Structure based design of 11β-HSD1 inhibitors.

PubMed

Singh, Suresh; Tice, Colin

2010-11-01

Controlling elevated tissue-specific levels of cortisol may provide a novel therapeutic approach for treating metabolic syndrome. This concept has spurred large scale medicinal chemistry efforts in the pharmaceutical industry for the design of 11β-HSD1 inhibitors. High resolution X-ray crystal structures of inhibitors in complex with the enzyme have facilitated the structure-based design of diverse classes of molecules. A summary of binding modes, trends in structure-activity relationships, and the pharmacodynamic data of inhibitors from each class is presented.

Structural Chemistry of Human RNA Methyltransferases.

PubMed

Schapira, Matthieu

2016-03-18

RNA methyltransferases (RNMTs) play important roles in RNA stability, splicing, and epigenetic mechanisms. They constitute a promising target class that is underexplored by the medicinal chemistry community. Information of relevance to drug design can be extracted from the rich structural coverage of human RNMTs. In this work, the structural chemistry of this protein family is analyzed in depth. Unlike most methyltransferases, RNMTs generally feature a substrate-binding site that is largely open on the cofactor-binding pocket, favoring the design of bisubstrate inhibitors. Substrate purine or pyrimidines are often sandwiched between hydrophobic walls that can accommodate planar ring systems. When the substrate base is laying on a shallow surface, a 5' flanking base is sometimes anchored in a druggable cavity. The cofactor-binding site is structurally more diverse than in protein methyltransferases and more druggable in SPOUT than in Rossman-fold enzymes. Finally, conformational plasticity observed both at the substrate and cofactor binding sites may be a challenge for structure-based drug design. The landscape drawn here may inform ongoing efforts toward the discovery of the first human RNMT inhibitors.

Medicinal Chemistry Projects Requiring Imaginative Structure-Based Drug Design Methods.

PubMed

Moitessier, Nicolas; Pottel, Joshua; Therrien, Eric; Englebienne, Pablo; Liu, Zhaomin; Tomberg, Anna; Corbeil, Christopher R

2016-09-20

Computational methods for docking small molecules to proteins are prominent in drug discovery. There are hundreds, if not thousands, of documented examples-and several pertinent cases within our research program. Fifteen years ago, our first docking-guided drug design project yielded nanomolar metalloproteinase inhibitors and illustrated the potential of structure-based drug design. Subsequent applications of docking programs to the design of integrin antagonists, BACE-1 inhibitors, and aminoglycosides binding to bacterial RNA demonstrated that available docking programs needed significant improvement. At that time, docking programs primarily considered flexible ligands and rigid proteins. We demonstrated that accounting for protein flexibility, employing displaceable water molecules, and using ligand-based pharmacophores improved the docking accuracy of existing methods-enabling the design of bioactive molecules. The success prompted the development of our own program, Fitted, implementing all of these aspects. The primary motivation has always been to respond to the needs of drug design studies; the majority of the concepts behind the evolution of Fitted are rooted in medicinal chemistry projects and collaborations. Several examples follow: (1) Searching for HDAC inhibitors led us to develop methods considering drug-zinc coordination and its effect on the pKa of surrounding residues. (2) Targeting covalent prolyl oligopeptidase (POP) inhibitors prompted an update to Fitted to identify reactive groups and form bonds with a given residue (e.g., a catalytic residue) when the geometry allows it. Fitted-the first fully automated covalent docking program-was successfully applied to the discovery of four new classes of covalent POP inhibitors. As a result, efficient stereoselective syntheses of a few screening hits were prioritized rather than synthesizing large chemical libraries-yielding nanomolar inhibitors. (3) In order to study the metabolism of POP inhibitors by

Recent development of small molecule glutaminase inhibitors.

PubMed

Song, Minsoo; Kim, Soong-Hyun; Im, Chun Young; Hwang, Hee-Jong

2018-05-24

Glutaminase (GLS) which is responsible for the conversion of glutamine to glutamate plays vital role in up-regulating cell metabolism for tumor cell growth, and is considered as a valuable therapeutic target for cancer treatment. Based on this important function of glutaminase in cancer, several GLS inhibitors have been developed from both academia and industries. Most importantly, Calithera Biosciences Inc. is actively developing glutaminase inhibitor CB-839 for the treatment of various cancers in phase 1 and 2 clinical trials at present. In this review, it is discussed about recent efforts to develop small molecule glutaminase inhibitors targeting glutamine metabolism both in the preclinical and clinical studies. In particular, more emphasis is placed on CB-839 since it is the only small molecule GLS inhibitor being studied in clinical setting. Inhibition mechanism is discussed based on x-ray structure study of thiadiazole derivatives as well. Finally, recent medicinal chemistry efforts to develop a new class of GLS inhibitors are given herein in the hope of providing useful information for GLS inhibitors of the next generation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Benzotriazole a Corrosion Inhibitor for Antiques: Some Practical Surface Chemistry.

ERIC Educational Resources Information Center

Walker, Robert

1980-01-01

Describes the structure and inhibitive properties of Benzotriazole. The chemical may be employed as an inhibitor to reduce corrosion of articles during storage or display. It may be applied to copper and copper-based antiques as well as to silver and other metals. (Author/JN)

Attenuating Staphylococcus aureus Virulence Gene Regulation: A Medicinal Chemistry Perspective

PubMed Central

2013-01-01

Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two-component signal transduction systems. There is now an emerging body of evidence to suggest that the blockade of S. aureus virulence gene expression significantly attenuates infection in experimental models. In this Perspective, we will provide insights into medicinal chemistry strategies for the development of chemical reagents that have the capacity to inhibit staphylococcal virulence expression. These reagents can be broadly grouped into four categories: (1) competitive inhibitors of the accessory gene regulator (agr) quorum sensing system, (2) inhibitors of AgrA–DNA interactions, (3) RNAIII transcription inhibitors, and (4) inhibitors of the SarA family of transcriptional regulators. We discuss the potential of specific examples of antivirulence agents for the management and treatment of staphylococcal infections. PMID:23294220

Structure-Activity Relationship Analysis of 3-phenylcoumarin-Based Monoamine Oxidase B Inhibitors

NASA Astrophysics Data System (ADS)

Rauhamäki, Sanna; Postila, Pekka A.; Niinivehmas, Sanna; Kortet, Sami; Schildt, Emmi; Pasanen, Mira; Manivannan, Elangovan; Ahinko, Mira; Koskimies, Pasi; Nyberg, Niina; Huuskonen, Pasi; Multamäki, Elina; Pasanen, Markku; Juvonen, Risto O.; Raunio, Hannu; Huuskonen, Juhani; Pentikäinen, Olli T.

2018-03-01

Monoamine oxidase B (MAO-B) catalyzes deamination of monoamines such as neurotransmitters dopamine and norepinephrine. Accordingly, small-molecule MAO-B inhibitors potentially alleviate the symptoms of dopamine-linked neuropathologies such as depression or Parkinson’s disease. Coumarin with a functionalized 3-phenyl ring system is a promising scaffold for building potent MAO-B inhibitors. Here, a vast set of 3-phenylcoumarin derivatives was designed using virtual combinatorial chemistry or rationally de novo and synthesized using microwave chemistry. The derivatives inhibited the MAO-B at 100 nM - 1 µM. The IC50 value of the most potent derivative 1 was 56 nM. A docking-based structure-activity relationship analysis summarizes the atom-level determinants of the MAO-B inhibition by the derivatives. Finally, the cross-reactivity of the derivatives was tested against monoamine oxidase A and a specific subset of enzymes linked to estradiol metabolism, known to have coumarin-based inhibitors. Overall, the results indicate that the 3-phenylcoumarins, especially derivative 1, present unique pharmacological features worth considering in future drug development.

Saccharomyces cerevisiae as a platform for assessing sphingolipid lipid kinase inhibitors

PubMed Central

Agah, Sayeh; Mendelson, Anna J.; Eletu, Oluwafunmilayo T.; Barkey-Bircann, Peter; Gesualdi, James

2018-01-01

Successful medicinal chemistry campaigns to discover and optimize sphingosine kinase inhibitors require a robust assay for screening chemical libraries and for determining rank order potencies. Existing assays for these enzymes are laborious, expensive and/or low throughput. The toxicity of excessive levels of phosphorylated sphingoid bases for the budding yeast, Saccharomyces cerevisiae, affords an assay wherein inhibitors added to the culture media rescue growth in a dose-dependent fashion. Herein, we describe our adaptation of a simple, inexpensive, and high throughput assay for assessing inhibitors of sphingosine kinase types 1 and 2 as well as ceramide kinase and for testing enzymatic activity of sphingosine kinase type 2 mutants. The assay was validated using recombinant enzymes and generally agrees with the rank order of potencies of existing inhibitors. PMID:29672528

Advances in the discovery of cathepsin K inhibitors on bone resorption.

PubMed

Lu, Jun; Wang, Maolin; Wang, Ziyue; Fu, Zhongqi; Lu, Aiping; Zhang, Ge

2018-12-01

Cathepsin K (Cat K), highly expressed in osteoclasts, is a cysteine protease member of the cathepsin lysosomal protease family and has been of increasing interest as a target of medicinal chemistry efforts for its role in bone matrix degradation. Inhibition of the Cat K enzyme reduces bone resorption and thus, has rendered the enzyme as an attractive target for anti-resorptive osteoporosis therapy. Over the past decades, considerable efforts have been made to design and develop highly potent, excellently selective and orally applicable Cat K inhibitors. These inhibitors are derived from synthetic compounds or natural products, some of which have passed preclinical studies and are presently in clinical trials at different stages of advancement. In this review, we briefly summarised the historic development of Cat K inhibitors and discussed the relationship between structures of inhibitors and active sites in Cat K for the purpose of guiding future development of inhibitors.

Adenosine mimetics as inhibitors of NAD+-dependent histone deacetylases, from kinase to sirtuin inhibition.

PubMed

Trapp, Johannes; Jochum, Anne; Meier, Rene; Saunders, Laura; Marshall, Brett; Kunick, Conrad; Verdin, Eric; Goekjian, Peter; Sippl, Wolfgang; Jung, Manfred

2006-12-14

NAD+-dependent histone deacetylases, sirtuins, cleave acetyl groups from lysines of histones and other proteins to regulate their activity. Identification of potent selective inhibitors would help to elucidate sirtuin biology and could lead to useful therapeutic agents. NAD+ has an adenosine moiety that is also present in the kinase cofactor ATP. Kinase inhibitors based upon adenosine mimesis may thus also target NAD+-dependent enzymes. We present a systematic approach using adenosine mimics from one cofactor class (kinase inhibitors) as a viable method to generate new lead structures in another cofactor class (sirtuin inhibitors). Our findings have broad implications for medicinal chemistry and specifically for sirtuin inhibitor design. Our results also raise a question as to whether selectivity profiling for kinase inhibitors should be limited to ATP-dependent targets.

USSR and Eastern Europe Scientific Abstracts, Chemistry, Number 60

DTIC Science & Technology

1978-07-12

OF AROMATIC AND HETEROCYCLIC ANALOGUES OF THE NATURAL GROWTH INHIBITOR - ABSCISIC ACID Tashkent KHIMIYA PRIRODNYKH SOYEDINENIY in Russian No 1, 1978...Chemistry of Natural Products, Academy of Sciences UzSSR, Tashkent [Abstract] Aryl analogues of abscisic acid were obtained by the Reformatskii...heterocyclic nuclei with carboethoxy-methylene- triphenylphosphorane led to the formation of furyl and hetero-cyclic analogues of abscisic acid . The

Study on Synergistic Mechanism of Inhibitor Mixture Based on Electron Transfer Behavior

PubMed Central

Han, Peng; He, Yang; Chen, Changfeng; Yu, Haobo; Liu, Feng; Yang, Hong; Ma, Yue; Zheng, Yanjun

2016-01-01

Mixing is an important method to improve the performance of surfactants due to their synergistic effect. The changes in bonding interaction and adsorption structure of IM and OP molecules before and after co-adsorbed on Fe(001) surface is calculated by DFTB+ method. It is found that mixture enable the inhibitor molecules with higher EHOMO donate more electrons while the inhibitor molecules with lower ELUMO accept more electrons, which strengthens the bonding interaction of both inhibitor agent and inhibitor additive with metal surface. Meanwhile, water molecules in the compact layer of double electric layer are repulsed and the charge transfer resistance during the corrosion process increases. Accordingly, the correlation between the frontier orbital (EHOMO and ELUMO of inhibitor molecules and the Fermi level of metal) and inhibition efficiency is determined. Finally, we propose a frontier orbital matching principle for the synergistic effect of inhibitors, which is verified by electrochemical experiments. This frontier orbital matching principle provides an effective quantum chemistry calculation method for the optimal selection of inhibitor mixture. PMID:27671332

Omarigliptin (MK-3102): A Novel Long-Acting DPP-4 Inhibitor for Once-Weekly Treatment of Type 2 Diabetes

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

Biftu, Tesfaye; Sinha-Roy, Ranabir; Chen, Ping

In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.

Tyrosine sulfation modulates activity of tick-derived thrombin inhibitors

NASA Astrophysics Data System (ADS)

Thompson, Robert E.; Liu, Xuyu; Ripoll-Rozada, Jorge; Alonso-García, Noelia; Parker, Benjamin L.; Pereira, Pedro José Barbosa; Payne, Richard J.

2017-09-01

Madanin-1 and chimadanin are two small cysteine-free thrombin inhibitors that facilitate blood feeding in the tick Haemaphysalis longicornis. Here, we report a post-translational modification—tyrosine sulfation—of these two proteins that is critical for potent anti-thrombotic and anticoagulant activity. Inhibitors produced in baculovirus-infected insect cells displayed heterogeneous sulfation of two tyrosine residues within each of the proteins. One-pot ligation-desulfurization chemistry enabled access to homogeneous samples of all possible sulfated variants of the proteins. Tyrosine sulfation of madanin-1 and chimadanin proved crucial for thrombin inhibitory activity, with the doubly sulfated variants three orders of magnitude more potent than the unmodified inhibitors. The three-dimensional structure of madanin-1 in complex with thrombin revealed a unique mode of inhibition, with the sulfated tyrosine residues binding to the basic exosite II of the protease. The importance of tyrosine sulfation within this family of thrombin inhibitors, together with their unique binding mode, paves the way for the development of anti-thrombotic drug leads based on these privileged scaffolds.

Amino acid sequence of a trypsin inhibitor from a Spirometra (Spirometra erinaceieuropaei).

PubMed

Sanda, A; Uchida, A; Itagaki, T; Kobayashi, H; Inokuchi, N; Koyama, T; Iwama, M; Ohgi, K; Irie, M

2001-12-01

A trypsin inhibitor that is highly homologous with bovine pancreatic trypsin inhibitor (BPTI) was co-purified along with RNase from Spirometra (Spirometra erinaceieuropaei). The amino acid sequence of this inhibitor (SETI) and the nucleotide sequence of the cDNA encoding this protein were determined by protein chemistry and gene technology. SETI contains 68 amino acid residues and has a molecular mass of 7,798 Da. SETI has 31 amino acid residues that are identical with BPTI's sequence, including 6 half-cystine and 5 aromatic amino acid residues. The active site Lys residue in BPTI is replaced by an Arg residue in SETI. SETI is an effective inhibitor of trypsin and moderately inhibits a-chymotrypsin, but less inhibits elastase or subtilisin. SETI was expressed by E. coli containing a PelB vector carrying the SETI encoding cDNA; an expression yield of 0.68 mg/l was obtained. The phylogenetic relationship of SETI and the other BPTI-like trypsin inhibitors was analyzed using most likelihood inference methods.

Emerging lipid-lowering drugs: squalene synthase inhibitors.

PubMed

Elsayed, Raghda K; Evans, Jeffery D

2008-06-01

Lapaquistat was the only squalene synthase inhibitor in Phase III clinical trials in Europe and the United States, but was recently discontinued from clinical development. Unlike statins, the inhibition of de novo cholesterol biosynthesis by lapaquistat does not deplete mevalonate, a precursor of isoprenoids. Isoprenoids are critical in cell growth and metabolism. The present review will focus on the chemistry, pharmacology, and lipid-lowering effects of novel squalene synthase inhibitors. A search of Pubmed, IPA, and GoogleScholar for studies (animal and human) and review articles published in English between 1990 and April 2008, using the search terms "squalene synthase inhibitors" or "lapaquistat". All clinical trials identified were then cross-referenced for their citations. All literature identified was then complied for this analysis. Lapaquistat mainly targets LDL-C, but may have some effect on HDL-C and TG. Preliminary reports on Phase II and Phase III associated lapaquistat 100 mg with elevated hepatic enzymes. Hepatotoxicity, possible drug-drug interaction with statins, and the investigation of a statin/coenzyme Q10 combination are among the few challenges that impeded lapaquistat's clinical development.

Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations.

PubMed

Yu, Zhe; Ma, Yu-chi; Ai, Jing; Chen, Dan-qi; Zhao, Dong-mei; Wang, Xin; Chen, Yue-lei; Geng, Mei-yu; Xiong, Bing; Cheng, Mao-sheng; Shen, Jing-Kang

2013-11-01

To decipher the molecular interactions between c-Met and its type I inhibitors and to facilitate the design of novel c-Met inhibitors. Based on the prototype model inhibitor 1, four ligands with subtle differences in the fused aromatic rings were synthesized. Quantum chemistry was employed to calculate the binding free energy for each ligand. Symmetry-adapted perturbation theory (SAPT) was used to decompose the binding energy into several fundamental forces to elucidate the determinant factors. Binding free energies calculated from quantum chemistry were correlated well with experimental data. SAPT calculations showed that the predominant driving force for binding was derived from a sandwich π-π interaction with Tyr-1230. Arg-1208 was the differentiating factor, interacting with the 6-position of the fused aromatic ring system through the backbone carbonyl with a force pattern similar to hydrogen bonding. Therefore, a hydrogen atom must be attached at the 6-position, and changing the carbon atom to nitrogen caused unfavorable electrostatic interactions. The theoretical studies have elucidated the determinant factors involved in the binding of type I inhibitors to c-Met.

Polyphenol oxidase inhibitor from blue mussel (Mytilus edulis) extract.

PubMed

Schulbach, Kurt F; Johnson, Jodie V; Simonne, Amarat H; Kim, Jeong-Mok; Jeong, Yoonhwa; Yagiz, Yavuz; Marshall, Maurice R

2013-03-01

Enzymatic browning remains a problem for the fruit and vegetable industry, especially new emerging markets like pre-cuts. A crude inhibitor from blue mussel (Mytilus edulis) showed broad inhibition for apple (58%), mushroom (32%), and potato (44%) polyphenol oxidase (PPO) and was further characterized. Inhibition increased as the concentration of inhibitor increased in the reaction mixture eventually leveling off at a maximum inhibition of 92% for apple PPO. The inhibitor was capable of bleaching the brown color formed in the reaction mixture with apple PPO. Identification of the inhibitor by mass spectrometry and high-performance liquid chromatography revealed it to be hypotaurine (C2 H7 NO2 S). Hypotaurine and other sulfinic acid analogs (methane and benzene sulfinic acids) showed very good inhibition for apple PPO at various concentrations with the highest inhibition occurring at 500 μM for hypotaurine (89%), methane sulfinic acid (100%), and benzene sulfinic acid (100%). An inhibitor found in the expressed liquid from blue mussel shows very good inhibition on enzymatic browning. Since this enzyme is responsible for losses to the fruit and vegetable industry, natural inhibitors that prevent browning would be valuable. Finding alternative chemistries that inhibit browning and understanding their mode of action would be beneficial to the fruit and vegetable industries and their segments such as pre-cuts, juices, and so on. Inhibitors from products ingested by consumers are more acceptable as natural ingredients. © 2013 Institute of Food Technologists®

O-(Triazolyl)methyl carbamates as a novel and potent class of FAAH inhibitors

PubMed Central

Colombano, Giampiero; Albani, Clara; Ottonello, Giuliana; Ribeiro, Alison; Scarpelli, Rita; Tarozzo, Glauco; Daglian, Jennifer; Jung, Kwang-Mook; Piomelli, Daniele; Bandiera, Tiziano

2015-01-01

Inhibition of fatty acid amide hydrolase (FAAH) activity is under investigation as a valuable strategy for the treatment of several disorders, including pain and drug addiction. A number of potent FAAH inhibitors belonging to different chemical classes have been disclosed. O-aryl carbamates are one of the most representative families. In the search for novel FAAH inhibitors, we synthesized a series of O-(1,2,3-triazol-4-yl)methyl carbamate derivatives exploiting the copper-catalyzed [3 + 2] cycloaddition reaction between azides and alkynes (click chemistry). We explored structure-activity relationships within this new class of compounds and identified potent inhibitors of both rat and human FAAH with IC50 values in the single-digit nanomolar range. PMID:25338703

The Chemically Elegant Proton Pump Inhibitors

PubMed Central

Roche, Victoria F.

2006-01-01

Medicinal chemistry instruction at Creighton University is designed to provide an in-depth scientifically grounded and clinically relevant learning experience for pharmacy students. Each topic covered in the 2-semester required course sequence is selected based on the general utility of the compounds in question and/or the therapeutic importance of the drugs in treating life-threatening diseases. All lessons provided to campus- and Web-based students by the author are in the form of a descriptive and conversational narrative and course requirements are in place to assure that students read the lesson prior to the class period in which it is discussed. Learning tools and aids are provided to help students more readily discern the most critical aspects of each lesson, to practice required critical thinking and structure analysis skills, and to self-assess competency in meeting specific learning objectives. This manuscript illustrates this approach by sharing a lesson on the chemistry and clinically relevant structure-activity relationships of proton pump inhibitors. PMID:17149430

Using computer-aided drug design and medicinal chemistry strategies in the fight against diabetes.

PubMed

Semighini, Evandro P; Resende, Jonathan A; de Andrade, Peterson; Morais, Pedro A B; Carvalho, Ivone; Taft, Carlton A; Silva, Carlos H T P

2011-04-01

The aim of this work is to present a simple, practical and efficient protocol for drug design, in particular Diabetes, which includes selection of the illness, good choice of a target as well as a bioactive ligand and then usage of various computer aided drug design and medicinal chemistry tools to design novel potential drug candidates in different diseases. We have selected the validated target dipeptidyl peptidase IV (DPP-IV), whose inhibition contributes to reduce glucose levels in type 2 diabetes patients. The most active inhibitor with complex X-ray structure reported was initially extracted from the BindingDB database. By using molecular modification strategies widely used in medicinal chemistry, besides current state-of-the-art tools in drug design (including flexible docking, virtual screening, molecular interaction fields, molecular dynamics, ADME and toxicity predictions), we have proposed 4 novel potential DPP-IV inhibitors with drug properties for Diabetes control, which have been supported and validated by all the computational tools used herewith.

Energetic factors determining the binding of type I inhibitors to c-Met kinase: experimental studies and quantum mechanical calculations

PubMed Central

Yu, Zhe; Ma, Yu-chi; Ai, Jing; Chen, Dan-qi; Zhao, Dong-mei; Wang, Xin; Chen, Yue-lei; Geng, Mei-yu; Xiong, Bing; Cheng, Mao-sheng; Shen, Jing-kang

2013-01-01

Aim: To decipher the molecular interactions between c-Met and its type I inhibitors and to facilitate the design of novel c-Met inhibitors. Methods: Based on the prototype model inhibitor 1, four ligands with subtle differences in the fused aromatic rings were synthesized. Quantum chemistry was employed to calculate the binding free energy for each ligand. Symmetry-adapted perturbation theory (SAPT) was used to decompose the binding energy into several fundamental forces to elucidate the determinant factors. Results: Binding free energies calculated from quantum chemistry were correlated well with experimental data. SAPT calculations showed that the predominant driving force for binding was derived from a sandwich π–π interaction with Tyr-1230. Arg-1208 was the differentiating factor, interacting with the 6-position of the fused aromatic ring system through the backbone carbonyl with a force pattern similar to hydrogen bonding. Therefore, a hydrogen atom must be attached at the 6-position, and changing the carbon atom to nitrogen caused unfavorable electrostatic interactions. Conclusion: The theoretical studies have elucidated the determinant factors involved in the binding of type I inhibitors to c-Met. PMID:24056705

Structure-Guided Strategy for the Development of Potent Bivalent ERK Inhibitors

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

Lechtenberg, Bernhard C.; Mace, Peter D.; Sessions, E. Hampton

ERK is the effector kinase of the RAS-RAF-MEK-ERK signaling cascade, which promotes cell transformation and malignancy in many cancers and is thus a major drug target in oncology. Kinase inhibitors targeting RAF or MEK are already used for the treatment of certain cancers, such as melanoma. Although the initial response to these drugs can be dramatic, development of drug resistance is a major challenge, even with combination therapies targeting both RAF and MEK. Importantly, most resistance mechanisms still rely on activation of the downstream effector kinase ERK, making it a promising target for drug development efforts. Here, we report themore » design and structural/functional characterization of a set of bivalent ERK inhibitors that combine a small molecule inhibitor that binds to the ATP-binding pocket with a peptide that selectively binds to an ERK protein interaction surface, the D-site recruitment site (DRS). Our studies show that the lead bivalent inhibitor, SBP3, has markedly improved potency compared to the small molecule inhibitor alone. Unexpectedly, we found that SBP3 also binds to several ERK-related kinases that contain a DRS, highlighting the importance of experimentally verifying the predicted specificity of bivalent inhibitors. However, SBP3 does not target any other kinases belonging to the same CMGC branch of the kinome. Additionally, our modular click chemistry inhibitor design facilitates the generation of different combinations of small molecule inhibitors with ERK-targeting peptides.« less

[A novel dipeptidyl peptidase IV inhibitors developed through scaffold hopping and drug splicing strategy].

PubMed

Wang, Shan-Chun; Zeng, Li-Li; Ding, Yu-Yang; Zeng, Shao-Gao; Song, Hong-Rui; Hu, Wen-Hui; Xie, Hui

2014-01-01

Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.

Inhibitors of the HSP90 molecular chaperone: attacking the master regulator in cancer.

PubMed

McDonald, Edward; Workman, Paul; Jones, Keith

2006-01-01

The heat shock protein 90 (HSP90) chaperones represent some 1-2% of all cellular protein and are key players in protein quality control in cells. They are over expressed in many human cancers and the fact that many oncogenic proteins are clients has prompted much recent research on HSP90 inhibitors as new cancer therapeutics. A brief introduction is followed by a detailed review of the various classes of inhibitors, both natural product-based and synthetic, that have emerged over the last decade. The natural products geldanamycin, radicicol and novobiocin have provided the start points for new drugs in this area and their medicinal chemistry is reviewed, including the exciting recent results emerging from clinical trials using geldanamycin analogues. The detailed understanding of the binding mode of these compounds to HSP90 has been significantly enhanced by X-ray crystallography of HSP90 constructs co-crystallised with various ligands. Efforts to replace the natural product inhibitors with more drug-like synthetic compounds have mushroomed over the last 4 years. The purines and the 3,4-diarylpyrazoles have proven to be the most successful and their medicinal chemistry is reviewed with particular emphasis on structure-based design. Protein/ligand co-crystal structures have shown that conserved water molecules in the active site are a vital part of the hydrogen-bonding network established on binding both natural product and synthetic inhibitors. Medicinal chemists have used this information to develop high affinity lead compounds. Recent research provides the platform for exciting developments in the area of HSP90 inhibition over the next few years.

Virtual High-Throughput Screening for Matrix Metalloproteinase Inhibitors.

PubMed

Choi, Jun Yong; Fuerst, Rita

2017-01-01

Structure-based virtual screening (SBVS) is a common method for the fast identification of hit structures at the beginning of a medicinal chemistry program in drug discovery. The SBVS, described in this manuscript, is focused on finding small molecule hits that can be further utilized as a starting point for the development of inhibitors of matrix metalloproteinase 13 (MMP-13) via structure-based molecular design. We intended to identify a set of structurally diverse hits, which occupy all subsites (S1'-S3', S2, and S3) centering the zinc containing binding site of MMP-13, by the virtual screening of a chemical library comprising more than ten million commercially available compounds. In total, 23 compounds were found as potential MMP-13 inhibitors using Glide docking followed by the analysis of the structural interaction fingerprints (SIFt) of the docked structures.

Bringing research into a first semester organic chemistry laboratory with the multistep synthesis of carbohydrate-based HIV inhibitor mimics.

PubMed

Pontrello, Jason K

2015-01-01

Benefits of incorporating research experiences into laboratory courses have been well documented, yet examples of research projects designed for the first semester introductory organic chemistry lab course are extremely rare. To address this deficiency, a Carbohydrate-Based human immunodeficiency virus (HIV) Inhibitor project consisting of a synthetic scheme of four reactions was developed for and implemented in the first semester organic lab. Students carried out the synthetic reactions during the last 6 of 10 total labs in the course, generating carbohydrate-based dimeric target molecules modeled after published dimers with application in HIV therapy. The project was designed to provide a research experience through use of literature procedures for reactions performed, exploration of variation in linker length in the target structure, and synthesis of compounds not previously reported in the scientific literature. Project assessment revealed strong student support, indicating enhanced engagement and interest in the course as a direct result of the use of scientific literature and the applications of the synthesized carbohydrate-based molecules. Regardless of discussed challenges in designing a research project for the first semester lab course, the finding from data analysis that a project implemented in the first semester lab had significantly greater student impact than a second semester project should provide motivation for development of additional research projects for a first semester organic course. © 2015 The International Union of Biochemistry and Molecular Biology.

Metalloprotease Peptide Inhibitors: A Semester-Long Organic Synthetic Research Project for the Introductory Laboratory Course

ERIC Educational Resources Information Center

Pontrello, Jason K.

2015-01-01

A semester-long research project to synthesize unique compounds designed after published metalloprotease peptide inhibitors is presented. The research project encompasses a set of nine organic chemistry reactions traditionally taught in the second semester lab course, and the procedures are derived from scientific literature. The two principle…

Approved and Experimental Small-Molecule Oncology Kinase Inhibitor Drugs: A Mid-2016 Overview.

PubMed

Fischer, Peter M

2017-03-01

Kinase inhibitor research is a comparatively recent branch of medicinal chemistry and pharmacology and the first small-molecule kinase inhibitor, imatinib, was approved for clinical use only 15 years ago. Since then, 33 more kinase inhibitor drugs have received regulatory approval for the treatment of a variety of cancers and the volume of reports on the discovery and development of kinase inhibitors has increased to an extent where it is now difficult-even for those working in the field-easily to keep an overview of the compounds that are being developed, as currently there are 231 such compounds, targeting 38 different protein and lipid kinases (not counting isoforms), in clinical use or under clinical investigation. The purpose of this review is thus to provide an overview of the biomedical rationales for the kinases being targeted on the one hand, and the design principles, as well as chemical, pharmacological, pharmaceutical, and toxicological kinase inhibitor properties, on the other hand. Two issues that are especially important in kinase inhibitor research, target selectivity and drug resistance, as well as the underlying structural concepts, are discussed in general terms and in the context of relevant kinases and their inhibitors. © 2016 Wiley Periodicals, Inc.

Glycine Transporters and Their Inhibitors

NASA Astrophysics Data System (ADS)

Gilfillan, Robert; Kerr, Jennifer; Walker, Glenn; Wishart, Grant

Glycine plays a ubiquitous role in many biological processes. In the central nervous system it serves as an important neurotransmitter acting as an agonist at strychnine-sensitive glycine receptors and as an essential co-agonist with glutamate at the NMDA receptor complex. Control of glycine concentrations in the vicinity of these receptors is mediated by the specific glycine transporters, GlyT1 and GlyT2. Inhibition of these transporters has been postulated to be of potential benefit in several therapeutic indications including schizophrenia and pain. In this review we discuss our current knowledge of glycine transporters and focus on recent advances in the medicinal chemistry of GlyT1 and GlyT2 inhibitors.

Natural Products as Aromatase Inhibitors

PubMed Central

Balunas, Marcy J.; Su, Bin; Brueggemeier, Robert W.; Kinghorn, A. Douglas

2010-01-01

With the clinical success of several synthetic aromatase inhibitors (AIs) in the treatment of postmenopausal estrogen receptor-positive breast cancer, researchers have also been investigating also the potential of natural products as AIs. Natural products from terrestrial and marine organisms provide a chemically diverse array of compounds not always available through current synthetic chemistry techniques. Natural products that have been used traditionally for nutritional or medicinal purposes (e.g., botanical dietary supplements) may also afford AIs with reduced side effects. A thorough review of the literature regarding natural product extracts and secondary metabolites of plant, microbial, and marine origin that have been shown to exhibit aromatase inhibitory activity is presented herein. PMID:18690828

Targeted Fluoro Positioning for the Discovery of a Potent and Highly Selective Matrix Metalloproteinase Inhibitor.

PubMed

Fischer, Thomas; Riedl, Rainer

2017-04-01

Invited for this month's cover picture is the group of Professor Rainer Riedl from the Institute of Chemistry and Biotechnology at the Zurich University of Applied Sciences (ZHAW), Switzerland. The cover picture depicts the structure-based design of a drug-like small molecule inhibitor of matrix metalloproteinase-13 (MMP-13) with a combined dual binding motif. The targeted introduction of a single fluoro atom was of vital importance for the optimization of the inhibitor. For more details, read the full text of the Communication at 10.1002/open.201600158.

Zinc oxide nanoparticles as novel alpha-amylase inhibitors

NASA Astrophysics Data System (ADS)

Dhobale, Sandip; Thite, Trupti; Laware, S. L.; Rode, C. V.; Koppikar, Soumya J.; Ghanekar, Ruchika-Kaul; Kale, S. N.

2008-11-01

Amylase inhibitors, also known as starch blockers, contain substances that prevent dietary starches from being absorbed by the body via inhibiting breakdown of complex sugars to simpler ones. In this sense, these materials are projected as having potential applications in diabetes control. In this context, we report on zinc oxide nanoparticles as possible alpha-amylase inhibitors. Zinc oxide nanoparticles have been synthesized using soft-chemistry approach and 1-thioglycerol was used as a surfactant to yield polycrystalline nanoparticles of size ˜18 nm, stabilized in wurtzite structure. Conjugation study and structural characterization have been done using x-ray diffraction technique, Fourier transform infrared spectroscopy, UV-visible spectroscopy, and transmission electron microscopy. Cytotoxicity studies on human fibrosarcoma (HT-1080) and skin carcinoma (A-431) cell lines as well as mouse primary fibroblast cells demonstrate that up to a dose of 20 μg/ml, ZnO nanoparticles are nontoxic to the cells. We report for the first time the alpha-amylase inhibitory activity of ZnO nanoparticles wherein an optimum dose of 20 μg/ml was sufficient to exhibit 49% glucose inhibition at neutral pH and 35 °C temperature. This inhibitory activity was similar to that obtained with acarbose (a standard alpha-amylase inhibitor), thereby projecting ZnO nanoparticles as novel alpha-amylase inhibitors.

The synthesis of a tritium, carbon-14, and stable isotope-labeled cathepsin C inhibitors.

PubMed

Allen, Paul; Bragg, Ryan A; Caffrey, Moya; Ericsson, Cecilia; Hickey, Michael J; Kingston, Lee P; Elmore, Charles S

2017-02-01

As part of a medicinal chemistry program aimed at developing a highly potent and selective cathepsin C inhibitor, tritium, carbon-14, and stable isotope-labeled materials were required. The synthesis of tritium-labeled methanesulfonate 5 was achieved via catalytic tritiolysis of a chloro precursor, albeit at a low radiochemical purity of 67%. Tritium-labeled AZD5248 was prepared via a 3-stage synthesis, utilizing amide-directed hydrogen isotope exchange. Carbon-14 and stable isotope-labeled AZD5248 were successfully prepared through modifications of the medicinal chemistry synthetic route, enabling the use of available labeled intermediates. Copyright © 2016 John Wiley & Sons, Ltd.

From supramolecular chemistry towards constitutional dynamic chemistry and adaptive chemistry.

PubMed

Lehn, Jean-Marie

2007-02-01

Supramolecular chemistry has developed over the last forty years as chemistry beyond the molecule. Starting with the investigation of the basis of molecular recognition, it has explored the implementation of molecular information in the programming of chemical systems towards self-organisation processes, that may occur either on the basis of design or with selection of their components. Supramolecular entities are by nature constitutionally dynamic by virtue of the lability of non-covalent interactions. Importing such features into molecular chemistry, through the introduction of reversible bonds into molecules, leads to the emergence of a constitutional dynamic chemistry, covering both the molecular and supramolecular levels. It considers chemical objects and systems capable of responding to external solicitations by modification of their constitution through component exchange or reorganisation. It thus opens the way towards an adaptive and evolutive chemistry, a further step towards the chemistry of complex matter.

Constitutional dynamic chemistry: bridge from supramolecular chemistry to adaptive chemistry.

PubMed

Lehn, Jean-Marie

2012-01-01

Supramolecular chemistry aims at implementing highly complex chemical systems from molecular components held together by non-covalent intermolecular forces and effecting molecular recognition, catalysis and transport processes. A further step consists in the investigation of chemical systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined functional supramolecular architectures by self-assembly from their components, thus behaving as programmed chemical systems. Supramolecular chemistry is intrinsically a dynamic chemistry in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when the molecular entity contains covalent bonds that may form and break reversibility, so as to allow a continuous change in constitution by reorganization and exchange of building blocks. These features define a Constitutional Dynamic Chemistry (CDC) on both the molecular and supramolecular levels.CDC introduces a paradigm shift with respect to constitutionally static chemistry. The latter relies on design for the generation of a target entity, whereas CDC takes advantage of dynamic diversity to allow variation and selection. The implementation of selection in chemistry introduces a fundamental change in outlook. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization with selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation.The merging of the features: -information and programmability, -dynamics and reversibility, -constitution and structural diversity, points to the emergence of adaptive and evolutive chemistry, towards a chemistry of complex matter.

Click Chemistry-based Discovery of [3-Hydroxy-5-(1H-1,2,3-triazol-4-yl)picolinoyl]glycines as Orally Active Hypoxia Inducing Factor Prolyl Hydroxylase Inhibitors with Favorable Safety Profiles for the Treatment of Anemia.

PubMed

Wu, Yue; Jiang, Zhensheng; Li, Zhihong; Gu, Jing; You, Qi-Dong; Zhang, Xiaojin

2018-06-01

As a gene associated with anemia, the erythropoiesis gene is physiologically expressed under hypoxia regulated by hypoxia-inducing factor-α (HIF-α). Thus, stabilizing HIF-α is a potent strategy to stimulate the expression and secretion of erythropoiesis. In this study we applied click chemistry to the discovery of HIF prolyl hydroxylase 2 (HIF-PHD2) inhibitors for the first time and a series of triazole compounds showed preferable inhibitory activity in fluorescence polarization assay. Of particular note was the orally active HIF-PHD inhibitor 15i (IC50 = 62.23 nM), which was almost ten times more active than the phase III drug FG-4592 (IC50 = 591.4 nM). Furthermore, it can upregulate the hemoglobin of cisplatin induced anemia mice (120 g/L) to normal levels (160 g/L) with no apparent toxicity observed in vivo. These results confirm that triazole compound 15i is a promising candidate for the treatment of renal anemia.

Microscale High-Throughput Experimentation as an Enabling Technology in Drug Discovery: Application in the Discovery of (Piperidinyl)pyridinyl-1H-benzimidazole Diacylglycerol Acyltransferase 1 Inhibitors.

PubMed

Cernak, Tim; Gesmundo, Nathan J; Dykstra, Kevin; Yu, Yang; Wu, Zhicai; Shi, Zhi-Cai; Vachal, Petr; Sperbeck, Donald; He, Shuwen; Murphy, Beth Ann; Sonatore, Lisa; Williams, Steven; Madeira, Maria; Verras, Andreas; Reiter, Maud; Lee, Claire Heechoon; Cuff, James; Sherer, Edward C; Kuethe, Jeffrey; Goble, Stephen; Perrotto, Nicholas; Pinto, Shirly; Shen, Dong-Ming; Nargund, Ravi; Balkovec, James; DeVita, Robert J; Dreher, Spencer D

2017-05-11

Miniaturization and parallel processing play an important role in the evolution of many technologies. We demonstrate the application of miniaturized high-throughput experimentation methods to resolve synthetic chemistry challenges on the frontlines of a lead optimization effort to develop diacylglycerol acyltransferase (DGAT1) inhibitors. Reactions were performed on ∼1 mg scale using glass microvials providing a miniaturized high-throughput experimentation capability that was used to study a challenging S N Ar reaction. The availability of robust synthetic chemistry conditions discovered in these miniaturized investigations enabled the development of structure-activity relationships that ultimately led to the discovery of soluble, selective, and potent inhibitors of DGAT1.

MULTI-ANALYTE CHEMISTRY METHODS FOR PESTICIDES WHICH ARE ACETOLACTATE SYNTHASE (ALS) INHIBITORS IN SOIL

EPA Science Inventory

A joint EPA/state/industry working group has developed several multi-analyte methods to analyze soils for low ppb (parts per billion) levels of herbicides (such as sulfonylureas, imidazolinones, and sulfonamides) that are acetolactate synthase (ALS) inhibitors and may cause phyto...

Combination of Synthetic Chemistry and Live-Cell Imaging Identified a Rapid Cell Division Inhibitor in Tobacco and Arabidopsis thaliana.

PubMed

Nambo, Masakazu; Kurihara, Daisuke; Yamada, Tomomi; Nishiwaki-Ohkawa, Taeko; Kadofusa, Naoya; Kimata, Yusuke; Kuwata, Keiko; Umeda, Masaaki; Ueda, Minako

2016-11-01

Cell proliferation is crucial to the growth of multicellular organisms, and thus the proper control of cell division is important to prevent developmental arrest or overgrowth. Nevertheless, tools for controlling cell proliferation are still poor in plant. To develop novel tools, we focused on a specific compound family, triarylmethanes, whose members show various antiproliferative activities in animals. By combining organic chemistry to create novel and diverse compounds containing the triarylmethyl moiety and biological screens based on live-cell imaging of a fluorescently labeled tobacco Bright Yellow-2 (BY-2) culture cell line (Nicotiana tabacum), we isolated (3-furyl)diphenylmethane as a strong but partially reversible inhibitor of plant cell division. We also found that this agent had efficient antiproliferative activity in developing organs of Arabidopsis thaliana without causing secondary defects in cell morphology, and induced rapid cell division arrest independent of the cell cycle stage. Given that (3-furyl)diphenylmethane did not affect the growth of a human cell line (HeLa) and a budding yeast (Saccharomyces cerevisiae), it should act specifically on plants. Taking our results together, we propose that the combination of desired chemical synthesis and detailed biological analysis is an effective tool to create novel drugs, and that (3-furyl)diphenylmethane is a specific antiproliferative agent for plants. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Chemical Reactivity Theory Study of Advanced Glycation Endproduct Inhibitors.

PubMed

Frau, Juan; Glossman-Mitnik, Daniel

2017-02-02

Several compounds with the known ability to perform as inhibitors of advanced glycation endproducts (AGE) have been studied with Density Functional Theory (DFT) through the use of anumberofdensityfunctionalswhoseaccuracyhasbeentestedacrossabroadspectrumofdatabases in Chemistry and Physics. The chemical reactivity descriptors for these systems have been calculated through Conceptual DFT in an attempt to relate their intrinsic chemical reactivity with the ability to inhibit the action of glycating carbonyl compounds on amino acids and proteins. This knowledge could be useful in the design and development of new drugs which can be potential medicines for diabetes and Alzheimer's disease.

GNE-886: A Potent and Selective Inhibitor of the Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain (CECR2).

PubMed

Crawford, Terry D; Audia, James E; Bellon, Steve; Burdick, Daniel J; Bommi-Reddy, Archana; Côté, Alexandre; Cummings, Richard T; Duplessis, Martin; Flynn, E Megan; Hewitt, Michael; Huang, Hon-Ren; Jayaram, Hariharan; Jiang, Ying; Joshi, Shivangi; Kiefer, James R; Murray, Jeremy; Nasveschuk, Christopher G; Neiss, Arianne; Pardo, Eneida; Romero, F Anthony; Sandy, Peter; Sims, Robert J; Tang, Yong; Taylor, Alexander M; Tsui, Vickie; Wang, Jian; Wang, Shumei; Wang, Yongyun; Xu, Zhaowu; Zawadzke, Laura; Zhu, Xiaoqin; Albrecht, Brian K; Magnuson, Steven R; Cochran, Andrea G

2017-07-13

The biological function of bromodomains, epigenetic readers of acetylated lysine residues, remains largely unknown. Herein we report our efforts to discover a potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome region candidate 2 (CECR2). Screening of our internal medicinal chemistry collection led to the identification of a pyrrolopyridone chemical lead, and subsequent structure-based drug design led to a potent and selective CECR2 bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound.

Pinpoint chemical modification of Asp160 in the 49 kDa subunit of bovine mitochondrial complex I via a combination of ligand-directed tosyl chemistry and click chemistry.

