbert

2015-05-01

On the Moon, water molecules and other volatiles are thought to migrate along ballistic trajectories. Here, this migration process is described in terms of a two-dimensional partial differential equation for the surface concentration, based on the probability distribution of thermal ballistic hops. A random-walk model, a corresponding diffusion coefficient, and a continuum description are provided. In other words, a surface-bounded exosphere is described purely in terms of quantities on the surface, which can provide computational and conceptual advantages. The derived continuum equation can be used to calculate the steady-state distribution of the surface concentration of volatile water molecules. An analytic steady-state solution is obtained for an equatorial ring; it reveals the width and mass of the pileup of molecules at the morning terminator.

Printing enzymatic reactions.

PubMed

Tian, Junfei; Shen, Wei

2011-02-07

We used relief and planographic printing methods to print the catalytic effect of an enzyme, but not the enzyme molecules, onto paper. Printing enzymatic reactions have applications in bioactive papers, low-cost diagnostics, anti-counterfeiting devices and advanced packaging materials. These methods can create novel printing effects on commodity surfaces for advanced applications.

Application of miRNAs as Biomarkers of Exposure and Effects in Risk Evaluation

EPA Science Inventory

Of the known epigenetic mechanisms, non-coding RNA and more specifically, microRNA (miRNA), offer the most immediate promise for risk assessment applications because these molecules can serve as excellent biomarkers of toxicity. The advantages of miRNA versus more classical prot...

15kD Granulysin for Monocyte Differentiation: A New Immunotherapeutic for Both in vivo and ex vivo Applications | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a method of enhancing immune response in patients by using 15 kD granulysin. Granulysin, a proinflammatory molecule, is broadly applicable for the treatment of several diseases.

From Periodic Properties to a Periodic Table Arrangement

ERIC Educational Resources Information Center

Besalú, Emili

2013-01-01

A periodic table is constructed from the consideration of periodic properties and the application of the principal components analysis technique. This procedure is useful for objects classification and data reduction and has been used in the field of chemistry for many applications, such as lanthanides, molecules, or conformers classification.…

Process optimization for maximizing the rheology modifying properties of pectic hydrocolloids recovered from steam exploded biomass

USDA-ARS?s Scientific Manuscript database

Pectic hydrocolloids from citrus peel waste are highly functional molecules whose utility and application have expanded well beyond their traditional use in jams and jellies. They are now finding applications in health, pharmaceutical and personal care products as well as functioning as emulsifiers,...

Nanoarchitectonics of molecular aggregates: science and technology.

PubMed

Ramanathan, Muruganathan; Hong, Kunlun; Ji, Qingmin; Yonamine, Yusuke; Hill, Jonathan P; Ariga, Katsuhiko

2014-01-01

The field of making, studying and using molecular aggregates, in which the individual molecules (monomers) are arranged in a regular fashion, has come a long way. Taking control over the aggregation of small molecules and polymers in bulk, on surfaces and at interfaces pose a considerable challenge for their utilization in modern high tech applications. In this review, we provide a detailed insight into recent trends in molecular aggregates from the perspectives of nanoarchitectonics.

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

Visco, Donald Patrick, Jr.; Faulon, Jean-Loup Michel; Roe, Diana C.

This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

Nanoarchitectonics of Molecular Aggregates: Science and Technology

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

Ramanathan, Nathan Muruganathan; Hong, Kunlun; Ji, Dr. Qingmin

2014-01-01

The field of making, studying and using molecular aggregates, in which the individual molecules (monomers) are arranged in a regular fashion, has come a long way. Taking control over the aggregation of small molecules and polymers in bulk, on surfaces and at interfaces pose a considerable challenge for their utilization in modern high tech applications. In this review we provide a detailed insight into recent trends in molecular aggregates from the perspectives of nanoarchitectonics.

Zero-mode waveguide nanophotonic structures for single molecule characterization

NASA Astrophysics Data System (ADS)

Crouch, Garrison M.; Han, Donghoon; Bohn, Paul W.