PubMed

Masuya, Takahiro; Murai, Masatoshi; Morisaka, Hironobu; Miyoshi, Hideto

2014-12-16

Through a ligand-directed tosyl (LDT) chemistry strategy using the synthetic acetogenin ligand AL1, we succeeded in the pinpoint alkynylation (-C≡CH) of Asp160 in the 49 kDa subunit of bovine complex I, which may be located in the inner part of the putative quinone binding cavity of the enzyme [Masuya, T., et al. (2014) Biochemistry, 53, 2307-2317]. This study provided a promising technique for diverse chemical modifications of complex I. To further improve this technique for its adaptation to intact complex I, we here synthesized the new acetogenin ligand AL2, possessing an azido (-N₃) group in place of the terminal alkyne in AL1, and attempted the pinpoint azidation of complex I in bovine heart submitochondrial particles. Careful proteomic analyses revealed that, just as in the case of AL1, azidation occurred at 49 kDa Asp160 with a reaction yield of ∼50%, verifying the high site specificity of our LDT chemistry using acetogenin ligands. This finding prompted us to speculate that a reactivity of the azido group incorporated into Asp160 (Asp160-N₃) against externally added chemicals can be employed to characterize the structural features of the quinone/inhibitor binding cavity. Consequently, we used a ring-strained cycloalkyne possessing a rhodamine fluorophore (TAMRA-DIBO), which can covalently attach to an azido group via so-called click chemistry without Cu¹⁺ catalysis, as the reaction partner of Asp160-N₃. We found that bulky TAMRA-DIBO is capable of reacting directly with Asp160-N₃ in intact complex I. Unexpectedly, the presence of an excess amount of short-chain ubiquinones as well as some strong inhibitors (e.g., quinazoline and fenpyroximate) did not interfere with the reaction between TAMRA-DIBO and Asp160-N₃; nevertheless, bullatacin, a member of the natural acetogenins, markedly interfered with this reaction. Taking the marked bulkiness of TAMRA-DIBO into consideration, it appears to be difficult to reconcile these results with the

Fragment-based discovery of potent inhibitors of the anti-apoptotic MCL-1 protein.

PubMed

Petros, Andrew M; Swann, Steven L; Song, Danying; Swinger, Kerren; Park, Chang; Zhang, Haichao; Wendt, Michael D; Kunzer, Aaron R; Souers, Andrew J; Sun, Chaohong

2014-03-15

Apoptosis is regulated by the BCL-2 family of proteins, which is comprised of both pro-death and pro-survival members. Evasion of apoptosis is a hallmark of malignant cells. One way in which cancer cells achieve this evasion is thru overexpression of the pro-survival members of the BCL-2 family. Overexpression of MCL-1, a pro-survival protein, has been shown to be a resistance factor for Navitoclax, a potent inhibitor of BCL-2 and BCL-XL. Here we describe the use of fragment screening methods and structural biology to drive the discovery of novel MCL-1 inhibitors from two distinct structural classes. Specifically, cores derived from a biphenyl sulfonamide and salicylic acid were uncovered in an NMR-based fragment screen and elaborated using high throughput analog synthesis. This culminated in the discovery of selective and potent inhibitors of MCL-1 that may serve as promising leads for medicinal chemistry optimization efforts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemistry Rocks: Redox Chemistry as a Geologic Tool.

ERIC Educational Resources Information Center

Burns, Mary Sue

2001-01-01

Applies chemistry to earth science, uses rocks in chemistry laboratories, and teaches about transition metal chemistry, oxidation states, and oxidation-reduction reactions from firsthand experiences. (YDS)

Discovery and development of pyrazole-scaffold Hsp90 inhibitors.

PubMed

McDonald, Edward; Jones, Keith; Brough, Paul A; Drysdale, Martin J; Workman, Paul

2006-01-01

This review explains why the chaperone Hsp90 is an exciting protein target for the discovery of new drugs to treat cancer in the clinic, and summarises the properties of natural product derived inhibitors before relating the discovery and current state of development of synthetic pyrazole compounds. Blockade of Hsp90 results in reduced cellular levels of several proteins implicated in cancer including CDK4, ERBB2 and C-RAF, and causes simultaneous inhibition of cancer cell proliferation in culture and of tumor xenograft growth in vivo. Hsp90 has an ATPase domain that is necessary for its Hsp chaperone function, and X-ray crystallography has shown that natural product inhibitors (geldanamycin, radicicol) of Hsp90 function bind to this domain. High throughput assays focusing on the ATPase activity of Hsp90 were developed and used to discover novel chemical starting points for cancer drug discovery. The discovery, synthesis and SAR of 3,4-diaryl pyrazoles is described. X-Ray crystallography of protein-inhibitor complexes revealed important interactions involving the resorcinol substituent at C-3, and these X-ray structures strongly influenced subsequent medicinal chemistry research that has resulted in highly potent inhibitors with sub-micromolar activity in cells. SAR and X-ray data are summarised for analogues in which the 4-phenyl substituent is replaced by amides or piperazine derivatives. Prospects for the pyrazoles as they progress towards clinical development are discussed in relation to current Phase I trials with derivatives of geldanamycin.

Medicinal Chemistry and Molecular Modeling: An Integration to Teach Drug Structure-Activity Relationship and the Molecular Basis of Drug Action

ERIC Educational Resources Information Center

Carvalho, Ivone; Borges, Aurea D. L.; Bernardes, Lilian S. C.

2005-01-01

The use of computational chemistry and the protein data bank (PDB) to understand and predict the chemical and molecular basis involved in the drug-receptor interactions is discussed. A geometrical and chemical overview of the great structural similarity in the substrate and inhibitor is provided.

Significant steps in the evolution of analytical chemistry--is the today's analytical chemistry only chemistry?

PubMed

Karayannis, Miltiades I; Efstathiou, Constantinos E

2012-12-15

In this review the history of chemistry and specifically the history and the significant steps of the evolution of analytical chemistry are presented. In chronological time spans, covering the ancient world, the middle ages, the period of the 19th century, and the three evolutional periods, from the verge of the 19th century to contemporary times, it is given information for the progress of chemistry and analytical chemistry. During this period, analytical chemistry moved gradually from its pure empirical nature to more rational scientific activities, transforming itself to an autonomous branch of chemistry and a separate discipline. It is also shown that analytical chemistry moved gradually from the status of exclusive serving the chemical science, towards serving, the environment, health, law, almost all areas of science and technology, and the overall society. Some recommendations are also directed to analytical chemistry educators concerning the indispensable nature of knowledge of classical analytical chemistry and the associated laboratory exercises and to analysts, in general, why it is important to use the chemical knowledge to make measurements on problems of everyday life. Copyright © 2012 Elsevier B.V. All rights reserved.

The radiation chemistry of nuclear reactor decontaminating reagents

NASA Astrophysics Data System (ADS)

Sellers, Robin M.

Processes involved in the radiation chemistry of some typical nuclear reactor decontaminating reagents including complexing, reducing and oxidising agents are described. It is concluded that radiation-induced decomposition is only likely to be a problem with dilute formulations, and/or with minor additives such as corrosion inhibitors which are not protected from attack by the other constituents. Addition of a "sacrificial" compound may be necessary to overcome this. The importance of considering loss of function, rather than the decomposition rate of the starting material, is emphasised. Reagents based on low oxidation state metal ions (LOMI) can be regenerated by the radiation field in the presence of formate ion.

Synthetic Aziridines in Medicinal Chemistry: A Mini-Review.

PubMed

Singh, Girija S

2016-01-01

Azaheterocyclic compounds are well-known to have diverse types of biological activity. Among them, azacyclopropanes, commonly referred as aziridines, occupy a prominent place in synthetic organic and medicinal chemistry due to its occurrence in natural resources, complexity involved in synthesis due to ring-strain, building blocks in organic synthesis, and its biological properties. Several novel compounds containing aziridine ring have been designed and synthesized recently by medicinal chemists for evaluating their biological profile. A number of compounds are reported as cysteine protease inhibitors, antibacterial, antifungal, anticancer, antileishmanial, and antimalarial agents. This review article summarizes the biological activity of such compounds. The preparation of such compounds is also described.

Translating HDAC inhibitors in Friedrich's ataxia

PubMed Central

Soragni, Elisabetta; Gottesfeld, Joel M

2016-01-01

Introduction Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by expansion of a GAA·TTC triplet in the first intron of the FXN gene, encoding the essential mitochondrial protein frataxin. Repeat expansion results in transcriptional silencing through an epigenetic mechanism, resulting in significant decreases in frataxin protein in affected individuals. Since the FXN protein coding sequence is unchanged in FRDA, an attractive therapeutic approach for this disease would be to increase transcription of pathogenic alleles with small molecules that target the silencing mechanism. Areas covered We review the evidence that histone postsynthetic modifications and heterochromatin formation are responsible for FXN gene silencing in FRDA, along with efforts to reverse silencing with drugs that target histone modifying enzymes. Chemical and pharmacological properties of histone deacetylase (HDAC) inhibitors, which reverse silencing, together with enzyme target profiles and kinetics of inhibition, are discussed. Two HDAC inhibitors have been studied in human clinical trials and the properties of these compounds are compared and contrasted. Efforts to improve on bioavailability, metabolic stability, and target activity are reviewed. Expert opinion 2-aminobenzamide class I HDAC inhibitors are attractive therapeutic small molecules for FRDA. These molecules increase FXN gene expression in human neuronal cells derived from patient induced pluripotent stem cells, and in two mouse models for the disease, as well as in circulating lymphocytes in patients treated in a phase Ib clinical trial. Medicinal chemistry efforts have identified compounds with improved brain penetration, metabolic stability and efficacy in the human neuronal cell model. A clinical candidate will soon be identified for further human testing. PMID:28392990

Structure-activity relationship of ortho- and meta-phenol based LFA-1 ICAM inhibitors.

PubMed

Lin, Edward Yin-Shiang; Guckian, Kevin M; Silvian, Laura; Chin, Donovan; Boriack-Sjodin, P Ann; van Vlijmen, Herman; Friedman, Jessica E; Scott, Daniel M

2008-10-01

LFA-1 ICAM inhibitors based on ortho- and meta-phenol templates were designed and synthesized by Mitsunobu chemistry. The selection of targets was guided by X-ray co-crystal data, and led to compounds which showed an up to 30-fold increase in potency over reference compound 1 in the LFA-1/ICAM1-Ig assay. The most active compound exploited a new hydrogen bond to the I-domain and exhibited subnanomolar potency.

Multi-Protein Dynamic Combinatorial Chemistry: A Novel Strategy that Leads to Simultaneous Discovery of Subfamily-Selective Inhibitors for Nucleic Acid Demethylases FTO and ALKBH3.

PubMed

Das, Mohua; Tianming, Yang; Jinghua, Dong; Prasetya, Fransisca; Yiming, Xie; Wong, Kendra; Cheong, Adeline; Woon, Esther C Y

2018-06-19

Dynamic combinatorial chemistry (DCC) is a powerful supramolecular approach for discovering ligands for biomolecules. To date, most, if not all, biologically-templated DCC employ only a single biomolecule in directing the self-assembly process. To expand the scope and potential of DCC, herein, we developed a novel multi-protein DCC strategy which combines the discriminatory power of zwitterionic 'thermal-tag' with the sensitivity of differential scanning fluorimetry. This strategy enables the discovery of ligands against several proteins of interest concurrently. It is remarkably sensitive and could differentiate the binding of ligands to structurally-similar subfamily members, which is extremely challenging to achieve. Through this approach, we were able to simultaneously identify subfamily-selective probes against two clinically important epigenetic enzymes, FTO (7; IC₅₀ = 2.6 µM) and ALKBH3 (8; IC₅₀ = 3.7 µM). To our knowledge, this is the first report of a subfamily-selective ALKBH3 inhibitor. The developed strategy could, in principle, be adapted to a broad range of proteins, thus it shall be of widespread scientific interest. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymyxins and quinazolines are LSD1/KDM1A inhibitors with unusual structural features.

PubMed

Speranzini, Valentina; Rotili, Dante; Ciossani, Giuseppe; Pilotto, Simona; Marrocco, Biagina; Forgione, Mariantonietta; Lucidi, Alessia; Forneris, Federico; Mehdipour, Parinaz; Velankar, Sameer; Mai, Antonello; Mattevi, Andrea

2016-09-01

Because of its involvement in the progression of several malignant tumors, the histone lysine-specific demethylase 1 (LSD1) has become a prominent drug target in modern medicinal chemistry research. We report on the discovery of two classes of noncovalent inhibitors displaying unique structural features. The antibiotics polymyxins bind at the entrance of the substrate cleft, where their highly charged cyclic moiety interacts with a cluster of positively charged amino acids. The same site is occupied by quinazoline-based compounds, which were found to inhibit the enzyme through a most peculiar mode because they form a pile of five to seven molecules that obstruct access to the active center. These data significantly indicate unpredictable strategies for the development of epigenetic inhibitors.

Forensic Chemistry

NASA Astrophysics Data System (ADS)

Bell, Suzanne

2009-07-01

Forensic chemistry is unique among chemical sciences in that its research, practice, and presentation must meet the needs of both the scientific and the legal communities. As such, forensic chemistry research is applied and derivative by nature and design, and it emphasizes metrology (the science of measurement) and validation. Forensic chemistry has moved away from its analytical roots and is incorporating a broader spectrum of chemical sciences. Existing forensic practices are being revisited as the purview of forensic chemistry extends outward from drug analysis and toxicology into such diverse areas as combustion chemistry, materials science, and pattern evidence.

Structure-Guided Discovery of Novel, Potent, and Orally Bioavailable Inhibitors of Lipoprotein-Associated Phospholipase A2.

PubMed

Liu, Qiufeng; Huang, Fubao; Yuan, Xiaojing; Wang, Kai; Zou, Yi; Shen, Jianhua; Xu, Yechun

2017-12-28

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a promising therapeutic target for atherosclerosis, Alzheimer's disease, and diabetic macular edema. Here we report the identification of novel sulfonamide scaffold Lp-PLA2 inhibitors derived from a relatively weak fragment. Similarity searching on this fragment followed by molecular docking leads to the discovery of a micromolar inhibitor with a 300-fold potency improvement. Subsequently, by the application of a structure-guided design strategy, a successful hit-to-lead optimization was achieved and a number of Lp-PLA2 inhibitors with single-digit nanomolar potency were obtained. After preliminary evaluation of the properties of drug-likeness in vitro and in vivo, compound 37 stands out from this congeneric series of inhibitors for good inhibitory activity and favorable oral bioavailability in male Sprague-Dawley rats, providing a quality candidate for further development. The present study thus clearly demonstrates the power and advantage of integrally employing fragment screening, crystal structures determination, virtual screening, and medicinal chemistry in an efficient lead discovery project, providing a good example for structure-based drug design.

Ligand-based virtual screening and inductive learning for identification of SIRT1 inhibitors in natural products.

PubMed

Sun, Yunan; Zhou, Hui; Zhu, Hongmei; Leung, Siu-wai

2016-01-25

Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase, and its dysregulation can lead to ageing, diabetes, and cancer. From 346 experimentally confirmed SIRT1 inhibitors, an inhibitor structure pattern was generated by inductive logic programming (ILP) with DMax Chemistry Assistant software. The pattern contained amide, amine, and hetero-aromatic five-membered rings, each of which had a hetero-atom and an unsubstituted atom at a distance of 2. According to this pattern, a ligand-based virtual screening of 1 444 880 active compounds from Chinese herbs identified 12 compounds as inhibitors of SIRT1. Three compounds (ZINC08790006, ZINC08792229, and ZINC08792355) had high affinity (-7.3, -7.8, and -8.6 kcal/mol, respectively) for SIRT1 as estimated by molecular docking software AutoDock Vina. This study demonstrated a use of ILP and background knowledge in machine learning to facilitate virtual screening.

Ligand-based virtual screening and inductive learning for identification of SIRT1 inhibitors in natural products

NASA Astrophysics Data System (ADS)

Sun, Yunan; Zhou, Hui; Zhu, Hongmei; Leung, Siu-Wai

2016-01-01

Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase, and its dysregulation can lead to ageing, diabetes, and cancer. From 346 experimentally confirmed SIRT1 inhibitors, an inhibitor structure pattern was generated by inductive logic programming (ILP) with DMax Chemistry Assistant software. The pattern contained amide, amine, and hetero-aromatic five-membered rings, each of which had a hetero-atom and an unsubstituted atom at a distance of 2. According to this pattern, a ligand-based virtual screening of 1 444 880 active compounds from Chinese herbs identified 12 compounds as inhibitors of SIRT1. Three compounds (ZINC08790006, ZINC08792229, and ZINC08792355) had high affinity (-7.3, -7.8, and -8.6 kcal/mol, respectively) for SIRT1 as estimated by molecular docking software AutoDock Vina. This study demonstrated a use of ILP and background knowledge in machine learning to facilitate virtual screening.

Chemistry Notes.

ERIC Educational Resources Information Center

School Science Review, 1982

1982-01-01

Presents background information, laboratory procedures, classroom materials/activities, and experiments for chemistry. Topics include superheavy elements, polarizing power and chemistry of alkali metals, particulate carbon from combustion, tips for the chemistry laboratory, interesting/colorful experiments, behavior of bismuth (III) iodine, and…

Clinical chemistry through Clinical Chemistry: a journal timeline.

PubMed

Rej, Robert

2004-12-01

The establishment of the modern discipline of clinical chemistry was concurrent with the foundation of the journal Clinical Chemistry and that of the American Association for Clinical Chemistry in the late 1940s and early 1950s. To mark the 50th volume of this Journal, I chronicle and highlight scientific milestones, and those within the discipline, as documented in the pages of Clinical Chemistry. Amazing progress has been made in the field of laboratory diagnostics over these five decades, in many cases paralleling-as well as being bolstered by-the rapid pace in the development of computer technologies. Specific areas of laboratory medicine particularly well represented in Clinical Chemistry include lipids, endocrinology, protein markers, quality of laboratory measurements, molecular diagnostics, and general advances in methodology and instrumentation.

DanceChemistry: Helping Students Visualize Chemistry Concepts through Dance Videos

ERIC Educational Resources Information Center

Tay, Gidget C.; Edwards, Kimberly D.

2015-01-01

A visual aid teaching tool, the DanceChemistry video series, has been developed to teach fundamental chemistry concepts through dance. These educational videos portray chemical interactions at the molecular level using dancers to represent chemical species. Students reported that the DanceChemistry videos helped them visualize chemistry ideas in a…

Defined Host–Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer

PubMed Central

Ostadhossein, Fatemeh; Misra, Santosh K.; Mukherjee, Prabuddha; Ostadhossein, Alireza; Daza, Enrique; Tiwari, Saumya; Mittal, Shachi; Gryka, Mark C.; Bhargava, Rohit

2017-01-01

Signal transducer and activator of transcription factor 3 (STAT-3) is known to be overexpressed in cancer stem cells. Poor solubility and variable drug absorption are linked to low bioavailability and decreased efficacy. Many of the drugs regulating STAT-3 expression lack aqueous solubility; hence hindering efficient bioavailability. A theranostics nanoplatform based on luminescent carbon particles decorated with cucurbit[6]uril is introduced for enhancing the solubility of niclosamide, a STAT-3 inhibitor. The host–guest chemistry between cucurbit[6]uril and niclosamide makes the delivery of the hydrophobic drug feasible while carbon nanoparticles enhance cellular internalization. Extensive physicochemical characterizations confirm successful synthesis. Subsequently, the host–guest chemistry of niclosamide and cucurbit[6]uril is studied experimentally and computationally. In vitro assessments in human breast cancer cells indicate approximately twofold enhancement in IC50 of drug. Fourier transform infrared and fluorescence imaging demonstrate efficient cellular internalization. Furthermore, the catalytic biodegradation of the nanoplatforms occur upon exposure to human myeloperoxidase in short time. In vivo studies on athymic mice with MCF-7 xenograft indicate the size of tumor in the treatment group is half of the controls after 40 d. Immunohistochemistry corroborates the downregulation of STAT-3 phosphorylation. Overall, the host–guest chemistry on nanocarbon acts as a novel arsenal for STAT-3 inhibition. PMID:27545321

Synthesis and structure-activity relationship of histone deacetylase (HDAC) inhibitors with triazole-linked cap group.

PubMed

Chen, Po C; Patil, Vishal; Guerrant, William; Green, Patience; Oyelere, Adegboyega K

2008-05-01

Histone deacetylase (HDAC) inhibition is a recent, clinically validated therapeutic strategy for cancer treatment. Small molecule HDAC inhibitors identified so far fall in to three distinct structural motifs: the zinc-binding group (ZBG), a hydrophobic linker, and a recognition cap group. Here we report the suitability of a 1,2,3-triazole ring as a surface recognition cap group-linking moiety in suberoylanilide hydroxamic acid-like (SAHA-like) HDAC inhibitors. Using "click" chemistry (Huisgen cycloaddition reaction), several triazole-linked SAHA-like hydroxamates were synthesized. Structure-activity relationship revealed that the position of the triazole moiety as well as the identity of the cap group markedly affected the in vitro HDAC inhibition and cell growth inhibitory activities of this class of compounds.

Exploring Additional Dimensions of Complexity in Inhibitor Design for Serine β-Lactamases: Mechanistic and Intra- and Inter-molecular Chemistry Approaches

PubMed Central

van den Akker, Focco; Bonomo, Robert A.

2018-01-01

As a bacterial resistance strategy, serine β-lactamases have evolved from cell wall synthesizing enzymes known as penicillin-binding proteins (PBP), by not only covalently binding β-lactam antibiotics but, also acquiring mechanisms of deacylating these antibiotics. This critical deacylation step leads to release of hydrolyzed and inactivated β-lactams, thereby providing resistance for the bacteria against these antibiotics targeting the cell wall. To combat β-lactamase-mediated antibiotic resistance, numerous β-lactamase inhibitors were developed that utilize various strategies to inactivate the β-lactamase. Most of these compounds are “mechanism-based” inhibitors that in some manner mimic the β-lactam substrate, having a carbonyl moiety and a negatively charged carboxyl or sulfate group. These compounds form a covalent adduct with the catalytic serine via an initial acylation step. To increase the life-time of the inhibitory covalent adduct intermediates, a remarkable array of different strategies was employed to improve inhibition potency. Such approaches include post-acylation intra- and intermolecular chemical rearrangements as well as affecting the deacylation water. These approaches transform the inhibitor design process from a 3-dimensional problem (i.e., XYZ coordinates) to one with additional dimensions of complexity as the reaction coordinate and time spent at each chemical state need to be taken into consideration. This review highlights the mechanistic intricacies of the design efforts of the β-lactamase inhibitors which so far have resulted in the development of “two generations” and 5 clinically available inhibitors. PMID:29675000

Identification of a Novel Family of BRAF[superscript V600E] Inhibitors

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

Qin, Jie; Xie, Peng; Ventocilla, Christian

The BRAF oncoprotein is mutated in about half of malignant melanomas and other cancers, and a kinase activating single valine to glutamate substitution at residue 600 (BRAF{sup V600E}) accounts for over 90% of BRAF-mediated cancers. Several BRAF{sup V600E} inhibitors have been developed, although they harbor some liabilities, thus motivating the development of other BRAF{sup V600E} inhibitor options. We report here the use of an ELISA based high-throughput screen to identify a family of related quinolol/naphthol compounds that preferentially inhibit BRAF{sup V600E} over BRAF{sup WT} and other kinases. We also report the X-ray crystal structure of a BRAF/quinolol complex revealing themore » mode of inhibition, employ structure-based medicinal chemistry efforts to prepare naphthol analogues that inhibit BRAF{sup V600E} in vitro with IC{sub 50} values in the 80-200 nM range under saturating ATP concentrations, and demonstrate that these compounds inhibit MAPK signaling in melanoma cells. Prospects for improving the potency and selectivity of these inhibitors are discussed.« less

Found in translation: how preclinical research is guiding the clinical development of the BCL-2-selective inhibitor venetoclax

PubMed Central

Leverson, Joel D.; Sampath, Deepak; Souers, Andrew J.; Rosenberg, Saul H.; Fairbrother, Wayne J.; Amiot, Martine; Konopleva, Marina; Letai, Anthony

2017-01-01

Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high priority goal for cancer therapy. After decades of effort, drug discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL-2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL-2 biology, were essential to the development of BH3 mimetics such as the BCL-2-selective inhibitor venetoclax. We review a number of preclinical studies that have deepened our understanding of BCL-2 biology and facilitated the clinical development of venetoclax. PMID:29146569

A class of selective antibacterials derived from a protein kinase inhibitor pharmacophore

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

Miller, J. Richard; Dunham, Steve; Mochalkin, Igor

2009-06-25

As the need for novel antibiotic classes to combat bacterial drug resistance increases, the paucity of leads resulting from target-based antibacterial screening of pharmaceutical compound libraries is of major concern. One explanation for this lack of success is that antibacterial screening efforts have not leveraged the eukaryotic bias resulting from more extensive chemistry efforts targeting eukaryotic gene families such as G protein-coupled receptors and protein kinases. Consistent with a focus on antibacterial target space resembling these eukaryotic targets, we used whole-cell screening to identify a series of antibacterial pyridopyrimidines derived from a protein kinase inhibitor pharmacophore. In bacteria, the pyridopyrimidinesmore » target the ATP-binding site of biotin carboxylase (BC), which catalyzes the first enzymatic step of fatty acid biosynthesis. These inhibitors are effective in vitro and in vivo against fastidious Gram-negative pathogens including Haemophilus influenzae. Although the BC active site has architectural similarity to those of eukaryotic protein kinases, inhibitor binding to the BC ATP-binding site is distinct from the protein kinase-binding mode, such that the inhibitors are selective for bacterial BC. In summary, we have discovered a promising class of potent antibacterials with a previously undescribed mechanism of action. In consideration of the eukaryotic bias of pharmaceutical libraries, our findings also suggest that pursuit of a novel inhibitor leads for antibacterial targets with active-site structural similarity to known human targets will likely be more fruitful than the traditional focus on unique bacterial target space, particularly when structure-based and computational methodologies are applied to ensure bacterial selectivity.« less

Chemistry for whom? Gender awareness in teaching and learning chemistry

NASA Astrophysics Data System (ADS)

Andersson, Kristina

2017-06-01

Marie Ståhl and Anita Hussénius have defined what discourses dominate national tests in chemistry for Grade 9 in Sweden by using feminist, critical didactic perspectives. This response seeks to expand the results in Ståhl and Hussénius's article Chemistry inside an epistemological community box!— Discursive exclusions and inclusions in the Swedish national tests in chemistry, by using different facets of gender awareness. The first facet—Gender awareness in relations to the test designers' own conceptions—highlighted how the gender order where women are subordinated men becomes visible in the national tests as a consequence of the test designers internalized conceptions. The second facet—Gender awareness in relation to chemistry—discussed the hierarchy between discourses within chemistry. The third facet—Gender awareness in relation to students—problematized chemistry in relation to the students' identity formation. In summary, I suggest that the different discourses can open up new ways to interpret chemistry and perhaps dismantle the hegemonic chemistry discourse.

Discovery of novel anti-HIV agents via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry-based approach.

PubMed

Gao, Ping; Sun, Lin; Zhou, Junsu; Li, Xiao; Zhan, Peng; Liu, Xinyong

2016-09-01

In recent years, a variety of new synthetic methodologies and concepts have been proposed in the search for new pharmaceutical lead structures and optimization. Notably, the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry approach has drawn great attention and has become a powerful tool for the generation of privileged medicinal skeletons in the discovery of anti-HIV agents. This is due to the high degree of reliability, complete specificity (chemoselectivity and regioselectivity), mild conditions, and the biocompatibility of the reactants. Herein, the authors describe the progress thus far on the discovery of novel anti-HIV agents via the CuAAC click chemistry-based approach. CuAAC click chemistry is a proven protocol for synthesizing triazole products which could serve as basic pharmacophores, act as replacements of traditional scaffold or substituent modification, be a linker of dual-target or dual-site inhibitors and more for the discovery of novel anti-HIV agents. What's more, it also provides convenience and feasibility for dynamic combinatorial chemistry and in situ screening. It is envisioned that click chemistry will draw more attention and make more contributions in anti-HIV drug discovery in the future.

How chemistry supports cell biology: the chemical toolbox at your service.

PubMed

Wijdeven, Ruud H; Neefjes, Jacques; Ovaa, Huib

2014-12-01

Chemical biology is a young and rapidly developing scientific field. In this field, chemistry is inspired by biology to create various tools to monitor and modulate biochemical and cell biological processes. Chemical contributions such as small-molecule inhibitors and activity-based probes (ABPs) can provide new and unique insights into previously unexplored cellular processes. This review provides an overview of recent breakthroughs in chemical biology that are likely to have a significant impact on cell biology. We also discuss the application of several chemical tools in cell biology research. Copyright © 2014 Elsevier Ltd. All rights reserved.

Discovery of a fluorene class of compounds as inhibitors of botulinum neurotoxin serotype E by virtual screening.

PubMed

Kumar, Gyanendra; Agarwal, Rakhi; Swaminathan, Subramanyam

2012-02-28

Botulinum neurotoxins are one of the most poisonous biological substances known to humans and present a potential bioterrorism threat. There are no therapeutic interventions developed so far. Here, we report the first small molecule non-peptide inhibitor for botulinum neurotoxin serotype E discovered by structure-based virtual screening and propose a mechanism for its inhibitory activity. This journal is © The Royal Society of Chemistry 2012

Connecting biology and organic chemistry introductory laboratory courses through a collaborative research project.

PubMed

Boltax, Ariana L; Armanious, Stephanie; Kosinski-Collins, Melissa S; Pontrello, Jason K

2015-01-01

Modern research often requires collaboration of experts in fields, such as math, chemistry, biology, physics, and computer science to develop unique solutions to common problems. Traditional introductory undergraduate laboratory curricula in the sciences often do not emphasize connections possible between the various disciplines. We designed an interdisciplinary, medically relevant, project intended to help students see connections between chemistry and biology. Second term organic chemistry laboratory students designed and synthesized potential polymer inhibitors or inducers of polyglutamine protein aggregation. The use of novel target compounds added the uncertainty of scientific research to the project. Biology laboratory students then tested the novel potential pharmaceuticals in Huntington's disease model assays, using in vitro polyglutamine peptide aggregation and in vivo lethality studies in Drosophila. Students read articles from the primary literature describing the system from both chemical and biological perspectives. Assessment revealed that students emerged from both courses with a deeper understanding of the interdisciplinary nature of biology and chemistry and a heightened interest in basic research. The design of this collaborative project for introductory biology and organic chemistry labs demonstrated how the local interests and expertise at a university can be drawn from to create an effective way to integrate these introductory courses. Rather than simply presenting a series of experiments to be replicated, we hope that our efforts will inspire other scientists to think about how some aspect of authentic work can be brought into their own courses, and we also welcome additional collaborations to extend the scope of the scientific exploration. © 2015 The International Union of Biochemistry and Molecular Biology.

Reverse transcriptase inhibitors as microbicides.

PubMed

Lewi, Paul; Heeres, Jan; Ariën, Kevin; Venkatraj, Muthusamy; Joossens, Jurgen; Van der Veken, Pieter; Augustyns, Koen; Vanham, Guido

2012-01-01

The CAPRISA 004 study in South Africa has accelerated the development of vaginal and rectal microbicides containing antiretrovirals that target specific enzymes in the reproduction cycle of HIV, especially reverse transcriptase inhibitors (RTI). In this review we discuss the potential relevance of HIV-1 RTIs as microbicides, focusing in the nucleotide RTI tenofovir and six classes of nonnucleoside RTIs (including dapivirine, UC781, urea and thiourea PETTs, DABOs and a pyrimidinedione). Although tenofovir and dapivirine appear to be most advanced in clinical trials as potential microbicides, several issues remain unresolved, e.g., the importance of nonhuman primates as a "gatekeeper" for clinical trials, the emergence and spread of drug-resistant mutants, the combination of microbicides that target different phases of viral reproduction and the accessibility to microbicides in low-income countries. Thus, here we discuss the latest research on RTI as microbicides in the light of the continuing spread of the HIV pandemic from the point of view of medicinal chemistry, virological, and pharmaceutical studies.

Peer Mentoring in the General Chemistry and Organic Chemistry Laboratories: The Pinacol Rearrangement--An Exercise in NMR and IR Spectroscopy for General Chemistry and Organic Chemistry Laboratories

ERIC Educational Resources Information Center

Arrington, Caleb A.; Hill, Jameica B.; Radfar, Ramin; Whisnant, David M.; Bass, Charles G.

2008-01-01

This article describes a discovery experiment for general chemistry and organic chemistry labs. Although the pinacol rearrangement has been employed in undergraduate organic laboratories before, in this application organic chemistry students act as mentors to students of general chemistry. Students work together using distillation--a new technique…

Exploration of fluorine chemistry at the multidisciplinary interface of chemistry and biology.

PubMed

Ojima, Iwao

2013-07-05

Over the last three decades, my engagement in "fluorine chemistry" has evolved substantially because of the multidisciplinary nature of the research programs. I began my research career as a synthetic chemist in organometallic chemistry and homogeneous catalysis directed toward organic synthesis. Then, I was brought into a very unique world of "fluorine chemistry" in the end of 1970s. I started exploring the interface of fluorine chemistry and transition metal homogeneous catalysis first, which was followed by amino acids, peptides, and peptidomimetics for medicinal chemistry. Since then, I have been exploring the interfaces of fluorine chemistry and multidisciplinary fields of research involving medicinal chemistry, chemical biology, cancer biology, and molecular imaging. This perspective intends to cover my fruitful endeavor in the exploration of fluorine chemistry at the multidisciplinary interface of chemistry and biology in a chronological order to show the evolution of my research interest and strategy.

Chemistry: Experiments, Demonstrations and Other Activities Suggested for Chemistry.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

This publication is a handbook used in conjunction with the course of study in chemistry developed through the New York State Education Department and The University of the State of New York. It contains experiments, demonstrations, and other activities for a chemistry course. Areas covered include the science of chemistry, the atomic structure of…

Berberine as a natural source inhibitor for mild steel in 1 M H 2SO 4

NASA Astrophysics Data System (ADS)

Li, Yan; Zhao, Peng; Liang, Qiang; Hou, Baorong

2005-12-01

Berberine was abstracted from coptis chinensis and its inhibition efficiency on corrosion of mild steel in 1 M H 2SO 4 was investigated through weight loss experiment, electrochemical techniques and scanning electronic microscope (SEM) with energy disperse spectrometer (EDS). The weight loss results showed that berberine is an excellent corrosion inhibitor for mild steel immersed in 1 M H 2SO 4. Potentiodynamic curves suggested that berberine suppressed both cathodic and anodic processes for its concentrations higher than 1.0 × 10 -4 M and mainly cathodic reaction was suppressed for lower concentrations. The Nyquist diagrams of impedance for mild steel in 1 M H 2SO 4 containing berberine with different concentrations showed one capacitive loop, and the polarization resistance increased with the inhibitor concentration rising. A good fit to Flory-Huggins isotherm was obtained between surface coverage degree and inhibitor concentration. The surface morphology and EDS analysis for mild steel specimens in sulfuric acid in the absence and presence of the inhibitor also proved the results obtained by the weight loss and electrochemical experiments. The correlation of inhibition effect and molecular structure of berberine was then discussed by quantum chemistry study.

Discovery of d-amino acid oxidase inhibitors based on virtual screening against the lid-open enzyme conformation.

PubMed

Szilágyi, Bence; Skok, Žiga; Rácz, Anita; Frlan, Rok; Ferenczy, György G; Ilaš, Janez; Keserű, György M

2018-06-01

d-Amino acid oxidase (DAAO) inhibitors are typically small polar compounds with often suboptimal pharmacokinetic properties. Features of the native binding site limit the operational freedom of further medicinal chemistry efforts. We therefore initiated a structure based virtual screening campaign based on the X-ray structures of DAAO complexes where larger ligands shifted the loop (lid opening) covering the native binding site. The virtual screening of our in-house collection followed by the in vitro test of the best ranked compounds led to the identification of a new scaffold with micromolar IC 50 . Subsequent SAR explorations enabled us to identify submicromolar inhibitors. Docking studies supported by in vitro activity measurements suggest that compounds bind to the active site with a salt-bridge characteristic to DAAO inhibitor binding. In addition, displacement of and interaction with the loop covering the active site contributes significantly to the activity of the most potent compounds. Copyright © 2018 Elsevier Ltd. All rights reserved.

Defined Host-Guest Chemistry on Nanocarbon for Sustained Inhibition of Cancer.

PubMed

Ostadhossein, Fatemeh; Misra, Santosh K; Mukherjee, Prabuddha; Ostadhossein, Alireza; Daza, Enrique; Tiwari, Saumya; Mittal, Shachi; Gryka, Mark C; Bhargava, Rohit; Pan, Dipanjan

2016-08-22

Signal transducer and activator of transcription factor 3 (STAT-3) is known to be overexpressed in cancer stem cells. Poor solubility and variable drug absorption are linked to low bioavailability and decreased efficacy. Many of the drugs regulating STAT-3 expression lack aqueous solubility; hence hindering efficient bioavailability. A theranostics nanoplatform based on luminescent carbon particles decorated with cucurbit[6]uril is introduced for enhancing the solubility of niclosamide, a STAT-3 inhibitor. The host-guest chemistry between cucurbit[6]uril and niclosamide makes the delivery of the hydrophobic drug feasible while carbon nanoparticles enhance cellular internalization. Extensive physicochemical characterizations confirm successful synthesis. Subsequently, the host-guest chemistry of niclosamide and cucurbit[6]uril is studied experimentally and computationally. In vitro assessments in human breast cancer cells indicate approximately twofold enhancement in IC 50 of drug. Fourier transform infrared and fluorescence imaging demonstrate efficient cellular internalization. Furthermore, the catalytic biodegradation of the nanoplatforms occur upon exposure to human myeloperoxidase in short time. In vivo studies on athymic mice with MCF-7 xenograft indicate the size of tumor in the treatment group is half of the controls after 40 d. Immunohistochemistry corroborates the downregulation of STAT-3 phosphorylation. Overall, the host-guest chemistry on nanocarbon acts as a novel arsenal for STAT-3 inhibition. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-hepatitis C virus activity and toxicity of type III phosphatidylinositol-4-kinase beta inhibitors.

PubMed

Lamarche, M J; Borawski, J; Bose, A; Capacci-Daniel, C; Colvin, R; Dennehy, M; Ding, J; Dobler, M; Drumm, J; Gaither, L A; Gao, J; Jiang, X; Lin, K; McKeever, U; Puyang, X; Raman, P; Thohan, S; Tommasi, R; Wagner, K; Xiong, X; Zabawa, T; Zhu, S; Wiedmann, B

2012-10-01

Type III phosphatidylinositol-4-kinase beta (PI4KIIIβ) was previously implicated in hepatitis C virus (HCV) replication by small interfering RNA (siRNA) depletion and was therefore proposed as a novel cellular target for the treatment of hepatitis C. Medicinal chemistry efforts identified highly selective PI4KIIIβ inhibitors that potently inhibited the replication of genotype 1a and 1b HCV replicons and genotype 2a virus in vitro. Replicon cells required more than 5 weeks to reach low levels of 3- to 5-fold resistance, suggesting a high resistance barrier to these cellular targets. Extensive in vitro profiling of the compounds revealed a role of PI4KIIIβ in lymphocyte proliferation. Previously proposed functions of PI4KIIIβ in insulin secretion and the regulation of several ion channels were not perturbed with these inhibitors. Moreover, PI4KIIIβ inhibitors were not generally cytotoxic as demonstrated across hundreds of cell lines and primary cells. However, an unexpected antiproliferative effect in lymphocytes precluded their further development for the treatment of hepatitis C.

Anti-Hepatitis C Virus Activity and Toxicity of Type III Phosphatidylinositol-4-Kinase Beta Inhibitors

PubMed Central

LaMarche, M. J.; Borawski, J.; Bose, A.; Capacci-Daniel, C.; Colvin, R.; Dennehy, M.; Ding, J.; Dobler, M.; Drumm, J.; Gaither, L. A.; Gao, J.; Jiang, X.; Lin, K.; McKeever, U.; Puyang, X.; Raman, P.; Thohan, S.; Tommasi, R.; Wagner, K.; Xiong, X.; Zabawa, T.; Zhu, S.

2012-01-01

Type III phosphatidylinositol-4-kinase beta (PI4KIIIβ) was previously implicated in hepatitis C virus (HCV) replication by small interfering RNA (siRNA) depletion and was therefore proposed as a novel cellular target for the treatment of hepatitis C. Medicinal chemistry efforts identified highly selective PI4KIIIβ inhibitors that potently inhibited the replication of genotype 1a and 1b HCV replicons and genotype 2a virus in vitro. Replicon cells required more than 5 weeks to reach low levels of 3- to 5-fold resistance, suggesting a high resistance barrier to these cellular targets. Extensive in vitro profiling of the compounds revealed a role of PI4KIIIβ in lymphocyte proliferation. Previously proposed functions of PI4KIIIβ in insulin secretion and the regulation of several ion channels were not perturbed with these inhibitors. Moreover, PI4KIIIβ inhibitors were not generally cytotoxic as demonstrated across hundreds of cell lines and primary cells. However, an unexpected antiproliferative effect in lymphocytes precluded their further development for the treatment of hepatitis C. PMID:22825118

Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis.

PubMed

Ebert, Gregor; Allison, Cody; Preston, Simon; Cooney, James; Toe, Jesse G; Stutz, Michael D; Ojaimi, Samar; Baschuk, Nikola; Nachbur, Ueli; Torresi, Joseph; Silke, John; Begley, C Glenn; Pellegrini, Marc

2015-05-05

We have shown that cellular inhibitor of apoptosis proteins (cIAPs) impair clearance of hepatitis B virus (HBV) infection by preventing TNF-mediated killing/death of infected cells. A key question, with profound therapeutic implications, is whether this finding can be translated to the development of drugs that promote elimination of infected cells. Drug inhibitors of cIAPs were developed as cancer therapeutics to promote TNF-mediated tumor killing. These drugs are also known as Smac mimetics, because they mimic the action of the endogenous protein Smac/Diablo that antagonizes cIAP function. Here, we show using an immunocompetent mouse model of chronic HBV infection that birinapant and other Smac mimetics are able to rapidly reduce serum HBV DNA and serum HBV surface antigen, and they promote the elimination of hepatocytes containing HBV core antigen. The efficacy of Smac mimetics in treating HBV infection is dependent on their chemistry, host CD4(+) T cells, and TNF. Birinapant enhances the ability of entecavir, an antiviral nucleoside analog, to reduce viral DNA production in HBV-infected animals. These results indicate that birinapant and other Smac mimetics may have efficacy in treating HBV infection and perhaps, other intracellular infections.

Designing Inhibitors of Anthrax Toxin

PubMed Central

Nestorovich, Ekaterina M.; Bezrukov, Sergey M.

2014-01-01

Introduction Present-day rational drug design approaches are based on exploiting unique features of the target biomolecules, small- or macromolecule drug candidates, and physical forces that govern their interactions. The 2013 Nobel Prize in chemistry awarded “for the development of multiscale models for complex chemical systems” once again demonstrated the importance of the tailored drug discovery that reduces the role of the trial and error approach to a minimum. The “rational drug design” term is rather comprehensive as it includes all contemporary methods of drug discovery where serendipity and screening are substituted by the information-guided search for new and existing compounds. Successful implementation of these innovative drug discovery approaches is inevitably preceded by learning the physics, chemistry, and physiology of functioning of biological structures under normal and pathological conditions. Areas covered This article provides an overview of the recent rational drug design approaches to discover inhibitors of anthrax toxin. Some of the examples include small-molecule and peptide-based post-exposure therapeutic agents as well as several polyvalent compounds. The review also directs the reader to the vast literature on the recognized advances and future possibilities in the field. Expert opinion Existing options to combat anthrax toxin lethality are limited. With the only anthrax toxin inhibiting therapy (PA-targeting with a monoclonal antibody, raxibacumab) approved to treat inhalational anthrax, in our view, the situation is still insecure. The FDA’s animal rule for drug approval, which clears compounds without validated efficacy studies on humans, creates a high level of uncertainty, especially when a well-characterized animal model does not exist. Besides, unlike PA, which is known to be unstable, LF remains active in cells and in animal tissues for days. Therefore, the effectiveness of the post-exposure treatment of the individuals

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

PubMed

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

2017-07-13

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

Chemokine Receptor CCR5 Antagonist Maraviroc: Medicinal Chemistry and Clinical Applications

PubMed Central

Xu, Guoyan G.; Guo, Jia; Wu, Yuntao

2015-01-01

The human immunodeficiency virus (HIV) causes acquired immumodeficiency syndrome (AIDS), one of the worst global pandemic. The virus infects human CD4 T cells and macrophages, and causes CD4 depletion. HIV enters target cells through the binding of the viral envelope glycoprotein to CD4 and the chemokine coreceptor, CXCR4 or CCR5. In particular, the CCR5-utilizing viruses predominate in the blood during the disease course. CCR5 is expressed on the surface of various immune cells including macrophages, monocytes, microglia, dendric cells, and active memory CD4 T cells. In the human population, the CCR5 genomic mutation, CCR5Δ32, is associated with relative resistance to HIV. These findings paved the way for the discovery and development of CCR5 inhibitors to block HIV transmission and replication. Maraviroc, discovered as a CCR5 antagonist, is the only CCR5 inhibitor that has been approved by both US FDA and the European Medicines Agency (EMA) for treating HIV/AIDS patients. In this review, we summarize the medicinal chemistry and clinical studies of Maraviroc. PMID:25159165

Epitope targeting of tertiary protein structure enables target-guided synthesis of a potent in-cell inhibitor of botulinum neurotoxin.

PubMed

Farrow, Blake; Wong, Michelle; Malette, Jacquie; Lai, Bert; Deyle, Kaycie M; Das, Samir; Nag, Arundhati; Agnew, Heather D; Heath, James R

2015-06-08

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discovering Anti-platelet Drug Combinations with an Integrated Model of Activator-Inhibitor Relationships, Activator-Activator Synergies and Inhibitor-Inhibitor Synergies

PubMed Central

Lombardi, Federica; Golla, Kalyan; Fitzpatrick, Darren J.; Casey, Fergal P.; Moran, Niamh; Shields, Denis C.

2015-01-01

Identifying effective therapeutic drug combinations that modulate complex signaling pathways in platelets is central to the advancement of effective anti-thrombotic therapies. However, there is no systems model of the platelet that predicts responses to different inhibitor combinations. We developed an approach which goes beyond current inhibitor-inhibitor combination screening to efficiently consider other signaling aspects that may give insights into the behaviour of the platelet as a system. We investigated combinations of platelet inhibitors and activators. We evaluated three distinct strands of information, namely: activator-inhibitor combination screens (testing a panel of inhibitors against a panel of activators); inhibitor-inhibitor synergy screens; and activator-activator synergy screens. We demonstrated how these analyses may be efficiently performed, both experimentally and computationally, to identify particular combinations of most interest. Robust tests of activator-activator synergy and of inhibitor-inhibitor synergy required combinations to show significant excesses over the double doses of each component. Modeling identified multiple effects of an inhibitor of the P2Y12 ADP receptor, and complementarity between inhibitor-inhibitor synergy effects and activator-inhibitor combination effects. This approach accelerates the mapping of combination effects of compounds to develop combinations that may be therapeutically beneficial. We integrated the three information sources into a unified model that predicted the benefits of a triple drug combination targeting ADP, thromboxane and thrombin signaling. PMID:25875950

National Chemistry Week 2000: JCE Resources in Food Chemistry

NASA Astrophysics Data System (ADS)

Jacobsen, Erica K.

2000-10-01

November brings another National Chemistry Week, and this year's theme is food chemistry. I was asked to collect and evaluate JCE resources for use with this theme, a project that took me deep into past issues of JCE and yielded many treasures. Here we present the results of searches for food chemistry information and activities. While the selected articles are mainly at the high school and college levels, there are some excellent ones for the elementary school level and some that can be adapted for younger students. The focus of all articles is on the chemistry of food itself. Activities that only use food to demonstrate a principle other than food chemistry are not included. Articles that cover household products such as cleansers and pharmaceuticals are also not included. Each article has been characterized as a demonstration, experiment, calculation, activity, or informational item; several fit more than one classification. Also included are keywords and an evaluation as to which levels the article may serve.

Chemistry in the Comics: Part 2. Classic Chemistry.

ERIC Educational Resources Information Center

Carter, Henry A.

1989-01-01

Describes topics in chemistry as related in the Classics Illustrated publications. Provides a list from "The Pioneers of Science" series with issue date, number, and biograhical topic. Lists references to topics in chemistry. Presents many pages from these comics. (MVL)

The Significance of the Origin of Physical Chemistry for Physical Chemistry Education: The Case of Electrolyte Solution Chemistry

ERIC Educational Resources Information Center

de Berg, Kevin Charles

2014-01-01

Physical Chemistry's birth was fraught with controversy, a controversy about electrolyte solution chemistry which has much to say about how scientific knowledge originates, matures, and responds to challenges. This has direct implications for the way our students are educated in physical chemistry in particular and science in general. The…

Chemistry on Stamps.

ERIC Educational Resources Information Center

Schreck, James O.

1986-01-01

Suggests how postage stamps can be incorporated into chemistry teaching. Categories considered include emergence of chemistry as a science, metric system, atoms (and molecules and ions), stoichiometry, energy relationships in chemical systems, chemical bonding, nuclear chemistry, biochemistry, geochemistry, matter (gases, liquids, and solids),…

Computational Approaches for Designing Protein/Inhibitor Complexes and Membrane Protein Variants

NASA Astrophysics Data System (ADS)

Vijayendran, Krishna Gajan

Drug discovery of small-molecule protein inhibitors is a vast enterprise that involves several scientific disciplines (i.e. genomics, cell biology, x-ray crystallography, chemistry, computer science, statistics), with each discipline focusing on a particular aspect of the process. In this thesis, I use computational and experimental approaches to explore the most fundamental aspect of drug discovery: the molecular interactions of small-molecules inhibitors with proteins. In Part I (Chapters I and II), I describe how computational docking approaches can be used to identify structurally diverse molecules that can inhibit multiple protein targets in the brain. I illustrate this approach using the examples of microtubule-stabilizing agents and inhibitors of cyclooxygenase(COX)-I and 5-lipoxygenase (5-LOX). In Part II (Chapters III and IV), I focus on membrane proteins, which are notoriously difficult to work with due to their low natural abundances, low yields for heterologous over expression, and propensities toward aggregation. I describe a general approach for designing water-soluble variants of membrane proteins, for the purpose of developing cell-free, label-free, detergent-free, solution-phase studies of protein structure and small-molecule binding. I illustrate this approach through the design of a water-soluble variant of the membrane protein Smoothened, wsSMO. This wsSMO stands to serve as a first-step towards developing membrane protein analogs of this important signaling protein and drug target.

Novel Triazole-Quinoline Derivatives as Selective Dual Binding Site Acetylcholinesterase Inhibitors.

PubMed

Mantoani, Susimaire P; Chierrito, Talita P C; Vilela, Adriana F L; Cardoso, Carmen L; Martínez, Ana; Carvalho, Ivone

2016-02-05

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. Currently, the only strategy for palliative treatment of AD is to inhibit acetylcholinesterase (AChE) in order to increase the concentration of acetylcholine in the synaptic cleft. Evidence indicates that AChE also interacts with the β-amyloid (Aβ) protein, acting as a chaperone and increasing the number and neurotoxicity of Aβ fibrils. It is known that AChE has two binding sites: the peripheral site, responsible for the interactions with Aβ, and the catalytic site, related with acetylcholine hydrolysis. In this work, we reported the synthesis and biological evaluation of a library of new tacrine-donepezil hybrids, as a potential dual binding site AChE inhibitor, containing a triazole-quinoline system. The synthesis of hybrids was performed in four steps using the click chemistry strategy. These compounds were evaluated as hAChE and hBChE inhibitors, and some derivatives showed IC50 values in the micro-molar range and were remarkably selective towards hAChE. Kinetic assays and molecular modeling studies confirm that these compounds block both catalytic and peripheral AChE sites. These results are quite interesting since the triazole-quinoline system is a new structural scaffold for AChE inhibitors. Furthermore, the synthetic approach is very efficient for the preparation of target compounds, allowing a further fruitful new chemical library optimization.

Is Chemistry Attractive for Pupils? Czech Pupils' Perception of Chemistry

ERIC Educational Resources Information Center

Kubiatko, Milan

2015-01-01

Chemistry is an important subject due to understanding the composition and structure of the things around us. The main aim of the study was to find out the perception of chemistry by lower secondary school pupils. The partial aims were to find out the influence of gender, year of study and favorite subject on the perception of chemistry. The…

Synthesis, QSAR, and Molecular Dynamics Simulation of Amidino-substituted Benzimidazoles as Dipeptidyl Peptidase III Inhibitors.

PubMed

Rastija, Vesna; Agić, Dejan; Tomiš, Sanja; Nikolič, Sonja; Hranjec, Marijana; Grace, Karminski-Zamola; Abramić, Marija

2015-01-01

A molecular modeling study is performed on series of benzimidazol-based inhibitors of human dipeptidyl peptidase III (DPP III). An eight novel compounds were synthesized in excellent yields using green chemistry approach. This study is aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of human DPP III activity using Quantitative Structure-Activity Relationship (QSAR) analysis, and to understand the mechanism of one of the most potent inhibitor binding into the active site of this enzyme, by molecular dynamics (MD) simulations. The best model obtained includes S3K and RDF045m descriptors which have explained 89.4 % of inhibitory activity. Depicted moiety for strong inhibition activity matches to the structure of most potent compound. MD simulation has revealed importance of imidazolinyl and phenyl groups in the mechanism of binding into the active site of human DPP III.

Towards "Bildung"-Oriented Chemistry Education

ERIC Educational Resources Information Center

Sjöström, Jesper

2013-01-01

This paper concerns "Bildung"-oriented chemistry education, based on a reflective and critical discourse of chemistry. It is contrasted with the dominant type of chemistry education, based on the mainstream discourse of chemistry. "Bildung"-oriented chemistry education includes not only content knowledge in chemistry, but also…

Green Chemistry Metrics with Special Reference to Green Analytical Chemistry.

PubMed

Tobiszewski, Marek; Marć, Mariusz; Gałuszka, Agnieszka; Namieśnik, Jacek

2015-06-12

The concept of green chemistry is widely recognized in chemical laboratories. To properly measure an environmental impact of chemical processes, dedicated assessment tools are required. This paper summarizes the current state of knowledge in the field of development of green chemistry and green analytical chemistry metrics. The diverse methods used for evaluation of the greenness of organic synthesis, such as eco-footprint, E-Factor, EATOS, and Eco-Scale are described. Both the well-established and recently developed green analytical chemistry metrics, including NEMI labeling and analytical Eco-scale, are presented. Additionally, this paper focuses on the possibility of the use of multivariate statistics in evaluation of environmental impact of analytical procedures. All the above metrics are compared and discussed in terms of their advantages and disadvantages. The current needs and future perspectives in green chemistry metrics are also discussed.

Exploration of Fluorine Chemistry at the Multidisciplinary Interface of Chemistry and Biology

PubMed Central

Ojima, Iwao

2013-01-01

Over the last three decades, my engagement in “fluorine chemistry” has evolved substantially, because of the multidisciplinary nature of the research programs. I began my research career as a synthetic chemist in organometallic chemistry and homogeneous catalysis directed toward organic synthesis. Then, I was brought into a very unique world of “fluorine chemistry” in the end of 1970s. I started exploring the interface of fluorine chemistry and transition metal homogeneous catalysis first, which was followed by amino acids, peptides, and peptidomimetics for medicinal chemistry. Since then, I have been exploring the interfaces of fluorine chemistry and multidisciplinary fields of research involving medicinal chemistry, chemical biology, cancer biology and molecular imaging. This perspective intends to cover my fruitful endeavor in the exploration of fluorine chemistry at the multidisciplinary interface of chemistry and biology in a chronological order to show the evolution of my research interest and strategy. PMID:23614876

A New Chemistry Course for Non-Chemistry Majors.

ERIC Educational Resources Information Center

Ariel, Magda; And Others

1982-01-01

A two-semester basic chemistry course for nonchemistry engineering majors is described. First semester provides introductory chemistry for freshmen while second semester is "customer-oriented," based on a departmental choice of three out of six independent modules. For example, aeronautical engineering "customers" would select…

College Chemistry: how a textbook can reveal the values embedded in chemistry.

PubMed

Bensaude-Vincent, Bernadette

2007-12-01

This paper explores the norms, values and ethical attitudes that Linus Pauling wanted to convey to his students in his famous textbook College Chemistry. In this classic textbook, Pauling aimed to introduce beginners into the world of chemistry by presenting chemistry as a systematic science based on a collection of empirical data and a recent theoretical framework. In doing so, he expressed his epistemic and didactic choices clearly. College Chemistry therefore offers an ideal opportunity to examine some of the norms at the core of chemistry's 'moral economy'.

Targeting Mitogen-activated Protein Kinase-activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts to Lead Small Molecule Inhibitors to Clinical Trials

PubMed Central

Fiore, Mario; Forli, Stefano; Manetti, Fabrizio

2015-01-01

The p38/MAPK-activated kinase 2 (MK2) pathway is involved in a series of pathological conditions (inflammation diseases and metastasis) and in the resistance mechanism to antitumor agents. None of the p38 inhibitors entered advanced clinical trials because of their unwanted systemic side effects. For this reason, MK2 was identified as an alternative target to block the pathway, but avoiding the side effects of p38 inhibition. However, ATP-competitive MK2 inhibitors suffered from low solubility, poor cell permeability, and scarce kinase selectivity. Fortunately, non-ATP-competitive inhibitors of MK2 have been already discovered that allowed circumventing the selectivity issue. These compounds showed the additional advantage to be effective at lower concentrations in comparison to the ATP-competitive inhibitors. Therefore, although the significant difficulties encountered during the development of these inhibitors, MK2 is still considered as an attractive target to treat inflammation and related diseases, to prevent tumor metastasis, and to increase tumor sensitivity to chemotherapeutics. PMID:26502061

Tracking chemistry self-efficacy and achievement in a preparatory chemistry course

NASA Astrophysics Data System (ADS)

Garcia, Carmen Alicia

Self-efficacy is a person's own perception about performing a task with a certain level of proficiency (Bandura, 1986). An important affective aspect of learning chemistry is chemistry self-efficacy (CSE). Several researchers have found chemistry self-efficacy to be a fair predictor of achievement in chemistry. This study was done in a college preparatory chemistry class for science majors exploring chemistry self-efficacy and its change as it relates to achievement. A subscale of CAEQ, Chemistry Attitudes and Experiences Questionnaire (developed by Dalgety et al, 2003) as well as student interviews were used to determine student chemistry self-efficacy as it changed during the course. The questionnaire was given to the students five times during the semester: in the first class and the class before each the four tests taken through the semester. Twenty-six students, both men and women, of the four major races/ethnicities were interviewed three times during the semester and events that triggered changes in CSE were followed through the interviews. HLM (hierarchical linear modeling) was used to model the results of the CSE surveys. Among the findings, women who started at significantly lower CSE than men accomplished a significant gain by the end of the semester. Blacks' CSE trends through the semester were found to be significantly different from the rest of the ethnicities.

Green Chemistry Pedagogy

NASA Astrophysics Data System (ADS)

Kolopajlo, Larry

2017-02-01

This chapter attempts to show how the practice of chemistry teaching and learning is enriched by the incorporation of green chemistry (GC) into lectures and labs. To support this viewpoint, evidence from a wide range of published papers serve as a cogent argument that GC attracts and engages both science and nonscience students, enhances chemistry content knowledge, and improves the image of the field, while preparing the world for a sustainable future. Published pedagogy associated with green and sustainable chemistry is critically reviewed and discussed.

Transuranic Computational Chemistry.

PubMed

Kaltsoyannis, Nikolas

2018-02-26

Recent developments in the chemistry of the transuranic elements are surveyed, with particular emphasis on computational contributions. Examples are drawn from molecular coordination and organometallic chemistry, and from the study of extended solid systems. The role of the metal valence orbitals in covalent bonding is a particular focus, especially the consequences of the stabilization of the 5f orbitals as the actinide series is traversed. The fledgling chemistry of transuranic elements in the +II oxidation state is highlighted. Throughout, the symbiotic interplay of experimental and computational studies is emphasized; the extraordinary challenges of experimental transuranic chemistry afford computational chemistry a particularly valuable role at the frontier of the periodic table. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemistry Notes

ERIC Educational Resources Information Center

School Science Review, 1976

1976-01-01

Described are eight chemistry experiments and demonstrations applicable to introductory chemistry courses. Activities include: measure of lattice enthalpy, Le Chatelier's principle, decarboxylation of soap, use of pocket calculators in pH measurement, and making nylon. (SL)

Inhibitors of HIV-protease from computational design. A history of theory and synthesis still to be fully appreciated.

PubMed

Berti, Federico; Frecer, Vladimir; Miertus, Stanislav

2014-01-01

Despite the fact that HIV-Protease is an over 20 years old target, computational approaches to rational design of its inhibitors still have a great potential to stimulate the synthesis of new compounds and the discovery of new, potent derivatives, ever capable to overcome the problem of drug resistance. This review deals with successful examples of inhibitors identified by computational approaches, rather than by knowledge-based design. Such methodologies include the development of energy and scoring functions, docking protocols, statistical models, virtual combinatorial chemistry. Computations addressing drug resistance, and the development of related models as the substrate envelope hypothesis are also reviewed. In some cases, the identified structures required the development of synthetic approaches in order to obtain the desired target molecules; several examples are reported.

Chemistry and Art.

ERIC Educational Resources Information Center

Berry, Martyn

1999-01-01

Describes a Chemistry and Art project developed for secondary students and teachers sponsored by the National Gallery and The Royal Society of Chemistry in the United Kingdom. Discusses aspects of the techniques used in creating five paintings as well as the chemistry involved in their making, deterioration, conservation, and restoration.…

Teaching School Chemistry.

ERIC Educational Resources Information Center

Waddington, D. J., Ed.

This eight-chapter book is intended for use by chemistry teachers, curriculum developers, teacher educators, and other key personnel working in the field of chemical education. The chapters are: (1) "The Changing Face of Chemistry" (J. A. Campbell); (2) "Curriculum Innovation in School Chemistry" (R. B. Ingel and A. M.…

ENVIRONMENTAL CHEMISTRY

EPA Science Inventory

Environmental chemistry is applied to estimating the exposure of ecosystems and humans to various chemical environmental stressors. Among the stressors of concern are mercury, pesticides, and arsenic. Advanced analytical chemistry techniques are used to measure these stressors ...

Exploring the Sources of Turkish Pre-Service Chemistry Teachers' Chemistry Self-Efficacy Beliefs

ERIC Educational Resources Information Center

Uzuntiryaki, Esen

2008-01-01

This study aimed to examine the underlying sources in developing chemistry self-efficacy beliefs of Turkish pre-service chemistry teachers. For this purpose, the College Chemistry Selfefficacy Scale (CCSS) was administered to 20 pre-service chemistry teachers. Then, phenomenological approach was employed and semi-structured interviews were…

History of Chemistry.

ERIC Educational Resources Information Center

Servos, John W.

1985-01-01

Discusses the development of chemistry in the United States by considering: (1) chemistry as an evolving body of ideas/techniques, and as a set of conceptual resources affecting and affected by the development of other sciences; and (2) chemistry related to the history of American social and economic institutions and practices. (JN)

Chemistry Notes.

ERIC Educational Resources Information Center

School Science Review, 1983

1983-01-01

Presents background information, laboratory procedures, classroom materials/activities, and chemistry experiments. Topics include sublimation, electronegativity, electrolysis, experimental aspects of strontianite, halide test, evaluation of present and future computer programs in chemistry, formula building, care of glass/saturated calomel…

Chemistry Notes

ERIC Educational Resources Information Center

School Science Review, 1972

1972-01-01

Thirteen ideas are presented that may be of use to chemistry teachers. Topics covered include vitamin C, industrial chemistry, electrical conductivity, electrolysis, alkali metals, vibration modes infra-red, dynamic equilibrium, and some new demonstrations in gaseous combinations. (PS)

Chemistry Dashboard

EPA Pesticide Factsheets

The Chemistry Dashboard is part of a suite of dashboards developed by EPA to help evaluate the safety of chemicals. The Chemistry Dashboard provides access to a variety of information on over 700,000 chemicals currently in use.

Circumstellar chemistry

NASA Technical Reports Server (NTRS)

Glassgold, Alfred E.; Huggins, Patrick J.

1987-01-01

The study of the outer envelopes of cool evolved stars has become an active area of research. The physical properties of CS envelopes are presented. Observations of many wavelengths bands are relevant. A summary of observations and a discussion of theoretical considerations concerning the chemistry are summarized. Recent theoretical considerations show that the thermal equilibrium model is of limited use for understanding the chemistry of the outer CS envelopes. The theoretical modeling of the chemistry of CS envelopes provides a quantitive test of chemical concepts which have a broader interest than the envelopes themselves.

Exploiting nature's rich source of proteasome inhibitors as starting points in drug development.

PubMed

Gräwert, Melissa Ann; Groll, Michael

2012-02-01

Cancer is the No. 2 cause of death in the Western world and one of the most expensive diseases to treat. Thus, it is not surprising, that every major pharmaceutical and biotechnology company has a blockbuster oncology product. In 2003, Millennium Pharmaceuticals entered the race with Velcade®, a first-in-class proteasome inhibitor that has been approved by the FDA for treatment of multiple myeloma and its sales have passed the billion dollar mark. Velcade®'s extremely toxic boronic acid pharmacophore, however, contributes to a number of severe side effects. Nevertheless, the launching of this product has validated the proteasome as a target in fighting cancer and further proteasome inhibitors have entered the market as anti-cancer drugs. Additionally, proteasome inhibitors have found application as crop protection agents, anti-parasitics, immunosuppressives, as well as in new therapies for muscular dystrophies and inflammation. Many of these compounds are based on microbial metabolites. In this review, we emphasize the important role of the structural elucidation of the various unique binding mechanisms of these compounds that have been optimized throughout evolution to target the proteasome. Based on this knowledge, medicinal chemists have further optimized these natural products, resulting in potential drugs with reduced off-target activities. This journal is © The Royal Society of Chemistry 2012

Chemistry Notes.

ERIC Educational Resources Information Center

School Science Review, 1981

1981-01-01

Outlines laboratory procedures, demonstrations, teaching suggestions, and content information related to chemistry. Topics include polarizing power; calorimetry and momentum; microcomputers in school chemistry; a constant-volume dispenser for liquids, floating magnets, and crystal lattices; preparation of chromium; and solvent polarity and…

Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and Kill Malignant Breast Tumor Cells

DTIC Science & Technology

2017-05-01

DATE : May 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012...currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE May 2017 2. REPORT TYPE Annual 3. DATES COVERED...chemistry efforts to synthesize a non-radioactive tethered Hsp90 inhibitor, methods developed for stannylation of the molecule such that it can be

Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2).

PubMed

Futatsugi, Kentaro; Kung, Daniel W; Orr, Suvi T M; Cabral, Shawn; Hepworth, David; Aspnes, Gary; Bader, Scott; Bian, Jianwei; Boehm, Markus; Carpino, Philip A; Coffey, Steven B; Dowling, Matthew S; Herr, Michael; Jiao, Wenhua; Lavergne, Sophie Y; Li, Qifang; Clark, Ronald W; Erion, Derek M; Kou, Kou; Lee, Kyuha; Pabst, Brandon A; Perez, Sylvie M; Purkal, Julie; Jorgensen, Csilla C; Goosen, Theunis C; Gosset, James R; Niosi, Mark; Pettersen, John C; Pfefferkorn, Jeffrey A; Ahn, Kay; Goodwin, Bryan

2015-09-24

The medicinal chemistry and preclinical biology of imidazopyridine-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) is described. A screening hit 1 with low lipophilic efficiency (LipE) was optimized through two key structural modifications: (1) identification of the pyrrolidine amide group for a significant LipE improvement, and (2) insertion of a sp(3)-hybridized carbon center in the core of the molecule for simultaneous improvement of N-glucuronidation metabolic liability and off-target pharmacology. The preclinical candidate 9 (PF-06424439) demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models.

Identification of quinazoline based inhibitors of IRAK4 for the treatment of inflammation

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

Smith, Graham F.; Altman, Michael D.; Andresen, Brian

Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R and TLR based signaling. Therefore selective inhibition of the kinase activity of this protein represents an attractive target for the treatment of inflammatory diseases. Medicinal chemistry optimization of high throughput screening (HTS) hits with the help of structure based drug design led to the identification of orally-bioavailable quinazoline based IRAK4 inhibitors with excellent pharmacokinetic profile and kinase selectivity. These highly selective IRAK4 compounds show activity in vivo via oral dosing in a TLR7 driven model of inflammation.

Art in Chemistry: Chemistry in Art. Second Edition

ERIC Educational Resources Information Center

Greenberg, Barbara R.; Patterson, Dianne

2008-01-01

This textbook integrates chemistry and art with hands-on activities and fascinating demonstrations that enable students to see and understand how the science of chemistry is involved in the creation of art. It investigates such topics as color integrated with electromagnetic radiation, atoms, and ions; paints integrated with classes of matter,…

Chemistry, Poetry, and Artistic Illustration: An Interdisciplinary Approach to Teaching and Promoting Chemistry

NASA Astrophysics Data System (ADS)

Furlan, Ping Y.; Kitson, Herbert; Andes, Cynthia

2007-10-01

This article describes a successful interdisciplinary collaboration among chemistry, humanities and English faculty members, who utilized poetry and artistic illustration to help students learn, appreciate, and enjoy chemistry. Students taking general chemistry classes were introduced to poetry writing and museum-type poster preparation during one class period. They were then encouraged to use their imagination and creativity to brainstorm and write chemistry poems or humors on the concepts and principles covered in the chemistry classes and artistically illustrate their original work on posters. The project, 2 3 months in length, was perceived by students as effective at helping them learn chemistry and express their understanding in a fun, personal, and creative way. The instructors found students listened to the directives because many posters were witty, clever, and eye-catching. They showed fresh use of language and revealed a good understanding of chemistry. The top posters were created by a mix of A-, B-, and C-level students. The fine art work, coupled with poetry, helped chemistry come alive on campus, providing an aesthetic presentation of materials that engaged the general viewer.

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

PubMed Central

Lee, Eunjo; Song, Min-ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung

2016-01-01

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats. PMID:27610034

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

PubMed

Lee, Eunjo; Song, Min-Ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

2016-09-01

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

An α-Helix-Mimicking 12,13-Helix: Designed α/β/γ-Foldamers as Selective Inhibitors of Protein-Protein Interactions.

PubMed

Grison, Claire M; Miles, Jennifer A; Robin, Sylvie; Wilson, Andrew J; Aitken, David J

2016-09-05

A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein-protein interactions (PPIs). In this work, trans-2-aminocyclobutanecarboxylic acid (tACBC) was used as the key β-amino acid component in the design of α/β/γ-peptides to structurally mimic a native α-helix. Suitably functionalized α/β/γ-peptides assume an α-helix-mimicking 12,13-helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild-type α-peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/hDM2 interaction. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Biosynthetic inorganic chemistry.

PubMed

Lu, Yi

2006-08-25

Inorganic chemistry and biology can benefit greatly from each other. Although synthetic and physical inorganic chemistry have been greatly successful in clarifying the role of metal ions in biological systems, the time may now be right to utilize biological systems to advance coordination chemistry. One such example is the use of small, stable, easy-to-make, and well-characterized proteins as ligands to synthesize novel inorganic compounds. This biosynthetic inorganic chemistry is possible thanks to a number of developments in biology. This review summarizes the progress in the synthesis of close models of complex metalloproteins, followed by a description of recent advances in using the approach for making novel compounds that are unprecedented in either inorganic chemistry or biology. The focus is mainly on synthetic "tricks" learned from biology, as well as novel structures and insights obtained. The advantages and disadvantages of this biosynthetic approach are discussed.

An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors.

PubMed

Pagano, Nicholas; Teriete, Peter; Mattmann, Margrith E; Yang, Li; Snyder, Beth A; Cai, Zhaohui; Heil, Marintha L; Cosford, Nicholas D P

2017-12-01

Continuous flow (microfluidic) chemistry was employed to prepare a small focused library of dihydropyrimidinone (DHPM) derivatives. Compounds in this class have been reported to exhibit activity against the human immunodeficiency virus (HIV), but their molecular target had not been identified. We tested the initial set of DHPMs in phenotypic assays providing a hit (1i) that inhibited the replication of the human immunodeficiency virus HIV in cells. Flow chemistry-driven optimization of 1i led to the identification of HIV replication inhibitors such as 1l with cellular potency comparable with the clinical drug nevirapine (NVP). Mechanism of action (MOA) studies using cellular and biochemical assays coupled with 3D fingerprinting and in silico modeling demonstrated that these drug-like probe compounds exert their effects by inhibiting the viral reverse transcriptase polymerase (RT). This led to the design and synthesis of the novel DHPM 1at that inhibits the replication of drug resistant strains of HIV. Our work demonstrates that combining flow chemistry-driven analogue refinement with phenotypic assays, in silico modeling and MOA studies is a highly effective strategy for hit-to-lead optimization applicable to the discovery of future therapeutic agents. Copyright © 2017. Published by Elsevier Ltd.

Infusing the Chemistry Curriculum with Green Chemistry Using Real-World Examples, Web Modules, and Atom Economy in Organic Chemistry Courses

ERIC Educational Resources Information Center

Cann, Michael C.; Dickneider, Trudy A.

2004-01-01

Green chemistry is the awareness of the damaging environmental effects due to chemical research and inventions. There is emphasis on a need to include green chemistry in synthesis with atom economy in organic chemistry curriculum to ensure an environmentally conscious future generation of chemists, policy makers, health professionals and business…

Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit.

PubMed

Backes, Bradley J; Longenecker, Kenton; Hamilton, Gregory L; Stewart, Kent; Lai, Chunqiu; Kopecka, Hana; von Geldern, Thomas W; Madar, David J; Pei, Zhonghua; Lubben, Thomas H; Zinker, Bradley A; Tian, Zhenping; Ballaron, Stephen J; Stashko, Michael A; Mika, Amanda K; Beno, David W A; Kempf-Grote, Anita J; Black-Schaefer, Candace; Sham, Hing L; Trevillyan, James M

2007-04-01

A novel series of pyrrolidine-constrained phenethylamines were developed as dipeptidyl peptidase IV (DPP4) inhibitors for the treatment of type 2 diabetes. The cyclohexene ring of lead-like screening hit 5 was replaced with a pyrrolidine to enable parallel chemistry, and protein co-crystal structural data guided the optimization of N-substituents. Employing this strategy, a >400x improvement in potency over the initial hit was realized in rapid fashion. Optimized compounds are potent and selective inhibitors with excellent pharmacokinetic profiles. Compound 30 was efficacious in vivo, lowering blood glucose in ZDF rats that were allowed to feed freely on a mixed meal.

International year of Chemistry 2011. A guide to the history of clinical chemistry.

PubMed

Kricka, Larry J; Savory, John

2011-08-01

This review was written as part of the celebration of the International Year of Chemistry 2011. In this review we provide a chronicle of the history of clinical chemistry, with a focus on North America. We outline major methodological advances and trace the development of professional societies and journals dedicated to clinical chemistry. This review also serves as a guide to reference materials for those interested in the history of clinical chemistry. The various resources available, in sound recordings, videos, moving images, image and document archives, museums, and websites dedicated to diagnostic company timelines, are surveyed. These resources provide a map of how the medical subspecialty of clinical chemistry arrived at its present state. This information will undoubtedly help visionaries to determine in which direction clinical chemistry will move in the future.

Why Teach Environmental Chemistry?

ERIC Educational Resources Information Center

Gardner, Marjorie H.

1974-01-01

Discusses the importance of teaching environmental chemistry in secondary school science classes, and outlines five examples of environmental chemistry problems that focus on major concepts of chemistry and have critical implications for human survival and well-being. (JR)

Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library

NASA Astrophysics Data System (ADS)

Litovchick, Alexander; Dumelin, Christoph E.; Habeshian, Sevan; Gikunju, Diana; Guié, Marie-Aude; Centrella, Paolo; Zhang, Ying; Sigel, Eric A.; Cuozzo, John W.; Keefe, Anthony D.; Clark, Matthew A.

2015-06-01

A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library, and successfully identified inhibitors of the enzyme soluble epoxide hydrolase.

Introducing Chemistry Students to the "Real World" of Chemistry

ERIC Educational Resources Information Center

Brown, Michael E.; Cosser, Ronald C.; Davies-Coleman, Michael T.; Kaye, Perry T.; Klein, Rosalyn; Lamprecht, Emmanuel; Lobb, Kevin; Nyokong, Tebello; Sewry, Joyce D.; Tshentu, Zenixole R.; van der Zeyde, Tino; Watkins, Gareth M.

2010-01-01

A majority of chemistry graduates seek employment in a rapidly changing chemical industry. Our attempts to provide the graduates with skills in entrepreneurship and the ability to understand and communicate with their chemical engineering colleagues, in addition to their fundamental knowledge of chemistry, are described. This is done at…

Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors.

PubMed

Halland, Nis; Schmidt, Friedemann; Weiss, Tilo; Saas, Joachim; Li, Ziyu; Czech, Jörg; Dreyer, Matthias; Hofmeister, Armin; Mertsch, Katharina; Dietz, Uwe; Strübing, Carsten; Nazare, Marc

2015-01-08

From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due to their rigid structure.

Logic, History, and the Chemistry Textbook: I. Does Chemistry Have a Logical Structure?

ERIC Educational Resources Information Center

Jensen, William B.

1998-01-01

Presents the first of three invited keynote lectures from the 1995 conference of the New England Association of Chemistry Teachers. Discusses the relevance of the history of chemistry to the teaching of chemistry. Contains 27 references. (DDR)

Spherical harmonics coefficients for ligand-based virtual screening of cyclooxygenase inhibitors.

PubMed

Wang, Quan; Birod, Kerstin; Angioni, Carlo; Grösch, Sabine; Geppert, Tim; Schneider, Petra; Rupp, Matthias; Schneider, Gisbert

2011-01-01

Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort.

Design, synthesis and biological evaluation of LBM-A5 derivatives as potent P-glycoprotein-mediated multidrug resistance inhibitors.

PubMed

Wu, Yuxiang; Pan, Miaobo; Dai, Yuxuan; Liu, Baomin; Cui, Jian; Shi, Wei; Qiu, Qianqian; Huang, Wenlong; Qian, Hai

2016-05-15

A novel series of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) inhibitors with triazol-N-phenethyl-tetrahydroisoquinoline or triazol-N-ethyl-tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 4 showed a comparable activity with the known potent P-gp inhibitor WK-X-34 with lower cytotoxicity toward K562 cells (IC50>100μM). Compared with VRP, compound 4 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 4 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 4 could remarkably increase the intracellular accumulation of Adriamycin (ADM) in K562/A02 cells as well as inhibit rhodamine-123 (Rh123) efflux from the cells. These results suggested that compound 4 may represent a promising candidate for developing P-gp-mediated MDR inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Newer treatments of psoriasis regarding IL-23 inhibitors, phosphodiesterase 4 inhibitors, and Janus kinase inhibitors.

PubMed

Wcisło-Dziadecka, Dominika; Zbiciak-Nylec, Martyna; Brzezińska-Wcisło, Ligia; Bebenek, Katarzyna; Kaźmierczak, Agata

2017-11-01

The rapid progress of genetic engineering furthermore opens up new prospects in the therapy of this difficult-to-treat disease. IL-23 inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and Janus kinase (JAK) inhibitors are currently encouraging further research. Two drugs which are IL-23 inhibitors are now in phase III of clinical trials. The aim of the action of both drugs is selective IL-23 inhibition by targeting the p19 subunit. Guselkumab is a fully human monoclonal antibody. Tildrakizumab is a humanized monoclonal antibody, which also belongs to IgG class and is targeted to subunit p19 of interleukin 23 (IL-23). Phosphodiesterase inhibitors exert an anti-inflammatory action and their most common group is the PDE4 family. PDE4 inhibits cAMP, which reduces the inflammatory response of the pathway of Th helper lymphocytes, Th17, and type 1 interferon which modulates the production of anti-inflammatory cytokines such as IL-10 interleukins. The Janus kinase (JAK) signaling pathway plays an important role in the immunopathogenesis of psoriasis. Tofacitinib suppresses the expression of IL-23, IL-17A, IL-17F, and IL-22 receptors during the stimulation of lymphocytes. Ruxolitinib is a selective inhibitor of JAK1 and JAK2 kinases and the JAK-STAT signaling pathway. This article is a review of the aforementioned drugs as described in the latest available literature. © 2017 Wiley Periodicals, Inc.

A Quantum Chemistry Concept Inventory for Physical Chemistry Classes

ERIC Educational Resources Information Center

Dick-Perez, Marilu; Luxford, Cynthia J.; Windus, Theresa L.; Holme, Thomas

2016-01-01

A 14-item, multiple-choice diagnostic assessment tool, the quantum chemistry concept inventory or QCCI, is presented. Items were developed based on published student misconceptions and content coverage and then piloted and used in advanced physical chemistry undergraduate courses. In addition to the instrument itself, data from both a pretest,…

Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry.

PubMed

Wang, F; Jiao, P; Qi, M; Frezza, M; Dou, Q P; Yan, B

2010-01-01

Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn "cancer-promoting" copper into anti-cancer agents.

Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax.

PubMed

Leverson, Joel D; Sampath, Deepak; Souers, Andrew J; Rosenberg, Saul H; Fairbrother, Wayne J; Amiot, Martine; Konopleva, Marina; Letai, Anthony

2017-12-01

Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax. We review a number of preclinical studies that have deepened our understanding of BCL2 biology and facilitated the clinical development of venetoclax. Significance: Basic research into the pathways governing programmed cell death have paved the way for the discovery of apoptosis-inducing agents such as venetoclax, a BCL2-selective inhibitor that was recently approved by the FDA and the European Medicines Agency. Preclinical studies aimed at identifying BCL2-dependent tumor types have translated well into the clinic thus far and will likely continue to inform the clinical development of venetoclax and other BCL2 family inhibitors. Cancer Discov; 7(12); 1376-93. ©2017 AACR. ©2017 American Association for Cancer Research.

Green Chemistry and Education.

ERIC Educational Resources Information Center

Hjeresen, Dennis L.; Schutt, David L.; Boese, Janet M.

2000-01-01

Many students today are profoundly interested in the sustainability of their world. Introduces Green Chemistry and its principles with teaching materials. Green Chemistry is the use of chemistry for pollution prevention and the design of chemical products and processes that are environmentally benign. (ASK)

CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil

PubMed Central

Almqvist, Helena; Axelsson, Hanna; Jafari, Rozbeh; Dan, Chen; Mateus, André; Haraldsson, Martin; Larsson, Andreas; Molina, Daniel Martinez; Artursson, Per; Lundbäck, Thomas; Nordlund, Pär

2016-01-01

Target engagement is a critical factor for therapeutic efficacy. Assessment of compound binding to native target proteins in live cells is therefore highly desirable in all stages of drug discovery. We report here the first compound library screen based on biophysical measurements of intracellular target binding, exemplified by human thymidylate synthase (TS). The screen selected accurately for all the tested known drugs acting on TS. We also identified TS inhibitors with novel chemistry and marketed drugs that were not previously known to target TS, including the DNA methyltransferase inhibitor decitabine. By following the cellular uptake and enzymatic conversion of known drugs we correlated the appearance of active metabolites over time with intracellular target engagement. These data distinguished a much slower activation of 5-fluorouracil when compared with nucleoside-based drugs. The approach establishes efficient means to associate drug uptake and activation with target binding during drug discovery. PMID:27010513

An α‐Helix‐Mimicking 12,13‐Helix: Designed α/β/γ‐Foldamers as Selective Inhibitors of Protein–Protein Interactions

PubMed Central

Grison, Claire M.; Miles, Jennifer A.; Robin, Sylvie

2016-01-01

Abstract A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein–protein interactions (PPIs). In this work, trans‐2‐aminocyclobutanecarboxylic acid (tACBC) was used as the key β‐amino acid component in the design of α/β/γ‐peptides to structurally mimic a native α‐helix. Suitably functionalized α/β/γ‐peptides assume an α‐helix‐mimicking 12,13‐helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild‐type α‐peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/hDM2 interaction. PMID:27467859

SEDIMENT AND POREWATER CHEMISTRY

EPA Science Inventory

This chapter reviews sediment chemistry, its effect on porewater chemistry and how this chemistry changes from place to place. We focus on the overall chemical environment of the sediments, for which a great deal is known from studies on sediment diagenesis and from which some pr...

A new class of HIV-1 protease inhibitor: the crystallographic structure, inhibition and chemical synthesis of an aminimide peptide isostere.

PubMed

Rutenber, E E; McPhee, F; Kaplan, A P; Gallion, S L; Hogan, J C; Craik, C S; Stroud, R M

1996-09-01

The essential role of HIV-1 protease (HIV-1 PR) in the viral life cycle makes it an attractive target for the development of substrate-based inhibitors that may find efficacy as anti-AIDS drugs. However, resistance has arisen to potent peptidomimetic drugs necessitating the further development of novel chemical backbones for diversity based chemistry focused on probing the active site for inhibitor interactions and binding modes that evade protease resistance. AQ148 is a potent inhibitor of HIV-1 PR and represents a new class of transition state analogues incorporating an aminimide peptide isostere. A 3-D crystallographic structure of AQ148, a tetrapeptide isostere, has been determined in complex with its target HIV-1 PR to a resolution of 2.5 A and used to evaluate the specific structural determinants of AQ148 potency and to correlate structure-activity relationships within the class of related compounds. AQ148 is a competitive inhibitor of HIV-1 PR with a Ki value of 137 nM. Twenty-nine derivatives have been synthesized and chemical modifications have been made at the P1, P2, P1', and P2' sites. The atomic resolution structure of AQ148 bound to HIV-1 PR reveals both an inhibitor binding mode that closely resembles that of other peptidomimetic inhibitors and specific protein/inhibitor interactions that correlate with structure-activity relationships. The structure provides the basis for the design, synthesis and evaluation of the next generation of hydroxyethyl aminimide inhibitors. The aminimide peptide isostere is a scaffold with favorable biological properties well suited to both the combinatorial methods of peptidomimesis and the rational design of potent and specific substrate-based analogues.

CHEMISTRY, A GUIDE FOR TEACHERS.

ERIC Educational Resources Information Center

WHEELER, HUBERT

THE VOLUME INCLUDES AN INTRODUCTION, THE COURSE CONTENT IN CHEMISTRY, AND FIVE APPENDIXES OF USEFUL INFORMATION. THE CHEMISTRY COURSE CONTENT IS FURTHER SUBDIVIDED INTO FIVE SECTIONS--(1) THE OVERVIEW, (2) CHEMICAL REACTIONS, (3) CHEMICAL BONDING AND MOLECULAR ARCHITECTURE, (4) DESCRIPTIVE CHEMISTRY, AND (5) ADVANCED CHEMISTRY. EACH OF THE FIVE…

Chemistry, Poetry, and Artistic Illustration: An Interdisciplinary Approach to Teaching and Promoting Chemistry

ERIC Educational Resources Information Center

Furlan, Ping Y.; Kitson, Herbert; Andes, Cynthia

2007-01-01

This article describes a successful interdisciplinary collaboration among chemistry, humanities and English faculty members, who utilized poetry and artistic illustration to help students learn, appreciate, and enjoy chemistry. Students taking general chemistry classes were introduced to poetry writing and museum-type poster preparation during one…

Discovery of Dengue Virus NS4B Inhibitors

PubMed Central

Wang, Qing-Yin; Dong, Hongping; Zou, Bin; Karuna, Ratna; Wan, Kah Fei; Zou, Jing; Susila, Agatha; Yip, Andy; Shan, Chao; Yeo, Kim Long; Xu, Haoying; Ding, Mei; Chan, Wai Ling; Gu, Feng; Seah, Peck Gee; Liu, Wei; Lakshminarayana, Suresh B.; Kang, CongBao; Lescar, Julien; Blasco, Francesca; Smith, Paul W.

2015-01-01

ABSTRACT The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50, >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo. Our

Creation of a Novel Class of Potent and Selective MutT Homologue 1 (MTH1) Inhibitors Using Fragment-Based Screening and Structure-Based Drug Design.

PubMed

Rahm, Fredrik; Viklund, Jenny; Trésaugues, Lionel; Ellermann, Manuel; Giese, Anja; Ericsson, Ulrika; Forsblom, Rickard; Ginman, Tobias; Günther, Judith; Hallberg, Kenth; Lindström, Johan; Persson, Lars Boukharta; Silvander, Camilla; Talagas, Antoine; Díaz-Sáez, Laura; Fedorov, Oleg; Huber, Kilian V M; Panagakou, Ioanna; Siejka, Paulina; Gorjánácz, Mátyás; Bauser, Marcus; Andersson, Martin

2018-03-22

Recent literature has both suggested and questioned MTH1 as a novel cancer target. BAY-707 was just published as a target validation small molecule probe for assessing the effects of pharmacological inhibition of MTH1 on tumor cell survival, both in vitro and in vivo. (1) In this report, we describe the medicinal chemistry program creating BAY-707, where fragment-based methods were used to develop a series of highly potent and selective MTH1 inhibitors. Using structure-based drug design and rational medicinal chemistry approaches, the potency was increased over 10,000 times from the fragment starting point while maintaining high ligand efficiency and drug-like properties.

Perspectives and new aspects of metalloproteinases' inhibitors in therapy of CNS disorders: from chemistry to medicine.

PubMed

Boguszewska-Czubara, Anna; Budzynska, Barbara; Skalicka-Wozniak, Krystyna; Kurzepa, Jacek

2018-05-13

Matrix metalloproteinases (MMPs) play a key role in remodelling of the extracellular matrix (ECM) and, at the same time, influence cell differentiation, migration, proliferation and survival. Their importance in variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders has been known for many years but special attention should be paid on the role of MMPs in the central nervous system (CNS) disorders. Till now, there are not many well documented physiological MMP target proteins in the brain and only some pathological ones. Numerous neurodegenerative diseases is a consequence or result in disturbed remodeling of brain ECM, therefore proper action of MMPs as well as control of their activity may play crucial roles in the development and the progress of these diseases. In present review we discuss the role of metalloproteinase inhibitors, from the well-known natural endogenous tissue inhibitors of metalloproteinases (TIMPs) through exogenous synthetic ones like (4-phenoxyphenylsulfonyl)methylthiirane (SB-3CT), tetracyclines, batimastat (BB-94) and FN-439. As the MMP-TIMP system has been well described in physiological development as well as in pathological conditions mainly in neoplasctic diseases, the knowledge about the enzymatic system in mammalian brain tissue remain still poorly understood in this context. Therefore, we focus on MMPs inhibition in the context of physiological function of adult brain as well as pathological conditions including neurodegenerative diseases, brain injuries and others. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library

PubMed Central

Litovchick, Alexander; Dumelin, Christoph E.; Habeshian, Sevan; Gikunju, Diana; Guié, Marie-Aude; Centrella, Paolo; Zhang, Ying; Sigel, Eric A.; Cuozzo, John W.; Keefe, Anthony D.; Clark, Matthew A.

2015-01-01

A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library, and successfully identified inhibitors of the enzyme soluble epoxide hydrolase. PMID:26061191

Relational Analysis of College Chemistry-Major Students' Conceptions of and Approaches to Learning Chemistry

ERIC Educational Resources Information Center

Li, Wei-Ting; Liang, Jyh-Chong; Tsai, Chin-Chung

2013-01-01

The purpose of this research was to examine the relationships between conceptions of learning and approaches to learning in chemistry. Two questionnaires, conceptions of learning chemistry (COLC) and approaches to learning chemistry (ALC), were developed to identify 369 college chemistry-major students' (220 males and 149 females) conceptions of…

Plasma chemistry as a tool for green chemistry, environmental analysis and waste management.