2018-05-01

Single-molecule characterization has become a crucial research tool in the chemical and life sciences, but limitations, such as limited concentration range, inability to control molecular distributions in space, and intrinsic phenomena, such as photobleaching, present significant challenges. Recent developments in non-classical optics and nanophotonics offer promising routes to mitigating these restrictions, such that even low affinity (K D ~ mM) biomolecular interactions can be studied. Here we introduce and review specific nanophotonic devices used to support single molecule studies. Optical nanostructures, such as zero-mode waveguides (ZMWs), are usually fabricated in thin gold or aluminum films and serve to confine the observation volume of optical microspectroscopy to attoliter to zeptoliter volumes. These simple nanostructures allow individual molecules to be isolated for optical and electrochemical analysis, even when the molecules of interest are present at high concentration (µM–mM) in bulk solution. Arrays of ZMWs may be combined with optical probes such as single molecule fluorescence, single molecule fluorescence resonance energy transfer, and fluorescence correlation spectroscopy for distributed analysis of large numbers of single-molecule reactions or binding events in parallel. Furthermore, ZMWs may be used as multifunctional devices, for example by combining optical and electrochemical functions in a single discrete architecture to achieve electrochemical ZMWs. In this review, we will describe the optical properties, fabrication, and applications of ZMWs for single-molecule studies, as well as the integration of ZMWs into systems for chemical and biochemical analysis.

Decelerating and Trapping Large Polar Molecules.

PubMed

Patterson, David

2016-11-18

Manipulating the motion of large polyatomic molecules, such as benzonitrile (C 6 H 5 CN), presents significant difficulties compared to the manipulation of diatomic molecules. Although recent impressive results have demonstrated manipulation, trapping, and cooling of molecules as large as CH 3 F, no general technique for trapping such molecules has been demonstrated, and cold neutral molecules larger than 5 atoms have not been trapped (M. Zeppenfeld, B. G. U. Englert, R. Glöckner, A. Prehn, M. Mielenz, C. Sommer, L. D. van Buuren, M. Motsch, G. Rempe, Nature 2012, 491, 570-573). In particular, extending Stark deceleration and electrostatic trapping to such species remains challenging. Here, we propose to combine a novel "asymmetric doublet state" Stark decelerator with recently demonstrated slow, cold, buffer-gas-cooled beams of closed-shell volatile molecules to realize a general system for decelerating and trapping samples of a broad range of volatile neutral polar prolate asymmetric top molecules. The technique is applicable to most stable volatile molecules in the 100-500 AMU range, and would be capable of producing trapped samples in a single rotational state and at a motional temperature of hundreds of mK. Such samples would immediately allow for spectroscopy of unprecedented resolution, and extensions would allow for further cooling and direct observation of slow intramolecular processes such as vibrational relaxation and Hertz-level tunneling dynamics. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determining the exact number of dye molecules attached to colloidal CdSe/ZnS quantum dots in Förster resonant energy transfer assemblies

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

Kaiser, Uwe; Jimenez de Aberasturi, Dorleta; Vázquez-González, Margarita

2015-01-14

Semiconductor quantum dots functionalized with organic dye molecules are important tools for biological sensor applications. Energy transfer between the quantum dot and the attached dyes can be utilized for sensing. Though important, the determination of the real number of dye molecules attached per quantum dot is rather difficult. In this work, a method will be presented to determine the number of ATTO-590 dye molecules attached to CdSe/ZnS quantum dots based on time resolved spectral analysis. The energy transfer from the excited quantum dot to the attached ATTO-590 dye leads to a reduced lifetime of the quantum dot's excitons. The highermore » the concentration of dye molecules, the shorter the excitonic lifetime becomes. However, the number of dye molecules attached per quantum dot will vary. Therefore, for correctly explaining the decay of the luminescence upon photoexcitation of the quantum dot, it is necessary to take into account the distribution of the number of dyes attached per quantum dot. A Poisson distribution of the ATTO-590 dye molecules not only leads to excellent agreement between experimental and theoretical decay curves but also additionally yields the average number of dye molecules attached per quantum dot. In this way, the number of dyes per quantum dot can be conveniently determined.« less

Single crystal X-ray diffraction, spectroscopic and mass spectrometric studies of furanocoumarin peucedanin.