PubMed

Mollah, M Y; Schennach, R; Patscheider, J; Promreuk, S; Cocke, D L

2000-12-15

The applications of plasma chemistry to environmental problems and to green chemistry are emerging fields that offer unique opportunities for advancement. There has been substantial progress in the application of plasmas to analytical diagnostics and to waste reduction and waste management. This review discusses the chemistry and physics necessary to a basic understanding of plasmas, something that has been missing from recent technical reviews. The current status of plasmas in environmental chemistry is summarized and emerging areas of application for plasmas are delineated. Plasmas are defined and discussed in terms of their properties that make them useful for environmental chemistry. Information is drawn from diverse fields to illustrate the potential applications of plasmas in analysis, materials modifications and hazardous waste treatments.

Development of a Rapid Fluorescence-Based High-Throughput Screening Assay to Identify Novel Kynurenine 3-Monooxygenase Inhibitor Scaffolds.

PubMed

Jacobs, K R; Guillemin, G J; Lovejoy, D B

2018-02-01

Kynurenine 3-monooxygenase (KMO) is a well-validated therapeutic target for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD) and Huntington's disease (HD). This work reports a facile fluorescence-based KMO assay optimized for high-throughput screening (HTS) that achieves a throughput approximately 20-fold higher than the fastest KMO assay currently reported. The screen was run with excellent performance (average Z' value of 0.80) from 110,000 compounds across 341 plates and exceeded all statistical parameters used to describe a robust HTS assay. A subset of molecules was selected for validation by ultra-high-performance liquid chromatography, resulting in the confirmation of a novel hit with an IC 50 comparable to that of the well-described KMO inhibitor Ro-61-8048. A medicinal chemistry program is currently underway to further develop our novel KMO inhibitor scaffolds.

Design, Synthesis, and Biological Evaluation of an Allosteric Inhibitor of HSET that Targets Cancer Cells with Supernumerary Centrosomes

PubMed Central

Watts, Ciorsdaidh A.; Richards, Frances M.; Bender, Andreas; Bond, Peter J.; Korb, Oliver; Kern, Oliver; Riddick, Michelle; Owen, Paul; Myers, Rebecca M.; Raff, Jordan; Gergely, Fanni; Jodrell, Duncan I.; Ley, Steven V.

2013-01-01

Summary Centrosomes associate with spindle poles; thus, the presence of two centrosomes promotes bipolar spindle assembly in normal cells. Cancer cells often contain supernumerary centrosomes, and to avoid multipolar mitosis and cell death, these are clustered into two poles by the microtubule motor protein HSET. We report the discovery of an allosteric inhibitor of HSET, CW069, which we designed using a methodology on an interface of chemistry and biology. Using this approach, we explored millions of compounds in silico and utilized convergent syntheses. Only compound CW069 showed marked activity against HSET in vitro. The inhibitor induced multipolar mitoses only in cells containing supernumerary centrosomes. CW069 therefore constitutes a valuable tool for probing HSET function and, by reducing the growth of cells containing supernumerary centrosomes, paves the way for new cancer therapeutics. PMID:24210220

Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors

PubMed Central

2014-01-01

From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due to their rigid structure. PMID:25589934

Rasagiline (TVP-1012): a new selective monoamine oxidase inhibitor for Parkinson's disease.

PubMed

Guay, David R P

2006-12-01

This article reviews the chemistry, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, drug-interaction potential, indications, dosing, and potential role of rasagiline mesylate, a new selective monoamine oxidase (MAO) type B (MAO-B) inhibitor, in the treatment of Parkinson's disease. A MEDLINE/PUBMED search (1986 through September 2006) was conducted to identify studies involving rasagiline written in English. Additional references were obtained from the bibliographies of these studies. All studies evaluating any aspect of rasagiline, including in vitro, in vivo (animal), and human studies, were reviewed. Rasagiline mesylate was developed with the goal of producing a selective MAO-B inhibitor that is not metabolized to (presumed) toxic metabolites (eg, amphetamine and methamphetamine, which are byproducts of the metabolism of selegiline, another selective MAO-B inhibitor). In vitro and in vivo data have confirmed the drug's selectivity for MAO-B. Rasagiline is almost completely eliminated by oxidative metabolism (catalyzed by cytochrome P-450 [CYP] isozyme 1A2) followed by renal excretion of conjugated parent compound and metabolites. Drug clearance is sufficiently slow to allow once-daily dosing. Several studies have documented its efficacy as monotherapy for early-stage disease and as adjunctive therapy in L-dopa recipients with motor fluctuations. As monotherapy, rasagiline is well tolerated with an adverse-effect profile similar to that of placebo. As adjunctive therapy, it exhibits the expected adverse effects of dopamine excess, which can be ameliorated by reducing the L-dopa dosage. CYP1A2 inhibitors slow the elimination of rasagiline and mandate dosage reduction. Hepatic impairment has an analogous effect. The recommended dosage regimens for monotherapy and adjunctive therapy are 1 and 0.5 mg PO QD, respectively. Despite the well-documented selectivity of rasagiline, the manufacturer recommends virtually all of the dietary (vis

Metalloporphyrins as Oxidation Catalysts: Moving toward "Greener" Chemistry in the Inorganic Chemistry Laboratory

ERIC Educational Resources Information Center

Clark, Rose A.; Stock, Anne E.; Zovinka, Edward P.

2012-01-01

Training future chemists to be aware of the environmental impact of their work is of fundamental importance to global society. To convince chemists to embrace sustainability, the integration of green chemistry across the entire chemistry curriculum is a necessary step. This experiment expands the reach of green chemistry techniques into the…

Cocrystal Controlled Solid-State Synthesis: A Green Chemistry Experiment for Undergraduate Organic Chemistry

ERIC Educational Resources Information Center

Cheney, Miranda L.; Zaworotko, Michael J.; Beaton, Steve; Singer, Robert D.

2008-01-01

Green chemistry has become an important area of concern for all chemists from practitioners in the pharmaceutical industry to professors and the students they teach and is now being incorporated into lectures of general and organic chemistry courses. However, there are relatively few green chemistry experiments that are easily incorporated into…

Chemistry for Potters.

ERIC Educational Resources Information Center

Denio, Allen A.

1980-01-01

Relates pottery making to chemistry by providing chemical information about clay, its origin, composition, properties, and changes that occur during firing; also describes glaze compositions, examples of redox chemistry, salt glazing, crystalline glazes, and problems in toxicity. (CS)

A Virtual Screen Discovers Novel, Fragment-Sized Inhibitors of Mycobacterium tuberculosis InhA

PubMed Central

Perryman, Alexander L.; Yu, Weixuan; Wang, Xin; Ekins, Sean; Forli, Stefano; Li, Shao-Gang; Freundlich, Joel S.; Tonge, Peter J.; Olson, Arthur J.

2015-01-01

Isoniazid (INH) is usually administered to treat latent Mycobacterium tuberculosis (Mtb) infections, and is used in combination therapy to treat active tuberculosis disease (TB). Unfortunately, resistance to this drug is hampering its clinical effectiveness. INH is a prodrug that must be activated by Mtb catalase peroxidase (KatG) before it can inhibit InhA (Mtb enoyl-acyl-carrier-protein reductase). Isoniazid-resistant cases of TB found in clinical settings usually involve mutations in or deletion of katG, which abrogate INH activation. Compounds that inhibit InhA without requiring prior activation by KatG would not be affected by this resistance mechanism and hence would display continued potency against these drug-resistant isolates of Mtb. Virtual screening experiments versus InhA in the GO Fight Against Malaria project (GO FAM) were designed to discover new scaffolds that display base stacking interactions with the NAD cofactor. GO FAM experiments included targets from other pathogens, including Mtb, when they had structural similarity to a malaria target. Eight of the sixteen soluble compounds identified by docking against InhA plus visual inspection were modest inhibitors and did not require prior activation by KatG. The best two inhibitors discovered are both fragment-sized compounds and displayed Ki values of 54 and 59 μM, respectively. Importantly, the novel inhibitors discovered have low structural similarity to known InhA inhibitors and, thus, help expand the number of chemotypes on which future medicinal chemistry efforts can be focused. These new fragment hits could eventually help advance the fight against INH-resistant Mtb strains, which pose a significant global health threat. PMID:25636146

Amino derivatives of glycyrrhetinic acid as potential inhibitors of cholinesterases.

PubMed

Schwarz, Stefan; Lucas, Susana Dias; Sommerwerk, Sven; Csuk, René

2014-07-01

The development of remedies against the Alzheimer's disease (AD) is one of the biggest challenges in medicinal chemistry nowadays. Although not completely understood, there are several strategies fighting this disease or at least bringing some relief. During the progress of AD, the level of acetylcholine (ACh) decreases; hence, a therapy using inhibitors should be of some benefit to the patients. Drugs presently used for the treatment of AD inhibit the two ACh controlling enzymes, acetylcholinesterase as well as butyrylcholinesterase; hence, the design of selective inhibitors is called for. Glycyrrhetinic acid seems to be an interesting starting point for the development of selective inhibitors. Although its glycon, glycyrrhetinic acid is known for being an AChE activator, several derivatives, altered in position C-3 and C-30, exhibited remarkable inhibition constants in micro-molar range. Furthermore, five representative compounds were subjected to three more enzyme assays (on carbonic anhydrase II, papain and the lipase from Candida antarctica) to gain information about the selectivity of the compounds in comparison to other enzymes. In addition, photometric sulforhodamine B assays using murine embryonic fibroblasts (NiH 3T3) were performed to study the cytotoxicity of these compounds. Two derivatives, bearing either a 1,3-diaminopropyl or a 1H-benzotriazolyl residue, showed a BChE selective inhibition in the single-digit micro-molar range without being cytotoxic up to 30μM. In silico molecular docking studies on the active sites of AChE and BChE were performed to gain a molecular insight into the mode of action of these compounds and to explain the pronounced selectivity for BChE. Copyright © 2014 Elsevier Ltd. All rights reserved.

Discovery of natural mouse serum derived HIV-1 entry inhibitor(s).

PubMed

Wei, M; Chen, Y; Xi, J; Ru, S; Ji, M; Zhang, D; Fang, Q; Tang, B

Among rationally designed human immunodeficiency virus 1 (HIV-1) inhibitors, diverse natural factors have showed as potent anti-HIV activity in human blood. We have discovered that the boiled supernatant of healthy mouse serum could suppress HIV-1 entry, and exhibited reduced inhibitory activity after trypsin digestion. Further analysis demonstrated that only the fraction containing 10-25 K proteins could inhibit HIV-1 mediated cell-cell fusion. These results suggest that the 10-25 K protein(s) is novel natural HIV-1 entry inhibitor(s). Our findings provide important information about novel natural HIV entry inhibitors in mouse serum.

Compact dry chemistry instruments.

PubMed

Terashima, K; Tatsumi, N

1999-01-01

Compact dry chemistry instruments are designed for use in point-of-care-testing (POCT). These instruments have a number of advantages, including light weight, compactness, ease of operation, and the ability to provide accurate results in a short time with a very small sample volume. On the other hand, reagent costs are high compared to liquid method. Moreover, differences in accuracy have been found between dry chemistry and the liquid method in external quality assessment scheme. This report examines reagent costs and shows how the total running costs associated with dry chemistry are actually lower than those associated with the liquid method. This report also describes methods for minimizing differences in accuracy between dry chemistry and the liquid method. Use of these measures is expected to increase the effectiveness of compact dry chemistry instruments in POCT applications.

Chemistry in Context: Analysis of Thematic Chemistry Videos Available Online

ERIC Educational Resources Information Center

Christensson, Camilla; Sjöström, Jesper

2014-01-01

United Nations declared 2011 to be the International Year of Chemistry. The Swedish Chemical Society chose twelve themes, one for each month, to highlight the connection of chemistry with everyday life. Examples of themes were fashion, climate change, love, sports, communication, health issues, and food. From the themes various context-based…

Chemistry of americium

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

Schulz, W.W.

1976-01-01

Essential features of the descriptive chemistry of americium are reviewed. Chapter titles are: discovery, atomic and nuclear properties, collateral reading, production and uses, chemistry in aqueous solution, metal, alloys, and compounds, and, recovery, separation, purification. Author and subject indexes are included. (JCB)

National Chemistry Teacher Safety Survey

NASA Astrophysics Data System (ADS)

Plohocki, Barbra A.

This study evaluated the status of secondary school instructional chemistry laboratory safety using a survey instrument which focused on Teacher background Information, Laboratory Safety Equipment, Facility Safety, General Safety, and a Safety Content Knowledge Survey. A fifty question survey instrument based on recent research and questions developed by the researcher was mailed to 500 secondary school chemistry teachers who participated in the 1993 one-week Woodrow Wilson National Fellowship Foundation Chemistry Institute conducted at Princeton University, New Jersey. The data received from 303 respondents was analyzed by t tests and Analysis of Variance (ANOVA). The level of significance for the study was set at ~\\ <.05. There was no significant mean difference in test performance on the Safety Content Knowledge Survey and secondary school chemistry teachers who have had undergraduate and/or graduate safety training and those who have not had undergraduate and/or graduate safety training. Secondary school chemistry teachers who attended school district sponsored safety inservices did not score higher on the Safety Content Knowledge Survey than teachers who did not attend school district sponsored safety inservice sessions. The type of school district (urban, suburban, or rural) had no significant correlation to the type of laboratory safety equipment found in the instructional chemistry laboratory. The certification area (chemistry or other type of certificate which may or may not include chemistry) of the secondary school teacher had no significant correlation to the type of laboratory equipment found in the instructional chemistry laboratory. Overall, this study indicated a majority of secondary school chemistry teachers were interested in attending safety workshops applicable to chemistry safety. Throughout this research project, many teachers indicated they were not adequately instructed on the collegiate level in science safety and had to rely on common

Structure-Based Drug Design of Novel Potent and Selective Tetrahydropyrazolo[1,5- a ]pyrazines as ATR Inhibitors

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

Barsanti, Paul A.; Aversa, Robert J.; Jin, Xianming

A saturation strategy focused on improving the selectivity and physicochemical properties of ATR inhibitor HTS hit 1 led to a novel series of highly potent and selective tetrahydropyrazolo[1,5-a]pyrazines. Use of PI3Kα mutants as ATR crystal structure surrogates was instrumental in providing cocrystal structures to guide the medicinal chemistry designs. Detailed DMPK studies involving cyanide and GSH as trapping agents during microsomal incubations, in addition to deuterium-labeled compounds as mechanistic probes uncovered the molecular basis for the observed CYP3A4 TDI in the series.

Promoting Chemistry Learning through Undergraduate Work Experience in the Chemistry Lab: A Practical Approach

ERIC Educational Resources Information Center

Yu, Hong-Bin

2015-01-01

Hiring undergraduate lab assistants in chemistry departments is common in college. However, few studies have focused on promoting undergraduate chemistry learning and thinking skills through this work experience in chemistry teaching laboratories. This article discusses the strategy we implemented in the lab assistant program. The…

Lead optimization toward proof-of-concept tools for Huntington's disease within a 4-(1H-pyrazol-4-yl)pyrimidine class of pan-JNK inhibitors.

PubMed

Wityak, John; McGee, Kevin F; Conlon, Michael P; Song, Ren Hua; Duffy, Bryan C; Clayton, Brent; Lynch, Michael; Wang, Gwen; Freeman, Emily; Haber, James; Kitchen, Douglas B; Manning, David D; Ismail, Jiffry; Khmelnitsky, Yuri; Michels, Peter; Webster, Jeff; Irigoyen, Macarena; Luche, Michele; Hultman, Monica; Bai, Mei; Kuok, IokTeng D; Newell, Ryan; Lamers, Marieke; Leonard, Philip; Yates, Dawn; Matthews, Kim; Ongeri, Lynette; Clifton, Steve; Mead, Tania; Deupree, Susan; Wheelan, Pat; Lyons, Kathy; Wilson, Claire; Kiselyov, Alex; Toledo-Sherman, Leticia; Beconi, Maria; Muñoz-Sanjuan, Ignacio; Bard, Jonathan; Dominguez, Celia

2015-04-09

Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole.

Development of a novel class of B-RafV600E-selective inhibitors through virtual screening and hierarchical hit optimization

PubMed Central

Kong, Xiangqian; Qin, Jie; Li, Zeng; Vultur, Adina; Tong, Linjiang; Feng, Enguang; Rajan, Geena; Liu, Shien; Lu, Junyan; Liang, Zhongjie; Zheng, Mingyue; Zhu, Weiliang; Jiang, Hualiang; Herlyn, Meenhard; Liu, Hong; Marmorstein, Ronen; Luo, Cheng

2012-01-01

Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-RafV600E mutant exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, we described the development of novel B-RafV600E selective inhibitors via multi-step virtual screening and hierarchical hit optimization. Nine hit compounds with low micromolar IC50 values were identified as B-RafV600E inhibitors through virtual screening. Subsequent scaffold-based analogue searching and medicinal chemistry efforts significantly improved both the inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q possess nanomolar IC50 values with selectivity for B-RafV600E in vitro and exclusive cytotoxicity against B-RafV600E harboring cancer cells. PMID:22875039

ST7612AA1, a thioacetate-ω(γ-lactam carboxamide) derivative selected from a novel generation of oral HDAC inhibitors.

PubMed

Giannini, Giuseppe; Vesci, Loredana; Battistuzzi, Gianfranco; Vignola, Davide; Milazzo, Ferdinando M; Guglielmi, Mario Berardino; Barbarino, Marcella; Santaniello, Mosè; Fantò, Nicola; Mor, Marco; Rivara, Silvia; Pala, Daniele; Taddei, Maurizio; Pisano, Claudio; Cabri, Walter

2014-10-23

A systematic study of medicinal chemistry aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group (ZBG) and of an amide-lactam in the ω-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new class of potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, and efficient synthetic approaches were used to synthesize a library of these new derivatives, which were then submitted to a screening for HDAC inhibition as well as to a preliminary in vitro assessment of their antiproliferative activity. Molecular docking into HDAC crystal structures suggested a binding mode for these thiol derivatives consistent with the stereoselectivity observed upon insertion of amide-lactam substituents in the ω-position. ST7612AA1 (117), selected as a drug candidate for further development, showed an in vitro activity in the nanomolar range associated with a remarkable in vivo antitumor activity, highly competitive with the most potent HDAC inhibitors, currently under clinical trials. A preliminary study of PK and metabolism is also illustrated.

Development of a novel class of B-Raf(V600E)-selective inhibitors through virtual screening and hierarchical hit optimization.

PubMed

Kong, Xiangqian; Qin, Jie; Li, Zeng; Vultur, Adina; Tong, Linjiang; Feng, Enguang; Rajan, Geena; Liu, Shien; Lu, Junyan; Liang, Zhongjie; Zheng, Mingyue; Zhu, Weiliang; Jiang, Hualiang; Herlyn, Meenhard; Liu, Hong; Marmorstein, Ronen; Luo, Cheng

2012-09-28

Oncogenic mutations in critical nodes of cellular signaling pathways have been associated with tumorigenesis and progression. The B-Raf protein kinase, a key hub in the canonical MAPK signaling cascade, is mutated in a broad range of human cancers and especially in malignant melanoma. The most prevalent B-Raf(V600E) mutant exhibits elevated kinase activity and results in constitutive activation of the MAPK pathway, thus making it a promising drug target for cancer therapy. Herein, we describe the development of novel B-Raf(V600E) selective inhibitors via multi-step virtual screening and hierarchical hit optimization. Nine hit compounds with low micromolar IC(50) values were identified as B-Raf(V600E) inhibitors through virtual screening. Subsequent scaffold-based analogue searching and medicinal chemistry efforts significantly improved both the inhibitor potency and oncogene selectivity. In particular, compounds 22f and 22q possess nanomolar IC(50) values with selectivity for B-Raf(V600E)in vitro and exclusive cytotoxicity against B-Raf(V600E) harboring cancer cells.

Undergraduate Chemistry Laboratory

ERIC Educational Resources Information Center

Bretz, Stacey Lowery; Fay, Michael; Bruck, Laura B.; Towns, Marcy H.

2013-01-01

Forty chemistry faculty from American Chemical Society-approved departments were interviewed to determine their goals for undergraduate chemistry laboratory. Faculty were stratified by type of institution, departmental success with regard to National Science Foundation funding for laboratory reform, and level of laboratory course. Interview…

Cooking with Chemistry.

ERIC Educational Resources Information Center

Grosser, Arthur E.

1984-01-01

Suggests chemistry of cooking and analysis of culinary recipes as subject matter for introducing chemistry to an audience, especially to individuals with neutral or negative attitudes toward science. Includes sample recipes and experiments and a table listing scientific topics with related cooking examples. (JN)

Chemistry from Issues.

ERIC Educational Resources Information Center

Harding, Jan; Donaldson, Jim

1986-01-01

Describes the "Chemistry from Issues" project at Chelsea College. Provides the background information, rationale, and overall structure of a proposed course about the importance of chemistry to common culture. Outlines one module about the British steel industry that has been taught at King's College. (TW)

The quadruple bottom line: the advantages of incorporating Green Chemistry into the undergraduate chemistry major

NASA Astrophysics Data System (ADS)

Bodner, George M.

2017-08-01

When the author first became involved with the Green Chemistry movement, he noted that his colleagues in industry who were involved in one of the ACS Green Chemistry Institute® industrial roundtables emphasized the take-home message they described as the "triple bottom line." They noted that introducing Green Chemistry in industrial settings had economic, social, and environmental benefits. As someone who first went to school at age 5, and has been "going to school" most days for 65 years, it was easy for the author to see why introducing Green Chemistry into academics had similar beneficial effects within the context of economic, social and environmental domains at the college/university level. He was prepared to understand why faculty who had taught traditional courses often saw the advantage of incorporating Green Chemistry into the courses they teach. What was not as obvious is why students who were encountering chemistry for the first time were often equally passionate about the Green Chemistry movement. Recent attention has been paid, however, to a model that brings clarity to the hitherto vague term of "relevance" that might explain why integrating Green Chemistry into the undergraduate chemistry classroom can achieve a "quadruple bottom-line" for students because of potentially positive effects of adding a domain of "relevance" to the existing economic, social, and environmental domains.

N-Alkyl Urea Hydroxamic Acids as a New Class of Peptide Deformylase Inhibitors with Antibacterial Activity

PubMed Central

Hackbarth, Corinne J.; Chen, Dawn Z.; Lewis, Jason G.; Clark, Kirk; Mangold, James B.; Cramer, Jeffrey A.; Margolis, Peter S.; Wang, Wen; Koehn, Jim; Wu, Charlotte; Lopez, S.; Withers III, George; Gu, Helen; Dunn, Elina; Kulathila, R.; Pan, Shi-Hao; Porter, Wilma L.; Jacobs, Jeff; Trias, Joaquim; Patel, Dinesh V.; Weidmann, Beat; White, Richard J.; Yuan, Zhengyu

2002-01-01

Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents. All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P1′ site. Using a combination of iterative parallel synthesis and traditional medicinal chemistry, we have identified a new class of PDF inhibitors with N-alkyl urea at the P1′ site. Compounds with MICs of ≤4 μg/ml against gram-positive and gram-negative pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae, have been identified. The concentrations needed to inhibit 50% of enzyme activity (IC50s) for Escherichia coli Ni-PDF were ≤0.1 μM, demonstrating the specificity of the inhibitors. In addition, these compounds were very selective for PDF, with IC50s of consistently >200 μM for matrilysin and other mammalian metalloproteases. Structure-activity relationship analysis identified preferred substitutions resulting in improved potency and decreased cytotoxity. One of the compounds (VRC4307) was cocrystallized with PDF, and the enzyme-inhibitor structure was determined at a resolution of 1.7 Å. This structural information indicated that the urea compounds adopt a binding position similar to that previously determined for succinate hydroxamates. Two compounds, VRC4232 and VRC4307, displayed in vivo efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9 mg/kg of body weight, respectively. These N-alkyl urea hydroxamic acids provide a starting point for identifying new PDF inhibitors that can serve as antimicrobial agents. PMID:12183225

Design and synthetic considerations of matrix metalloproteinase inhibitors.

PubMed

Skotnicki, J S; Zask, A; Nelson, F C; Albright, J D; Levin, J I

1999-06-30

Experimental evidence confirms that the matrix metalloproteinases (MMPs) play a fundamental role in a wide variety of pathologic conditions that involve connective tissue destruction including osteoarthritis and rheumatoid arthritis, tumor metastasis and angiogenesis, corneal ulceration, multiple sclerosis, periodontal disease, and atherosclerosis. Modulation of MMP regulation is possible at several biochemical sites, but direct inhibition of enzyme action provides a particularly attractive target for therapeutic intervention. Hypotheses concerning inhibition of specific MMP(s) with respect to disease target and/or side-effect profile have emerged. Examples are presented of recent advances in medicinal chemistry approaches to the design of matrix metalloproteinase inhibitors (MMPIs), approaches that address structural requirements and that influence potency, selectivity, and bioavailability. Two important approaches to the design, synthesis, and biological evaluation of MMPIs are highlighted: (1) the invention of alternatives to hydroxamic acid zinc chelators and (2) the construction of nonpeptide scaffolds. One current example in each of these two approaches from our own work is described.

The Journal of Kitchen Chemistry: A Tool for Instructing the Preparation of a Chemistry Journal Article

ERIC Educational Resources Information Center

Meyers, Jonathan K.; LeBaron, Tyler W.; Collins, David C.

2014-01-01

Writing assignments are typically incorporated into chemistry courses in an attempt to enhance the learning of chemistry or to teach technical writing to chemistry majors. This work addresses the development of chemistry-major writing skills by focusing on the rigorous guidelines and conventions associated with the preparation of a journal…

Green Chemistry: Progress and Barriers

NASA Astrophysics Data System (ADS)

Green, Sarah A.

2016-10-01

Green chemistry can advance both the health of the environment and the primary objectives of the chemical enterprise: to understand the behavior of chemical substances and to use that knowledge to make useful substances. We expect chemical research and manufacturing to be done in a manner that preserves the health and safety of workers; green chemistry extends that expectation to encompass the health and safety of the planet. While green chemistry may currently be treated as an independent branch of research, it should, like safety, eventually become integral to all chemistry activities. While enormous progress has been made in shifting from "brown" to green chemistry, much more effort is needed to effect a sustainable economy. Implementation of new, greener paradigms in chemistry is slow because of lack of knowledge, ends-justify-the-means thinking, systems inertia, and lack of financial or policy incentives.

Life's Biological Chemistry: A Destiny or Destination Starting from Prebiotic Chemistry?

PubMed

Krishnamurthy, Ramanarayanan

2018-06-05

Research into understanding the origins -and evolution- of life has long been dominated by the concept of taking clues from extant biology and extrapolating its molecules and pathways backwards in time. This approach has also guided the search for solutions to the problem of how contemporary biomolecules would have arisen directly from prebiotic chemistry on early earth. However, the continuing difficulties in finding universally convincing solutions in connecting prebiotic chemistry to biological chemistry should give us pause, and prompt us to rethink this concept of treating extant life's chemical processes as the sole end goal and, therefore, focusing only -and implicitly- on the respective extant chemical building blocks. Rather, it may be worthwhile "to set aside the goal" and begin with what would have been plausible prebiotic reaction mixtures (which may have no obvious or direct connection to life's chemical building blocks and processes) - and allow their chemistries and interactions, under different geochemical constraints, to guide and illuminate as to what processes and systems can emerge. Such a conceptual approach gives rise to the prospect that chemistry of life-as-we-know-it is not the only result (not a "destiny"), but one that has emerged among many potential possibilities (a "destination"). This postulate, in turn, could impact the way we think about chemical signatures and criteria used in the search for alternative and extraterrestrial "life". As a bonus, we may discover the chemistries and pathways naturally that led to the emergence of life as we know it. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Supramolecular analytical chemistry.

PubMed

Anslyn, Eric V

2007-02-02

A large fraction of the field of supramolecular chemistry has focused in previous decades upon the study and use of synthetic receptors as a means of mimicking natural receptors. Recently, the demand for synthetic receptors is rapidly increasing within the analytical sciences. These classes of receptors are finding uses in simple indicator chemistry, cellular imaging, and enantiomeric excess analysis, while also being involved in various truly practical assays of bodily fluids. Moreover, one of the most promising areas for the use of synthetic receptors is in the arena of differential sensing. Although many synthetic receptors have been shown to yield exquisite selectivities, in general, this class of receptor suffers from cross-reactivities. Yet, cross-reactivity is an attribute that is crucial to the success of differential sensing schemes. Therefore, both selective and nonselective synthetic receptors are finding uses in analytical applications. Hence, a field of chemistry that herein is entitled "Supramolecular Analytical Chemistry" is emerging, and is predicted to undergo increasingly rapid growth in the near future.

Chemistry for Whom? Gender Awareness in Teaching and Learning Chemistry

ERIC Educational Resources Information Center

Andersson, Kristina

2017-01-01

Marie Ståhl and Anita Hussénius have defined what discourses dominate national tests in chemistry for Grade 9 in Sweden by using feminist, critical didactic perspectives. This response seeks to expand the results in Ståhl and Hussénius's article "Chemistry inside an epistemological community box!--Discursive exclusions and inclusions in the…

Reaction-Map of Organic Chemistry

ERIC Educational Resources Information Center

Murov, Steven

2007-01-01

The Reaction-Map of Organic Chemistry lists all the most commonly studied reactions in organic chemistry on one page. The discussed Reaction-Map will act as another learning aide for the students, making the study of organic chemistry much easier.

Forensic Chemistry--A Symposium Collection.

ERIC Educational Resources Information Center

Journal of Chemical Education, 1985

1985-01-01

Presents a collection of articles to provide chemistry teachers with resource materials to add forensic chemistry units to their chemistry courses. Topics range from development of forensic science laboratory courses and mock-crime scenes to forensic serology and analytical techniques. (JN)

Drain the lysosome: Development of the novel orally available autophagy inhibitor ROC-325.

PubMed

Carew, Jennifer S; Nawrocki, Steffan T

2017-04-03

Although macroautophagy/autophagy is a key contributor to malignant pathogenesis and therapeutic resistance, there are few FDA-approved agents that significantly affect this pathway. We used medicinal chemistry strategies to develop ROC-325, an orally available novel inhibitor of lysosomal-mediated autophagy. Detailed in vitro and in vivo studies in preclinical models of renal cell carcinoma demonstrated that ROC-325 triggered the hallmark features of lysosomal autophagy inhibition, was very well tolerated, and exhibited significant superiority with respect to autophagy inhibition and anticancer activity over hydroxychloroquine. Our findings support the clinical investigation of the safety and preliminary efficacy of ROC-325 in patients with autophagy-dependent malignancies and other disorders where aberrant autophagy contributes to disease pathogenesis.

Turkish Chemistry Teachers' Views about Secondary School Chemistry Curriculum: A Perspective from Environmental Education

ERIC Educational Resources Information Center

Icoz, Omer Faruk

2015-01-01

Teachers' views about environmental education (EE) have been regarded as one of the most important concerns in education for sustainability. In secondary school chemistry curriculum, there are several subjects about EE embedded in the chemistry subjects in Turkey. This study explores three chemistry teachers' views about to what extent the…

Developing an online chemistry laboratory for non-chemistry majors

NASA Astrophysics Data System (ADS)

Poole, Jacqueline H.

Distance education, also known as online learning, is student-centered/self-directed educational opportunities. This style of learning is expanding in scope and is increasingly being accepted throughout the academic curriculum as a result of its flexibility for the student as well as the cost-effectiveness for the institution. Nevertheless, the introduction of online science courses including chemistry and physics have lagged behind due to the challenge of re-creation of the hands-on laboratory learning experience. This dissertation looks at the effectiveness of the design of a series of chemistry laboratory experiments for possible online delivery that provide students with simulated hands-on experiences. One class of college Chemistry 101 students conducted chemistry experiments inside and outside of the physical laboratory using instructions on Blackboard and Late Nite Labs(TM). Learning outcomes measured by (a) pretests, (b) written laboratory reports, (c) posttest assessments, (d) student reactions as determined by a questionnaire, and (e) a focus group interview were utilized to compare both types of laboratory experiences. The research findings indicated learning outcomes achieved by students outside of the traditional physical laboratory were statistically greater than the equivalent face-to-face instruction in the traditional laboratory. Evidence from student reactions comparing both types of laboratory formats (online and traditional face-to-face) indicated student preference for the online laboratory format. The results are an initial contribution to the design of a complete sequence of experiments that can be performed independently by online students outside of the traditional face-to-face laboratory that will satisfy the laboratory requirement for the two-semester college Chemistry 101 laboratory course.

Chemistry and Biology

ERIC Educational Resources Information Center

Wigston, David L.

1970-01-01

Discusses the relationship between chemisty and biology in the science curriculum. Points out the differences in perception of the disciplines, which the physical scientists favoring reductionism. Suggests that biology departments offer a special course for chemistry students, just as the chemistry departments have done for biology students.…

Vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors: development and validation of predictive 3-D QSAR models through extensive ligand- and structure-based approaches

NASA Astrophysics Data System (ADS)

Ragno, Rino; Ballante, Flavio; Pirolli, Adele; Wickersham, Richard B.; Patsilinakos, Alexandros; Hesse, Stéphanie; Perspicace, Enrico; Kirsch, Gilbert

2015-08-01

Vascular endothelial growth factor receptor-2, (VEGFR-2), is a key element in angiogenesis, the process by which new blood vessels are formed, and is thus an important pharmaceutical target. Here, 3-D quantitative structure-activity relationship (3-D QSAR) were used to build a quantitative screening and pharmacophore model of the VEGFR-2 receptors for design of inhibitors with improved activities. Most of available experimental data information has been used as training set to derive optimized and fully cross-validated eight mono-probe and a multi-probe quantitative models. Notable is the use of 262 molecules, aligned following both structure-based and ligand-based protocols, as external test set confirming the 3-D QSAR models' predictive capability and their usefulness in design new VEGFR-2 inhibitors. From a survey on literature, this is the first generation of a wide-ranging computational medicinal chemistry application on VEGFR2 inhibitors.

Understanding the Impact of a General Chemistry Course on Students' Transition to Organic Chemistry

ERIC Educational Resources Information Center

Collins-Webb, Alexandra; Jeffery, Kathleen A.; Sweeder, Ryan D.

2016-01-01

The move from general chemistry to organic chemistry can be a challenge for students as it often involves a transition from quantitatively-oriented to mechanistically-oriented thinking. This study found that the design of the general chemistry course can change the student experience of this transition as assessed by a reflective survey. The…

42 CFR 493.839 - Condition: Chemistry.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Chemistry. 493.839 Section 493.839... These Tests § 493.839 Condition: Chemistry. The specialty of chemistry includes for the purposes of proficiency testing the subspecialties of routine chemistry, endocrinology, and toxicology. ...

42 CFR 493.839 - Condition: Chemistry.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Chemistry. 493.839 Section 493.839... These Tests § 493.839 Condition: Chemistry. The specialty of chemistry includes for the purposes of proficiency testing the subspecialties of routine chemistry, endocrinology, and toxicology. ...

42 CFR 493.839 - Condition: Chemistry.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Chemistry. 493.839 Section 493.839... These Tests § 493.839 Condition: Chemistry. The specialty of chemistry includes for the purposes of proficiency testing the subspecialties of routine chemistry, endocrinology, and toxicology. ...

42 CFR 493.839 - Condition: Chemistry.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Chemistry. 493.839 Section 493.839... These Tests § 493.839 Condition: Chemistry. The specialty of chemistry includes for the purposes of proficiency testing the subspecialties of routine chemistry, endocrinology, and toxicology. ...

42 CFR 493.839 - Condition: Chemistry.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Chemistry. 493.839 Section 493.839... These Tests § 493.839 Condition: Chemistry. The specialty of chemistry includes for the purposes of proficiency testing the subspecialties of routine chemistry, endocrinology, and toxicology. ...

Virtually going green: The role of quantum computational chemistry in reducing pollution and toxicity in chemistry

NASA Astrophysics Data System (ADS)

Stevens, Jonathan

2017-07-01

Continuing advances in computational chemistry has permitted quantum mechanical calculation to assist in research in green chemistry and to contribute to the greening of chemical practice. Presented here are recent examples illustrating the contribution of computational quantum chemistry to green chemistry, including the possibility of using computation as a green alternative to experiments, but also illustrating contributions to greener catalysis and the search for greener solvents. Examples of applications of computation to ambitious projects for green synthetic chemistry using carbon dioxide are also presented.

Chemistry Cube Game - Exploring Basic Principles of Chemistry by Turning Cubes.

PubMed

Müller, Markus T

2018-02-01

The Chemistry Cube Game invites students at secondary school level 1 and 2 to explore basic concepts of chemistry in a playful way, either as individuals or in teams. It consists of 15 different cubes, 9 cubes for different acids, their corresponding bases and precursors, and 6 cubes for different reducing and oxidising agents. The cubes can be rotated in those directions indicated. Each 'allowed' vertical or horizontal rotation of 90° stands for a chemical reaction or a physical transition. Two different games and playing modes are presented here: First, redox chemistry is introduced for the formation of salts from elementary metals and non-metals. Second, the speciation of acids and bases at different pH-values is shown. The cubes can be also used for games about environmental chemistry such as the carbon and sulphur cycle, covering the topic of acid rain, or the nitrogen cycle including ammoniac synthesis, nitrification and de-nitrification.

Science Update: Inorganic Chemistry.

ERIC Educational Resources Information Center

Rawls, Rebecca

1981-01-01

Describes areas of inorganic chemistry which have changed dramatically in the past year or two, including photochemistry, electrochemistry, organometallic complexes, inorganic reaction theory, and solid state chemistry. (DS)

Puzzling through General Chemistry: A Light-Hearted Approach to Engaging Students with Chemistry Content

ERIC Educational Resources Information Center

Boyd, Susan L.

2007-01-01

Several puzzles are designed to be used by chemistry students as learning tools and teach them basic chemical concepts. The topics of the puzzles are based on the chapters from Chemistry, The Central Science used in general chemistry course and the puzzles are in various forms like crosswords, word searches, number searches, puzzles based on…

Chemistry beyond positivism.

PubMed

Brandt, Werner W

2003-05-01

Chemistry is often thought to be quite factual, and therefore might be considered close to the "positivist" ideal of a value-free science. A closer look, however, reveals that the field is coupled to the invisible realm of values, meanings, and purpose in various ways, and chemists interact with that realm loosely and unevenly. Tacit knowledge is one important locus of such interactions. We are concerned in this essay with two questions. What is the nature of the knowledge when we are in the early stages of discovery? and In what ways does the hidden reality we are seeking affect our search for an understanding of it? The first question is partly answered by Polanyi's theory of tacit knowledge, while the second one leads us to realize the limitations of our language when discussing "reality"-or certain chemical experimental results. A strictly positivist approach is of little use, but so is the opposite, the complete disregard of facts. The contrast between positivism and non-formulable aspects of scientific reasoning amounts to a paradox that needs to be analyzed and can lead to a "connected" chemistry. This in turn resembles networks described by Schweber and is more concerned than the chemistry "as it is" with aspects such as the image of chemistry, the challenges chemists face as citizens, and chemistry in liberal education.

Effective Chemistry Communication in Informal Environments

ERIC Educational Resources Information Center

National Academies Press, 2016

2016-01-01

Chemistry plays a critical role in daily life, impacting areas such as medicine and health, consumer products, energy production, the ecosystem, and many other areas. Communicating about chemistry in informal environments has the potential to raise public interest and understanding of chemistry around the world. However, the chemistry community…

Making Sense of the Arrow-Pushing Formalism among Chemistry Majors Enrolled in Organic Chemistry

ERIC Educational Resources Information Center

Ferguson, Robert; Bodner, George M.

2008-01-01

This paper reports results of a qualitative study of sixteen students enrolled in a second year organic chemistry course for chemistry and chemical engineering majors. The focus of the study was student use of the arrow-pushing formalism that plays a central role in both the teaching and practice of organic chemistry. The goal of the study was to…

Growing your green chemistry mindset

NASA Astrophysics Data System (ADS)

Kosmas, Steven

2017-08-01

The purpose of this article is not to delineate the steps to move across the continuum to being a greener chemist, but to analyse the cognitive processes involved in fostering a green chemistry growth mindset (GCGM) [Dweck C. (2006) Mindset: The New Psychology of Success. New York, NY: Ballatine]. The focus is on changing the mindset, which inevitably will lead to a more mindful approach to chemistry practices before the laboratory begins. A green chemistry fixed mindset (GCFM) is closed to making improvements, since the attitude is that the techniques and processes in the laboratory are already employing a green chemistry mindset [Dweck C. (2006) Mindset: The New Psychology of Success. New York, NY: Ballatine]. The problem with the GCFM is that it precludes the possibility of making improvements. However, the GCGM employs a continuous, intentional focus on the attitude towards green chemistry, with the ultimate goal being a change in chemistry practices that is greener. The focus of this article will be on the GCGM.

Supplemental instruction in chemistry

NASA Astrophysics Data System (ADS)

Lundeberg, Mary A.

This study was designed to measure some effects of supplemental instruction in chemistry. Supplemental instruction is a peer-led cooperative learning program that encourages students to develop conceptual understanding by articulating both understandings and misconceptions in a think-aloud fashion. Supplemental instruction was offered three hours weekly outside of class and lab time for students in four classes of General Organic and Biological Chemistry. Over a two-year period 108 students volunteered to participate in this program; 45 students did not participate. As measured by final grades in chemistry and responses to a questionnaire, supplemental instruction was effective in increasing students' achievement in chemistry. Further research is needed to determine the in-depth effects of supplemental instruction on students' learning, problem solving, and self-esteem.

First-in-class inhibitor of the T cell receptor for the treatment of autoimmune diseases.

PubMed

Borroto, Aldo; Reyes-Garau, Diana; Jiménez, M Angeles; Carrasco, Esther; Moreno, Beatriz; Martínez-Pasamar, Sara; Cortés, José R; Perona, Almudena; Abia, David; Blanco, Soledad; Fuentes, Manuel; Arellano, Irene; Lobo, Juan; Heidarieh, Haleh; Rueda, Javier; Esteve, Pilar; Cibrián, Danay; Martinez-Riaño, Ana; Mendoza, Pilar; Prieto, Cristina; Calleja, Enrique; Oeste, Clara L; Orfao, Alberto; Fresno, Manuel; Sánchez-Madrid, Francisco; Alcamí, Antonio; Bovolenta, Paola; Martín, Pilar; Villoslada, Pablo; Morreale, Antonio; Messeguer, Angel; Alarcon, Balbino

2016-12-21

Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding concomitant opportunistic infections. Antigen binding to the T cell receptor (TCR) triggers the recruitment of the cytosolic adaptor protein Nck to a proline-rich sequence in the cytoplasmic tail of the TCR's CD3ε subunit. Through virtual screening and using combinatorial chemistry, we have generated an orally available, low-molecular weight inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC 50 (median inhibitory concentration) ~1 nM. By modulating TCR signaling, the inhibitor prevented the development of psoriasis and asthma and, furthermore, exerted a long-lasting therapeutic effect in a model of autoimmune encephalomyelitis. However, it did not prevent the generation of a protective memory response against a mouse pathogen, suggesting that the compound might not exert its effects through immunosuppression. These results suggest that inhibiting an immediate TCR signal has promise for treating a broad spectrum of human T cell-mediated autoimmune and inflammatory diseases. Copyright © 2016, American Association for the Advancement of Science.

42 CFR 493.929 - Chemistry.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Chemistry. 493.929 Section 493.929 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.929 Chemistry. The subspecialties under the specialty of chemistry for which a proficiency testing program may offer proficiency testing are routine...

42 CFR 493.929 - Chemistry.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Chemistry. 493.929 Section 493.929 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.929 Chemistry. The subspecialties under the specialty of chemistry for which a proficiency testing program may offer proficiency testing are routine...

42 CFR 493.929 - Chemistry.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Chemistry. 493.929 Section 493.929 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.929 Chemistry. The subspecialties under the specialty of chemistry for which a proficiency testing program may offer proficiency testing are routine...

42 CFR 493.929 - Chemistry.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Chemistry. 493.929 Section 493.929 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.929 Chemistry. The subspecialties under the specialty of chemistry for which a proficiency testing program may offer proficiency testing are routine...

42 CFR 493.929 - Chemistry.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Chemistry. 493.929 Section 493.929 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.929 Chemistry. The subspecialties under the specialty of chemistry for which a proficiency testing program may offer proficiency testing are routine...

Opportunities in Chemistry.

ERIC Educational Resources Information Center

National Academy of Sciences - National Research Council, Washington, DC.

Because of the changes occurring in the chemical sciences, a new survey of chemistry and its intellectual and economic impact was clearly needed. This report presents a current assessment of the status of chemistry and of the future opportunities in the field. This analysis contains: (1) an introductory chapter (establishing the need for the…

Perceptions of Chemistry: Why Is the Common Perception of Chemistry, the Most Visual of Sciences, So Distorted?

ERIC Educational Resources Information Center

Habraken, Clarisse L.

1996-01-01

Highlights the need to reinvigorate chemistry education by means of the visual-spatial approach, an approach wholly in conformance with the way modern chemistry is thought about and practiced. Discusses the changing world, multiple intelligences, imagery, chemistry's pictorial language, and perceptions in chemistry. Presents suggestions on how to…

Contribution from philosophy of chemistry to chemistry education: In a case of ionic liquids as technochemistry

NASA Astrophysics Data System (ADS)

Mudzakir, Ahmad; Hernani, Widhiyanti, Tuszie; Sudrajat, Devi Pratiwi

2017-08-01

Traditional chemistry education is commonly handing down of concepts, principles, and theories, such as mechanical properties, the relationship between structure and properties as well as chemical structure and chemical bonding theory, to students without engaging them in the processes of chemical inquiry. This practice leads to the lack of opportunity for the students to construct an appropriate understanding of these concepts, principles, and theories. Students are also rarely facilitated in modeling the structure and function of matter themselves. This situation shows that the philosophy of chemistry has not received as much attention from chemistry educators. The main idea of this paper is to embed philosophy of chemistry through the implementation of technochemistry in chemistry education. One of the most interesting and rapidly developing areas of modern chemistry, technologies and engineering is Ionic Liquids (ILs) as an emerging knowledge on technochemistry which can be applied to chemistry education. The developments between academic researchers and industrial developments in the ILs area are conducted in parallel. In order to overcome the existing problems of scientific development in chemistry education, the science and technology of ILs can be used for reconceptualizing the teaching and learning of chemistry to embrace the epistemology in chemistry. This study promises a potential contribution by philosophy of chemistry. The main objectives of this study are to develop: (i) a perspective based on philosophy of science considerations (rational reconstruction) in order to understand ionic liquids and (ii) teaching materials that can be used to enhance pre-service teacher's view of nature of science and technology (VNOST). The method used in the study is analytical-descriptive (elementarization), i.e. the first step in the model of educational reconstruction (MER). This study concludes that the development of the concepts and their applications of ionic

Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

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

Jin, Hyeon-Ok; Hong, Sung-Eun; Kim, Chang Soon

2015-08-15

Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H + ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or concanamycin A) enhanced synergistic cell death compared to treatments with each drugmore » alone. Treatment with bafilomycin A1 or concanamycin A led to the induction of Bnip3 expression in an Hif-1α dependent manner. Knock-down of Hif-1α or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1, suggesting that Hif-1α/Bnip3 induction promoted resistance to cell death induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1α and Bnip3 expression induced by the vATPase inhibitors, suggesting that they enhanced the sensitivity of the cells to these inhibitors by decreasing Hif-1α/Bnip3 expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of NSCLC cells to vATPase inhibitors by decreasing Hif-1α/Bnip3 expression. We suggest that combined treatment with EGFR TKIs and vATPase inhibitors is potentially effective for the treatment of NSCLC. - Highlights: • Co-treatment with EGFR TKIs and vATPase inhibitors induces synergistic cell death • EGFR TKIs enhance cell sensitivity to vATPase inhibitors via Hif-1α downregulation • Co-treatment of these inhibitors is potentially effective for the treatment of NSCLC.« less

ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors.

PubMed

Halasi, Marianna; Wang, Ming; Chavan, Tanmay S; Gaponenko, Vadim; Hay, Nissim; Gartel, Andrei L

2013-09-01

NAC (N-acetyl-L-cysteine) is commonly used to identify and test ROS (reactive oxygen species) inducers, and to inhibit ROS. In the present study, we identified inhibition of proteasome inhibitors as a novel activity of NAC. Both NAC and catalase, another known scavenger of ROS, similarly inhibited ROS levels and apoptosis associated with H₂O₂. However, only NAC, and not catalase or another ROS scavenger Trolox, was able to prevent effects linked to proteasome inhibition, such as protein stabilization, apoptosis and accumulation of ubiquitin conjugates. These observations suggest that NAC has a dual activity as an inhibitor of ROS and proteasome inhibitors. Recently, NAC was used as a ROS inhibitor to functionally characterize a novel anticancer compound, piperlongumine, leading to its description as a ROS inducer. In contrast, our own experiments showed that this compound depicts features of proteasome inhibitors including suppression of FOXM1 (Forkhead box protein M1), stabilization of cellular proteins, induction of ROS-independent apoptosis and enhanced accumulation of ubiquitin conjugates. In addition, NAC, but not catalase or Trolox, interfered with the activity of piperlongumine, further supporting that piperlongumine is a proteasome inhibitor. Most importantly, we showed that NAC, but not other ROS scavengers, directly binds to proteasome inhibitors. To our knowledge, NAC is the first known compound that directly interacts with and antagonizes the activity of proteasome inhibitors. Taken together, the findings of the present study suggest that, as a result of the dual nature of NAC, data interpretation might not be straightforward when NAC is utilized as an antioxidant to demonstrate ROS involvement in drug-induced apoptosis.

Chemistry 200, 300 Interim Guide.

ERIC Educational Resources Information Center

Manitoba Dept. of Education, Winnipeg.

This guide, developed for the chemistry 200, 300 program in Manitoba, is designed to articulate with previous science courses, provide concepts, processes, and skills which will enable students to continue in chemistry-related areas, and relate chemistry to practical applications in everyday life. It includes a program overview (with program goals…

Revitalizing chemistry laboratory instruction

NASA Astrophysics Data System (ADS)

McBride, Phil Blake

This dissertation involves research in three major domains of chemical education as partial fulfillment of the requirements for the Ph.D. program in chemistry at Miami University with a major emphasis on chemical education, and concurrent study in organic chemistry. Unit I, Development and Assessment of a Column Chromatography Laboratory Activity, addresses the domain of Instructional Materials Development and Testing. This unit outlines the process of developing a publishable laboratory activity, testing and revising that activity, and subsequently sharing that activity with the chemical education community. A laboratory activity focusing on the separation of methylene blue and sodium fluorescein was developed to demonstrate the effects of both the stationary and mobile phase in conducting a separation. Unit II, Bringing Industry to the Laboratory, addresses the domain of Curriculum Development and Testing. This unit outlines the development of the Chemistry of Copper Mining module, which is intended for use in high school or undergraduate college chemistry. The module uses the learning cycle approach to present the chemistry of the industrial processes of mining copper to the students. The module includes thirteen investigations (three of which are web-based and ten which are laboratory experiments) and an accompanying interactive CD-ROM, which provides an explanation of the chemistry used in copper mining with a virtual tour of an operational copper mine. Unit III, An Alternative Method of Teaching Chemistry. Integrating Lecture and the Laboratory, is a project that addresses the domain of Research in Student Learning. Fundamental Chemistry was taught at Eastern Arizona College as an integrated lecture/laboratory course that met in two-hour blocks on Monday, Wednesday, and Friday. The students taking this integrated course were compared with students taking the traditional 1-hour lectures held on Monday, Wednesday, and Friday, with accompanying 3-hour lab on

'Click Chemistry' in the preparation of porous polymer-basedparticulate stationary phases for mu-HPLC separation of peptides andproteins

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

Slater, Michael; Snauko, Marian; Svec, Frantisek

With the use of the copper(I)-catalyzed (3 + 2) azide-alkynecycloaddition, an element of "click chemistry," stationary phasescarrying long alkyl chains or soybean trypsin inhibitor have beenprepared for use in HPLC separations in the reversed-phase and affinitymodes, respectively. The ligands were attached via a triazole ring tosize monodisperse porous beads containing either alkyne or azide pendantfunctionalities. Alkyne-containing beads prepared by directcopolymerization of propargyl acrylate with ethylene dimethacrylate wereallowed to react with azidooctadecane to give a reversed-phase sorbent.Azide-functionalized beads were prepared by chemical modification ofglycidyl methacrylate particles. Subsequent reaction with a terminalaliphatic alkyne produced a reversed-phase sorbent similar to thatobtained from themore » alkyne beads. Soybean trypsin inhibitor wasfunctionalized with N-(4-pentynoyloxy) succinimide to carry alkyne groupsand then allowed to react with the azide-containing beads to produce anaffinity sorbent for trypsin. The performance of these stationary phaseswas demonstrated with the HPLC separations of a variety of peptides andproteins.« less

Polyphenol oxidase inhibitor(s) from German cockroach (Blattella germanica) extract

USDA-ARS?s Scientific Manuscript database

An extract from German cockroach appears effective in inhibiting browning on apples and potatoes. Successful identification of inhibitor(s) of PPO from German cockroach would be useful to the fruit and vegetable segments of the food industry, due to the losses they incur from enzymatic browning. Ide...

Six Pillars of Organic Chemistry

ERIC Educational Resources Information Center

Mullins, Joseph J.

2008-01-01

This article describes an approach to teaching organic chemistry, which is to have students build their knowledge of organic chemistry upon a strong foundation of the fundamental concepts of the subject. Specifically, the article focuses upon a core set of concepts that I call "the six pillars of organic chemistry": electronegativity, polar…

Parkinson's disease management. Part II- discovery of MAO-B inhibitors based on nitrogen heterocycles and analogues.

PubMed

Reis, Joana; Encarnação, Igor; Gaspar, Alexandra; Morales, Aliuska; Milhazes, Nuno; Borges, Fernanda

2012-01-01

Parkinson's disease (PD) is a neurodegenerative disorder mainly characterized by a progressive neurodegeneration of the dopaminergic neurons. The available pharmacological therapy for PD aims to stop the progress of symptoms, reduce disability, slowing the neurodegenerative process and/or preventing long-term complications along the therapy. The main strategic developments that have led to progress in the medical management of PD have focused on improvements in dopaminergic therapies. Despite all the recent research, there are only a few classes of drugs approved for the treatment of motor related symptoms of PD which primarily act on the dopaminergic neurons system: L-dopa, dopamine agonists, monoamine oxidase-B (MAO-B) and catechol-O-methyl transferase (COMT) inhibitors. Anticholinergic drugs and glutamate antagonists are also available but are not commonly used in routine practice. As no effective therapeutic strategy has yet been attended, other solutions must be investigated. Privileged structures, such as indoles, arylpiperazines, biphenyls and benzopyranes are currently ascribed as helpful approaches. Different families of nitrogen and oxygen heterocycles, such as pyrazoles, hydrazinylthiazoles, xanthones, coumarins or chromones have also been extensively used as scaffolds in medicinal chemistry programs for searching novel MAO-B inhibitors. Nitrogen derivatives play a key role in this subject with several studies pointing out hydrazines, thiazoles or indoles as important scaffolds for the development of novel MAO-B inhibitors. This review comprises an overview of the state of the art on the actual pharmacological therapy for PD followed by a specific focus on the discovery and development of nitrogen-based heterocyclic compounds analogues as promising MAO-B inhibitors.

Environmental chemistry: Volume A

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

Yen, T.F.

1999-08-01

This is an extensive introduction to environmental chemistry for engineering and chemical professionals. The contents of Volume A include a brief review of basic chemistry prior to coverage of litho, atmo, hydro, pedo, and biospheres.

Seeing the Chemistry around Me--Helping Students Identify the Relevance of Chemistry to Everyday Life

ERIC Educational Resources Information Center

Moore, Tracy Lynn

2012-01-01

The study attempted to determine whether the use of a series of reading and response assignments decreased students' perceptions of chemistry difficulty and enhanced students' perceptions of the relevance of chemistry in their everyday lives. Informed consent volunteer students enrolled in General Chemistry II at a community college in the…

Comparison of orbital chemistry with crustal thickness and lunar sample chemistry

NASA Technical Reports Server (NTRS)

Schonfeld, E.

1977-01-01

A correlation between orbital chemistry (FeO, Al2O3, Mg/Al, MgO/FeO, Th) and the lunar crustal thickness is examined. The correlation suggests either lack of complete homogenization by lateral or vertical mixing, or lateral variation in the differentiation process. In addition, links between orbital chemistry and lunar sample chemistry are investigated. In regions with crustal thickness between 100 and 110 km, gabbroic anorthosites are very abundant, while in regions with crustal thickness of about 80 km anorthositic gabbros are frequent. Special attention is given to the distribution of low-potassium Fra Mauro basalt, found in high concentrations in regions with 50 to 60 km crustal thickness.

Dipeptidyl peptidase-IV inhibitor use associated with increased risk of ACE inhibitor-associated angioedema.

PubMed

Brown, Nancy J; Byiers, Stuart; Carr, David; Maldonado, Mario; Warner, Barbara Ann

2009-09-01

Dipeptidyl peptidase-IV (DPP-IV) inhibitors decrease degradation of the incretins. DPP-IV inhibitors also decrease degradation of peptides, such as substance P, that may be involved in the pathogenesis of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. This study tested the hypothesis that DPP-IV inhibition affects risk of clinical angioedema, by comparing the incidence of angioedema in patients treated with the DPP-IV inhibitor vildagliptin versus those treated with comparator in Phase III randomized clinical trials. Prospectively defined angioedema-related events were adjudicated in a blinded fashion by an internal medicine adjudication committee and expert reviewer. Concurrent ACE inhibitor or angiotensin receptor blocker exposure was ascertained from case report forms. Study drug exposure was ascertained from unblinded data from phase III studies. Odds ratios and 95% confidence intervals comparing angioedema risk in vildagliptin-treated and comparator-treated patients were calculated for the overall population and for patients taking ACE inhibitors or angiotensin receptor blockers, using both an analysis of pooled data and a meta-analysis (Peto method). Overall, there was no association between vildagliptin use and angioedema. Among individuals taking an ACE inhibitor, however, vildagliptin use was associated with an increased risk of angioedema (14 confirmed cases among 2754 vildagliptin users versus 1 case among 1819 comparator users: odds ratio 4.57 [95% confidence interval 1.57 to 13.28]) in the meta-analysis. Vildagliptin use may be associated with increased risk of angioedema among patients taking ACE inhibitors, although absolute risk is small. Physicians confronted with angioedema in a patient taking an ACE inhibitor and DPP-IV inhibitor should consider this possible drug-drug interaction.

Creating a Context for Chemistry

NASA Astrophysics Data System (ADS)

Truman Schwartz, A.

Until relatively recently, the teaching of chemistry at the college and university level in the United States has been quite traditional and oriented primarily toward the preparation of chemists. Students not concentrating in the sciences have often been poorly served by existing courses. Chemistry in Context: Applying Chemistry to Society, a textbook for nonscience majors developed under the sponsorship of the American Chemical Society, is an effort to address the needs and interests of this audience. The book introduces the phenomena and principles of chemistry within the context of socially significant issues such as global warming, ozone depletion, alternate energy sources, nutrition, and genetic engineering. The chemistry is presented as needed to inform an understanding of the central topics, and the text features student-centered activities designed to promote critical thinking and risk-benefit analysis as well as an understanding of chemical principles. This paper summarizes the origin, development, content, pedagogy, evaluation, and influence of Chemistry in Context and considers its potential implications for other disciplines and the instruction of science majors.

Removal of inhibitor(s) of the polymerase chain reaction from formalin fixed, paraffin wax embedded tissues.

PubMed

An, S F; Fleming, K A

1991-11-01

A problem associated with use of the polymerase chain reaction to amplify specific DNA fragments from formalin fixed, paraffin wax embedded tissues is the not infrequent failure of amplification. One possible reason for this could be the presence of inhibitor(s), which interfere with the activity of the reaction. It has been shown that such inhibitor(s) exist when amplifying the human beta globin gene (which exists in human genomic DNA as a single copy gene) from routine clinical samples. A variety of methods to remove such inhibitor(s) were investigated. The results indicate that inhibitor(s) are removed by proteinase K digestion, followed by purification with phenol/chloroform, and centrifugation through a Centricon-30 membrane (30,000 molecular weight cut off). Other factors, including the length and concentration of the DNA sequence to be amplified, can also affect amplification.

Active Learning Applications in the History of Chemistry: Pre-Service Chemistry Teachers' Level of Knowledge and Views

ERIC Educational Resources Information Center

Sendur, Gülten; Polat, Merve; Toku, Abdullah; Kazanci, Coskun

2014-01-01

This study aims to investigate the effects of a History and Philosophy of Chemistry-I course based on active learning applications on the level of knowledge of pre-service chemistry teachers about the history of chemistry. The views of pre-service chemistry teachers about these activities were also investigated. The study was carried out with 38…

The Status of Chemistry in Two-Year Colleges: Results from a Survey of Chemistry Departments.

ERIC Educational Resources Information Center

Ryan, Mary Ann; Wesemann, Jodi L.; Boese, Janet M.; Neuschatz, Michael

In the fall of 2001, the American Chemical Society (ACS) conducted a survey of two-year college chemistry departments to obtain basic data on chemistry faculty and chemistry courses taught at college. A questionnaire sent to appropriate representatives (department chairs, program heads, or deans) from 1195 campuses generated a 77% response rate.…

Chemistry Experiments

NASA Technical Reports Server (NTRS)

Brasseur, Guy; Remsberg, Ellis; Purcell, Patrick; Bhatt, Praful; Sage, Karen H.; Brown, Donald E.; Scott, Courtney J.; Ko, Malcolm K. W.; Tie, Xue-Xi; Huang, Theresa

1999-01-01

The purpose of the chemistry component of the model comparison is to assess to what extent differences in the formulation of chemical processes explain the variance between model results. Observed concentrations of chemical compounds are used to estimate to what degree the various models represent realistic situations. For readability, the materials for the chemistry experiment are reported in three separate sections. This section discussed the data used to evaluate the models in their simulation of the source gases and the Nitrogen compounds (NO(y)) and Chlorine compounds (Cl(y)) species.

A unifying concept of coccolithophore sensitivity to changing carbonate chemistry embedded in an ecological framework

NASA Astrophysics Data System (ADS)

Bach, Lennart Thomas; Riebesell, Ulf; Gutowska, Magdalena A.; Federwisch, Luisa; Schulz, Kai Georg

2015-06-01

Coccolithophores are a group of unicellular phytoplankton species whose ability to calcify has a profound influence on biogeochemical element cycling. Calcification rates are controlled by a large variety of biotic and abiotic factors. Among these factors, carbonate chemistry has gained considerable attention during the last years as coccolithophores have been identified to be particularly sensitive to ocean acidification. Despite intense research in this area, a general concept harmonizing the numerous and sometimes (seemingly) contradictory responses of coccolithophores to changing carbonate chemistry is still lacking to date. Here, we present the "substrate-inhibitor concept" which describes the dependence of calcification rates on carbonate chemistry speciation. It is based on observations that calcification rate scales positively with bicarbonate (HCO3-), the primary substrate for calcification, and carbon dioxide (CO2), which can limit cell growth, whereas it is inhibited by protons (H+). This concept was implemented in a model equation, tested against experimental data, and then applied to understand and reconcile the diverging responses of coccolithophorid calcification rates to ocean acidification obtained in culture experiments. Furthermore, we (i) discuss how other important calcification-influencing factors (e.g. temperature and light) could be implemented in our concept and (ii) embed it in Hutchinson's niche theory, thereby providing a framework for how carbonate chemistry-induced changes in calcification rates could be linked with changing coccolithophore abundance in the oceans. Our results suggest that the projected increase of H+ in the near future (next couple of thousand years), paralleled by only a minor increase of inorganic carbon substrate, could impede calcification rates if coccolithophores are unable to fully adapt. However, if calcium carbonate (CaCO3) sediment dissolution and terrestrial weathering begin to increase the oceans' HCO3

11(th) National Meeting of Organic Chemistry and 4(th) Meeting of Therapeutic Chemistry.

PubMed

Sousa, Maria Emília; Araújo, Maria João; do Vale, Maria Luísa; Andrade, Paula B; Branco, Paula; Gomes, Paula; Moreira, Rui; Pinho E Melo, Teresa M V D; Freitas, Victor

2016-03-17

For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight complementarities and to promote new synergies. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report.

Complex Autocatalysis in Simple Chemistries.

PubMed

Virgo, Nathaniel; Ikegami, Takashi; McGregor, Simon

2016-01-01

Life on Earth must originally have arisen from abiotic chemistry. Since the details of this chemistry are unknown, we wish to understand, in general, which types of chemistry can lead to complex, lifelike behavior. Here we show that even very simple chemistries in the thermodynamically reversible regime can self-organize to form complex autocatalytic cycles, with the catalytic effects emerging from the network structure. We demonstrate this with a very simple but thermodynamically reasonable artificial chemistry model. By suppressing the direct reaction from reactants to products, we obtain the simplest kind of autocatalytic cycle, resulting in exponential growth. When these simple first-order cycles are prevented from forming, the system achieves superexponential growth through more complex, higher-order autocatalytic cycles. This leads to nonlinear phenomena such as oscillations and bistability, the latter of which is of particular interest regarding the origins of life.

A Synergistic Combination of Advanced Separation and Chemical Scale Inhibitor Technologies for Efficient Use of Imparied Water As Cooling Water in Coal-based Power Plants

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

Jasbir Gill

2010-08-30

Nalco Company is partnering with Argonne National Laboratory (ANL) in this project to jointly develop advanced scale control technologies that will provide cost-effective solutions for coal-based power plants to operate recirculating cooling water systems at high cycles using impaired waters. The overall approach is to use combinations of novel membrane separations and scale inhibitor technologies that will work synergistically, with membrane separations reducing the scaling potential of the cooling water and scale inhibitors extending the safe operating range of the cooling water system. The project started on March 31, 2006 and ended in August 30, 2010. The project was amore » multiyear, multi-phase project with laboratory research and development as well as a small pilot-scale field demonstration. In Phase 1 (Technical Targets and Proof of Concept), the objectives were to establish quantitative technical targets and develop calcite and silica scale inhibitor chemistries for high stress conditions. Additional Phase I work included bench-scale testing to determine the feasibility of two membrane separation technologies (electrodialysis ED and electrode-ionization EDI) for scale minimization. In Phase 2 (Technology Development and Integration), the objectives were to develop additional novel scale inhibitor chemistries, develop selected separation processes, and optimize the integration of the technology components at the laboratory scale. Phase 3 (Technology Validation) validated the integrated system's performance with a pilot-scale demonstration. During Phase 1, Initial evaluations of impaired water characteristics focused on produced waters and reclaimed municipal wastewater effluents. Literature and new data were collected and evaluated. Characteristics of produced waters vary significantly from one site to another, whereas reclaimed municipal wastewater effluents have relatively more uniform characteristics. Assessment to date confirmed that calcite and

Putting a Human Face on Chemistry: A Project for Liberal Arts Chemistry.

ERIC Educational Resources Information Center

Kriz, George; Popejoy, Kate

A collaborative project in liberal arts chemistry, involving faculty in chemistry and science education, is described. The project includes various components: an introductory test (DAST) to examine students' perceptions of scientists, a group library research exercise, oral and written presentation of the results of the library research, a…

Research for the advancement of green chemistry practice: Studies in atmospheric and educational chemistry

NASA Astrophysics Data System (ADS)

Cullipher, Steven Gene

Green chemistry is a philosophy of chemistry that emphasizes a decreasing dependence on limited non-renewable resources and an increasing focus on preventing pollution byproducts of the chemical industry. In short, it is the discipline of chemistry practiced through the lens of environmental stewardship. In an effort to advance the practice of green chemistry, three studies will be described that have ramifications for the practice. The first study examines the atmospheric oxidation of a hydrofluorinated ether, a third-generation CFC replacement compound with primarily unknown atmospheric degradation products. Determination of these products has the potential to impact decisions on refrigerant usage in the future. The second study examines chemistry students' development of understanding benefits-costs-risks analysis when presented with two real-world scenarios: refrigerant choice and fuel choice. By studying how benefits-costs-risks thinking develops, curricular materials and instructional approaches can be designed to better foster the development of an ability that is both necessary for green chemists and important in daily decision-making for non-chemists. The final study uses eye tracking technology to examine students' abilities to interpret molecular properties from structural information in the context of global warming. Such abilities are fundamental if chemists are to appropriately assess risks and hazards of chemistry practice.

Infrared Lasers in Chemistry.

ERIC Educational Resources Information Center

John, Phillip

1982-01-01

Selected infrared laser chemistry topics are discussed including carbon dioxide lasers, infrared quanta and molecules, laser-induced chemistry, structural isomerization (laser purification, sensitized reactions, and dielectric breakdown), and fundamental principles of laser isotope separation, focusing on uranium isotope separation. (JN)

On the use of L-012, a luminol-based chemiluminescent probe, for detecting superoxide and identifying inhibitors of NADPH oxidase: A re-evaluation

PubMed Central

Zielonka, Jacek; Lambeth, J. David; Kalyanaraman, Balaraman

2014-01-01

L-012, a luminol-based chemiluminescent (CL) probe, is widely used in vitro and in vivo to detect NADPH oxidase (Nox)-derived superoxide (O2·−) and identify Nox inhibitors. Yet understanding of the free radical chemistry of L-012 probe is still lacking. We report that peroxidase and H2O2 induce superoxide dismutase (SOD)-sensitive, L-012-derived CL in the presence of oxygen. O2·− alone does not react with L-012 to emit luminescence. Self-generated O2·− during oxidation of L-012 and luminol-analogs artifactually induce CL inhibitable by SOD. These aspects make assays based on luminol analogs less than ideal for specific detection and identification of O2·− and NOX inhibitors. PMID:24080119

Carboxylesterase inhibitors

PubMed Central

Hatfield, M. Jason; Potter, Philip M.

2011-01-01

Introduction Carboxylesterases play major roles in the hydrolysis of numerous therapeutically active compounds. This is, in part, due to the prevalence of the ester moiety in these small molecules. However, the impact these enzymes may play on drug stability and pharmacokinetics is rarely considered prior to molecule development. Therefore, the application of selective inhibitors of this class of proteins may have utility in modulating the metabolism, distribution and toxicity of agents that are subjected to enzyme hydrolysis. Areas covered This review details the development of all such compounds dating back to 1986, but principally focuses on the very recent identification of selective human carboxylesterases inhibitors. Expert opinion The implementation of carboxylesterase inhibitors may significantly revolutionize drug discovery. Such molecules may allow for improved efficacy of compounds inactivated by this class of enzymes and/or reduce the toxicity of agents that are activated by these proteins. Furthermore, since lack of carboxylesterase activity appears to have no obvious biological consequence, these compounds could be applied in combination with virtually any esterified drug. Therefore, inhibitors of these proteins may have utility in altering drug hydrolysis and distribution in vivo. The characteristics, chemical and biological properties, and potential uses of such agents, are discussed here. PMID:21609191

Supramolecular chemistry-general principles and selected examples from anion recognition and metallosupramolecular chemistry.

PubMed

Albrecht, Markus

2007-12-01

This review gives an introduction into supramolecular chemistry describing in the first part general principles, focusing on terms like noncovalent interaction, molecular recognition, self-assembly, and supramolecular function. In the second part those will be illustrated by simple examples from our laboratories. Supramolecular chemistry is the science that bridges the gap between the world of molecules and nanotechnology. In supramolecular chemistry noncovalent interactions occur between molecular building blocks, which by molecular recognition and self-assembly form (functional) supramolecular entities. It is also termed the "chemistry of the noncovalent bond." Molecular recognition is based on geometrical complementarity based on the "key-and-lock" principle with nonshape-dependent effects, e.g., solvatization, being also highly influential. Self-assembly leads to the formation of well-defined aggregates. Hereby the overall structure of the target ensemble is controlled by the symmetry features of the certain building blocks. Finally, the aggregates can possess special properties or supramolecular functions, which are only found in the ensemble but not in the participating molecules. This review gives an introduction on supramolecular chemistry and illustrates the fundamental principles by recent examples from our group.

Does a Course on the History and Philosophy of Chemistry Have Any Effect on Prospective Chemistry Teachers' Perceptions? The Case of Chemistry and the Chemist

ERIC Educational Resources Information Center

Sendur, G.; Polat, M.; Kazanci, C.

2017-01-01

The creative comparisons prospective chemistry teachers make about "chemistry" and the "chemist" may reflect how they perceive these concepts. In this sense, it seems important to determine which creative comparisons prospective teachers make with respect to these and how these can change after the history of chemistry is…

11th National Meeting of Organic Chemistry and 4th Meeting of Therapeutic Chemistry

PubMed Central

Sousa, Maria Emília; Araújo, Maria João; do Vale, Maria Luísa; Andrade, Paula B.; Branco, Paula; Gomes, Paula; Moreira, Rui; Pinho e Melo, Teresa M.V.D.; Freitas, Victor

2016-01-01

For the first time under the auspices of Sociedade Portuguesa de Química, the competences of two important fields of Chemistry are brought together into a single event, the 11st National Organic Chemistry Meeting and the the 4th National Medicinal Chemistry Meeting, to highlight complementarities and to promote new synergies. Abstracts of plenary lectures, oral communications, and posters presented during the meeting are collected in this report. PMID:27102166

The future of discovery chemistry: quo vadis? Academic to industrial--the maturation of medicinal chemistry to chemical biology.

PubMed

Hoffmann, Torsten; Bishop, Cheryl

2010-04-01

At Roche, we set out to think about the future role of medicinal chemistry in drug discovery in a project involving both Roche internal stakeholders and external experts in drug discovery chemistry. To derive a coherent strategy, selected scientists were asked to take extreme positions and to derive two orthogonal strategic options: chemistry as the traditional mainstream science and chemistry as the central entrepreneurial science. We believe today's role of medicinal chemistry in industry has remained too narrow. To provide the innovation that industry requires, medicinal chemistry must play its part and diversify at pace with our increasing understanding of chemical biology and network pharmacology. 2010 Elsevier Ltd. All rights reserved.

Recent advances in medicinal chemistry of sulfonamides. Rational design as anti-tumoral, anti-bacterial and anti-inflammatory agents.

PubMed

Shah, Syed Shoaib Ahmad; Rivera, Gildardo; Ashfaq, Muhammad

2013-01-01

Now-a-days, cancer is becoming one of the major problems of public health in the world. Pharmacology treatment is a way to increase quality and long life. Predominantly, in last decade sulfonamide derivatives have been described as potential carbonic anhydrase inhibitors. In the present work, we describe recent advances during the last decade in medicinal chemistry of sulfonamides derivatives with some examples of rational design as anti-tumoral, antibacterial and anti-inflammatory agents. We show strategy design, structure-activity relationship, biological activity and advances of new sulfonamide compounds that have more health significance than some clinically used sulfonamides.

A model of CO-CH4 global transport/chemistry. I - Chemistry model

NASA Technical Reports Server (NTRS)

Peters, L. K.; Kitada, T.

1980-01-01

A simplified chemistry model was developed to incorporate the CO-CH4 chemistry into the global transport model of these compounds. CO is important because of its effects on atmospheric chemistry and is partly responsible for controlling the hydroxyl radical (OH) concentration in the troposphere. The model includes the photodissociation rate coefficients expressed as functions of solar zenith angle and altitude, and it was applied to determine the sensitivity of the OH concentration to trace gaseous species, such as NOx, O3, and H2O. Also, the concentrations and diurnal variations of OH and HO2, and the contribution of individual reactions to OH generation and consumption were calculated.

Reconsidering Learning Difficulties and Misconceptions in Chemistry: Emergence in Chemistry and Its Implications for Chemical Education

ERIC Educational Resources Information Center

Tümay, Halil

2016-01-01

Identifying students' misconceptions and learning difficulties and finding effective ways of addressing them has been one of the major concerns in chemistry education. However, the chemistry education community has paid little attention to determining discipline-specific aspects of chemistry that can lead to learning difficulties and…

Intelligent Chemistry Management System (ICMS)--A new approach to steam generator chemistry control

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

Barto, R.J.; Farrell, D.M.; Noto, F.A.

1986-04-01

The Intelligent Chemistry Management System (ICMS) is a new tool which assists in steam generator chemistry control. Utilizing diagnostic capabilities, the ICMS will provide utility and industrial boiler operators, system chemists, and plant engineers with a tool for monitoring, diagnosing, and controlling steam generator system chemistry. By reducing the number of forced outages through early identification of potentially detrimental conditions, suggestion of possible causes, and execution of corrective actions, improvements in unit availability and reliability will result. The system monitors water and steam quality at a number of critical locations in the plant.

Brushing Up on Chemistry.

ERIC Educational Resources Information Center

Trantow, Ashley

2002-01-01

Presents an activity designed for use during National Chemistry Week 2002 with the theme "Chemistry Keeps Us Clean". Allows students to discover more about a cleaning product they use everyday. Students make their own toothpaste and compare its properties with those of commercial toothpaste. (MM)

WATER CHEMISTRY ASSESSMENT METHODS

EPA Science Inventory

This section summarizes and evaluates the surfce water column chemistry assessment methods for USEPA/EMAP-SW, USGS-NAQA, USEPA-RBP, Oho EPA, and MDNR-MBSS. The basic objective of surface water column chemistry assessment is to characterize surface water quality by measuring a sui...

Curation of inhibitor-target data: process and impact on pathway analysis.

PubMed

Devidas, Sreenivas

2009-01-01

The past decade has seen a significant emergence in the availability and use of pathway analysis tools. The workflow that is supported by most of the pathway analysis tools is limited to either of the following: a. a network of genes based on the input data set, or b. the resultant network filtered down by a few criteria such as (but not limited to) i. disease association of the genes in the network; ii. targets known to be the target of one or more launched drugs; iii. targets known to be the target of one or more compounds in clinical trials; and iv. targets reasonably known to be potential candidate or clinical biomarkers. Almost all the tools in use today are biased towards the biological side and contain little, if any, information on the chemical inhibitors associated with the components of a given biological network. The limitation resides as follows: The fact that the number of inhibitors that have been published or patented is probably several fold (probably greater than 10-fold) more than the number of published protein-protein interactions. Curation of such data is both expensive and time consuming and could impact ROI significantly. The non-standardization associated with protein and gene names makes mapping reasonably non-straightforward. The number of patented and published inhibitors across target classes increases by over a million per year. Therefore, keeping the databases current becomes a monumental problem. Modifications required in the product architectures to accommodate chemistry-related content. GVK Bio has, over the past 7 years, curated the compound-target data that is necessary for the addition of such compound-centric workflows. This chapter focuses on identification, curation and utility of such data.

Chemistry inside an Epistemological Community Box! Discursive Exclusions and Inclusions in Swedish National Tests in Chemistry

ERIC Educational Resources Information Center

Ståhl, Marie; Hussénius, Anita

2017-01-01

This study examined the Swedish national tests in chemistry for implicit and explicit values. The chemistry subject is understudied compared to biology and physics and students view chemistry as their least interesting science subject. The Swedish national science assessments aim to support equitable and fair evaluation of students, to concretize…

A Comparison of Secondary Chemistry Courses and Chemistry Teacher Preparation Programs in Iowa and Saint Petersburg, Russia

NASA Astrophysics Data System (ADS)

Sanger, Michael J.; Brincks, Erik L.; Phelps, Amy J.; Pak, Maria S.; Lyovkin, Antony N.

2001-09-01

This paper, which is a result of the collaboration between the University of Northern Iowa (UNI) in Cedar Falls, Iowa, and Herzen State Pedagogical University of Russia in Saint Petersburg, compares the 7-12 chemistry courses in Iowa and Saint Petersburg and the chemistry teacher preparation programs at UNI and Herzen. Differences in the 7-12 chemistry courses include curriculum design (spiral versus layer cake), students' extracurricular activities, and access to technology in the classroom. Differences in the chemistry teacher preparation programs include the number of methods and chemistry content courses required, the number of chemistry teaching majors, the proportion of teaching majors enrolled in the different natural science programs, and the typical minors and endorsements received by these majors. Although we noted many differences in chemistry instruction between Iowa and Saint Petersburg, the secondary and college instructors still face many similar issues, which include overcoming student chemophobia, improving students' algorithmic and problem-solving skills, improving students' conceptual understanding at the particulate level, and dealing with shortages in qualified secondary science teachers.

On Study of New Progress and Application of Coordination Chemistry in Chemistry and Chemical Industry in Recent Years

NASA Astrophysics Data System (ADS)

Zhang, Yunshen

2017-12-01

Coordination chemistry refers to a branch of chemistry, and its research results are widely used in industry and people's daily life. Many edge disciplines emerge during the development, which propels the process of disciplines and technology. This paper briefly discusses new progress of coordination chemistry and its application in chemistry and chemical industry in recent years.

Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

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

Coteron, Jose M.; Marco, Maria; Esquivias, Jorge

2012-02-27

Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model,more » can be synthesized by a simple route, and rodent pharmacokinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.« less

Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor.

PubMed

Mulvihill, Mark J; Cooke, Andrew; Rosenfeld-Franklin, Maryland; Buck, Elizabeth; Foreman, Ken; Landfair, Darla; O'Connor, Matthew; Pirritt, Caroline; Sun, Yingchaun; Yao, Yan; Arnold, Lee D; Gibson, Neil W; Ji, Qun-Sheng

2009-09-01

The IGF-1 receptor (IGF-1R) has been implicated in the promotion of tumorigenesis, metastasis and resistance to cancer therapies. Therefore, this receptor has become a major focus for the development of anticancer agents. Our lead optimization efforts that blended structure-based design and empirical medicinal chemistry led to the discovery of OSI-906, a novel small-molecule dual IGF-1R/insulin receptor (IR) kinase inhibitor. OSI-906 potently and selectively inhibits autophosphorylation of both human IGF-1R and IR, displays in vitro antiproliferative effects in a variety of tumor cell lines and shows robust in vivo anti-tumor efficacy in an IGF-1R-driven xenograft model when administered orally once daily. OSI-906 is a novel, potent, selective and orally bioavailable dual IGF-1R/IR kinase inhibitor with favorable preclinical drug-like properties, which has demonstrated in vivo efficacy in tumor models and is currently in clinical testing.

ENVIRONMENTAL CHEMISTRY CAREERS IN GOVERNMENT AGENCIES

EPA Science Inventory

Careers in chemistry and chemistry related fields can be very rewarding and enriching. Being an environmental chemist for a government agency requires a broad background in the field of chemistry. A knowledge of the operation of several analytical and preparatory instruments is...

NUCLEAR CHEMISTRY ANNUAL REPORT 1970

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

Authors, Various

Papers are presented for the following topics: (1) Nuclear Structure and Nuclear Properties - (a) Nuclear Spectroscopy and Radioactivity; (b) Nuclear Reactions and Scattering; (c) Nuclear Theory; and (d) Fission. (2) Chemical and Atomic Physics - (a) Atomic and Molecular Spectroscopy; and (b) Hyperfine Interactions. (3) Physical, Inorganic, and Analytical Chemistry - (a) X-Ray Crystallography; (b) Physical and Inorganic Chemistry; (c) Radiation Chemistry; and (d) Chemical Engineering. (4) Instrumentation and Systems Development.

Eleventh international symposium on radiopharmaceutical chemistry

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

NONE

This document contains abstracts of papers which were presented at the Eleventh International Symposium on Radiopharmaceutical Chemistry. Sessions included: radiopharmaceuticals for the dopaminergic system, strategies for the production and use of labelled reactive small molecules, radiopharmaceuticals for measuring metabolism, radiopharmaceuticals for the serotonin and sigma receptor systems, labelled probes for molecular biology applications, radiopharmaceuticals for receptor systems, radiopharmaceuticals utilizing coordination chemistry, radiolabelled antibodies, radiolabelling methods for small molecules, analytical techniques in radiopharmaceutical chemistry, and analytical techniques in radiopharmaceutical chemistry.

Student academic achievement in college chemistry

NASA Astrophysics Data System (ADS)

Tabibzadeh, Kiana S.

General Chemistry is required for variety of baccalaureate degrees, including all medical related fields, engineering, and science majors. Depending on the institution, the prerequisite requirement for college level General Chemistry varies. The success rate for this course is low. The purpose of this study is to examine the factors influencing student academic achievement and retention in General Chemistry at the college level. In this study student achievement is defined by those students who earned grades of "C" or better. The dissertation contains in-depth studies on influence of Intermediate Algebra as a prerequisite compared to Fundamental Chemistry for student academic achievement and student retention in college General Chemistry. In addition the study examined the extent and manner in which student self-efficacy influences student academic achievement in college level General Chemistry. The sample for this part of the study is 144 students enrolled in first semester college level General Chemistry. Student surveys determined student self-efficacy level. The statistical analyses of study demonstrated that Fundamental Chemistry is a better prerequisite for student academic achievement and student retention. The study also found that student self-efficacy has no influence on student academic achievement. The significance of this study will be to provide data for the purpose of establishing a uniform and most suitable prerequisite for college level General Chemistry. Finally the variables identified to influence student academic achievement and enhance student retention will support educators' mission to maximize the students' ability to complete their educational goal at institutions of higher education.

Chemistry Education Research Trends: 2004-2013

ERIC Educational Resources Information Center

Teo, Tang Wee; Goh, Mei Ting; Yeo, Leck Wee

2014-01-01

This paper presents findings from a content analysis of 650 empirical chemistry education research papers published in two top-tiered chemistry education journals "Chemistry Education Research and Practice" and "Journal of Chemical Education," and four top-tiered science education journals "International Journal of Science…

40 CFR 158.2290 - Residue chemistry.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Residue chemistry. 158.2290 Section... REQUIREMENTS FOR PESTICIDES Antimicrobial Pesticide Data Requirements § 158.2290 Residue chemistry. (a) General... determine the residue chemistry data requirements for antimicrobial pesticide products. Notes that apply to...

40 CFR 158.2290 - Residue chemistry.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Residue chemistry. 158.2290 Section... REQUIREMENTS FOR PESTICIDES Antimicrobial Pesticide Data Requirements § 158.2290 Residue chemistry. (a) General... determine the residue chemistry data requirements for antimicrobial pesticide products. Notes that apply to...

Chemistry Outreach Project to High Schools Using a Mobile Chemistry Laboratory, ChemKits, and Teacher Workshops

ERIC Educational Resources Information Center

Long, Gary L.; Bailey, Carol A.; Bunn, Barbara B.; Slebodnick, Carla; Johnson, Michael R.; Derozier, Shad

2012-01-01

The Chemistry Outreach Program (ChOP) of Virginia Tech was a university-based outreach program that addressed the needs of high school chemistry classes in underfunded rural and inner-city school districts. The primary features of ChOP were a mobile chemistry laboratory (MCL), a shipping-based outreach program (ChemKits), and teacher workshops.…

Using Chemistry Teaching Aids Based Local Wisdom as an Alternative Media for Chemistry Teaching and Learning

ERIC Educational Resources Information Center

Priyambodo, Erfan; Wulaningrum, Safira

2017-01-01

Students have difficulties in relating the chemistry phenomena they learned and the life around them. It is necessary to have teaching aids which can help them to relate between chemistry with the phenomena occurred in everyday life, which is chemistry's teaching aids based on local wisdom. There are 3 teaching aids which used in chemistry…

School Chemistry: The Need for Transgression

NASA Astrophysics Data System (ADS)

Talanquer, Vicente

2013-07-01

Studies of the philosophy of chemistry over the past 15 years suggest that chemistry is a hybrid science which mixes scientific pursuits with technological applications. Dominant universal characterizations of the nature of science thus fail to capture the essence of the discipline. The central goal of this position paper is to encourage reflection about the extent to which dominant views about quality science education based on universal views of scientific practices may constrain school chemistry. In particular, we discuss how these predominant ideas restrict the development of chemistry curricula and instructional approaches that may better support the learning of the ideas and practices that studies of the philosophy of chemistry suggest are at the core of the discipline. Our analysis suggests that philosophical studies about the nature of chemistry invite us to transgress traditional educational boundaries between science and technology, inquiry and design, content and process, and to reconceptualize school chemistry as a paradigmatic techno scientific subject. To support these changes, chemical education researchers should expand the scope of their investigations to better understand how students and teachers reason about and engage in more authentic ways of chemical thinking and doing.

Chemistry, College Level. Annotated Bibliography of Tests.

ERIC Educational Resources Information Center

Educational Testing Service, Princeton, NJ. Test Collection.

Most of the 30 tests cited in this bibliography are those of the American Chemical Society. Subjects covered include physical chemistry, organic chemistry, inorganic chemistry, analytical chemistry, and other specialized areas. The tests are designed only for advanced high school, and both bachelor/graduate degree levels of college students. This…

40 CFR 158.2210 - Product chemistry.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Product chemistry. 158.2210 Section... REQUIREMENTS FOR PESTICIDES Antimicrobial Pesticide Data Requirements § 158.2210 Product chemistry. The product chemistry data requirements of subpart D of this part apply to antimicrobial products covered by this...

40 CFR 158.2210 - Product chemistry.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Product chemistry. 158.2210 Section... REQUIREMENTS FOR PESTICIDES Antimicrobial Pesticide Data Requirements § 158.2210 Product chemistry. The product chemistry data requirements of subpart D of this part apply to antimicrobial products covered by this...

KIDFamMap: a database of kinase-inhibitor-disease family maps for kinase inhibitor selectivity and binding mechanisms

PubMed Central

Chiu, Yi-Yuan; Lin, Chih-Ta; Huang, Jhang-Wei; Hsu, Kai-Cheng; Tseng, Jen-Hu; You, Syuan-Ren; Yang, Jinn-Moon

2013-01-01

Kinases play central roles in signaling pathways and are promising therapeutic targets for many diseases. Designing selective kinase inhibitors is an emergent and challenging task, because kinases share an evolutionary conserved ATP-binding site. KIDFamMap (http://gemdock.life.nctu.edu.tw/KIDFamMap/) is the first database to explore kinase-inhibitor families (KIFs) and kinase-inhibitor-disease (KID) relationships for kinase inhibitor selectivity and mechanisms. This database includes 1208 KIFs, 962 KIDs, 55 603 kinase-inhibitor interactions (KIIs), 35 788 kinase inhibitors, 399 human protein kinases, 339 diseases and 638 disease allelic variants. Here, a KIF can be defined as follows: (i) the kinases in the KIF with significant sequence similarity, (ii) the inhibitors in the KIF with significant topology similarity and (iii) the KIIs in the KIF with significant interaction similarity. The KIIs within a KIF are often conserved on some consensus KIDFamMap anchors, which represent conserved interactions between the kinase subsites and consensus moieties of their inhibitors. Our experimental results reveal that the members of a KIF often possess similar inhibition profiles. The KIDFamMap anchors can reflect kinase conformations types, kinase functions and kinase inhibitor selectivity. We believe that KIDFamMap provides biological insights into kinase inhibitor selectivity and binding mechanisms. PMID:23193279

Chemistry in Microfluidic Channels

ERIC Educational Resources Information Center

Chia, Matthew C.; Sweeney, Christina M.; Odom, Teri W.