PubMed

Bartnik, Magdalena; Arczewska, Marta; Hoser, Anna A; Mroczek, Tomasz; Kamiński, Daniel M; Głowniak, Kazimierz; Gagoś, Mariusz; Woźniak, Krzysztof

2014-01-01

The structure of peucedanin, isolated from Peucedanum tauricum Bieb. (Apiaceae), has been established using single crystal X-ray diffraction. This furanocoumarin isolated from the light petroleum extract of P. tauricum fruits was characterized by high resolution EI-MS, sATR-FTIR and 2D NMR spectroscopic techniques. The EI-MS showed the typical fragmentation pattern of methoxyfuranocoumarins. Extensive 1D (1H and 13C) as well as 2D NMR data enabled complete assignment of the carbon atoms in the peucedanin molecule. The FTIR data confirms intermolecular hydrogen bonding between peucedanin molecules in polar solvents. Peucedanin crystallises in the R-3 space group from the trigonal system with one molecule in the asymmetric part of the unit cell. The crystal lattice of peucedanin consists of the molecules arranged in separate columns. They are related by two fold screw axes and centres of symmetry. Interestingly, peucedanin columns form two channels per unit cell with a diameter of 7.5angstrom going through the crystal lattice in the Z-direction. These channels are filled with disordered water molecules, which are surrounded by hydrophobic methyl groups and are located exactly at the centres of the channels. The peucedanin molecules are stacked in a single column with the opposite orientation of the neighbouring molecules. These results could be interesting in further application of this molecule, for example in biological tests of its activity.

Fluorescence imaging of single-molecule retention trajectories in reversed-phase chromatographic particles.

PubMed

Cooper, Justin T; Peterson, Eric M; Harris, Joel M

2013-10-01

Due to its high specific surface area and chemical stability, porous silica is used as a support structure in numerous applications, including heterogeneous catalysis, biomolecule immobilization, sensors, and liquid chromatography. Reversed-phase liquid chromatography (RPLC), which uses porous silica support particles, has become an indispensable separations tool in quality control, pharmaceutics, and environmental analysis requiring identification of compounds in mixtures. For complex samples, the need for higher resolution separations requires an understanding of the time scale of processes responsible for analyte retention in the stationary phase. In the present work, single-molecule fluorescence imaging is used to observe transport of individual molecules within RPLC porous silica particles. This technique allows direct measurement of intraparticle molecular residence times, intraparticle diffusion rates, and the spatial distribution of molecules within the particle. On the basis of the localization uncertainty and characteristic measured diffusion rates, statistical criteria were developed to resolve the frame-to-frame behavior of molecules into moving and stuck events. The measured diffusion coefficient of moving molecules was used in a Monte Carlo simulation of a random-walk model within the cylindrical geometry of the particle diameter and microscope depth-of-field. The simulated molecular transport is in good agreement with the experimental data, indicating transport of moving molecules in the porous particle is described by a random-walk. Histograms of stuck-molecule event times, locations, and their contributions to intraparticle residence times were also characterized.

Parasitic helminths: a pharmacopeia of anti-inflammatory molecules.

PubMed

Johnston, M J G; MacDonald, J A; McKay, D M

2009-02-01

Infection with parasitic helminths takes a heavy toll on the health and well-being of humans and their domestic livestock, concomitantly resulting in major economic losses. Analyses have consistently revealed bioactive molecules in extracts of helminths or in their excretory/secretory products that modulate the immune response of the host. It is our view that parasitic helminths are an untapped source of immunomodulatory substances that, in pure form, could become new drugs (or models for drug design) to treat disease. Here, we illustrate the range of immunomodulatory molecules in selected parasitic trematodes, cestodes and nematodes, their impact on the immune cells in the host and how the host may recognize these molecules. There are many examples of the partial characterization of helminth-derived immunomodulatory molecules, but these have not yet translated into new drugs, reflecting the difficulty of isolating and fully characterizing proteins, glycoproteins and lipid-based molecules from small amounts of parasite material. However, this should not deter the investigator, since analytical techniques are now being used to accrue considerable structural information on parasite-derived molecules, even when only minute quantities of tissue are available. With the introduction of methodologies to purify and structurally-characterize molecules from small amounts of tissue and the application of high throughput immunological assays, one would predict that an assessment of parasitic helminths will yield a variety of novel drug candidates in the coming years.