2011-01-01

General chemistry introduces principles such as acid-base chemistry, mixing, and precipitation that are usually demonstrated in bulk solutions. In this laboratory experiment, we describe how chemical reactions can be performed in a microfluidic channel to show advanced concepts such as laminar fluid flow and controlled precipitation. Three sets of…

Movies in Chemistry Education

ERIC Educational Resources Information Center

Pekdag, Bulent; Le Marechal, Jean-Francois

2010-01-01

This article reviews numerous studies on chemistry movies. Movies, or moving pictures, are important elements of multimedia and signify a privileged or motivating means of presenting knowledge. Studies on chemistry movies show that the first movie productions in this field were devoted to university lectures or documentaries. Shorter movies were…

Greener Approaches to Undergraduate Chemistry Experiments.

ERIC Educational Resources Information Center

Kirchhoff, Mary, Ed.; Ryan, Mary Ann, Ed.

This laboratory manual introduces the idea of Green Chemistry, which is the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances. Instructional samples are included to help teachers integrate green chemistry into the college chemistry curriculum. Each laboratory includes: (1) a…

42 CFR 493.931 - Routine chemistry.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Routine chemistry. 493.931 Section 493.931 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.931 Routine chemistry. (a) Program content and frequency of challenge. To be approved for proficiency testing for routine chemistry, a program...

Supplemental Instruction in Physical Chemistry I

ERIC Educational Resources Information Center

Toby, Ellen; Scott, Timothy P.; Migl, David; Kolodzeji, Elizabeth

2016-01-01

Physical chemistry I at Texas A&M University is an upper division course requiring mathematical and analytical skills. As such, this course poses a major problem for many Chemistry, Engineering, Biochemistry and Genetics majors. Comparisons between participants and non-participants in Supplemental Instruction for physical chemistry were made…

42 CFR 493.931 - Routine chemistry.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Routine chemistry. 493.931 Section 493.931 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.931 Routine chemistry. (a) Program content and frequency of challenge. To be approved for proficiency testing for routine chemistry, a program...

42 CFR 493.931 - Routine chemistry.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Routine chemistry. 493.931 Section 493.931 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.931 Routine chemistry. (a) Program content and frequency of challenge. To be approved for proficiency testing for routine chemistry, a program...

42 CFR 493.931 - Routine chemistry.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Routine chemistry. 493.931 Section 493.931 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.931 Routine chemistry. (a) Program content and frequency of challenge. To be approved for proficiency testing for routine chemistry, a program...

42 CFR 493.931 - Routine chemistry.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Routine chemistry. 493.931 Section 493.931 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.931 Routine chemistry. (a) Program content and frequency of challenge. To be approved for proficiency testing for routine chemistry, a program...

Atmospheric Chemistry Experiment (ACE) Measurements of Tropospheric and Stratospheric Chemistry and Long-Term Trends

NASA Technical Reports Server (NTRS)

Rinsland, Curtis P.; Bernath, Peter; Boone, Chris; Nassar, Ray

2007-01-01

We highlight chemistry and trend measurement results from the Atmospheric Chemistry Experiment (ACE) which is providing precise middle troposphere to the lower thermosphere measurements with a 0.02/cm resolution Fourier transform spectrometer covering 750-4400/cm

Green analytical chemistry--theory and practice.

PubMed

Tobiszewski, Marek; Mechlińska, Agata; Namieśnik, Jacek

2010-08-01

This tutorial review summarises the current state of green analytical chemistry with special emphasis on environmentally friendly sample preparation techniques. Green analytical chemistry is a part of the sustainable development concept; its history and origins are described. Miniaturisation of analytical devices and shortening the time elapsing between performing analysis and obtaining reliable analytical results are important aspects of green analytical chemistry. Solventless extraction techniques, the application of alternative solvents and assisted extractions are considered to be the main approaches complying with green analytical chemistry principles.

Polymer Chemistry

NASA Technical Reports Server (NTRS)

Williams, Martha; Roberson, Luke; Caraccio, Anne

2010-01-01

This viewgraph presentation describes new technologies in polymer and material chemistry that benefits NASA programs and missions. The topics include: 1) What are Polymers?; 2) History of Polymer Chemistry; 3) Composites/Materials Development at KSC; 4) Why Wiring; 5) Next Generation Wiring Materials; 6) Wire System Materials and Integration; 7) Self-Healing Wire Repair; 8) Smart Wiring Summary; 9) Fire and Polymers; 10) Aerogel Technology; 11) Aerogel Composites; 12) Aerogels for Oil Remediation; 13) KSC's Solution; 14) Chemochromic Hydrogen Sensors; 15) STS-130 and 131 Operations; 16) HyperPigment; 17) Antimicrobial Materials; 18) Conductive Inks Formulations for Multiple Applications; and 19) Testing and Processing Equipment.

HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat.

PubMed

Fun, Axel; van Maarseveen, Noortje M; Pokorná, Jana; Maas, Renée Em; Schipper, Pauline J; Konvalinka, Jan; Nijhuis, Monique

2011-08-24

Maturation inhibitors are an experimental class of antiretrovirals that inhibit Human Immunodeficiency Virus (HIV) particle maturation, the structural rearrangement required to form infectious virus particles. This rearrangement is triggered by the ordered cleavage of the precursor Gag polyproteins into their functional counterparts by the viral enzyme protease. In contrast to protease inhibitors, maturation inhibitors impede particle maturation by targeting the substrate of protease (Gag) instead of the protease enzyme itself. Direct cross-resistance between protease and maturation inhibitors may seem unlikely, but the co-evolution of protease and its substrate, Gag, during protease inhibitor therapy, could potentially affect future maturation inhibitor therapy. Previous studies showed that there might also be an effect of protease inhibitor resistance mutations on the development of maturation inhibitor resistance, but the exact mechanism remains unclear. We used wild-type and protease inhibitor resistant viruses to determine the impact of protease inhibitor resistance mutations on the development of maturation inhibitor resistance. Our resistance selection studies demonstrated that the resistance profiles for the maturation inhibitor bevirimat are more diverse for viruses with a mutated protease compared to viruses with a wild-type protease. Viral replication did not appear to be a major factor during emergence of bevirimat resistance. In all in vitro selections, one of four mutations was selected: Gag V362I, A364V, S368N or V370A. The impact of these mutations on maturation inhibitor resistance and viral replication was analyzed in different protease backgrounds. The data suggest that the protease background affects development of HIV-1 resistance to bevirimat and the replication profiles of bevirimat-selected HIV-1. The protease-dependent bevirimat resistance and replication levels can be explained by differences in CA/p2 cleavage processing by the different

Undergraduate Chemistry Education: A Workshop Summary

ERIC Educational Resources Information Center

Sawyer, Keegan; Alper, Joe

2014-01-01

"Undergraduate Chemistry Education" is the summary of a workshop convened in May 2013 by the Chemical Science Roundtable of the National Research Council to explore the current state of undergraduate chemistry education. Research and innovation in undergraduate chemistry education has been done for many years, and one goal of this…

Natural product-based amyloid inhibitors.

PubMed

Velander, Paul; Wu, Ling; Henderson, Frances; Zhang, Shijun; Bevan, David R; Xu, Bin

2017-09-01

Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned. Copyright © 2017 Elsevier Inc. All rights reserved.

Natural product-based amyloid inhibitors

PubMed Central

Velander, Paul; Wu, Ling; Henderson, Frances; Zhang, Shijun; Bevan, David R.; Xu, Bin

2018-01-01

Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned. PMID:28390938

A Wet Chemistry Laboratory Cell

NASA Image and Video Library

2008-06-26

This picture of NASA Phoenix Mars Lander Wet Chemistry Laboratory WCL cell is labeled with components responsible for mixing Martian soil with water from Earth, adding chemicals and measuring the solution chemistry.

SGLT2 inhibitors.

PubMed

Dardi, I; Kouvatsos, T; Jabbour, S A

2016-02-01

Diabetes mellitus is a serious health issue and an economic burden, rising in epidemic proportions over the last few decades worldwide. Although several treatment options are available, only half of the global diabetic population achieves the recommended or individualized glycemic targets. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with a novel insulin-independent action. SGLT2 is a transporter found in the proximal renal tubules, responsible for the reabsorption of most of the glucose filtered by the kidney. Inhibition of SGLT2 lowers the blood glucose level by promoting the urinary excretion of excess glucose. Due to their insulin-independent action, SGLT2 inhibitors can be used with any degree of beta-cell dysfunction or insulin resistance, related to a very low risk of hypoglycemia. In addition to improving glycemic control, SGLT2 inhibitors have been associated with a reduction in weight and blood pressure when used as monotherapy or in combination with other antidiabetic agents in patients with type 2 diabetes mellitus (T2DM). Treatment with SGLT2 inhibitors is usually well tolerated; however, they have been associated with an increased incidence of urinary tract and genital infections, although these infections are usually mild and easy to treat. SGLT2 inhibitors are a promising new option in the armamentarium of drugs for patients with T2DM. Copyright © 2015 Elsevier Inc. All rights reserved.

A Discovery Chemistry Experiment on Buffers

ERIC Educational Resources Information Center

Kulevich, Suzanne E.; Herrick, Richard S.; Mills, Kenneth V.

2014-01-01

The Holy Cross Chemistry Department has designed and implemented an experiment on buffers as part of our Discovery Chemistry curriculum. The pedagogical philosophy of Discovery Chemistry is to make the laboratory the focal point of learning for students in their first two years of undergraduate instruction. We first pose questions in prelaboratory…

One-world chemistry and systems thinking

NASA Astrophysics Data System (ADS)

Matlin, Stephen A.; Mehta, Goverdhan; Hopf, Henning; Krief, Alain

2016-05-01

The practice and overarching mission of chemistry need a major overhaul in order to be fit for purpose in the twenty-first century and beyond. The concept of 'one-world' chemistry takes a systems approach that brings together many factors, including ethics and sustainability, that are critical to the future role of chemistry.

General chemistry courses that can affect achievement: An action research study in developing a plan to improve undergraduate chemistry courses

NASA Astrophysics Data System (ADS)

Shweikeh, Eman

Over the past 50 years, considerable research has been dedicated to chemistry education. In evaluating principal chemistry courses in higher education, educators have noted the learning process for first-year general chemistry courses may be challenging. The current study investigated perceptions of faculty, students and administrators on chemistry education at three institutions in Southern California. Via action research, the study sought to develop a plan to improve student engagement in general chemistry courses. A mixed method was utilized to analyze different perceptions on key factors determining the level of commitment and engagement in general chemistry education. The approach to chemistry learning from both a faculty and student perspective was examined including good practices, experiences and extent of active participation. The research study considered well-known measures of effective education with an emphasis on two key components: educational practices and student behavior. Institutional culture was inclusively assessed where cognitive expectations of chemistry teaching and learning were communicated. First, the extent in which faculty members are utilizing the "Seven Principles for Good Practice in Undergraduate Education" in their instruction was explored. Second, student attitudes and approaches toward chemistry learning were examined. The focus was on investigating student understanding of the learning process and the structure of chemistry knowledge. The seven categories used to measure students' expectations for learning chemistry were: effort, concepts, math link, reality link, outcome, laboratory, and visualization. This analysis represents the views of 16 faculty and 140 students. The results validated the assertion that students need some competencies and skills to tackle the challenges of the chemistry learning process to deeply engage in learning. A mismatch exists between the expectations of students and those of the faculty

Quantum Chemistry in Great Britain: Developing a Mathematical Framework for Quantum Chemistry

NASA Astrophysics Data System (ADS)

Simões, Ana; Gavroglu, Kostas

By 1935 quantum chemistry was already delineated as a distinct sub-discipline due to the contributions of Fritz London, Walter Heitler, Friedrich Hund, Erich Hückel, Robert Mulliken, Linus Pauling, John van Vleck and John Slater. These people are credited with showing that the application of quantum mechanics to the solution of chemical problems was, indeed, possible, especially so after the introduction of a number of new concepts and the adoption of certain approximation methods. And though a number of chemists had started talking of the formation of theoretical or, even, mathematical chemistry, a fully developed mathematical framework of quantum chemistry was still wanting. The work of three persons in particular-of John E. Lennard-Jones, Douglas R. Hartree, and Charles Alfred Coulson-has been absolutely crucial in the development of such a framework. In this paper we shall discuss the work of these three researchers who started their careers in the Cambridge tradition of mathematical physics and who at some point of their careers all became professors of applied mathematics. We shall argue that their work consisted of decisive contributions to the development of such a mathematical framework for quantum chemistry.

Digital biology and chemistry.

PubMed

Witters, Daan; Sun, Bing; Begolo, Stefano; Rodriguez-Manzano, Jesus; Robles, Whitney; Ismagilov, Rustem F

2014-09-07

This account examines developments in "digital" biology and chemistry within the context of microfluidics, from a personal perspective. Using microfluidics as a frame of reference, we identify two areas of research within digital biology and chemistry that are of special interest: (i) the study of systems that switch between discrete states in response to changes in chemical concentration of signals, and (ii) the study of single biological entities such as molecules or cells. In particular, microfluidics accelerates analysis of switching systems (i.e., those that exhibit a sharp change in output over a narrow range of input) by enabling monitoring of multiple reactions in parallel over a range of concentrations of signals. Conversely, such switching systems can be used to create new kinds of microfluidic detection systems that provide "analog-to-digital" signal conversion and logic. Microfluidic compartmentalization technologies for studying and isolating single entities can be used to reconstruct and understand cellular processes, study interactions between single biological entities, and examine the intrinsic heterogeneity of populations of molecules, cells, or organisms. Furthermore, compartmentalization of single cells or molecules in "digital" microfluidic experiments can induce switching in a range of reaction systems to enable sensitive detection of cells or biomolecules, such as with digital ELISA or digital PCR. This "digitizing" offers advantages in terms of robustness, assay design, and simplicity because quantitative information can be obtained with qualitative measurements. While digital formats have been shown to improve the robustness of existing chemistries, we anticipate that in the future they will enable new chemistries to be used for quantitative measurements, and that digital biology and chemistry will continue to provide further opportunities for measuring biomolecules, understanding natural systems more deeply, and advancing molecular and

Bioorganic and bioinorganic chemistry.

PubMed

Constable, Edwin C; Housecroft, Catherine E; Creus, Marc; Gademann, Karl; Giese, Bernd; Ward, Thomas R; Woggon, Wolf D; Chougnet, Antoinette

2010-01-01

The interdisciplinary projects in bioinorganic and bioorganic chemistry of the Department of Chemistry, University of Basel led to the preparation of new systems that mimic biologically important processes and to the discovery of compounds from natural sources which are very promising with respect to medical applications. The advances in these areas are reported here.

Student continuation in high school chemistry

NASA Astrophysics Data System (ADS)

Bowen, James Iddon

2006-12-01

This investigation originally intended to uncover teacher behaviors that encourage students to persist in AP Chemistry in a typical urban Texas high school. As the investigation progressed, however, alternative reasons were sought for the persistence of some students when it became apparent that teacher behaviors might not be a factor in the decision to select AP Chemistry at the school under observation. In response to this, "Branding", a business theory which suggests certain attractive aspects of a product are promoted as a way to improve sales, is introduced as an alternative way of thinking about persistence in chemistry. "Branding" can explain why some students continue to select chemistry in the face of disappointing teaching. It is also argued here that "Branding" can encourage more students to take chemistry in the future.

Combined treatment with MAO-A inhibitor and MAO-B inhibitor increases extracellular noradrenaline levels more than MAO-A inhibitor alone through increases in beta-phenylethylamine.

PubMed

Kitaichi, Yuji; Inoue, Takeshi; Nakagawa, Shin; Boku, Shuken; Izumi, Takeshi; Koyama, Tsukasa

2010-07-10

Monoamine oxidase inhibitors (MAO inhibitors) have been widely used as antidepressants. However, it remains unclear whether a difference exists between non-selective MAO inhibitors and selective MAO-A inhibitors in terms of their antidepressant effects. Using in vivo microdialysis methods, we measured extracellular noradrenaline and serotonin levels following administration of Ro 41-1049, a reversible MAO-A inhibitor and/or lazabemide, a reversible MAO-B inhibitor in the medial prefrontal cortex (mPFC) of rats. We examined the effect of local infusion of beta-phenylethylamine to the mPFC of rats on extracellular noradrenaline and serotonin levels. Furthermore, the concentrations of beta-phenylethylamine in the tissue of the mPFC after combined treatment with Ro 41-1049 and lazabemide were measured. The Ro 41-1049 alone and the combined treatment significantly increased extracellular noradrenaline levels compared with vehicle and lazabemide alone. Furthermore, the combined treatment increased noradrenaline levels significantly more than Ro 41-1049 alone did. The Ro 41-1049 alone and the combined treatment significantly increased extracellular serotonin levels compared with vehicle and lazabemide alone, but no difference in serotonin levels was found between the combined treatment group and the Ro 41-1049 group. Local infusion of low-dose beta-phenylethylamine increased extracellular noradrenaline levels, but not that of serotonin. Only the combined treatment significantly increased beta-phenylethylamine levels in tissues of the mPFC. Our results suggest that the combined treatment with a MAO-A inhibitor and a MAO-B inhibitor strengthens antidepressant effects because the combined treatment increases extracellular noradrenaline levels more than a MAO-A inhibitor alone through increases in beta-phenylethylamine. Copyright 2010 Elsevier B.V. All rights reserved.

The ACS Exams Institute Undergraduate Chemistry Anchoring Concepts Content Map II: Organic Chemistry

ERIC Educational Resources Information Center

Raker, Jeffrey; Holme, Thomas; Murphy, Kristen

2013-01-01

As a way to assist chemistry departments with programmatic assessment of undergraduate chemistry curricula, the ACS Examinations Institute is devising a map of the content taught throughout the undergraduate curriculum. The structure of the map is hierarchal, with large grain size at the top and more content detail as one moves "down"…

Education: Chemistry Faculties Gain Women Slowly.

ERIC Educational Resources Information Center

Chemical and Engineering News, 1984

1984-01-01

Highlights survey results on the status of females in full-time, tenured or tenure track faculty positions in chemistry. Indicates that males still dominate PhD-granting chemistry faculties and that, although the number of women is increasing, the increase is not proportionate to the rate at which they are earning chemistry PhDs. (JM)

Chemistry in the Two-Year College. Proceedings from Two-Year College Chemistry Conference and Papers of Special Interest to the Two-Year College Chemistry Teacher. 1971 No. 1.

ERIC Educational Resources Information Center

Chapman, Kenneth, Ed.

In this publication, issued twice per year, four major topics are discussed: (1) chemistry course content, including chemistry for nonscience students and nurses; (2) using media in chemistry, such as behavioral objectives and audio-tutorial aids; (3) chemical technology, with emphasis on the Chemical Technology Curriculum Project (Chem TeC); and…

Kinome-wide selectivity profiling of ATP-competitive mammalian target of rapamycin (mTOR) inhibitors and characterization of their binding kinetics.

PubMed

Liu, Qingsong; Kirubakaran, Sivapriya; Hur, Wooyoung; Niepel, Mario; Westover, Kenneth; Thoreen, Carson C; Wang, Jinhua; Ni, Jing; Patricelli, Matthew P; Vogel, Kurt; Riddle, Steve; Waller, David L; Traynor, Ryan; Sanda, Takaomi; Zhao, Zheng; Kang, Seong A; Zhao, Jean; Look, A Thomas; Sorger, Peter K; Sabatini, David M; Gray, Nathanael S

2012-03-23

An intensive recent effort to develop ATP-competitive mTOR inhibitors has resulted in several potent and selective molecules such as Torin1, PP242, KU63794, and WYE354. These inhibitors are being widely used as pharmacological probes of mTOR-dependent biology. To determine the potency and specificity of these agents, we have undertaken a systematic kinome-wide effort to profile their selectivity and potency using chemical proteomics and assays for enzymatic activity, protein binding, and disruption of cellular signaling. Enzymatic and cellular assays revealed that all four compounds are potent inhibitors of mTORC1 and mTORC2, with Torin1 exhibiting ∼20-fold greater potency for inhibition of Thr-389 phosphorylation on S6 kinases (EC(50) = 2 nM) relative to other inhibitors. In vitro biochemical profiling at 10 μM revealed binding of PP242 to numerous kinases, although WYE354 and KU63794 bound only to p38 kinases and PI3K isoforms and Torin1 to ataxia telangiectasia mutated, ATM and Rad3-related protein, and DNA-PK. Analysis of these protein targets in cellular assays did not reveal any off-target activities for Torin1, WYE354, and KU63794 at concentrations below 1 μM but did show that PP242 efficiently inhibited the RET receptor (EC(50), 42 nM) and JAK1/2/3 kinases (EC(50), 780 nM). In addition, Torin1 displayed unusually slow kinetics for inhibition of the mTORC1/2 complex, a property likely to contribute to the pharmacology of this inhibitor. Our results demonstrated that, with the exception of PP242, available ATP-competitive compounds are highly selective mTOR inhibitors when applied to cells at concentrations below 1 μM and that the compounds may represent a starting point for medicinal chemistry efforts aimed at developing inhibitors of other PI3K kinase-related kinases.

Development of the Connected Chemistry as Formative Assessment Pedagogy for High School Chemistry Teaching

ERIC Educational Resources Information Center

Park, Mihwa; Liu, Xiufeng; Waight, Noemi

2017-01-01

This paper describes the development of Connected Chemistry as Formative Assessment (CCFA) pedagogy, which integrates three promising teaching and learning approaches, computer models, formative assessments, and learning progressions, to promote student understanding in chemistry. CCFA supports student learning in making connections among the…

Zambian Pre-Service Chemistry Teachers' Views on Chemistry Education Goals and Challenges for Achieving Them in Schools

ERIC Educational Resources Information Center

Banda, Asiana; Mumba, Frackson; Chabalengula, Vivien M.

2014-01-01

This study examined Zambian preservice chemistry teachers' views on the goals of chemistry education, the importance of the goals, and challenges for achieving them in schools. The study sample was comprised of 59 pre-service chemistry teachers at the University of Zambia. Data were collected using a modified Likert-scale questionnaire that was…

Special Report: Chemistry of Comets.

ERIC Educational Resources Information Center

A'Hearn, Michael F.

1984-01-01

Discusses the chemistry of comets. How comets provide clues to the birth of the solar system, photolytic reactions on comets involving water, chemical modeling, nuclear chemistry, and research findings are among the areas considered. (JN)

Stratospheric chemistry and transport

NASA Technical Reports Server (NTRS)

Prather, Michael; Garcia, Maria M.

1990-01-01

A Chemical Tracer Model (CTM) that can use wind field data generated by the General Circulation Model (GCM) is developed to implement chemistry in the three dimensional GCM of the middle atmosphere. Initially, chemical tracers with simple first order losses such as N2O are used. Successive models are to incorporate more complex ozone chemistry.

Crocodile Chemistry. [CD-ROM].

ERIC Educational Resources Information Center

1999

This high school chemistry resource is an on-screen chemistry lab. In the program, students can experiment with a huge range of chemicals, choosing the form, quantity and concentrations. Dangerous or difficult experiments can be investigated safely and easily. A vast range of equipment can be set up, and complex simulations can be put together and…

Chemistry, A Syllabus for Secondary Schools.

ERIC Educational Resources Information Center

New York State Education Dept., Albany. Bureau of Secondary Curriculum Development.

This is a 1971 reprint of the chemistry syllabus printed in 1966 for the state of New York. This course of study presents a modern view of chemistry suitable for pupils with a wide range of skills and abilities. The outline of topics provides the unifying principles of chemistry together with related facts. The principles included in the outline…

EVOLVING FROM GREEN CHEMISTRY TO SUSTAINABLE CHEMISTRY

EPA Science Inventory

The twelve principles of green chemistry provide a foundation and pathway which allows researchers to incorporate greenness into existing reactions or when developing new technologies. Research from our laboratory has adopted many of these principles and utlizes them as a major c...

The Birthday of Organic Chemistry.

ERIC Educational Resources Information Center

Benfey, Otto Theodor; Kaufman, George B.

1979-01-01

Describes how the synthesis of urea, 150 years ago, was a major factor in breaking the artificial barrier that existed between organic and inorganic chemistry, and this contributed to the rapid growth of organic chemistry. (GA)

Methodology in diagnostic laboratory test research in clinical chemistry and clinical chemistry and laboratory medicine.

PubMed

Lumbreras-Lacarra, Blanca; Ramos-Rincón, José Manuel; Hernández-Aguado, Ildefonso

2004-03-01

The application of epidemiologic principles to clinical diagnosis has been less developed than in other clinical areas. Knowledge of the main flaws affecting diagnostic laboratory test research is the first step for improving its quality. We assessed the methodologic aspects of articles on laboratory tests. We included articles that estimated indexes of diagnostic accuracy (sensitivity and specificity) and were published in Clinical Chemistry or Clinical Chemistry and Laboratory Medicine in 1996, 2001, and 2002. Clinical Chemistry has paid special attention to this field of research since 1996 by publishing recommendations, checklists, and reviews. Articles were identified through electronic searches in Medline. The strategy combined the Mesh term "sensitivity and specificity" (exploded) with the text words "specificity", "false negative", and "accuracy". We examined adherence to seven methodologic criteria used in the study by Reid et al. (JAMA1995;274:645-51) of papers published in general medical journals. Three observers evaluated each article independently. Seventy-nine articles fulfilled the inclusion criteria. The percentage of studies that satisfied each criterion improved from 1996 to 2002. Substantial improvement was observed in reporting of the statistical uncertainty of indices of diagnostic accuracy, in criteria based on clinical information from the study population (spectrum composition), and in avoidance of workup bias. Analytical reproducibility was reported frequently (68%), whereas information about indeterminate results was rarely provided. The mean number of methodologic criteria satisfied showed a statistically significant increase over the 3 years in Clinical Chemistry but not in Clinical Chemistry and Laboratory Medicine. The methodologic quality of the articles on diagnostic test research published in Clinical Chemistry and Clinical Chemistry and Laboratory Medicine is comparable to the quality observed in the best general medical journals

Nuclear chemistry. Annual report, 1974

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

Conzett, H.E.; Edelstein, N.M.; Tsang, C.F.

1975-07-01

The 1974 Nuclear Chemistry Annual Report contains information on research in the following areas: nuclear science (nuclear spectroscopy and radioactivity, nuclear reactions and scattering, nuclear theory); chemical and atomic physics (heavy ion-induced atomic reactions, atomic and molecular spectroscopy, photoelectron spectroscopy and hyperfine interactions); physical, inorganic, and analytical chemistry (x-ray crystallography, physical and inorganic chemistry, geochemistry); and instrumentation. Thesis abstracts, 1974 publication titles, and an author index are also included. Papers having a significant amount of information are listed separately by title. (RWR)

Exploring Diverse Students' Trends in Chemistry Self-Efficacy throughout a Semester of College-Level Preparatory Chemistry

ERIC Educational Resources Information Center

Villafañe, Sachel M.; Garcia, C. Alicia; Lewis, Jennifer E.

2014-01-01

Chemistry self-efficacy has been defined as a student's beliefs about his or her own capability to perform a given chemistry task. These chemistry self-efficacy beliefs can be influenced by students' experiences in a course, and eventually, these beliefs could affect students' decisions to continue into STEM related-careers. In this study, we…

Evaluating the efficacy of a chemistry video game

NASA Astrophysics Data System (ADS)

Shapiro, Marina

A quasi-experimental design pre-test/post-test intervention study utilizing a within group analysis was conducted with 45 undergraduate college chemistry students that investigated the effect of implementing a game-based learning environment into an undergraduate college chemistry course in order to learn if serious educational games (SEGs) can be used to achieve knowledge gains of complex chemistry concepts and to achieve increase in students' positive attitude toward chemistry. To evaluate if students learn chemistry concepts by participating in a chemistry game-based learning environment, a one-way repeated measures analysis of variance (ANOVA) was conducted across three time points (pre-test, post-test, delayed post-test which were chemistry content exams). Results showed that there was an increase in exam scores over time. The results of the ANOVA indicated a statistically significant time effect. To evaluate if students' attitude towards chemistry increased as a result of participating in a chemistry game-based learning environment a paired samples t-test was conducted using a chemistry attitudinal survey by Mahdi (2014) as the pre- and post-test. Results of the paired-samples t-test indicated that there was no significant difference in pre-attitudinal scores and post-attitudinal scores.

Peptidase inhibitors in tick physiology.

PubMed

Parizi, L F; Ali, A; Tirloni, L; Oldiges, D P; Sabadin, G A; Coutinho, M L; Seixas, A; Logullo, C; Termignoni, C; DA Silva Vaz, I

2018-06-01

Peptidase inhibitors regulate a wide range of physiological processes involved in the interaction between hematophagous parasites and their hosts, including tissue remodeling, the immune response and blood coagulation. In tick physiology, peptidase inhibitors have a crucial role in adaptation to improve parasitism mechanisms, facilitating blood feeding by interfering with defense-related host peptidases. Recently, a larger number of studies on this topic led to the description of several new tick inhibitors displaying interesting novel features, for example a role in pathogen transmission to the host. A comprehensive review discussing these emerging concepts can therefore shed light on peptidase inhibitor functions, their relevance to tick physiology and their potential applications. Here, we summarize and examine the general characteristics, functional diversity and action of tick peptidase inhibitors with known physiological roles in the tick-host-pathogen interaction. © 2017 The Royal Entomological Society.

Inside HDAC with HDAC inhibitors.

PubMed

Bertrand, Philippe

2010-06-01

Histone deacetylase inhibitors are a large group of diverse molecules intrinsically able to inhibit cell proliferation in various cancer cell lines. Their apoptotic effects have been linked to the modulation in the expression of several regulatory tumor suppressor genes caused by the modified status of histone acetylation, a key event in chromatin remodelling. As the initial histone deacetylase activity of HDAC has been extended to other proteins, the possible other biological mechanisms modified by HDAC inhibitor treatments are still to be clarified. The need for HDAC isoform selective inhibitors is an important issue to serve this goal. This review discusses the approaches proposed by several research groups working on the synthesis of HDAC inhibitors, based on modelling studies and the way these findings were used to obtain new HDAC inhibitors with possible isoform selectivity. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Computational chemistry

NASA Technical Reports Server (NTRS)

Arnold, J. O.

1987-01-01

With the advent of supercomputers, modern computational chemistry algorithms and codes, a powerful tool was created to help fill NASA's continuing need for information on the properties of matter in hostile or unusual environments. Computational resources provided under the National Aerodynamics Simulator (NAS) program were a cornerstone for recent advancements in this field. Properties of gases, materials, and their interactions can be determined from solutions of the governing equations. In the case of gases, for example, radiative transition probabilites per particle, bond-dissociation energies, and rates of simple chemical reactions can be determined computationally as reliably as from experiment. The data are proving to be quite valuable in providing inputs to real-gas flow simulation codes used to compute aerothermodynamic loads on NASA's aeroassist orbital transfer vehicles and a host of problems related to the National Aerospace Plane Program. Although more approximate, similar solutions can be obtained for ensembles of atoms simulating small particles of materials with and without the presence of gases. Computational chemistry has application in studying catalysis, properties of polymers, all of interest to various NASA missions, including those previously mentioned. In addition to discussing these applications of computational chemistry within NASA, the governing equations and the need for supercomputers for their solution is outlined.

Cycloadditions in modern polymer chemistry.

PubMed

Delaittre, Guillaume; Guimard, Nathalie K; Barner-Kowollik, Christopher

2015-05-19

Synthetic polymer chemistry has undergone two major developments in the last two decades. About 20 years ago, reversible-deactivation radical polymerization processes started to give access to a wide range of polymeric architectures made from an almost infinite reservoir of functional building blocks. A few years later, the concept of click chemistry revolutionized the way polymer chemists approached synthetic routes. Among the few reactions that could qualify as click, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) initially stood out. Soon, many old and new reactions, including cycloadditions, would further enrich the synthetic macromolecular chemistry toolbox. Whether click or not, cycloadditions are in any case powerful tools for designing polymeric materials in a modular fashion, with a high level of functionality and, sometimes, responsiveness. Here, we wish to describe cycloaddition methodologies that have been reported in the last 10 years in the context of macromolecular engineering, with a focus on those developed in our laboratories. The overarching structure of this Account is based on the three most commonly encountered cycloaddition subclasses in organic and macromolecular chemistry: 1,3-dipolar cycloadditions, (hetero-)Diels-Alder cycloadditions ((H)DAC), and [2+2] cycloadditions. Our goal is to briefly describe the relevant reaction conditions, the advantages and disadvantages, and the realized polymer applications. Furthermore, the orthogonality of most of these reactions is highlighted because it has proven highly beneficial for generating unique, multifunctional polymers in a one-pot reaction. The overview on 1,3-dipolar cycloadditions is mostly centered on the application of CuAAC as the most travelled route, by far. Besides illustrating the capacity of CuAAC to generate complex polymeric architectures, alternative 1,3-dipolar cycloadditions operating without the need for a catalyst are described. In the area of (H)DA cycloadditions

Chemistry WebBook

National Institute of Standards and Technology Data Gateway

SRD 69 NIST Chemistry WebBook (Web, free access)   The NIST Chemistry WebBook contains: Thermochemical data for over 7000 organic and small inorganic compounds; thermochemistry data for over 8000 reactions; IR spectra for over 16,000 compounds; mass spectra for over 33,000 compounds; UV/Vis spectra for over 1600 compounds; electronic and vibrational spectra for over 5000 compounds; constants of diatomic molecules(spectroscopic data) for over 600 compounds; ion energetics data for over 16,000 compounds; thermophysical property data for 74 fluids.

STUDENT SUCCESS IN BEGINNING CHEMISTRY (CHEMISTRY 3) AT EL CAMINO COLLEGE, 1964-65.

ERIC Educational Resources Information Center

MOONEY, WILLIAM T.

THE PURPOSE OF THE STUDY WAS TO DETERMINE THE RELATIONSHIP BETWEEN STUDENTS' ACHIEVEMENT ON BEGINNING CHEMISTRY AND THEIR BACKGROUND PRIOR TO ENROLLMENT IN THE COURSE. OF THE 609 STUDENTS ENROLLED IN BEGINNING CHEMISTRY IN THE 1964-65 ACADEMIC YEAR, 45 PERCENT RECEIVED GRADES OF A, B, OR C. OF THE GROUP STUDIED, 23 PERCENT WERE REPEATING THE…

Cyclin-Dependent Kinase Inhibitors as Anticancer Therapeutics

PubMed Central

Corsino, Patrick E.; Narayan, Satya

2015-01-01

Cyclin-dependent kinases (CDKs) have been considered promising drug targets for a number of years, but most CDK inhibitors have failed rigorous clinical testing. Recent studies demonstrating clear anticancer efficacy and reduced toxicity of CDK4/6 inhibitors such as palbociclib and multi-CDK inhibitors such as dinaciclib have rejuvenated the field. Favorable results with palbociclib and its recent U.S. Food and Drug Administration approval demonstrate that CDK inhibitors with narrow selectivity profiles can have clinical utility for therapy based on individual tumor genetics. A brief overview of results obtained with ATP-competitive inhibitors such as palbociclib and dinaciclib is presented, followed by a compilation of new avenues that have been pursued toward the development of novel, non–ATP-competitive CDK inhibitors. These creative ways to develop CDK inhibitors are presented along with crystal structures of these agents complexed with CDK2 to highlight differences in their binding sites and mechanisms of action. The recent successes of CDK inhibitors in the clinic, combined with the potential for structure-based routes to the development of non–ATP-competitive CDK inhibitors, and evidence that CDK inhibitors may have use in suppressing chromosomal instability and in synthetic lethal drug combinations inspire optimism that CDK inhibitors will become important weapons in the fight against cancer. PMID:26018905

Syk inhibitors.

PubMed

Chihara, Kazuyasu; Kimura, Yukihiro; Honjo, Chisato; Takeuchi, Kenji; Sada, Kiyonao

2013-01-01

Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was isolated in University of Fukui in 1991. Syk is most highly expressed by haemopoietic cells and known to play crucial roles in the signal transduction through various immunoreceptors of the adaptive immune response. However, recent reports demonstrate that Syk also mediates other biological functions, such as innate immune response, osteoclast maturation, platelet activation and cellular adhesion. Moreover, ectopic expression of Syk by epigenetic changes is reported to cause retinoblastoma. Because of its critical roles on the cellular functions, the development of Syk inhibitors for clinical use has been desired. Although many candidate compounds were produced, none of them had progressed to clinical trials. However, novel Syk inhibitors were finally developed and its usefulness has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis and idiopathic thrombocytopenic purpura. In this review, we will summarize the history, structure and function of Syk, and then the novel Syk inhibitors and their current status. In addition, we will introduce our research focused on the functions of Syk on Dectin-1-mediated mast cell activation.

Organic Chemistry in Action! What Is the Reaction?

ERIC Educational Resources Information Center

O'Dwyer, Anne; Childs, Peter

2015-01-01

The "Organic Chemistry in Action!" ("OCIA!") program is a set of teaching resources designed to facilitate the teaching and learning of introductory level organic chemistry. The "OCIA!" program was developed in collaboration with practicing and experienced chemistry teachers, using findings from Chemistry Education…

The effects of residual platelets in plasma on plasminogen activator inhibitor-1 and plasminogen activator inhibitor-1-related assays.

PubMed

Pieters, Marlien; Barnard, Sunelle A; Loots, Du Toit; Rijken, Dingeman C

2017-01-01

Due to controversial evidence in the literature pertaining to the activity of plasminogen activator inhibitor-1 in platelets, we examined the effects of residual platelets present in plasma (a potential pre-analytical variable) on various plasminogen activator inhibitor-1 and plasminogen activator inhibitor-1-related assays. Blood samples were collected from 151 individuals and centrifuged at 352 and 1500 g to obtain plasma with varying numbers of platelet. In a follow-up study, blood samples were collected from an additional 23 individuals, from whom platelet-poor (2000 g), platelet-containing (352 g) and platelet-rich plasma (200 g) were prepared and analysed as fresh-frozen and after five defrost-refreeze cycles (to determine the contribution of in vitro platelet degradation). Plasminogen activator inhibitor-1 activity, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex, plasma clot lysis time, β-thromboglobulin and plasma platelet count were analysed. Platelet α-granule release (plasma β-thromboglobulin) showed a significant association with plasminogen activator inhibitor-1 antigen levels but weak associations with plasminogen activator inhibitor-1 activity and a functional marker of fibrinolysis, clot lysis time. Upon dividing the study population into quartiles based on β-thromboglobulin levels, plasminogen activator inhibitor-1 antigen increased significantly across the quartiles while plasminogen activator inhibitor-1 activity and clot lysis time tended to increase in the 4th quartile only. In the follow-up study, plasma plasminogen activator inhibitor-1 antigen was also significantly influenced by platelet count in a concentration-dependent manner. Plasma plasminogen activator inhibitor-1 antigen levels increased further after complete platelet degradation. Residual platelets in plasma significantly influence plasma plasminogen activator inhibitor-1 antigen levels mainly through release of

Complex Protostellar Chemistry

NASA Technical Reports Server (NTRS)

Nuth, Joseph A., III; Johnson, Natasha M.

2012-01-01

Two decades ago, our understanding chemistry in protostars was simple -- matter either fell into the central star or was trapped in planetary-scale objects. Some minor chemical changes might occur as the dust and gas fell inward, but such effects were overwhelmed by the much larger-scale processes that occurred even in bodies as small as asteroids. The chemistry that did occur in the nebula was relatively easy to model because the fall from the cold molecular cloud into the growing star was a one-way trip down a well-known temperature pressure gradient; the only free variable was time. However, just over 10 years ago it was suggested that some material could be processed in the inner nebula, flow outward, and become incorporated into comets. This outward flow was confirmed when the Stardust mission returned crystalline mineral fragments from Comet Wild 2 that must have been processed close to the Sun before they were incorporated into the comet. In this week's Science Express, Ciesla and Sandford demonstrate that even the outermost regions of the solar nebula can be a chemically active environment. Their finding could have consequences for the rest of the nebula. Our understanding of the chemistry in protostellar systems has made enormous progress over the last few decades, fueled by an increased awareness of the complex dynamics of these evolving energetic nebulae. We can no longer consider just the simple local environment to explain the composition of a planet, asteroid, or comet as was done in the past, but must now consider chemical processes that might take place within the nebula as a whole as well as the probability of transport and mixing the products of such reactions throughout the system. just as we now find it impossible to explain the complex chemistry of the terrestrial atmosphere without reference to detailed transport models that interconnect highly dissimilar chemical environments, so chemical models of protostars and of the solar nebula must

Fragment-based approaches to the discovery of kinase inhibitors.

PubMed

Mortenson, Paul N; Berdini, Valerio; O'Reilly, Marc

2014-01-01

Protein kinases are one of the most important families of drug targets, and aberrant kinase activity has been linked to a large number of disease areas. Although eminently targetable using small molecules, kinases present a number of challenges as drug targets, not least obtaining selectivity across such a large and relatively closely related target family. Fragment-based drug discovery involves screening simple, low-molecular weight compounds to generate initial hits against a target. These hits are then optimized to more potent compounds via medicinal chemistry, usually facilitated by structural biology. Here, we will present a number of recent examples of fragment-based approaches to the discovery of kinase inhibitors, detailing the construction of fragment-screening libraries, the identification and validation of fragment hits, and their optimization into potent and selective lead compounds. The advantages of fragment-based methodologies will be discussed, along with some of the challenges associated with using this route. Finally, we will present a number of key lessons derived both from our own experience running fragment screens against kinases and from a large number of published studies.

Chemistry and Heritage

NASA Astrophysics Data System (ADS)

Vittoria Barbarulo, Maria

2014-05-01

Chemistry is the central science, as it touches every aspect of the society we live in and it is intertwined with many aspects of our culture; in particular, the strong link between Chemistry and Archaeology and Art History is being explored, offering a penetrating insight into an area of growing interest from an educational point of view. A series of vital and vibrant examples (i.e., ancient bronzes composition, colour changes due to natural pigment decomposition, marble degradation) has been proposed, on one hand, to improve student understanding of the relationship between cultural and scientific issues arising from the examination, the conservation, and the maintenance of cultural Heritage, on the other, to illustrate the role of the underlying Chemistry. In some case studies, a survey of the most relevant atmospheric factors, which are involved in the deterioration mechanisms, has also been presented to the students. First-hand laboratory experiences have been providing an invaluable means of discovering the full and varied world of Chemistry. Furthermore, the promotion of an interdisciplinary investigation of a famous painting or fresco, involving the study of its nature and significance, the definition of its historical context, any related literature, the chemical knowledge of the materials used, may be an excellent occasion to experiment the Content and Language Integrated Learning (CLIL). The aim of this approach is to convey the important message that everyone has the responsibility to care for and preserve Heritage for the benefit of present and future generations.

Clickable prodrugs bearing potent and hydrolytically cleavable nicotinamide phosphoribosyltransferase inhibitors.

PubMed

Sadrerafi, Keivan; Mason, Emilia O; Lee, Mark W

2018-01-01

Our previous study indicated that carborane containing small-molecule 1-(hydroxymethyl)-7-(4'-( trans -3″-(3'″-pyridyl)acrylamido)butyl)-1,7-dicarbadodecaborane (hm-MC4-PPEA), was a potent inhibitor of nicotinamide phosphoribosyltransferase (Nampt). Nampt has been shown to be upregulated in most cancers and is a promising target for the treatment of many different types of cancers, including breast cancers. To increase the selectivity of hm-MC4-PPEA toward cancer cells, three prodrugs were synthesized with different hydrolyzable linkers: ester, carbonate, and carbamate. Using click chemistry a fluorophore was attached to these prodrugs to act as a model for our conjugation strategy and to serve as an aid for prodrug stability studies. The stabilities of these drug conjugates were tested in phosphate-buffered saline (PBS) at normothermia (37°C) using three different pH levels, 5.5, 7.5, and 9.5, as well as in horse serum at physiological pH. The stability of each was monitored using reversed-phase HPLC equipped with both diode array and fluorescence detection. The inhibitory activity of hm-MC4-PPEA was also measured using a commercially available colorimetric assay. The biological activities of the drug conjugates as well as those of the free drug (hm-MC4-PPEA), were evaluated using the MTT assay against the human breast cancer cell lines T47D and MCF7, as well as the noncancerous, transformed, Nampt-dependent human breast epithelium cell line 184A1. hm-MC4-PPEA showed to be a potent inhibitor of recombinant Nampt activity, exhibiting an IC50 concentration of 6.8 nM. The prodrugs showed great stability towards hydrolytic degradation under neutral, mildly acidic and mildly basic conditions. The carbamate prodrug also showed to be stable in rat serum. However, the carbonate and the ester prodrug release at various rates in serum presumably owing to the presence of several different classes of esterase. The biological activities of the drug conjugates correlate

Chemistry of Art and Color Sudoku Puzzles

ERIC Educational Resources Information Center

Welsh, Michael J.

2007-01-01

Sudoku puzzle format was used to teach light science and chemistry terms to students of Chemistry of Art and Color. The puzzles were used to motivate and encourage students to learn chemistry in an easier and in friendly fashion.

Use of combinatorial chemistry to speed drug discovery.

PubMed

Rádl, S

1998-10-01

IBC's International Conference on Integrating Combinatorial Chemistry into the Discovery Pipeline was held September 14-15, 1998. The program started with a pre-conference workshop on High-Throughput Compound Characterization and Purification. The agenda of the main conference was divided into sessions of Synthesis, Automation and Unique Chemistries; Integrating Combinatorial Chemistry, Medicinal Chemistry and Screening; Combinatorial Chemistry Applications for Drug Discovery; and Information and Data Management. This meeting was an excellent opportunity to see how big pharma, biotech and service companies are addressing the current bottlenecks in combinatorial chemistry to speed drug discovery. (c) 1998 Prous Science. All rights reserved.