Demonstration of sub-femtomole sensitivity for small molecules with microsphere ring resonator sensors

NASA Astrophysics Data System (ADS)

White, Ian M.; Oveys, Hesam; Fan, Xudong

2006-02-01

Optical microsphere resonators can function as highly sensitive bio/chemical sensors due to the large Q-factor, which leads to high light-matter interaction. The whispering gallery modes (WGM) arise at the surface of the microsphere, creating a highly enhanced optical field that interacts with matter on or near the microsphere surface. As a result, the spectral position of the WGM is extremely sensitive to refractive index changes near the surface, such as when bio/chemical molecules bind to the sphere. We show the potential feasibility of a microsphere ring resonator as a sensor for small molecules by demonstrating detection of sub-femtomole changes in SiO II molecules at the surface of the microsphere. In this experiment, the silica molecules act as an excellent model for small molecule analytes because of their 60 Dalton molecular weight, and because we know nearly the exact quantity of molecules at the surface, which enables a sensitivity characterization. We measure the spectral shifts in the WGMs when low concentrations of hydrofluoric acid (HF) are added to a solution that is being probed by the microsphere. As the HF molecules break apart the SiO II molecules at the sphere surface, the WGMs shift due to the sub-nano-scale decrease in the size of the microsphere. These calculations show that the sensitivity of this microsphere resonator is on the order of 500 attomoles. Our results will lead to the utilization of optical microspheres for detection of trace quantities of small molecules for such applications as drug discovery, environmental monitoring, and enzyme detection using peptide cleavage.

High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications.

PubMed

Stockwell, B R; Haggarty, S J; Schreiber, S L

1999-02-01

Fully adapting a forward genetic approach to mammalian systems requires efficient methods to alter systematically gene products without prior knowledge of gene sequences, while allowing for the subsequent characterization of these alterations. Ideally, these methods would also allow function to be altered in a temporally controlled manner. We report the development of a miniaturized cell-based assay format that enables a genetic-like approach to understanding cellular pathways in mammalian systems using small molecules, rather than mutations, as the source of gene-product alterations. This whole-cell immunodetection assay can sensitively detect changes in specific cellular macromolecules in high-density arrays of mammalian cells. Furthermore, it is compatible with screening large numbers of small molecules in nanoliter to microliter culture volumes. We refer to this assay format as a 'cytoblot', and demonstrate the use of cytoblotting to monitor biosynthetic processes such as DNA synthesis, and post-translational processes such as acetylation and phosphorylation. Finally, we demonstrate the applicability of these assays to natural-product screening through the identification of marine sponge extracts exhibiting genotype-specific inhibition of 5-bromodeoxyuridine incorporation and suppression of the anti-proliferative effect of rapamycin. We show that cytoblots can be used for high-throughput screening of small molecules in cell-based assays. Together with small-molecule libraries, the cytoblot assay can be used to perform chemical genetic screens analogous to those used in classical genetics and thus should be applicable to understanding a wide variety of cellular processes, especially those involving post-transitional modifications.

Imaging prototypical aromatic molecules on insulating surfaces: a review

NASA Astrophysics Data System (ADS)

Hoffmann-Vogel, R.

2018-01-01

Insulating substrates allow for in-plane contacted molecular electronics devices where the molecule is in contact with the insulator. For the development of such devices it is important to understand the interaction of molecules with insulating surfaces. As substrates, ionic crystals such as KBr, KCl, NaCl and CaF2 are discussed. The surface energies of these substrates are small and as a consequence intrinsic properties of the molecules, such as molecule–molecule interaction, become more important relative to interactions with the substrates. As prototypical molecules, three variants of graphene-related molecules are used, pentacene, C60 and PTCDA. Pentacene is a good candidate for molecular electronics applications due to its high charge carrier mobility. It shows mainly an upright standing growth mode and the morphology of the islands is strongly influenced by dewetting. A new second flat-lying phase of the molecule has been observed. Studying the local work function using the Kelvin method reveals details such as line defects in the center of islands. The local work function differences between the upright-standing and flat-lying phase can only be explained by charge transfer that is unusual on ionic crystalline surfaces. C60 nucleation and growth is explained by loosely bound molecules at kink sites as nucleation sites. The stability of C60 islands as a function of magic numbers is investigated. Peculiar island shapes are obtained from unusual dewetting processes already at work during growth, where molecules ‘climb’ to the second molecular layer. PTCDA is a prototypical semiconducting molecule with strong quadrupole moment. It grows in the form of elongated islands where the top and the facets can be molecularly resolved. In this way the precise molecular arrangement in the islands is revealed.

Chirality-sensitive microwave spectroscopy - application to terpene molecules

NASA Astrophysics Data System (ADS)

Schnell, Melanie

Most molecules of biochemical relevance are chiral. Even though the physical properties of two enantiomers are nearly identical, they might exhibit completely different biochemical effects, such as different odor in the case of carvone. In nature and as products of chemical syntheses, chiral molecules often exist in mixtures with other chiral molecules. The analysis of these complex mixtures to identify the molecular components, to determine which enantiomers are present, and to measure the enantiomeric excesses (ee) is still one of the challenging and very important tasks of analytical chemistry. We recently experimentally demonstrated a new method of differentiating enantiomeric pairs of chiral molecules in the gas phase. It is based on broadband rotational spectroscopy and is a three-wave mixing process that involves a closed cycle of three rotational transitions. The phase of the acquired signal bares the signature of the enantiomer, as it depends upon the product of the transition dipole moments. Furthermore, because the signal amplitude is proportional to the ee, this technique allows not only for determining which enantiomer is in excess, but also by how much. A unique advantage of our technique is that it can also be applied to mixtures of chiral molecules, even when the molecules are very similar. In my lecture, I will introduce the technique and give an update on the recent developments.

Synthesis of Dibenzo[hi,st]ovalene and Its Amplified Spontaneous Emission in a Polystyrene Matrix.

PubMed

Paternò, Giuseppe M; Chen, Qiang; Wang, Xiao-Ye; Liu, Junzhi; Motti, Silvia G; Petrozza, Annamaria; Feng, Xinliang; Lanzani, Guglielmo; Müllen, Klaus; Narita, Akimitsu; Scotognella, Francesco

2017-06-06

A large number of graphene molecules, or large polycyclic aromatic hydrocarbons (PAHs), have been synthesized and display various optoelectronic properties. Nevertheless, their potential for application in photonics has remained largely unexplored. Herein, we describe the synthesis of a highly luminescent and stable graphene molecule, namely a substituted dibenzo[hi,st]ovalene (DBO 1), with zigzag edges and elucidate its promising optical-gain properties by means of ultrafast transient absorption spectroscopy. Upon incorporation of DBO into an inert polystyrene matrix, amplified stimulated emission can be observed with a relatively low power threshold (ca. 60 μJ cm -2 ), thus highlighting its high potential for lasing applications. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of Quantum Chemistry Based Force Fields for Molecular Dynamics Simulations of Aromatic Polymers

NASA Technical Reports Server (NTRS)

Jaffe, Richard; Langhoff, Stephen R. (Technical Monitor)

1995-01-01

Ab initio quantum chemistry calculations for model molecules can be used to parameterize force fields for molecular dynamics simulations of polymers. Emphasis in our research group is on using quantum chemistry-based force fields for molecular dynamics simulations of organic polymers in the melt and glassy states, but the methodology is applicable to simulations of small molecules, multicomponent systems and solutions. Special attention is paid to deriving reliable descriptions of the non-bonded and electrostatic interactions. Several procedures have been developed for deriving and calibrating these parameters. Our force fields for aromatic polyimide simulations will be described. In this application, the intermolecular interactions are the critical factor in determining many properties of the polymer (including its color).

Photoacoustic spectroscopy of CO2 laser in the detection of gaseous molecules

NASA Astrophysics Data System (ADS)

Lima, G. R.; Sthel, M. S.; da Silva, M. G.; Schramm, D. U. S.; de Castro, M. P. P.; Vargas, H.

2011-01-01

The detection of trace gases is very important for a variety of applications, including the monitoring of atmospheric pollutants, industrial process control, measuring air quality in workplaces, research into fruits physiological processes and medical diagnosis of diseases through the analysis of exhaled gases. The implementation of these and many other applications requiring gas sensors able to meet high sensitivity and selectivity. In this work, a photoacoustic laser spectrometer with CO2 emission in the infrared range and a resonant photoacoustic cell was used. We obtain the resonance frequency of 2.4 kHz to photoacoustic cell, was estimated detection limit of the spectrometer for molecules of ethylene (C2H4), 16 ppbV and ammonia (NH3) 42 ppbV.

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

Braun, Efrem; Chen, Joseph J.; Schnell, Sondre K.