Teaching Lab Report Writing through Inquiry: A Green Chemistry Stoichiometry Experiment for General Chemistry

ERIC Educational Resources Information Center

Cacciatore, Kristen L.; Sevian, Hannah

2006-01-01

We present an alternative to a traditional first-year chemistry laboratory experiment. This experiment has four key features: students utilize stoichiometry, learn and apply principles of green chemistry, engage in authentic scientific inquiry, and discover why each part of a scientific lab report is necessary. The importance and essential…

General Chemistry Students' Understanding of Climate Change and the Chemistry Related to Climate Change

ERIC Educational Resources Information Center

Versprille, Ashley N.; Towns, Marcy H.

2015-01-01

While much is known about secondary students' perspectives of climate change, rather less is known about undergraduate students' perspectives. The purpose of this study is to investigate general chemistry students' understanding of the chemistry underlying climate change. Findings that emerged from the analysis of the 24 interviews indicate that…

Amplification without instability: applying fluid dynamical insights in chemistry and biology

NASA Astrophysics Data System (ADS)

McCoy, Jonathan H.

2013-11-01

While amplification of small perturbations often arises from instability, transient amplification is possible locally even in asymptotically stable systems. That is, knowledge of a system's stability properties can mislead one's intuition for its transient behaviors. This insight, which has an interesting history in fluid dynamics, has more recently been rediscovered in ecology. Surprisingly, many nonlinear fluid dynamical and ecological systems share linear features associated with transient amplification of noise. This paper aims to establish that these features are widespread in many other disciplines concerned with noisy systems, especially chemistry, cell biology and molecular biology. Here, using classic nonlinear systems and the graphical language of network science, we explore how the noise amplification problem can be reframed in terms of activatory and inhibitory interactions between dynamical variables. The interaction patterns considered here are found in a great variety of systems, ranging from autocatalytic reactions and activator-inhibitor systems to influential models of nerve conduction, glycolysis, cell signaling and circadian rhythms.

Synthesis of Lysine Methyltransferase Inhibitors

NASA Astrophysics Data System (ADS)

Ye, Tao; Hui, Chunngai

2015-07-01

Lysine methyltransferase which catalyze methylation of histone and nonhistone proteins, play a crucial role in diverse biological processes and has emerged as a promising target for the development of various human diseases, including cancer, inflammation, and psychiatric disorders. However, inhibiting Lysine methyltransferases selectively has presented many challenges to medicinal chemists. During the past decade, lysine methyltransferase inhibitors covering many different structural classes have been designed and developed. In this review, we describe the development of selective, small-molecule inhibitors of lysine methyltransferases with an emphasis on their discovery and chemical synthesis. We highlight the current state of lysine methyltransferase inhibitors and discuss future directions and opportunities for lysine methyltransferase inhibitor discovery.

Cyclin-Dependent Kinase Inhibitors as Anticancer Therapeutics.

PubMed

Law, Mary E; Corsino, Patrick E; Narayan, Satya; Law, Brian K

2015-11-01

Cyclin-dependent kinases (CDKs) have been considered promising drug targets for a number of years, but most CDK inhibitors have failed rigorous clinical testing. Recent studies demonstrating clear anticancer efficacy and reduced toxicity of CDK4/6 inhibitors such as palbociclib and multi-CDK inhibitors such as dinaciclib have rejuvenated the field. Favorable results with palbociclib and its recent U.S. Food and Drug Administration approval demonstrate that CDK inhibitors with narrow selectivity profiles can have clinical utility for therapy based on individual tumor genetics. A brief overview of results obtained with ATP-competitive inhibitors such as palbociclib and dinaciclib is presented, followed by a compilation of new avenues that have been pursued toward the development of novel, non-ATP-competitive CDK inhibitors. These creative ways to develop CDK inhibitors are presented along with crystal structures of these agents complexed with CDK2 to highlight differences in their binding sites and mechanisms of action. The recent successes of CDK inhibitors in the clinic, combined with the potential for structure-based routes to the development of non-ATP-competitive CDK inhibitors, and evidence that CDK inhibitors may have use in suppressing chromosomal instability and in synthetic lethal drug combinations inspire optimism that CDK inhibitors will become important weapons in the fight against cancer. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

A context based approach using Green Chemistry/Bio-remediation principles to enhance interest and learning of organic chemistry in a high school AP chemistry classroom

NASA Astrophysics Data System (ADS)

Miller, Tricia

The ability of our planet to sustain life and heal itself is not as predictable as it used to be. Our need for educated future scientists who know what our planet needs, and can passionately apply that knowledge to find solutions should be at the heart of science education today. This study of learning organic chemistry through the lens of the environmental problem "What should be done with our food scraps?" explores student interest, and mastery of certain concepts in organic chemistry. This Green Chemistry/ Bio-remediation context-based teaching approach utilizes the Nature MillRTM, which is an indoor food waste composting machine, to learn about organic chemistry, and how this relates to landfill reduction possibilities, and resource production. During this unit students collected food waste from their cafeteria, and used the Nature MillRTM to convert food waste into compost. The use of these hands on activities, and group discussions in a context-based environment enhanced their interest in organic chemistry, and paper chromatography. According to a one-tailed paired T-test, the result show that this context-based approach is a significant way to increase both student interest and mastery of the content.

News from Online: Green Chemistry

ERIC Educational Resources Information Center

Uffelman, Erich S.

2004-01-01

Green chemistry closely relates to energy and environmental problems, and includes the promotion of environmental friendly products and systems within the framework of renewable resources. Various websites on green chemistry are reviewed, one of which lists the 12 commandments of this particular subject.

A Collaborative, Wiki-Based Organic Chemistry Project Incorporating Free Chemistry Software on the Web

ERIC Educational Resources Information Center

Evans, Michael J.; Moore, Jeffrey S.

2011-01-01

In recent years, postsecondary instructors have recognized the potential of wikis to transform the way students learn in a collaborative environment. However, few instructors have embraced in-depth student use of chemistry software for the creation of interactive chemistry content on the Web. Using currently available software, students are able…

Time-dependent interstellar chemistry

NASA Technical Reports Server (NTRS)

Glassgold, A. E.

1985-01-01

Some current problems in interstellar chemistry are considered in the context of time-dependent calculations. The limitations of steady-state models of interstellar gas-phase chemistry are discussed, and attempts to chemically date interstellar clouds are reviewed. The importance of studying the physical and chemical properties of interstellar dust is emphasized. Finally, the results of a series of studies of collapsing clouds are described.

Impact of surface chemistry

PubMed Central

Somorjai, Gabor A.; Li, Yimin

2011-01-01

The applications of molecular surface chemistry in heterogeneous catalyst technology, semiconductor-based technology, medical technology, anticorrosion and lubricant technology, and nanotechnology are highlighted in this perspective. The evolution of surface chemistry at the molecular level is reviewed, and the key roles of surface instrumentation developments for in situ studies of the gas–solid, liquid–solid, and solid–solid interfaces under reaction conditions are emphasized. PMID:20880833

Science Project Ideas about Kitchen Chemistry. Revised Edition.

ERIC Educational Resources Information Center

Gardner, Robert

This book presents science experiments that can be conducted in the kitchen. Contents include: (1) "Safety First"; (2) "Chemistry in and Near the Kitchen Sink"; (3) "Chemistry in the Refrigerator"; (4) "Chemistry on the Stove"; (5) "Chemistry on the Kitchen Counter"; and (6) "Further Reading and Internet Addresses." (YDS)

Computing protein infrared spectroscopy with quantum chemistry.

PubMed

Besley, Nicholas A

2007-12-15

Quantum chemistry is a field of science that has undergone unprecedented advances in the last 50 years. From the pioneering work of Boys in the 1950s, quantum chemistry has evolved from being regarded as a specialized and esoteric discipline to a widely used tool that underpins much of the current research in chemistry today. This achievement was recognized with the award of the 1998 Nobel Prize in Chemistry to John Pople and Walter Kohn. As the new millennium unfolds, quantum chemistry stands at the forefront of an exciting new era. Quantitative calculations on systems of the magnitude of proteins are becoming a realistic possibility, an achievement that would have been unimaginable to the early pioneers of quantum chemistry. In this article we will describe ongoing work towards this goal, focusing on the calculation of protein infrared amide bands directly with quantum chemical methods.

Evaluation of Chemical Representations in Physical Chemistry Textbooks

ERIC Educational Resources Information Center

Nyachwaya, James M.; Wood, Nathan B.

2014-01-01

That different levels of representation are important for complete understanding of chemistry is an accepted fact in the chemistry education community. This study sought to uncover types of representations used in given physical chemistry textbooks. Textbooks play a central role in the teaching and learning of science (chemistry), and in some…

Fundamentals of Aqueous Microwave Chemistry

EPA Science Inventory

The first chemical revolution changed modern life with a host of excellent amenities and services, but created serious problems related to environmental pollution. After 150 years of current chemistry principles and practices, we need a radical change to a new type of chemistry k...

Chemistry laboratory safety manual available

NASA Technical Reports Server (NTRS)

Elsbrock, R. G.

1968-01-01

Chemistry laboratory safety manual outlines safe practices for handling hazardous chemicals and chemistry laboratory equipment. Included are discussions of chemical hazards relating to fire, health, explosion, safety equipment and procedures for certain laboratory techniques and manipulations involving glassware, vacuum equipment, acids, bases, and volatile solvents.

Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents

PubMed Central

Ververis, Katherine; Hiong, Alison; Karagiannis, Tom C; Licciardi, Paul V

2013-01-01

Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while

Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents.

PubMed

Ververis, Katherine; Hiong, Alison; Karagiannis, Tom C; Licciardi, Paul V

2013-01-01

Histone deacetylase (HDAC) inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents) as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza) and depsipeptide (romidepsin, Istodax). More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the advancement of these drugs, especially to facilitate the rational design of HDAC inhibitors that are effective as antineoplastic agents. This review will discuss the use of HDAC inhibitors as multitargeted therapies for malignancy. Further, we outline the pharmacology and mechanisms of action of HDAC inhibitors while

Phosphodiesterase 4 inhibitors.

PubMed

Zebda, Rema; Paller, Amy S

2018-03-01

Historically, drugs available for treating atopic dermatitis (AD) have been limited to topical corticosteroids and topical calcineurin inhibitors, with systemic immunosuppressants and phototherapy reserved for severe AD. Despite their efficacy and infrequent adverse events, phobia about the use of topical steroids and calcineurin inhibitors has limited their use. More targeted options with fewer systemic and cutaneous side effects are needed for treating AD. Phosphodiesterase 4 (PDE4) is involved in the regulation of proinflammatory cytokines via the degradation of cyclic adenosine monophosphate. PDE4 activity is increased in the inflammatory cells of patients with AD, leading to increased production of proinflammatory cytokines and chemokines. Targeting PDE4 reduces the production of these proinflammatory mediators in AD. Both topical and oral PDE4 inhibitors have a favorable safety profile. Crisaborole 2% ointment, a topical PDE4, is now US Food and Drug Administration-approved for children older than 2 years and adults in the treatment of AD. Crisaborole 2% ointment shows early and sustained improvement in disease severity and pruritus and other AD symptoms, with burning and/or stinging upon application as the only related adverse event. Other PDE4 inhibitors are currently in trials with promising efficacy and safety. Copyright © 2017. Published by Elsevier Inc.

Intermediate-energy nuclear chemistry workshop

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

Butler, G.W.; Giesler, G.C.; Liu, L.C.

1981-05-01

This report contains the proceedings of the LAMPF Intermediate-Energy Nuclear Chemistry Workshop held in Los Alamos, New Mexico, June 23-27, 1980. The first two days of the Workshop were devoted to invited review talks highlighting current experimental and theoretical research activities in intermediate-energy nuclear chemistry and physics. Working panels representing major topic areas carried out indepth appraisals of present research and formulated recommendations for future research directions. The major topic areas were Pion-Nucleus Reactions, Nucleon-Nucleus Reactions and Nuclei Far from Stability, Mesonic Atoms, Exotic Interactions, New Theoretical Approaches, and New Experimental Techniques and New Nuclear Chemistry Facilities.

Assessment of Chemistry Anxiety in a Two-Year College

ERIC Educational Resources Information Center

McCarthy, Wanda C.; Widanski, Bozena Barbara

2009-01-01

Chemistry anxiety encompasses apprehension regarding learning chemistry, evaluation in chemistry courses, and fears about handling chemicals. Our goal was to ascertain the prevalence of these three types of anxiety in college students enrolled in a two-year college. In our sample, chemistry-evaluation provoked the most chemistry anxiety followed…

Chemistry Is Dead. Long Live Chemistry!

PubMed

Lavis, Luke D

2017-10-03

Chemistry, once king of fluorescence microscopy, was usurped by the field of fluorescent proteins. The increased demands of modern microscopy techniques on the "photon budget" require better and brighter fluorophores, causing a renewed interest in synthetic dyes. Here, we review the recent advances in biochemistry, protein engineering, and organic synthesis that have allowed a triumphant return of chemical fluorophores to modern biological imaging.

The carbon chemistry of the moon.

NASA Technical Reports Server (NTRS)

Eglinton, G.; Maxwell, J. R.; Pillinger, C. T.

1972-01-01

The analysis of lunar samples has shown that the carbon chemistry of the moon is entirely different from the carbon chemistry of the earth. Lunar carbon chemistry is more closely related to cosmic physics than to conventional organic chemistry. Sources of carbon on the moon are considered, giving attention to meteorites and the solar wind. The approaches used in the analysis of the samples are discussed, taking into account the method of gas chromatography employed and procedures used by bioscience investigators in the study of the lunar fines. The presence of indigenous methane and carbide in the lunar fines was established. Reactions and processes taking place on the lunar surface are discussed.

Writing Chemistry Jingles as an Introductory Activity in a High School Chemistry Class

ERIC Educational Resources Information Center

Heid, Peter F.

2011-01-01

Starting the school year in an introductory high school chemistry class can be a challenge. The topic and approach is new to the students; many of the early chapters in the texts can be a bit tedious; and for many students the activities are uninspiring. My goal in the first few weeks of school is to hook the students on chemistry by getting them…

Applications of the Cambridge Structural Database in organic chemistry and crystal chemistry.

PubMed

Allen, Frank H; Motherwell, W D Samuel

2002-06-01

The Cambridge Structural Database (CSD) and its associated software systems have formed the basis for more than 800 research applications in structural chemistry, crystallography and the life sciences. Relevant references, dating from the mid-1970s, and brief synopses of these papers are collected in a database, DBUse, which is freely available via the CCDC website. This database has been used to review research applications of the CSD in organic chemistry, including supramolecular applications, and in organic crystal chemistry. The review concentrates on applications that have been published since 1990 and covers a wide range of topics, including structure correlation, conformational analysis, hydrogen bonding and other intermolecular interactions, studies of crystal packing, extended structural motifs, crystal engineering and polymorphism, and crystal structure prediction. Applications of CSD information in studies of crystal structure precision, the determination of crystal structures from powder diffraction data, together with applications in chemical informatics, are also discussed.

Synthesis-Spectroscopy Roadmap Problems: Discovering Organic Chemistry

ERIC Educational Resources Information Center

Kurth, Laurie L.; Kurth, Mark J.

2014-01-01

Organic chemistry problems that interrelate and integrate synthesis with spectroscopy are presented. These synthesis-spectroscopy roadmap (SSR) problems uniquely engage second-year undergraduate organic chemistry students in the personal discovery of organic chemistry. SSR problems counter the memorize-or-bust strategy that many students tend to…

Containment Sodium Chemistry Models in MELCOR.

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

Louie, David; Humphries, Larry L.; Denman, Matthew R

To meet regulatory needs for sodium fast reactors’ future development, including licensing requirements, Sandia National Laboratories is modernizing MELCOR, a severe accident analysis computer code developed for the U.S. Nuclear Regulatory Commission (NRC). Specifically, Sandia is modernizing MELCOR to include the capability to model sodium reactors. However, Sandia’s modernization effort primarily focuses on the containment response aspects of the sodium reactor accidents. Sandia began modernizing MELCOR in 2013 to allow a sodium coolant, rather than water, for conventional light water reactors. In the past three years, Sandia has been implementing the sodium chemistry containment models in CONTAIN-LMR, a legacy NRCmore » code, into MELCOR. These chemistry models include spray fire, pool fire and atmosphere chemistry models. Only the first two chemistry models have been implemented though it is intended to implement all these models into MELCOR. A new package called “NAC” has been created to manage the sodium chemistry model more efficiently. In 2017 Sandia began validating the implemented models in MELCOR by simulating available experiments. The CONTAIN-LMR sodium models include sodium atmosphere chemistry and sodium-concrete interaction models. This paper presents sodium property models, the implemented models, implementation issues, and a path towards validation against existing experimental data.« less

Chemistry Notes

ERIC Educational Resources Information Center

School Science Review, 1973

1973-01-01

Several ideas are proposed for chemistry teachers to try in their classrooms. Subjects included are polymerization of acrylate, polymerization of styrene, conductivity, pollution, preparation of chlorine, redox equations, chemiluminescence, and molecular sieves. (PS)

Modern analytical chemistry in the contemporary world

NASA Astrophysics Data System (ADS)

Šíma, Jan

2016-12-01

Students not familiar with chemistry tend to misinterpret analytical chemistry as some kind of the sorcery where analytical chemists working as modern wizards handle magical black boxes able to provide fascinating results. However, this approach is evidently improper and misleading. Therefore, the position of modern analytical chemistry among sciences and in the contemporary world is discussed. Its interdisciplinary character and the necessity of the collaboration between analytical chemists and other experts in order to effectively solve the actual problems of the human society and the environment are emphasized. The importance of the analytical method validation in order to obtain the accurate and precise results is highlighted. The invalid results are not only useless; they can often be even fatal (e.g., in clinical laboratories). The curriculum of analytical chemistry at schools and universities is discussed. It is referred to be much broader than traditional equilibrium chemistry coupled with a simple description of individual analytical methods. Actually, the schooling of analytical chemistry should closely connect theory and practice.

Chemical Principles Revisited: Petroleum Chemistry.

ERIC Educational Resources Information Center

Kolb, Doris; Kolb, Kenneth E.

1979-01-01

Presents an historical review of the role of petroleum in world history and information on the chemistry of petroleum. It is suggested that petroleum chemistry be discussed since within the next two decades oil and gas will provide the major portion of U.S. energy. (Author/SA)

Recent Advances in Cyanamide Chemistry: Synthesis and Applications.

PubMed

Prabhath, M R Ranga; Williams, Luke; Bhat, Shreesha V; Sharma, Pallavi

2017-04-12

The application of alkyl and aryl substituted cyanamides in synthetic chemistry has diversified multi-fold in recent years. In this review, we discuss recent advances (since 2012) in the chemistry of cyanamides and detail their application in cycloaddition chemistry, aminocyanation reactions, as well as electrophilic cyanide-transfer agents and their unique radical and coordination chemistry.

Superheavy element chemistry at GARIS

NASA Astrophysics Data System (ADS)

Haba, Hiromitsu

2016-12-01

A gas-jet transport system has been installed to the RIKEN GAs-filled Recoil Ion Separator, GARIS to start up SuperHeavy Element (SHE) chemistry. This system is a promising approach for exploring new frontiers in SHE chemistry: background radioactivities from unwanted by-products are suppressed, a high gas-jet transport yield is achieved, and new chemical reactions can be investigated. Useful radioisotopes of 261Rfa,b, 262Db, and 265Sga,b for chemical studies were produced in the reactions of 248Cm(18O,5n)261Rfa,b, 248Cm(19F,5n)262Db, and 248Cm(22Ne,5n)265Sga,b, respectively. They were successfully extracted to a chemistry laboratory by the gas-jet method. Production and decay properties of 261Rfa,b, 262Db, and 265Sga,b were investigated in detail with the rotating wheel apparatus for α- and spontaneous fission spectrometry. Present status and perspectives of the SHE chemistry at GARIS are also briefly presented.

Pierre-Joseph Macquer: Chemistry in the French Enlightenment.

PubMed

Lehman, Christine

2014-01-01

Despite recent studies of chemistry courses and of academic research at the beginning of the eighteenth century, the perception of chemistry in the French Enlightenment has often been overshadowed by Lavoisier's works. This article proposes three specific case studies selected from Pierre Joseph Macquer's (1718-84) rich career to show the continuous evolution of chemistry throughout the century: medicinal chemistry through the application of the Comte de La Garaye's metallic salt solutions, the emergence of industrial chemistry through a few of Macquer's evaluations at the Bureau du Commerce, and finally communal academic research through the experiments on diamonds using Tschirnhaus's lens. These examples attempt to illustrate the innovative, creative, dynamic, multicultural, and multifaceted chemistry of the Enlightenment.

The Chemistry of Planet Formation

NASA Astrophysics Data System (ADS)

Oberg, Karin I.

2017-01-01

Exo-planets are common, and they span a large range of compositions. The origins of the observed diversity of planetary compositions is largely unconstrained, but must be linked to the planet formation physics and chemistry. Among planets that are Earth-like, a second question is how often such planets form hospitable to life. A fraction of exo-planets are observed to be ‘physically habitable’, i.e. of the right temperature and bulk composition to sustain a water-based prebiotic chemistry, but this does not automatically imply that they are rich in the building blocks of life, in organic molecules of different sizes and kinds, i.e. that they are chemically habitable. In this talk I will argue that characterizing the chemistry of protoplanetary disks, the formation sites of planets, is key to address both the origins of planetary bulk compositions and the likelihood of finding organic matter on planets. The most direct path to constrain the chemistry in disks is to directly observe it. In the age of ALMA it is for the first time possible to image the chemistry of planet formation, to determine locations of disk snowlines, and to map the distributions of different organic molecules. Recent ALMA highlights include constraints on CO snowline locations, the discovery of spectacular chemical ring systems, and first detections of more complex organic molecules. Observations can only provide chemical snapshots, however, and even ALMA is blind to the majority of the chemistry that shapes planet formation. To interpret observations and address the full chemical complexity in disks requires models, both toy models and astrochemical simulations. These models in turn must be informed by laboratory experiments, some of which will be shown in this talk. It is thus only when we combine observational, theoretical and experimental constraints that we can hope to characterize the chemistry of disks, and further, the chemical compositions of nascent planets.

Teaching social responsibility in analytical chemistry.

PubMed

Valcárcel, M; Christian, G D; Lucena, R

2013-07-02

Analytical chemistry is key to the functioning of a modern society. From early days, ethics in measurements have been a concern and that remains today, especially as we have come to rely more on the application of analytical science in many aspects of our lives. The main aim of this Feature is to suggest ways of introducing the topic of social responsibility and its relation to analytical chemistry in undergraduate or graduate chemistry courses.

Plasma Chemistry of Vibrationally Nonequilibrium Molecules

DTIC Science & Technology

1993-11-01

WL-TR-93-2116 PLASMA CHEMISTRY OF VIBRATIONALLY NONEQUILIBRIUM MOLECULES AD-A279 630--, J. WILLIAM RICH DEPARTMENT OF MECHANICAL ENGINEERING D THE...1AT9E L. REPORT TYPE AND DATES COVERED ONLY Man"_November 1993 Final 09 July 1990_- 08 July 1993 4 MITL AND SUBTITLE S. FUNDNG NUMERS & Plasma Chemistry of...k14. SUBIECT TERMS 15. NUMBER OF PAGES Molecular Energy Transfer; Plasma Chemistry ; Ionization; 4% Vibrational Relaxation; Nitric Oxide; Carbon

Modern Analytical Chemistry in the Contemporary World

ERIC Educational Resources Information Center

Šíma, Jan

2016-01-01

Students not familiar with chemistry tend to misinterpret analytical chemistry as some kind of the sorcery where analytical chemists working as modern wizards handle magical black boxes able to provide fascinating results. However, this approach is evidently improper and misleading. Therefore, the position of modern analytical chemistry among…

European TV Brings Chemistry into the Home

ERIC Educational Resources Information Center

O'Sullivan, Dermot A.

1975-01-01

Describes television programs broadcast in the Netherlands and West Germany which explain what chemistry is all about. Both programs, planned under the direction of trained chemists, comprise 13 half-hour presentations and include segments on energy, polymers, chemical processes, the chemistry of life, atomic and molecular chemistry, and chemistry…

Writing in Chemistry: An Effective Learning Tool.

ERIC Educational Resources Information Center

Sherwood, Donna W.; Kovac, Jeffrey

1999-01-01

Presents some general strategies for using writing in chemistry courses based on experiences in developing a systematic approach to using writing as an effective learning tool in chemistry courses, and testing this approach in high-enrollment general chemistry courses at the University of Tennessee-Knoxville. Contains 18 references. (WRM)

Chemistry for Student Nurses: Applications-Based Learning

ERIC Educational Resources Information Center

El-Farargy, Nancy

2009-01-01

New chemistry materials were devised for pre university National Certificate (NC) nursing students studying chemistry at a further education college. Previously, preliminary work showed that students felt that the chemistry taught to them was irrelevant, boring and difficult. It was hoped that through an applications-led style curriculum…

Organic Chemistry Self Instructional Package 2: Methane.

ERIC Educational Resources Information Center

Zdravkovich, V.

This booklet, one of a series of 17 developed at Prince George's Community College, Largo, Maryland, provides an individualized, self-paced undergraduate organic chemistry instruction module designed to augment any course in organic chemistry but particularly those taught using the text "Organic Chemistry" by Morrison and Boyd. The…

Chemistry and Nanoscience News | Chemistry and Nanoscience Research | NREL

Science.gov Websites

News Chemistry and Nanoscience News December 7, 2017 News Release: NREL Develops Novel Method to Laboratory (NREL) establishes a novel catalytic method to produce renewable acrylonitrile using 3

Outlook Bright for Computers in Chemistry.

ERIC Educational Resources Information Center

Baum, Rudy M.

1981-01-01

Discusses the recent decision to close down the National Resource for Computation in Chemistry (NRCC), implications of that decision, and various alternatives in the field of computational chemistry. (CS)

A Chemistry Concept Reasoning Test

ERIC Educational Resources Information Center

Cloonan, Carrie A.; Hutchinson, John S.

2011-01-01

A Chemistry Concept Reasoning Test was created and validated providing an easy-to-use tool for measuring conceptual understanding and critical scientific thinking of general chemistry models and theories. The test is designed to measure concept understanding comparable to that found in free-response questions requiring explanations over…

Rethinking Undergraduate Physical Chemistry Curricula

ERIC Educational Resources Information Center

Miller, Stephen R.

2016-01-01

A summary of fundamental changes made to the undergraduate physical chemistry curriculum in the Chemistry Department at Gustavus Adolphus College (beginning in the 2013-2014 academic year) is presented. The yearlong sequence now consists of an introductory semester covering both quantum mechanics and thermodynamics/kinetics, followed by a second…

Prospective Chemistry and Science Teachers' Views and Metaphors about Chemistry and Chemical Studies

ERIC Educational Resources Information Center

Onen Ozturk, Fatma; Aglarci, Oya

2017-01-01

Purpose: The aim of this study was to examine the metaphors created by prospective chemistry and science teachers and their views about how the studies in the field of chemistry are carried out in relation to the grade level and department. Research Methods: Case study as a qualitative research design was used. Participants in the study included…

The Effect of Microscale Chemistry Experimentation on Students' Attitude and Motivation towards Chemistry Practical Work

ERIC Educational Resources Information Center

Abdullah, Mashita; Mohamed, Norita; Ismail, Zurida Hj

2007-01-01

Microscale chemistry is an approach to conducting chemistry practicals which can help overcome increased concerns about environmental pollution problems as well as rising laboratory costs. It is accomplished by using miniature labware and significantly reduced amounts of chemicals. This paper reports on students' attitudes and motivation towards…

42 CFR 493.1210 - Condition: Routine chemistry.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, § 493.1267...

Nuffield A-Level Chemistry: A Personal View

ERIC Educational Resources Information Center

Bailey, Roy

1972-01-01

Maintains that there are topics of thermodynamics and organic chemistry in Nuffield A-level chemistry program which should be reviewed critically for their content organization. The Nuffield course is considered better than the traditional courses in its educational value, yet highly biased for preparing students for college chemistry courses. (PS)

42 CFR 493.1210 - Condition: Routine chemistry.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, § 493.1267...

42 CFR 493.1210 - Condition: Routine chemistry.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, § 493.1267...

42 CFR 493.1210 - Condition: Routine chemistry.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, § 493.1267...

42 CFR 493.1210 - Condition: Routine chemistry.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Routine chemistry. 493.1210 Section 493....1210 Condition: Routine chemistry. If the laboratory provides services in the subspecialty of Routine chemistry, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, § 493.1267...

Elementary and brief introduction of hadronic chemistry

NASA Astrophysics Data System (ADS)

Tangde, Vijay M.

2013-10-01

The discipline, today known as Quantum Chemistry for atomic and subatomic level interactions has no doubt made a significant historical contributions to the society. Despite of its significant achievements, quantum chemistry is also known for its widespread denial of insufficiencies it inherits. An Italian-American Scientist Professor Ruggero Maria Santilli during his more than five decades of dedicated and sustained research has denounced the fact that quantum chemistry is mostly based on mere nomenclatures without any quantitative scientific contents. Professor R M Santilli first formulated the iso-, geno- and hyper-mathematics [1-4] that helped in understanding numerous diversified problems and removing inadequacies in most of the established and celebrated theories of 20th century physics and chemistry. This involves the isotopic, genotopic, etc. lifting of Lie algebra that generated Lie admissible mathematics to properly describe irreversible processes. The studies on Hadronic Mechanics in general and chemistry in particular based on Santilli's mathematics[3-5] for the first time has removed the very fundamental limitations of quantum chemistry [2, 6-8]. In the present discussion, we have briefly reviewed the conceptual foundations of Hadronic Chemistry that imparts the completeness to the Quantum Chemistry via an addition of effects at distances of the order of 1 fm (only) which are assumed to be Non-linear, Non-local, Non-potential, Non-hamiltonian and thus Non-unitary and its application in development of a new chemical species called Magnecules.

Reversal of Acetylcholinesterase Inhibitor Toxicity In Vivo by Inhibitors of Choline Transport.

DTIC Science & Technology

1983-10-31

the increased interaction of acetylcholine with the receptor resulting from the inhibition of the enzyme acetylcholinesterase. . Acetylcholinesterase...competitive inhibitors of acetylcholine at the enzyme receptor. The second category, "reversible" cholinesterase inhibitors, form covalent bonds with the...method of Ellman et al. (46) was used to determine the acetyicholinesterase activity in mouse brain homogenates. Briefly, the enzyme activity was

Identification of fermentation inhibitors in wood hydrolyzates and removal of inhibitors by ion exchange and liquid-liquid extraction

NASA Astrophysics Data System (ADS)

Luo, Caidian

1998-12-01

Common methods employed in the ethanol production from biomass consist of chemical or enzymatic degradation of biomass into sugars and then fermentation of sugars into ethanol or other chemicals. However, some degradation products severely inhibit the fermentation processes and substantially reduce the efficiency of ethanol production. How to remove inhibitors from the reaction product mixture and increase the production efficiency are critical in the commercialization of any processes of energy from biomass. The present study has investigated anion exchange and liquid-liquid extraction as potential methods for inhibitor removal. An analytical method has been developed to identify the fermentation inhibitors in a hydrolyzate. The majority of inhibitors present in hybrid poplar hydrolyzate have positively been identified. Ion exchange with weak basic Dowex-MWA-1 resin has been proved to be an effective mean to remove fermentation inhibitors from hybrid poplar hydrolyzate and significantly increase the fermentation productivity. Extraction with n-butanol might be a preferred way to remove inhibitors from wood hydrolyzates and improve the fermentability of sugars in the hydrolyzates. n-Butanol also removes some glucose, mannose and xylose from the hydrolyzate. Inhibitor identification reveals that lignin and sugar degradation compounds including both aromatic and aliphatic aldehydes and carboxylic acids formed in hydrolysis, plus fatty acids and other components from wood extractives are major fermentation inhibitors in Sacchromyces cerevisiae fermentation. There are 35 components identified as fermentation inhibitors. Among them, 4-hydroxy benzoic acid, 3,4-dihydroxy benzoic acid, syringic acid, syringaldehyde, and ferulic acid are among the most abundant aromatic inhibitors in hybrid poplar hydrolyzate. The conversion of aldehyde groups into carboxylic acid groups in the nitric acid catalyzed hydrolysis reduces the toxicity of the hydrolyzate. A wide spectrum of

Chemistry Modeling for Aerothermodynamics and TPS

NASA Technical Reports Server (NTRS)

Wang, Dunyou; Stallcop, James R.; Dateo, Christopher e.; Schwenke, David W.; Halicioglu, Timur; Huo, winifred M.

2005-01-01

Recent advances in supercomputers and highly scalable quantum chemistry software render computational chemistry methods a viable means of providing chemistry data for aerothermal analysis at a specific level of confidence. Four examples of first principles quantum chemistry calculations will be presented. Study of the highly nonequilibrium rotational distribution of a nitrogen molecule from the exchange reaction N + N2 illustrates how chemical reactions can influence rotational distribution. The reaction C2H + H2 is one example of a radical reaction that occurs during hypersonic entry into an atmosphere containing methane. A study of the etching of a Si surface illustrates our approach to surface reactions. A recently developed web accessible database and software tool (DDD) that provides the radiation profile of diatomic molecules is also described.

Chemistry Modeling for Aerothermodynamics and TPS

NASA Technical Reports Server (NTRS)

Wang, Dun-You; Stallcop, James R.; Dateo, Christopher E.; Schwenke, David W.; Haliciogiu, Timur; Huo, Winifred

2004-01-01

Recent advances in supercomputers and highly scalable quantum chemistry software render computational chemistry methods a viable means of providing chemistry data for aerothermal analysis at a specific level of confidence. Four examples of first principles quantum chemistry calculations will be presented. The study of the highly nonequilibrium rotational distribution of nitrogen molecule from the exchange reaction N + N2 illustrates how chemical reactions can influence the rotational distribution. The reaction C2H + H2 is one example of a radical reaction that occurs during hypersonic entry into a methane containing atmosphere. A study of the etching of Si surface illustrates our approach to surface reactions. A recently developed web accessible database and software tool (DDD) that provides the radiation profile of diatomic molecules is also described.

Static Chemistry in Disks or Clouds

NASA Astrophysics Data System (ADS)

Semenov, D.; Wiebe, D.

2006-11-01

This FORTRAN77 code can be used to model static, time-dependent chemistry in ISM and circumstellar disks. Current version is based on the OSU'06 gas-grain astrochemical network with all updates to the reaction rates, and includes surface chemistry from Hasegawa & Herbst (1993) and Hasegawa, Herbst, and Leung (1992). Surface chemistry can be modeled either with the standard rate equation approach or modified rate equation approach (useful in disks). Gas-grain interactions include sticking of neutral molecules to grains, dissociative recombination of ions on grains as well as thermal, UV, X-ray, and CRP-induced desorption of frozen species. An advanced X-ray chemistry and 3 grain sizes with power-law size distribution are also included. An deuterium extension to this chemical model is available.

Rho kinase inhibitors: a patent review (2012 - 2013).

PubMed

Feng, Yangbo; LoGrasso, Philip V

2014-03-01

The Rho kinase/ROCK is critical in vital signal transduction pathways central to many essential cellular activities. Since ROCK possess multiple substrates, modulation of ROCK activity is useful for treatment of many diseases. Significant progress has been made in the development of ROCK inhibitors over the past two years (Jan 2012 to Aug 2013). Patent search in this review was based on FPO IP Research and Communities and Espacenet Patent Search. In this review, patent applications will be classified into four groups for discussions. The grouping is mainly based on structures or scaffolds (groups 1 and 2) and biological functions of ROCK inhibitors (groups 3 and 4). These four groups are i) ROCK inhibitors based on classical structural elements for ROCK inhibition; ii) ROCK inhibitors based on new scaffolds; iii) bis-functional ROCK inhibitors; and iv) novel applications of ROCK inhibitors. Although currently only one ROCK inhibitor (fasudil) is used as a drug, more drugs based on ROCK inhibition are expected to be advanced into market in the near future. Several directions should be considered for future development of ROCK inhibitors, such as soft ROCK inhibitors, bis-functional ROCK inhibitors, ROCK2 isoform-selective inhibitors, and ROCK inhibitors as antiproliferation agents.

Automated Docking with Protein Flexibility in the Design of Femtomolar “Click Chemistry” Inhibitors of Acetylcholinesterase

PubMed Central

Morris, Garrett M.; Green, Luke G.; Radić, Zoran; Taylor, Palmer; Sharpless, K. Barry; Olson, Arthur J.; Grynszpan, Flavio

2013-01-01

The use of computer-aided structure-based drug design prior to synthesis has proven to be generally valuable in suggesting improved binding analogues of existing ligands.1 Here we describe the application of the program AutoDock2 to the design of a focused library that was used in the “click chemistry in-situ” generation of the most potent non-covalent inhibitor of the enzyme acetylcholinesterase (AChE) yet developed (Kd = ~100 fM).3 AutoDock version 3.0.5 has been widely distributed and successfully used to predict bound conformations of flexible ligands. Here, we also used a version of AutoDock which permits additional conformational flexibility in selected amino acid sidechains of the target protein. PMID:23451944

Inga laurina trypsin inhibitor (ILTI) obstructs Spodoptera frugiperda trypsins expressed during adaptive mechanisms against plant protease inhibitors.

PubMed

Machado, Suzy Wider; de Oliveira, Caio Fernando Ramalho; Zério, Neide Graciano; Parra, José Roberto Postali; Macedo, Maria Lígia Rodrigues

2017-08-01

Plant protease inhibitors (PIs) are elements of a common plant defense mechanism induced in response to herbivores. The fall armyworm, Spodoptera frugiperda, a highly polyphagous lepidopteran pest, responds to various PIs in its diet by expressing genes encoding trypsins. This raises the question of whether the PI-induced trypsins are also inhibited by other PIs, which we posed as the hypothesis that Inga laurina trypsin inhibitor (ILTI) inhibits PI-induced trypsins in S. frugiperda. In the process of testing our hypothesis, we compared its properties with those of selected PIs, soybean Kunitz trypsin inhibitor (SKTI), Inga vera trypsin inhibitor (IVTI), Adenanthera pavonina trypsin inhibitor (ApTI), and Entada acaciifolia trypsin inhibitor (EATI). We report that ILTI is more effective in inhibiting the induced S. frugiperda trypsins than SKTI and the other PIs, which supports our hypothesis. ILTI may be more appropriate than SKTI for studies regarding adaptive mechanisms to dietary PIs. © 2017 Wiley Periodicals, Inc.

750 Reasons To Celebrate Chemistry!

PubMed

Compton, Neville

2017-06-12

Time to reflect: This issue marks the 750th issue of Chemistry-A European Journal. The journal has played a significant role in changing chemistry. Its history has featured top papers from top authors for more than 20 years. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

"CHEM"opera for Chemistry Education

ERIC Educational Resources Information Center

Chung, Yong Hee

2013-01-01

"CHEM"opera is an opera blended with demonstrations of chemical reactions. It has been produced and performed twice by chemistry undergraduate students at Hallym University in South Korea. It aims to demonstrate interesting chemical reactions to chemistry students, children and the public and to facilitate their understanding of the role…

New Thinking in School Chemistry.

ERIC Educational Resources Information Center

Organisation for Economic Cooperation and Development, Paris (France).

This report contains the text of addresses given at a seminar on the status and development of the teaching of secondary school chemistry held in 1960 by the Organization for European Economic Development (now the Organization for Economic Cooperation and Development). The speakers considered advances in theoretical chemistry since 1900, the…

Dynamic combinatorial libraries: new opportunities in systems chemistry.

PubMed

Hunt, Rosemary A R; Otto, Sijbren

2011-01-21

Combinatorial chemistry is a tool for selecting molecules with special properties. Dynamic combinatorial chemistry started off aiming to be just that. However, unlike ordinary combinatorial chemistry, the interconnectedness of dynamic libraries gives them an extra dimension. An understanding of these molecular networks at systems level is essential for their use as a selection tool and creates exciting new opportunities in systems chemistry. In this feature article we discuss selected examples and considerations related to the advanced exploitation of dynamic combinatorial libraries for their originally conceived purpose of identifying strong binding interactions. Also reviewed are examples illustrating a trend towards increasing complexity in terms of network behaviour and reversible chemistry. Finally, new applications of dynamic combinatorial chemistry in self-assembly, transport and self-replication are discussed.

An Approach towards Teaching Green Chemistry Fundamentals

ERIC Educational Resources Information Center

van Arnum, Susan D.

2005-01-01

A useful metrics system for the assessment of the environmental impact of chemical processes is utilized to illustrate several of the principles of green chemistry. The use of this metrics system in conjunction with laboratory experiments in green chemistry would provide for reinforcement in both the theory and practice of green chemistry.

Organosilicon Chemistry.

DTIC Science & Technology

1982-12-01

Organosilicon Chemistry, March 13, 1981. San Diego State University, Organosilicon Chemstry -Silylene Reactivity, Noymber 13, 1981. California State University...Silylene Reactivity, January 4, 1982. University of Connecticut, Organosilicon Chemstry -Silylene Reactivity, Mrch 9, 1982. ...... .t~ . . .- -. . - -4

Precolumbian Chemistry.

ERIC Educational Resources Information Center

Robinson, Janet Bond

1995-01-01

Describes the content and development of a curriculum that provides an approach to descriptive chemistry and the history of technology through consideration of the pottery, metallurgy, pigments, dyes, agriculture, and medicine of pre-Columbian people. (DDR)

Development and Score Validation of a Chemistry Laboratory Anxiety Instrument (CLAI) for College Chemistry Students.

ERIC Educational Resources Information Center

Bowen, Craig W.

1999-01-01

Reports the development and score validation of an instrument for measuring anxieties students experience in college chemistry laboratories. Factor analysis of scores from 361 college students shows that the developed Chemistry Laboratory Anxiety Instrument measures five constructs. Results from a second sample of 598 students show that scores on…

Modeling the atmospheric chemistry of TICs

NASA Astrophysics Data System (ADS)

Henley, Michael V.; Burns, Douglas S.; Chynwat, Veeradej; Moore, William; Plitz, Angela; Rottmann, Shawn; Hearn, John

2009-05-01

An atmospheric chemistry model that describes the behavior and disposition of environmentally hazardous compounds discharged into the atmosphere was coupled with the transport and diffusion model, SCIPUFF. The atmospheric chemistry model was developed by reducing a detailed atmospheric chemistry mechanism to a simple empirical effective degradation rate term (keff) that is a function of important meteorological parameters such as solar flux, temperature, and cloud cover. Empirically derived keff functions that describe the degradation of target toxic industrial chemicals (TICs) were derived by statistically analyzing data generated from the detailed chemistry mechanism run over a wide range of (typical) atmospheric conditions. To assess and identify areas to improve the developed atmospheric chemistry model, sensitivity and uncertainty analyses were performed to (1) quantify the sensitivity of the model output (TIC concentrations) with respect to changes in the input parameters and (2) improve, where necessary, the quality of the input data based on sensitivity results. The model predictions were evaluated against experimental data. Chamber data were used to remove the complexities of dispersion in the atmosphere.

Organic Chemistry in Action! Developing an Intervention Program for Introductory Organic Chemistry to Improve Learners' Understanding, Interest, and Attitudes

ERIC Educational Resources Information Center

O'Dwyer, Anne; Childs, Peter

2014-01-01

The main areas of difficulty experienced by those teaching and learning organic chemistry at high school and introductory university level in Ireland have been identified, and the findings support previous studies in Ireland and globally. Using these findings and insights from chemistry education research (CER), the Organic Chemistry in Action!…

[Fish ovarian fluid contains protease inhibitors].

PubMed

Minin, A A; Ozerova, S G

2015-01-01

Studies of the conditions under which fish egg is activated spontaneously without the sperm showed that the egg retains the ability for fertilization in the ovarian (coelomic) fluid, which surrounds it in the gonad cavity after ovulation. Earlier, we showed that, in artificial media, the spontaneous activation is suppressed by protease inhibitors. In this study, we investigated the presence of natural protease inhibitors in the ovarian fluid and showed that the ovarian fluid of zebrafish and loach contains protease inhibitors, in particular, type I serpin a, a protein inhibitor of trypsin proteases.

Template-based de novo design for type II kinase inhibitors and its extented application to acetylcholinesterase inhibitors.

PubMed

Su, Bo-Han; Huang, Yi-Syuan; Chang, Chia-Yun; Tu, Yi-Shu; Tseng, Yufeng J

2013-10-31

There is a compelling need to discover type II inhibitors targeting the unique DFG-out inactive kinase conformation since they are likely to possess greater potency and selectivity relative to traditional type I inhibitors. Using a known inhibitor, such as a currently available and approved drug or inhibitor, as a template to design new drugs via computational de novo design is helpful when working with known ligand-receptor interactions. This study proposes a new template-based de novo design protocol to discover new inhibitors that preserve and also optimize the binding interactions of the type II kinase template. First, sorafenib (Nexavar) and nilotinib (Tasigna), two type II inhibitors with different ligand-receptor interactions, were selected as the template compounds. The five-step protocol can reassemble each drug from a large fragment library. Our procedure demonstrates that the selected template compounds can be successfully reassembled while the key ligand-receptor interactions are preserved. Furthermore, to demonstrate that the algorithm is able to construct more potent compounds, we considered kinase inhibitors and other protein dataset, acetylcholinesterase (AChE) inhibitors. The de novo optimization was initiated using a template compound possessing a less than optimal activity from a series of aminoisoquinoline and TAK-285 inhibiting type II kinases, and E2020 derivatives inhibiting AChE respectively. Three compounds with greater potency than the template compound were discovered that were also included in the original congeneric series. This template-based lead optimization protocol with the fragment library can help to design compounds with preferred binding interactions of known inhibitors automatically and further optimize the compounds in the binding pockets.

Histone Deacetylase Inhibitors as Anticancer Drugs.

PubMed

Eckschlager, Tomas; Plch, Johana; Stiborova, Marie; Hrabeta, Jan

2017-07-01

Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities.