Molecular simulations and NMR relaxometry experiments demonstrate that pure benzene or xylene confined in isoreticular metal–organic frameworks (IRMOFs) exhibit true vapor–liquid phase equilibria where the effective critical point may be reduced by tuning the structure of the MOF. Our results are consistent with vapor and liquid phases extending over many MOF unit cells. These results are counterintuitive since the MOF pore diameters are approximately the same length scale as the adsorbate molecules. As applications of these materials in catalysis, separations, and gas storage rely on the ability to tune the properties of adsorbed molecules, we anticipate that the ability tomore » systematically control the critical point, thereby preparing spatially inhomogeneous local adsorbate densities, could add a new design tool for MOF applications.« less

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

Braun, Efrem; Chen, Joseph J.; Schnell, Sondre K.

Molecular simulations and NMR relaxometry experiments demonstrate that pure benzene or xylene confined in isoreticular metal–organic frameworks (IRMOFs) exhibit true vapor–liquid phase equilibria where the effective critical point may be reduced by tuning the structure of the MOF. Our results are consistent with vapor and liquid phases extending over many MOF unit cells. These results are counterintuitive since the MOF pore diameters are approximately the same length scale as the adsorbate molecules. Lastly, as applications of these materials in catalysis, separations, and gas storage rely on the ability to tune the properties of adsorbed molecules, we anticipate that the abilitymore » to systematically control the critical point, thereby preparing spatially inhomogeneous local adsorbate densities, could add a new design tool for MOF applications.« less

2D nanomaterials assembled from sequence-defined molecules

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

Mu, Peng; Zhou, Guangwen; Chen, Chun-Long

Two dimensional (2D) nanomaterials have attracted broad interest owing to their unique physical and chemical properties with potential applications in electronics, chemistry, biology, medicine and pharmaceutics. Due to the current limitations of traditional 2D nanomaterials (e.g., graphene and graphene oxide) in tuning surface chemistry and compositions, 2D nanomaterials assembled from sequence-defined molecules (e.g., DNAs, proteins, peptides and peptoids) have recently been developed. They represent an emerging class of 2D nanomaterials with attractive physical and chemical properties. In this mini-review, we summarize the recent progress in the synthesis and applications of this type of sequence-defined 2D nanomaterials. The challenges and opportunitiesmore » in this new field are also discussed.« less

Block copolymer nanoassemblies for photodynamic therapy and diagnosis.

PubMed

Dickerson, Matthew; Bae, Younsoo

2013-11-01

Light can be a powerful therapeutic and diagnostic tool. Light-sensitive molecules can be used to develop locally targeted cancer therapeutics. This approach is known as photodynamic therapy (PDT). Similarly, it is possible to diagnose diseases and track the course of treatment in vivo using ligh-sensitive molecules. This methodology is referred to as photodynamic diagnosis (PDD). Despite the potential, many PDT and PDD agents have imperfect physiochemical properties for their successful clinical application. Nanotechnology may solve these issues by improving the viability of PDT and PDD. This review summarizes the current state of PDT and PDD development, the integration of nanotechnology in the field, and the prospective future applications, demonstrating the potential of PDT and PDD for improved cancer treatment and diagnosis.

Carbon nanotubes as templates for polymerized lipid assemblies

NASA Astrophysics Data System (ADS)

Thauvin, Cédric; Rickling, Stéphane; Schultz, Patrick; Célia, Hervé; Meunier, Stéphane; Mioskowski, Charles

2008-12-01

Amphiphilic molecules-molecules that have both hydrophobic and hydrophilic properties-can self-assemble in water to form diverse structures such as micelles, vesicles and tubes, and these nanostructures can be used for delivering drugs, stabilizing membrane proteins or as nanoreactors. We have previously shown that lipids can self-organize on the surface of single-walled carbon nanotubes into regular ring-shaped assemblies. Here we show that these lipid assemblies can be polymerized and isolated from the nanotube template by application of an electric field. We also demonstrate that these assemblies are monodispersed, water-soluble, and can dissolve various hydrophobic rylene dyes, fullerenes and membrane proteins. The stability of these constructs and their diverse applications will be useful in the fields of cosmetics, medicine and material sciences.

Single nickel-related defects in molecular-sized nanodiamonds for multicolor bioimaging: an ab initio study.

PubMed

Thiering, Gergő; Londero, Elisa; Gali, Adam

2014-10-21

Fluorescent nanodiamonds constitute an outstanding alternative to semiconductor quantum dots and dye molecules for in vivo biomarker applications, where the fluorescence comes from optically active point defects acting as color centers in the nanodiamonds. For practical purposes, these color centers should be photostable as a function of the laser power or the surface termination of nanodiamonds. Furthermore, they should exhibit a sharp and nearly temperature-independent zero-phonon line. In this study, we show by hybrid density functional theory calculations that nickel doped nanodiamonds exhibit the desired properties, thus opening the avenue to practical applications. In particular, harnessing the strong quantum confinement effect in molecule-sized nanodiamonds is very promising for achieving multicolor imaging by single nickel-related defects.

Single nickel-related defects in molecular-sized nanodiamonds for multicolor bioimaging: an ab initio study

NASA Astrophysics Data System (ADS)

Thiering, Gergő; Londero, Elisa; Gali, Adam

2014-09-01

Fluorescent nanodiamonds constitute an outstanding alternative to semiconductor quantum dots and dye molecules for in vivo biomarker applications, where the fluorescence comes from optically active point defects acting as color centers in the nanodiamonds. For practical purposes, these color centers should be photostable as a function of the laser power or the surface termination of nanodiamonds. Furthermore, they should exhibit a sharp and nearly temperature-independent zero-phonon line. In this study, we show by hybrid density functional theory calculations that nickel doped nanodiamonds exhibit the desired properties, thus opening the avenue to practical applications. In particular, harnessing the strong quantum confinement effect in molecule-sized nanodiamonds is very promising for achieving multicolor imaging by single nickel-related defects.

A Critical and Comparative Review of Fluorescent Tools for Live-Cell Imaging.

PubMed

Specht, Elizabeth A; Braselmann, Esther; Palmer, Amy E

2017-02-10

Fluorescent tools have revolutionized our ability to probe biological dynamics, particularly at the cellular level. Fluorescent sensors have been developed on several platforms, utilizing either small-molecule dyes or fluorescent proteins, to monitor proteins, RNA, DNA, small molecules, and even cellular properties, such as pH and membrane potential. We briefly summarize the impressive history of tool development for these various applications and then discuss the most recent noteworthy developments in more detail. Particular emphasis is placed on tools suitable for single-cell analysis and especially live-cell imaging applications. Finally, we discuss prominent areas of need in future fluorescent tool development-specifically, advancing our capability to analyze and integrate the plethora of high-content data generated by fluorescence imaging.

Two-potential approach for electron-molecular collisions at intermediate and high energies - Application to e-N2 scatterings

NASA Technical Reports Server (NTRS)

Choi, B. H.; Poe, R. T.; Sun, J. C.; Shan, Y.

1979-01-01

A general theoretical approach is proposed for the calculation of elastic, vibrational, and rotational transitions for electron-molecule scattering at intermediate and high-electron-impact energies. In this formulation, contributions to the scattering process come from the incoherent sum of two dominant potentials: a short-range shielded nuclear Coulomb potential from individual atomic centers, and a permanent/induced long-range potential. Application to e-N2 scattering from 50-500 eV incident electron energies has yielded good agreement with absolutely calibrated experiments. Comparisons with other theoretical approaches are made. The physical picture as well as the general features of electron-molecule scattering process are discussed within the framework of the two-potential approach.

Investigation of Carbohydrate Recognition via Computer Simulation

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

Johnson, Quentin R.; Lindsay, Richard J.; Petridis, Loukas

Carbohydrate recognition by proteins, such as lectins and other (bio)molecules, can be essential for many biological functions. Interest has arisen due to potential protein and drug design and future bioengineering applications. A quantitative measurement of carbohydrate-protein interaction is thus important for the full characterization of sugar recognition. Here, we focus on the aspect of utilizing computer simulations and biophysical models to evaluate the strength and specificity of carbohydrate recognition in this review. With increasing computational resources, better algorithms and refined modeling parameters, using state-of-the-art supercomputers to calculate the strength of the interaction between molecules has become increasingly mainstream. We reviewmore » the current state of this technique and its successful applications for studying protein-sugar interactions in recent years.« less