Histone Deacetylase Inhibitors as Anticancer Drugs

PubMed Central

Eckschlager, Tomas; Plch, Johana; Stiborova, Marie; Hrabeta, Jan

2017-01-01

Carcinogenesis cannot be explained only by genetic alterations, but also involves epigenetic processes. Modification of histones by acetylation plays a key role in epigenetic regulation of gene expression and is controlled by the balance between histone deacetylases (HDAC) and histone acetyltransferases (HAT). HDAC inhibitors induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Mechanisms of anticancer effects of HDAC inhibitors are not uniform; they may be different and depend on the cancer type, HDAC inhibitors, doses, etc. HDAC inhibitors seem to be promising anti-cancer drugs particularly in the combination with other anti-cancer drugs and/or radiotherapy. HDAC inhibitors vorinostat, romidepsin and belinostat have been approved for some T-cell lymphoma and panobinostat for multiple myeloma. Other HDAC inhibitors are in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed. Because of the reversibility of epigenetic changes during cancer development, the potency of epigenetic therapies seems to be of great importance. Here, we summarize the data on different classes of HDAC inhibitors, mechanisms of their actions and discuss novel results of preclinical and clinical studies, including the combination with other therapeutic modalities. PMID:28671573

Contextualising Nanotechnology in Chemistry Education

ERIC Educational Resources Information Center

O'Connor, Christine; Hayden, Hugh

2008-01-01

In recent years nanotechnology has become part of the content of many undergraduate chemistry and physics degree courses. This paper deals with the role of contextualisation of nanotechnology in the delivery of the content, as nanotechnology is only now being slowly integrated into many chemistry degree courses in Ireland and elsewhere. An…

Stereochemical Control in Carbohydrate Chemistry

ERIC Educational Resources Information Center

Batchelor, Rhys; Northcote, Peter T.; Harvey, Joanne E.; Dangerfield, Emma M.; Stocker, Bridget L.

2008-01-01

Carbohydrates, in the form of glycoconjugates, have recently been shown to control a wide range of cellular processes. Accordingly, students interested in the study of organic chemistry and biomedical sciences should be exposed to carbohydrate chemistry. To this end, we have developed a sequence of experiments that leads the student from the…

Chemistry Teachers' Views of Creativity

ERIC Educational Resources Information Center

Akkanat, Çigdem; Gökdere, Murat

2015-01-01

The purpose of this study was to determine chemistry teachers' views of creativity. In this study, phenomenology method, one of the qualitative research patterns, was used. The participants of this study were 13 chemistry teachers working in Amasya. A semi-structured interview form was used for data collection. By using NVivo 9 qualitative…

Chemistry: Coping with Change...Creatively.

ERIC Educational Resources Information Center

Barron, Marcelline A.

Developed for mathematics-shy high school chemistry students, this laboratory manual is suitable for use with any chemistry textbook. Seventy-three experiments, based on a theme of change, are grouped into 5 general areas: (1) 9 experiments focusing on skills needed in observing reality; (2) 19 experiments interpreting how reality changes,…

Chemistry for Artists and Art Buffs.

ERIC Educational Resources Information Center

Denio, Allen A.

1979-01-01

This course provides an attractive introduction to chemistry for a group of students who would normally avoid traditional chemistry courses. Topics include color, pigments, metals, ceramics, glass, paints, plastics, fibers, and dyes. (BB)

Plants and Chemistry: A Teaching Course Based on the Chemistry of Substances of Plant Origin

NASA Astrophysics Data System (ADS)

Andreoli, Katia; Calascibetta, Franco; Campanella, Luigi; Favero, Gabriele; Occhionero, Francesca

2002-08-01

Over the past few years, we developed an idea about the teaching of chemistry by determining the links between theory and the real world. The principles, concepts, and experimental procedures of chemistry were illustrated through an original approach based on useful substances obtained from plants. The starting point was substances that have always been obtained from trees and vegetables. The approach was implemented during many refresher courses for secondary school teachers of chemistry. The courses were divided into sections, each called "Plants and ...", dedicated to colors, odors, tastes, medicines and drugs, fibers, soaps, and alcoholic beverages. Each section consisted of a theoretical lesson followed by a laboratory session.

Targeting cancer with kinase inhibitors

PubMed Central

Gross, Stefan; Rahal, Rami; Stransky, Nicolas; Lengauer, Christoph; Hoeflich, Klaus P.

2015-01-01

Kinase inhibitors have played an increasingly prominent role in the treatment of cancer and other diseases. Currently, more than 25 oncology drugs that target kinases have been approved, and numerous additional therapeutics are in various stages of clinical evaluation. In this Review, we provide an in-depth analysis of activation mechanisms for kinases in cancer, highlight recent successes in drug discovery, and demonstrate the clinical impact of selective kinase inhibitors. We also describe the substantial progress that has been made in designing next-generation inhibitors to circumvent on-target resistance mechanisms, as well as ongoing strategies for combining kinase inhibitors in the clinic. Last, there are numerous prospects for the discovery of novel kinase targets, and we explore cancer immunotherapy as a new and promising research area for studying kinase biology. PMID:25932675

[ACE inhibitors and the kidney].

PubMed

Hörl, W H

1996-01-01

Treatment with ACE inhibitors results in kidney protection due to reduction of systemic blood pressure, intraglomerular pressure, an antiproliferative effect, reduction of proteinuria and a lipid-lowering effect in proteinuric patients (secondary due to reduction of protein excretion). Elderly patients with diabetes melitus, coronary heart disease or peripheral vascular occlusion are at risk for deterioration of kidney function due to a high frequency of renal artery stenosis in these patients. In patients with renal insufficiency dose reduction of ACE inhibitors is necessary (exception: fosinopril) but more important is the risk for development of hyperkalemia. Patients at risk for renal artery stenosis and patients pretreated with diuretics should receive a low ACE inhibitor dosage initially ("start low - go slow"). For compliance reasons once daily ACE inhibitor dosage is recommended.

Communities of Molecules: A Physical Chemistry Module.

ERIC Educational Resources Information Center

DeVoe, Howard

This book is one in the series of Interdisciplinary Approaches to Chemistry (IAC) designed to help students discover that chemistry is a lively science and actively used to pursue solutions to the important problems of today. It is expected for students to see how chemistry takes place continuously all around and to readily understand the daily…

Affordances of Instrumentation in General Chemistry Laboratories

ERIC Educational Resources Information Center

Sherman, Kristin Mary Daniels

2010-01-01

The purpose of this study is to find out what students in the first chemistry course at the undergraduate level (general chemistry for science majors) know about the affordances of instrumentation used in the general chemistry laboratory and how their knowledge develops over time. Overall, students see the PASCO(TM) system as a useful and accurate…

Diversity and Periodicity: An Inorganic Chemistry Module.

ERIC Educational Resources Information Center

Huheey, James

This book is one in a series of Interdisciplinary Approaches to Chemistry (IAC) designed to help students discover that chemistry is a lively science and actively used to pursue solutions to the important problems of today. It is expected for students to see how chemistry takes place continuously all around and to readily understand the daily…

Form and Function: An Organic Chemistry Module.

ERIC Educational Resources Information Center

Jarvis, Bruce; Mazzocchi, Paul

This book is one in the series of Interdisciplinary Approaches to Chemistry (IAC) designed to help students discover that chemistry is a lively science and actively used to pursue solutions to the important problems of today. It is expected for students to see how chemistry takes place continuously all around and to readily understand the daily…

Chemistry and cosmology.

PubMed

Black, John H

2006-01-01

The simplest elements, hydrogen and helium, offer a remarkably rich chemistry, which has controlled crucial features of the early evolution of the universe. Theoretical models of the origin of structure (stars, galaxies, clusters of galaxies, etc.) now incorporate this chemistry in some detail. In addition to the origin of structure, cosmologists are concerned with observational tests of competing world models. Primordial chemistry may give rise to some of the earliest departures from thermodynamic equilibrium in the universe. These effects may be observable as broad-band spectroscopic distortions of the cosmic background radiation, which otherwise exhibits a nearly perfect blackbody spectrum. The chemical history of the expanding universe is followed through a detailed calculation of the evolution of the abundances of H, H+, H-, H2, H2+, H3+, and other minor species. It is shown that continuous absorption by the small concentration of H- can produce a distortion in the cosmic background spectrum with a maximum at a frequency near nu/c = 9 cm-1 (wavelength 1.1 mm). The predicted effect lies only a factor of 5 below current limits. Its detection would provide an important test of our understanding of the recombination epoch of the universe.

Inhibitors of Ethylene Biosynthesis and Signaling.

PubMed

Schaller, G Eric; Binder, Brad M

2017-01-01

Ethylene is a gas biosynthesized by plants which has many physiological and developmental effects on their growth. Ethylene affects agriculturally and horticulturally important traits such as fruit ripening, post-harvest physiology, senescence, and abscission, and so ethylene action is often inhibited to improve the shelf life of fruits, vegetables, and cut flowers. Chemical inhibitors of ethylene action are also useful for research to characterize the mechanisms of ethylene biosynthesis and signal transduction, and the role that ethylene plays in various physiological processes. Here, we describe the use of three inhibitors commonly used for the study of ethylene action in plants: 2-aminoethoxyvinyl glycine (AVG), silver ions (Ag), and the gaseous compound 1-methylcyclopropene (1-MCP). AVG is an inhibitor of 1-aminocyclopropane-1-carboxylic acid (ACC) synthase, a key enzyme involved in ethylene biosynthesis. Silver and 1-MCP are both inhibitors of the ethylene receptors. Inhibitor use as well as off-target effects are described with a focus on ethylene responses in dark-grown Arabidopsis seedlings. Methods for the use of these inhibitors can be applied to other plant growth assays.

A development of chimeric VEGFR2 TK inhibitor based on two ligand conformers from PDB: 1Y6A complex--medicinal chemistry consequences of a TKs analysis.

PubMed

Lintnerová, Lucia; García-Caballero, Melissa; Gregáň, Fridrich; Melicherčík, Milan; Quesada, Ana R; Dobiaš, Juraj; Lác, Ján; Sališová, Marta; Boháč, Andrej

2014-01-24

VEGFR2 is an important mediator of angiogenesis and influences fate of some cancer stem cells. Here we analysed all 34 structures of VEGFR2 TK available from PDB database. From them a complex PDB: 1Y6A has an exceptional AAZ ligand bound to TK in form of two conformers (U- and S-shaped). This observation inspired us to develop three chimeric bispyridyl VEGFR2 inhibitors by combining structural features of both AAZ conformers and/or their relative ligand AAX (PDB: 1Y6B). Our most interesting inhibitor 22SYM has an enzymatic VEGFR2 TK activity (IC50: 15.1 nM) comparable or better to the active compounds from clinical drugs Nexavar and Sutent. 22SYM inhibits growth, migration and tube formation of endothelial cells (EC) and selectively induces EC apoptosis. 22SYM also inhibits in vivo angiogenesis in Zebrafish embryo assay. Additionally to the above results, we proved here that tyrosine kinases in an inactive form possessing Type I inhibitors can adopt both a closed or an opened conformation of kinase A-loop independently on their DFG-out arrangement. We proposed here that an activity of certain Type I inhibitors (e.g. 22SYM-like) in complex with DFG-out TK can be negatively influenced by collisions with a dynamically moving TK A-loop. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Identification of a new class of potent Cdc7 inhibitors designed by putative pharmacophore model: Synthesis and biological evaluation of 2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-ones.

PubMed

Kurasawa, Osamu; Oguro, Yuya; Miyazaki, Tohru; Homma, Misaki; Mori, Kouji; Iwai, Kenichi; Hara, Hideto; Skene, Robert; Hoffman, Isaac; Ohashi, Akihiro; Yoshida, Sei; Ishikawa, Tomoyasu; Cho, Nobuo

2017-04-01

Cell division cycle 7 (Cdc7) is a serine/threonine kinase that plays important roles in the regulation of DNA replication process. A genetic study indicates that Cdc7 inhibition can induce selective tumor-cell death in a p53-dependent manner, suggesting that Cdc7 is an attractive target for the treatment of cancers. In order to identify a new class of potent Cdc7 inhibitors, we generated a putative pharmacophore model based on in silico docking analysis of a known inhibitor with Cdc7 homology model. The pharmacophore model provided a minimum structural motif of Cdc7 inhibitor, by which preliminary medicinal chemistry efforts identified a dihydrothieno[3,2-d]-pyrimidin-4(1H)-one scaffold having a heteroaromatic hinge-binding moiety. The structure-activity relationship (SAR) studies resulted in the discovery of new, potent, and selective Cdc7 inhibitors 14a, c, e. Furthermore, the high selectivity of 14c, e for Cdc7 over Rho-associated protein kinase 1 (ROCK1) is discussed by utilizing a docking study with Cdc7 and ROCK2 crystal structures. Copyright © 2017 Elsevier Ltd. All rights reserved.

A crystalline protein-proteinase inhibitor from pinto bean seeds.

PubMed

Wang, D

1975-06-26

A crystalline protein-proteinase inhibitor has been isolated from seeds of Pinto bean (Phaseolus vulgaris cultvar. Pinto). It has an average molecular weight of 19 000 as estimated by gel filtration. This crystalline inhibitor is highly active against both bovine pancreatic trypsin and alpha-chymotrypsin. Complexes of both trypsin-inhibitor and alpha-chymotrypsin-inhibitor have been isolated. The inhibitor which was derived from the dissociated trypsin-inhibitor complex was only 62% as effective as the original compound against either enzyme. In contrast, the inhibitor obtained from alpha-chymotrypsin-inhibitor complex retained its full original inhibitory activity for trypsin, but only 25% of its original activity against alpha-chymotrypsin. The dissociated inhibitor from alpha-chymotrypsin-inhibitor compex, despite its full inhibitory activity, had been modified to such an extent that it could no longer form any precipitable complex with trypsin. The crystalline protein-proteinase inhibitor is not homogeneous and has been resolved into two distinct inhibitors in terms of their physical and chemical properties. These two inhibitors are designated as Pinto bean proteinase inhibitor I and II and their respective minimum molecular weights are 9100 and 10 000. They differ most strikingly in their amino acid composition in that inhibitor II is void of both valine and methionine.

Summer Course Promotes Polymer Chemistry for Small Colleges.

ERIC Educational Resources Information Center

Stinson, Stephen

1989-01-01

Describes a three-week summer program teaching selected chemistry faculty how to incorporate polymer chemistry into chemistry courses. In addition to lectures, the program conducted many experiments and provided a trip to industry laboratories. (YP)

Local Evaluation of Chemistry Journals

ERIC Educational Resources Information Center

Kraus, Joseph R.; Hansen, Rachel

2008-01-01

This paper reports on the evaluation of local usage statistics of a specific set of chemistry journals at the University of Denver in Colorado, USA. The objective of the study is to demonstrate that commercial publishers in chemistry charge considerably more for their journals than those from the non-commercial sector. There are three variables…

Plasma chemistry and its applications

NASA Technical Reports Server (NTRS)

Hozumi, K.

1980-01-01

The relationship between discharge phenomena and plasma chemistry, as well as the equipment and mechanisms of plasma chemical reactions are described. Various areas in which plasma chemistry is applied are surveyed, such as: manufacturing of semiconductor integrated circuits; synthetic fibers; high polymer materials for medical uses; optical lenses; and membrane filters (reverse penetration films).

Introducing Relativity into Quantum Chemistry

ERIC Educational Resources Information Center

Li, Wai-Kee; Blinder, S. M.

2011-01-01

It is not often realized by chemists that the special theory of relativity is behind several aspects of quantum chemistry. The Schrdinger equation itself is based on relations between space-time and energy-momentum four vectors. Electron spin is, of course, the most obvious manifestation of relativity. The chemistry of some heavy elements is…

Korean Kimchi Chemistry: A Multicultural Chemistry Connection

ERIC Educational Resources Information Center

Murfin, Brian

2009-01-01

Connecting science with different cultures is one way to interest students in science, to relate science to their lives, and at the same time to broaden their horizons in a variety of ways. In the lesson described here, students make kimchi, a delicious and popular Korean dish that can be used to explore many important chemistry concepts,…

Screening and Quantification of Aliphatic Primary Alkyl Corrosion Inhibitor Amines in Water Samples by Paper Spray Mass Spectrometry.

PubMed

Jjunju, Fred P M; Maher, Simon; Damon, Deidre E; Barrett, Richard M; Syed, S U; Heeren, Ron M A; Taylor, Stephen; Badu-Tawiah, Abraham K

2016-01-19

Direct analysis and identification of long chain aliphatic primary diamine Duomeen O (n-oleyl-1,3-diaminopropane), corrosion inhibitor in raw water samples taken from a large medium pressure water tube boiler plant water samples at low LODs (<0.1 pg) has been demonstrated for the first time, without any sample preparation using paper spray mass spectrometry (PS-MS). The presence of Duomeen O in water samples was confirmed via tandem mass spectrometry using collision-induced dissociation and supported by exact mass measurement and reactive paper spray experiments using an LTQ Orbitrap Exactive instrument. Data shown herein indicate that paper spray ambient ionization can be readily used as a rapid and robust method for in situ direct analysis of polymanine corrosion inhibitors in an industrial water boiler plant and other related samples in the water treatment industry. This approach was applied for the analysis of three complex water samples including feedwater, condensate water, and boiler water, all collected from large medium pressure (MP) water tube boiler plants, known to be dosed with varying amounts of polyamine and amine corrosion inhibitor components. Polyamine chemistry is widely used for example in large high pressure (HP) boilers operating in municipal waste and recycling facilities to prevent corrosion of metals. The samples used in this study are from such a facility in Coventry waste treatment facility, U.K., which has 3 × 40 tonne/hour boilers operating at 17.5 bar.

A comparison of atmospheric composition using the Carbon Bond and Regional Atmospheric Chemistry MechanismsChemistry Mechanisms

EPA Science Inventory

We incorporate the recently developed Regional Atmospheric Chemistry Mechanism (version 2, RACM2) into the Community Multiscale Air Quality modeling system for comparison with the existing 2005 Carbon Bond mechanism with updated toluene chemistry (CB05TU). Compared to CB05TU, RAC...

Understanding Photography as Applied Chemistry: Using Talbot's Calotype Process to Introduce Chemistry to Design Students

ERIC Educational Resources Information Center

Ro¨sch, Esther S.; Helmerdig, Silke

2017-01-01

Early photography processes were predestined to combine chemistry and art. William Henry Fox Talbot is one of the early photography pioneers. In 2-3 day workshops, design students without a major background in chemistry are able to define a reproducible protocol for Talbot's gallic acid containing calotype process. With the experimental concept…

Chemistry Notes.

ERIC Educational Resources Information Center

School Science Review, 1981

1981-01-01

Describes 13 activities, experiments and demonstrations, including the preparation of iron (III) chloride, simple alpha-helix model, investigating camping gas, redox reactions of some organic compounds, a liquid crystal thermometer, and the oxidation number concept in organic chemistry. (JN)

Integrating Computational Chemistry into the Physical Chemistry Curriculum

ERIC Educational Resources Information Center

Johnson, Lewis E.; Engel, Thomas

2011-01-01

Relatively few undergraduate physical chemistry programs integrate molecular modeling into their quantum mechanics curriculum owing to concerns about limited access to computational facilities, the cost of software, and concerns about increasing the course material. However, modeling exercises can be integrated into an undergraduate course at a…

Mass spectrometry. [in organic chemistry

NASA Technical Reports Server (NTRS)

Burlingame, A. L.; Shackleton, C. H. L.; Howe, I.; Chizhov, O. S.

1978-01-01

A review of mass spectrometry in organic chemistry is given, dealing with advances in instrumentation and computer techniques, selected topics in gas-phase ion chemistry, and applications in such fields as biomedicine, natural-product studies, and environmental pollution analysis. Innovative techniques and instrumentation are discussed, along with chromatographic-mass spectrometric on-line computer techniques, mass spectral interpretation and management techniques, and such topics in gas-phase ion chemistry as electron-impact ionization and decomposition, photoionization, field ionization and desorption, high-pressure mass spectrometry, ion cyclotron resonance, and isomerization reactions of organic ions. Applications of mass spectrometry are examined with respect to bio-oligomers and their constituents, biomedically important substances, microbiology, environmental organic analysis, and organic geochemistry.

Quality of dry chemistry testing.

PubMed

Nakamura, H; Tatsumi, N

1999-01-01

Since the development of the qualitative test paper for urine in 1950s, several kinds of dry-state-reagents and their automated analyzers have been developed. "Dry chemistry" has become to be called since the report on the development of quantitative test paper for serum bilirubin with reflectometer in the end of 1960s and dry chemistry has been world widely known since the presentation on the development of multilayer film reagent for serum biochemical analytes by Eastman Kodak Co at the 10th IFCC Meeting in the end of 1970s. We have reported test menu, results in external quality assessment, merits and demerits, and the future possibilities of dry chemistry.

[The primary structure of the alpha-amylase inhibitor Hoe 467A from Streptomyces tendae 4158. A new class of inhibitors].

PubMed

Aschauer, H; Vértesy, L; Nesemann, G; Braunitzer, G

1983-10-01

The native or modified alpha-amylase inhibitor Hoe 467A - isolated from the culture medium of Streptomyces tendae 4158 - and overlapping peptides were degraded by the automatic Edman technique. The oxidized or aminoethylated or oxidized and maleoylated inhibitor was digested with trypsin and the native inhibitor with pepsin. Further digestion with Staphylococcus aureus proteinase was also carried out. After peptic digestion two cystin peptides were isolated, which allowed the establishment of the disulfide bonds. The alpha-amylase inhibitor is a polypeptid consisting of 74 amino-acid residues with a molecular mass of 7958 Da. The inhibitor is composed of all naturally occurring amino acids except methionine and phenylalanine and shows no sequence homology to known inhibitors. The clinical and pharmacological importance in respect to the inhibitors ability for inactivation of human salivary and pancreatic alpha-amylase is discussed. Especially the proteinase resistance of the inhibitor enables a clinical application in human (e.g. Diabetes mellitus) per os.

Affordances of instrumentation in general chemistry laboratories

NASA Astrophysics Data System (ADS)

Sherman, Kristin Mary Daniels

The purpose of this study is to find out what students in the first chemistry course at the undergraduate level (general chemistry for science majors) know about the affordances of instrumentation used in the general chemistry laboratory and how their knowledge develops over time. Overall, students see the PASCO(TM) system as a useful and accurate measuring tool for general chemistry labs. They see the probeware as easy to use, portable, and able to interact with computers. Students find that the PASCO(TM) probeware system is useful in their general chemistry labs, more advanced chemistry labs, and in other science classes, and can be used in a variety of labs done in general chemistry. Students learn the affordances of the probeware through the lab manual, the laboratory teaching assistant, by trial and error, and from each other. The use of probeware systems provides lab instructors the opportunity to focus on the concepts illustrated by experiments and the opportunity to spend time discussing the results. In order to teach effectively, the instructor must know the correct name of the components involved, how to assemble and disassemble it correctly, how to troubleshoot the software, and must be able to replace broken or missing components quickly. The use of podcasts or Web-based videos should increase student understanding of affordances of the probeware.

Application of computer assisted combinatorial chemistry in antivirial, antimalarial and anticancer agents design

NASA Astrophysics Data System (ADS)

Burello, E.; Bologa, C.; Frecer, V.; Miertus, S.

Combinatorial chemistry and technologies have been developed to a stage where synthetic schemes are available for generation of a large variety of organic molecules. The innovative concept of combinatorial design assumes that screening of a large and diverse library of compounds will increase the probability of finding an active analogue among the compounds tested. Since the rate at which libraries are screened for activity currently constitutes a limitation to the use of combinatorial technologies, it is important to be selective about the number of compounds to be synthesized. Early experience with combinatorial chemistry indicated that chemical diversity alone did not result in a significant increase in the number of generated lead compounds. Emphasis has therefore been increasingly put on the use of computer assisted combinatorial chemical techniques. Computational methods are valuable in the design of virtual libraries of molecular models. Selection strategies based on computed physicochemical properties of the models or of a target compound are introduced to reduce the time and costs of library synthesis and screening. In addition, computational structure-based library focusing methods can be used to perform in silico screening of the activity of compounds against a target receptor by docking the ligands into the receptor model. Three case studies are discussed dealing with the design of targeted combinatorial libraries of inhibitors of HIV-1 protease, P. falciparum plasmepsin and human urokinase as potential antivirial, antimalarial and anticancer drugs. These illustrate library focusing strategies.

Chemistry inside an epistemological community box! Discursive exclusions and inclusions in Swedish National tests in Chemistry

NASA Astrophysics Data System (ADS)

Ståhl, Marie; Hussénius, Anita

2017-06-01

This study examined the Swedish national tests in chemistry for implicit and explicit values. The chemistry subject is understudied compared to biology and physics and students view chemistry as their least interesting science subject. The Swedish national science assessments aim to support equitable and fair evaluation of students, to concretize the goals in the chemistry syllabus and to increase student achievement. Discourse and multimodal analyses, based on feminist and critical didactic theories, were used to examine the test's norms and values. The results revealed that the chemistry discourse presented in the tests showed a traditional view of science from the topics discussed (for example, oil and metal), in the way women, men and youth are portrayed, and how their science interests are highlighted or neglected. An elitist view of science emerges from the test, with distinct gender and age biases. Students could interpret these biases as a message that only "the right type" of person may come into the chemistry epistemological community, that is, into this special sociocultural group that harbours a common view about this knowledge. This perspective may have an impact on students' achievement and thereby prevent support for an equitable and fair evaluation. Understanding the underlying evaluative meanings that come with science teaching is a question of democracy since it may affect students' feelings of inclusion or exclusion. The norms and values harboured in the tests will also affect teaching since the teachers are given examples of how the goals in the syllabus can be concretized.

40 CFR 158.310 - Product chemistry data requirements table.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Product chemistry data requirements...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Product Chemistry § 158.310 Product chemistry data... the product chemistry data requirements for a particular pesticide product. Notes that apply to an...

40 CFR 158.1410 - Residue chemistry data requirements table.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Residue chemistry data requirements...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Residue Chemistry § 158.1410 Residue chemistry data... the residue chemistry data requirements for a particular pesticide product. Notes that apply to an...

40 CFR 158.1410 - Residue chemistry data requirements table.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Residue chemistry data requirements...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Residue Chemistry § 158.1410 Residue chemistry data... the residue chemistry data requirements for a particular pesticide product. Notes that apply to an...

40 CFR 158.310 - Product chemistry data requirements table.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Product chemistry data requirements...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Product Chemistry § 158.310 Product chemistry data... the product chemistry data requirements for a particular pesticide product. Notes that apply to an...

40 CFR 158.1410 - Residue chemistry data requirements table.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Residue chemistry data requirements...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Residue Chemistry § 158.1410 Residue chemistry data... the residue chemistry data requirements for a particular pesticide product. Notes that apply to an...

40 CFR 158.1410 - Residue chemistry data requirements table.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Residue chemistry data requirements...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Residue Chemistry § 158.1410 Residue chemistry data... the residue chemistry data requirements for a particular pesticide product. Notes that apply to an...

40 CFR 158.310 - Product chemistry data requirements table.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Product chemistry data requirements...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Product Chemistry § 158.310 Product chemistry data... the product chemistry data requirements for a particular pesticide product. Notes that apply to an...

40 CFR 158.1410 - Residue chemistry data requirements table.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Residue chemistry data requirements...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Residue Chemistry § 158.1410 Residue chemistry data... the residue chemistry data requirements for a particular pesticide product. Notes that apply to an...

40 CFR 158.310 - Product chemistry data requirements table.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Product chemistry data requirements...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Product Chemistry § 158.310 Product chemistry data... the product chemistry data requirements for a particular pesticide product. Notes that apply to an...

40 CFR 158.310 - Product chemistry data requirements table.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Product chemistry data requirements...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Product Chemistry § 158.310 Product chemistry data... the product chemistry data requirements for a particular pesticide product. Notes that apply to an...

Inhibitors of Trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease

PubMed Central

KongThoo Lin, Paul; Costa, David M.; Perez-Cabezas, Begoña; Tavares, Joana; Roura-Ferrer, Meritxell; Ramos, Isbaal; Ronin, Céline; Major, Louise L.; Ciesielski, Fabrice; Pemberton, Iain K.; MacDougall, Jane; Ciapetti, Paola; Cordeiro-da-Silva, Anabela

2018-01-01

Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region’s leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2) proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1) is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP) derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd) (9), was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Å) to gain insight

Inhibitors of Trypanosoma cruzi Sir2 related protein 1 as potential drugs against Chagas disease.

PubMed

Gaspar, Luís; Coron, Ross P; KongThoo Lin, Paul; Costa, David M; Perez-Cabezas, Begoña; Tavares, Joana; Roura-Ferrer, Meritxell; Ramos, Isbaal; Ronin, Céline; Major, Louise L; Ciesielski, Fabrice; Pemberton, Iain K; MacDougall, Jane; Ciapetti, Paola; Smith, Terry K; Cordeiro-da-Silva, Anabela

2018-01-01

Chagas disease remains one of the most neglected diseases in the world despite being the most important parasitic disease in Latin America. The characteristic chronic manifestation of chagasic cardiomyopathy is the region's leading cause of heart-related illness, causing significant mortality and morbidity. Due to the limited available therapeutic options, new drugs are urgently needed to control the disease. Sirtuins, also called Silent information regulator 2 (Sir2) proteins have long been suggested as interesting targets to treat different diseases, including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have hinted at the possibility to exploit these enzymes as a possible drug targets. In the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1) is genetically validated as a drug target and biochemically characterized for its NAD+-dependent deacetylase activity and its inhibition by the classic sirtuin inhibitor nicotinamide, as well as by bisnaphthalimidopropyl (BNIP) derivatives, a class of parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti-parasitic activity against T. cruzi amastigotes in vitro were investigated. The compound BNIP Spermidine (BNIPSpd) (9), was found to be the most potent inhibitor of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity similar to the reference drug benznidazole against the medically important amastigotes, while having the highest selectivity index amongst the compounds tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease, possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of the compound, as well as alternative formulations may improve activity and pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in complex with p53 peptide substrate was obtained from low resolution X-ray data (3.5 Å) to gain insight

Effect of phosphodiesterase inhibitors in the bladder.

PubMed

Chughtai, Bilal; Ali, Aizaz; Dunphy, Claire; Kaplan, Steven A

2015-01-01

Many aging men will experience lower urinary tract symptoms (LUTS). Phosphodiesterase type 5 (PDE5) inhibitors have shown promise in treating LUTS in these patients. PDE5 inhibitors mediate their effects through several pathways including cAMP, NO/cGMP, K-channel modulated pathways, and the l -cysteine/H 2 S pathway. PDE5 inhibitors exert their effect in muscle cells, nerve fibers, and interstitial cells (ICs). The use of PDE5 inhibitors led to improvement in LUTS. This included urodynamic parameters. PDE5 inhibitors may play a significant role in LUTS due to their effect on the bladder rather than the prostate.

Bioorthogonal chemistry in bioluminescence imaging.

PubMed

Godinat, Aurélien; Bazhin, Arkadiy A; Goun, Elena A

2018-05-18

Bioorthogonal chemistry has developed significant over the past few decades, to the particular benefit of molecular imaging. Bioluminescence imaging (BLI) along with other imaging modalities have significantly benefitted from this chemistry. Here, we review bioorthogonal reactions that have been used to signific antly broaden the application range of BLI. Copyright © 2018. Published by Elsevier Ltd.

Turbulent Mixing Chemistry in Disks

NASA Astrophysics Data System (ADS)

Semenov, D.; Wiebe, D.

2006-11-01

A gas-grain chemical model with surface reaction and 1D/2D turbulent mixing is available for protoplanetary disks and molecular clouds. Current version is based on the updated UMIST'95 database with gas-grain interactions (accretion, desorption, photoevaporation, etc.) and modified rate equation approach to surface chemistry (see also abstract for the static chemistry code).

Organic Chemistry for the Gifted.

ERIC Educational Resources Information Center

deBeer, W. H. J.

In response to a serious shortage of chemists in South Africa, gifted secondary school students are enrolled in an enrichment program in organic chemistry and encouraged to consider chemistry or one of its related fields as a career. The introductory portion of the program involves approximately 90 hours over a 3-year period while the advanced…

Chemistry Notes.

ERIC Educational Resources Information Center

School Science Review, 1983

1983-01-01

Presents chemistry experiments, laboratory procedures, demonstrations, teaching suggestions, and classroom materials/activities. These include: game for teaching ionic formulas; method for balancing equations; description of useful redox series; computer programs (with listings) for water electrolysis simulation and for determining chemical…

Catalytic Chemistry.

ERIC Educational Resources Information Center

Borer, Londa; And Others

1996-01-01

Describes an approach for making chemistry relevant to everyday life. Involves the study of kinetics using the decomposition of hydrogen peroxide by vegetable juices. Allows students to design and carry out experiments and then draw conclusions from their results. (JRH)

Chemistry Notes.

ERIC Educational Resources Information Center

School Science Review, 1978

1978-01-01

Describes some laboratory apparatus, chemistry experiments and demonstrations, such as a Kofler block melting point apparatus, chromatographic investigation of the phosphoric acid, x-ray diffraction, the fountain experiment, endothermic sherbet, the measurement of viscosity, ionization energies and electronic configurations. (GA)

EVALUATING THE SUSTAINABILITY OF GREEN CHEMISTRIES

EPA Science Inventory

The U.S. EPA's National Risk Management Research Laboratory is developing a methodology for the evaluation of reaction chemistries. This methodology, called GREENSCOPE (Gauging Reaction Effectiveness for the ENvironmental Sustainability of Chemistries with a multi-Objective Proc...

Halogen Chemistry in the CMAQ Model

EPA Science Inventory

Halogens (iodine and bromine) emitted from oceans alter atmospheric chemistry and influence atmospheric ozone mixing ratio. We previously incorporated a representation of detailed halogen chemistry and emissions of organic and inorganic halogen species into the hemispheric Commun...

General Chemistry Courses That Can Affect Achievement: An Action Research Study in Developing a Plan to Improve Undergraduate Chemistry Courses

ERIC Educational Resources Information Center

Shweikeh, Eman

2014-01-01

Over the past 50 years, considerable research has been dedicated to chemistry education. In evaluating principal chemistry courses in higher education, educators have noted the learning process for first-year general chemistry courses may be challenging. The current study investigated perceptions of faculty, students and administrators on…

Thiopurine Drugs Repositioned as Tyrosinase Inhibitors

PubMed Central

Choi, Joonhyeok; Lee, You-Mie; Jee, Jun-Goo

2017-01-01

Drug repositioning is the application of the existing drugs to new uses and has the potential to reduce the time and cost required for the typical drug discovery process. In this study, we repositioned thiopurine drugs used for the treatment of acute leukaemia as new tyrosinase inhibitors. Tyrosinase catalyses two successive oxidations in melanin biosynthesis: the conversions of tyrosine to dihydroxyphenylalanine (DOPA) and DOPA to dopaquinone. Continuous efforts are underway to discover small molecule inhibitors of tyrosinase for therapeutic and cosmetic purposes. Structure-based virtual screening predicted inhibitor candidates from the US Food and Drug Administration (FDA)-approved drugs. Enzyme assays confirmed the thiopurine leukaemia drug, thioguanine, as a tyrosinase inhibitor with the inhibitory constant of 52 μM. Two other thiopurine drugs, mercaptopurine and azathioprine, were also evaluated for their tyrosinase inhibition; mercaptopurine caused stronger inhibition than thioguanine did, whereas azathioprine was a poor inhibitor. The inhibitory constant of mercaptopurine (16 μM) was comparable to that of the well-known inhibitor kojic acid (13 μM). The cell-based assay using B16F10 melanoma cells confirmed that the compounds inhibit mammalian tyrosinase. Particularly, 50 μM thioguanine reduced the melanin content by 57%, without apparent cytotoxicity. Cheminformatics showed that the thiopurine drugs shared little chemical similarity with the known tyrosinase inhibitors. PMID:29283382

EPA Environmental Chemistry Laboratory

NASA Technical Reports Server (NTRS)

1993-01-01

The Environmental Protection Agency's (EPA) Chemistry Laboratory (ECL) is a national program laboratory specializing in residue chemistry analysis under the jurisdiction of the EPA's Office of Pesticide Programs in Washington, D.C. At Stennis Space Center, the laboratory's work supports many federal anti-pollution laws. The laboratory analyzes environmental and human samples to determine the presence and amount of agricultural chemicals and related substances. Pictured, ECL chemists analyze environmental and human samples for the presence of pesticides and other pollutants.

Contextualized Chemistry Education: The American experience

NASA Astrophysics Data System (ADS)

Schwartz, A. Truman

2006-07-01

This paper is a survey of context-based chemistry education in the United States. It begins with a very brief overview of twentieth-century chemistry texts and teaching methods, followed by a short description of a pioneering secondary school text. The major emphasis is on post-secondary instruction and the central case study is provided by Chemistry in Context, a university text intended for students who are not specializing in science. The paper is more concerned with strategies for curriculum reform than with educational research, and the emphasis is more pragmatic than theoretical. A chronological sequence is used to trace the creation of Chemistry in Context. This developmental account is overlaid with the curricular representations of Goodlad and Van den Akker. The Ideal Curriculum was the goal, but the Formal Curriculum was created and revised as a consequence of iteration involving perceptions of the users, the implementation of the curriculum, the experience of students and teachers, and formal and informal assessment of what was attained. The paper also includes descriptions of other, more recent, context-based college chemistry curricula. It concludes with a list of problems and unanswered questions relating to this pedagogical approach.

General Chemistry Students' Goals for Chemistry Laboratory Coursework

ERIC Educational Resources Information Center

DeKorver, Brittland K.; Towns, Marcy H.

2015-01-01

Little research exists on college students' learning goals in chemistry, let alone specifically pertaining to laboratory coursework. Because students' learning goals are linked to achievement and dependent on context, research on students' goals in the laboratory context may lead to better understanding about the efficacy of lab curricula. This…

The Effect of an Individualized Laboratory Approach through Microscale Chemistry Experimentation on Students' Understanding of Chemistry Concepts, Motivation and Attitudes

ERIC Educational Resources Information Center

Abdullah, Mashita; Mohamed, Norita; Ismail, Zurida Hj

2009-01-01

The main goal of this study was to investigate whether the use of an individualized approach through microscale chemistry experiments in secondary schools can increase students' understanding of chemistry concepts, improve attitude towards chemistry practical work and motivation. Two comparable groups of Form Four students (16 years old)…

Incorporation of Medicinal Chemistry into the Organic Chemistry Curriculum

ERIC Educational Resources Information Center

Forbes, David C.

2004-01-01

Application of concepts presented in organic chemistry lecture using a virtual project involving the sythesis of medicinally important compounds is emphasized. The importance of reinforcing the concepts from lecture in lab, thus providing a powerful instructional means is discussed.

Prominent Chemists Team Up to Review Frontiers in Chemistry.

ERIC Educational Resources Information Center

Baum, Rudy M.

1989-01-01

Discusses a symposium which focused on the influence of inorganic chemistry on organic synthesis, the impact of organic chemistry on biochemistry and vice versa, chemical reaction dynamics, and advances in inorganic chemistry. Explains the purpose of the symposium was to illustrate the intellectual dynamism of modern chemistry. (MVL)

Chemistry in the Two-Year College, Vol. 11, 1973.

ERIC Educational Resources Information Center

Bardole, Jay, Ed.; Bardole, Ellen, Ed.

This publication, issued twice per year, includes proceedings from Two-Year College Chemistry Conferences and papers of special interest to the two-year college chemistry teacher. Relevant applications of chemistry are discussed, including the chemistry of flame retardance and photographic processes. Also discussed are topics related to the…

Discovering Drugs with DNA-Encoded Library Technology: From Concept to Clinic with an Inhibitor of Soluble Epoxide Hydrolase.

PubMed

Belyanskaya, Svetlana L; Ding, Yun; Callahan, James F; Lazaar, Aili L; Israel, David I

2017-05-04

DNA-encoded chemical library technology was developed with the vision of its becoming a transformational platform for drug discovery. The hope was that a new paradigm for the discovery of low-molecular-weight drugs would be enabled by combining the vast molecular diversity achievable with combinatorial chemistry, the information-encoding attributes of DNA, the power of molecular biology, and a streamlined selection-based discovery process. Here, we describe the discovery and early clinical development of GSK2256294, an inhibitor of soluble epoxide hydrolase (sEH, EPHX2), by using encoded-library technology (ELT). GSK2256294 is an orally bioavailable, potent and selective inhibitor of sEH that has a long half life and produced no serious adverse events in a first-time-in-human clinical study. To our knowledge, GSK2256294 is the first molecule discovered from this technology to enter human clinical testing and represents a realization of the vision that DNA-encoded chemical library technology can efficiently yield molecules with favorable properties that can be readily progressed into high-quality drugs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Friendship chemistry: An examination of underlying factors☆.

PubMed

Campbell, Kelly; Holderness, Nicole; Riggs, Matt

2015-06-01

Interpersonal chemistry refers to a connection between two individuals that exists upon first meeting. The goal of the current study is to identify beliefs about the underlying components of friendship chemistry. Individuals respond to an online Friendship Chemistry Questionnaire containing items that are derived from interdependence theory and the friendship formation literature. Participants are randomly divided into two subsamples. A principal axis factor analysis with promax rotation is performed on subsample 1 and produces 5 factors: Reciprocal candor, mutual interest, personableness, similarity, and physical attraction. A confirmatory factor analysis is conducted using subsample 2 and provides support for the 5-factor model. Participants with agreeable, open, and conscientious personalities more commonly report experiencing friendship chemistry, as do those who are female, young, and European/white. Responses from participants who have never experienced chemistry are qualitatively analyzed. Limitations and directions for future research are discussed.

Friendship chemistry: An examination of underlying factors☆

PubMed Central

Campbell, Kelly; Holderness, Nicole; Riggs, Matt

2015-01-01

Interpersonal chemistry refers to a connection between two individuals that exists upon first meeting. The goal of the current study is to identify beliefs about the underlying components of friendship chemistry. Individuals respond to an online Friendship Chemistry Questionnaire containing items that are derived from interdependence theory and the friendship formation literature. Participants are randomly divided into two subsamples. A principal axis factor analysis with promax rotation is performed on subsample 1 and produces 5 factors: Reciprocal candor, mutual interest, personableness, similarity, and physical attraction. A confirmatory factor analysis is conducted using subsample 2 and provides support for the 5-factor model. Participants with agreeable, open, and conscientious personalities more commonly report experiencing friendship chemistry, as do those who are female, young, and European/white. Responses from participants who have never experienced chemistry are qualitatively analyzed. Limitations and directions for future research are discussed. PMID:26097283

Some Exercises Reflecting Green Chemistry Concepts

ERIC Educational Resources Information Center

Song, Yu-Min; Wang, Yong-Cheng; Geng, Zhi-Yuan

2004-01-01

Some exercises to introduce students to the concept of green chemistry are given. By doing these exercises, students develop an appreciation for the role of green chemistry on feedstock substitution, milder reaction conditions, reduced environmental exposure, and resource conservation.

Invertase proteinaceous inhibitor of Cyphomandra betacea Sendt fruits.

PubMed

Ordóñez, R M; Isla, M I; Vattuone, M A; Sampietro, A R

2000-01-01

This work describes a new invertase proteinaceous inhibitor from Cyphomandra betacea Sendt. (tomate de arbol) fruits. The proteinaceous inhibitor was isolated and purified from a cell wall preparation. The pH stability, kinetics of the inhibition of the C. betacea invertase, inhibition of several higher plant invertases and lectin nature of the inhibitor were studied. The inhibitor structure involves a single polypeptide (Mr = 19000), as shown by gel filtration and SDS-PAGE determinations. N-terminal aminoacid sequence was determined. The properties and some structural features of the inhibitor are compared with the proteinaceous inhibitors from several plant species (Beta vulgaris L., Ipomoea batatas L. and Lycopersicon esculentum Mill.). All these inhibitors share lectinic properties, some common epitopes, some aminoacid sequences and a certain lack of specificity towards invertases of different species, genera and even plant family. In consequence, the inhibitors appear to belong to the same lectin family. It is now known that some lectins are part of the defence mechanism of higher plants against fungi and bacteria and this is a probable role of the proteinaceous inhibitors.

Chemistry Notes.

ERIC Educational Resources Information Center

School Science Review, 1983

1983-01-01

Presents chemistry experiments, laboratory procedures, demonstrations, and classroom materials/activities. These include: experiments on colloids, processing of uranium ore, action of heat on carbonates; color test for phenols and aromatic amines; solvent properties of non-electrolytes; stereoscopic applications/methods; a valency balance;…

The existence of imidazoline corrosion inhibitors

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

Martin, J.A.; Valone, F.W.

1985-05-01

Spectroscopic methods, i.e., Fourier transform infrared (FT-IR), carbon-13 nuclear magnetic reasonance (/sup 13/C NMR), and ultraviolet (UV) spectroscopy, were used to investigate the actual chemical composition of oilfield corrosion inhibitors. Inhibitor formulations consisting of an amide or imidazoline reacted with a dimer-trimer acid, along with an ethoxylated surfactant and an aromatic solvent, were used for these studies. /sup 13/C NMR and FT-IR spectra of these inhibitors, as well as spectra of pure imidazolines, showed that the imidazoline functional group was fairly rapidly hydrolyzed to the amide form. For instance, in FT-IR studies, the imine functional group decreased in intensity asmore » a function of time. Coincident with this was an increase in the intensities of the vibrational resonances attributed to the amide functionality. The relative molar ratio of imidazoline to amide in a corrosion inhibitor could be calculated via UV spectroscopy. Within a 20 day interval after inhibitor synthesis, this ratio decreased by a factor greater than 20. These results, as well as a discussion of their economic impact on oilfield corrosion inhibitor formulation, are presented in this paper.« less