jablonkagroup/rise_ai_scientists huggingface dataset:
Authors: Jozafina Milicaj | Bakar A. Hassan | Joy M. Cote | Carlos A. Ramirez-Mondragon | Nadiya Jaunbocus | Angelika Rafalowski | Kaelan R. Patel | Ramaiah Muthyala | Yuk Y. Sham | Erika A. Taylor
Source: bioRxiv (Cold Spring Harbor Laboratory) (preprint, 2021-10-04)
Field: Chemistry — Organic Chemistry

Discovery of Aminoglycosides as first in class, nanomolar inhibitors of Heptosyltransferase I Abstract A clinically relevant inhibitor for Heptosyltransferase I (HepI) has been sought after for many years and while many have designed novel small-molecule inhibitors, these compounds lack the bioavailability and potency necessary for therapeutic use. Extensive characterization of the HepI protein has provided valuable insight into the dynamic motions necessary for catalysis that could be targeted for inhibition. With the help of molecular dynamic simulations, aminoglycoside antibiotics were shown to be putative inhibitors for HepI and in this study, they were experimentally determined to be the first in-class nanomolar inhibitors of HepI with the best inhibitor demonstrating a K i of 600 +/- 90 nM. Detailed kinetic analyses were performed to determine the mechanism of inhibition while circular dichroism spectroscopy, intrinsic tryptophan fluorescence, docking, and MD simulations were used to corroborate kinetic experimental findings. Kinetic analysis methods include Lineweaver-Burk, Dixon, Cornish-Bowden and Mixed-Model of Inhibition which allowed for unambiguous assignment of inhibition mechanism for each inhibitor. In this study, we show that neomycin and kanamycin b are competitive inhibitors against the sugar acceptor substrate while tobramycin exhibits a mixed inhibitory effect and streptomycin is non-competitive. MD simulations also allowed us to suggest that the inhibitors bind tightly and inhibit catalytic dynamics due to a major desolvation penalty of the enzyme active site. While aminoglycosides have long been known as a class of potent antibiotics, they also have been scientifically shown to impact cell membrane stability, and we propose that inhibition of HepI contributes to this effect by disrupting lipopolysaccharide biosynthesis. Chemistry ; Docking (animal) ; Enzyme ; Non-competitive inhibition ; Aminoglycoside ; Biophysics ; Stereochemistry ; Biochemistry ; Antibiotics ; Biology Carbohydrate Chemistry and Synthesis ; RNA and protein synthesis mechanisms ; Escherichia coli research studies
Authors: Peng Du
Source: Scholarworks (University of Massachusetts Amherst) (article, 2021-04-01)
Field: Chemistry — Physical and Theoretical Chemistry

Adsorption of Biomolecules on Carbon-Based Nanomaterial as Affected by Surface Chemistry and Ionic Strength Many RNA interactions in cells occur in the form of loop-loop interactions, also known as a "kissing complex". In the bacterial and viral systems discussed here, there are transiently bound proteins involved that modulate the function of kissing complex. These proteins either stabilize the kissing complex or facilitate its conversion to extended duplex. I studied R1inv-R2inv kissing complex (KC), derivatived from RNAI-RNAII complex of <em>E.Coli</em>. Rop protein is known to stabilize the bent R1inv-R2inv KC against dissociation. The goal was to study structural change of this kissing complex after binding of the stabilizing Rop protein. In this work for the first time I used the orientation sensitivity of Fluorescence Resonance energy transfer (FRET) to measure an angular change in the structure of R1inv-R2inv kissing complex upon binding of Rop protein. Single-molecular-pair-FRET (spFRET) is often used to study distance fluctuations of single molecules, it is harder to capture angular changes using FRET, because rotational motion of the dyes tends to wash out the angular sensitivity. The effect of Rop protein on the conformation of the kissing complex is not known. Using fluorescence microscopy techniques we observe a change in twist angle of the KC with protein binding. The eight minimized energy structures reported for R1inv-R2inv KC show a small difference in end-to-end distance and a larger difference in twist and bend angles. From MD simulations I modeled FRET for these eight structures, also for these structures with addition of twist. By comparing the spFRET data with results of this first-principle model, I found the result is consistent with a -25<sup>o</sup> change in twist angle. My preliminary work on another kissing complex, Dimerization initiation site (DIS) of HIV-1 retrovirus, is also discussed. Nucleocapsid protein (NCp7) plays an important role in facilitating the kissing complex to extended duplex transition for DIS. My work on DIS kissing complex, was aimed at studying possible intermediates in kissing complex to duplex transition, and investigating the effect of proteins like Rop and NCp7. The construction of the TIRF-FRET instrument, methods for surface passivation, and the RNA sequence design are discussed. Adsorption ; Ionic strength ; Chemistry ; Biomolecule ; Nanomaterials ; Carbon fibers ; Nanotechnology ; Chemical engineering ; Ionic bonding ; Environmental chemistry ; Materials science ; Aqueous solution ; Ion ; Organic chemistry ; Composite number ; Composite material Various Chemistry Research Topics
Authors: Konstance Tsavdaris
Source:  (preprint, 2021-05-22)
Field: Chemistry — Analytical Chemistry

Cholesterol templated polymers : are they really specific binding materials? The technique of molecular imprinting creates template specific and selective polymer products with a large assortment of applications. For example, molecularly imprinted polymers (MIPs) may pose as a means to separate undesirable components, such as endocrine disruptors, from the environment. Taking advantage of β-cyclodextrin's abililty to form inclusion complexes with a number of guests has led scientists to use them as scaffolds in the synthesis of MIPs. Komiyana's approach of molecularly imprinting cholesterol with β-cyclodextrin was used as a starting point to apply MIPs as potential tools for trapping endocrine disruptors. This study presents results on the re-binding of cholesterol to a cholesterol-templated MIP and to a non-MIP (NMIP), as well as the binding of a series of structurally unrelated compounds to the cholesterol-templated MIP and NMIP. The results consistently show that cholesterol-templated MIPs synthesized using Komiyama's method lack specificity and selectivity for their template. This calls into question their efficacy as a tool for trapping endocrine disruptors. Molecularly imprinted polymer ; Molecular imprinting ; Cyclodextrin ; Cholesterol ; Polymer ; Chemistry ; Combinatorial chemistry ; Nanotechnology ; Imprinting (psychology) ; Selectivity ; Materials science ; Organic chemistry ; Biochemistry ; Catalysis Analytical chemistry methods development ; Mass Spectrometry Techniques and Applications ; Microfluidic and Capillary Electrophoresis Applications
Authors: Sunil Kumar | Abhilasha Mittal | Ashish K. Pathak | Gopal Garg | Sanjeev Kumar Sahu
Source: PLANT ARCHIVES (article, 2021-01-15)
Field: Chemistry — Organic Chemistry

DRUG LIKELINESS AND TOXICITY PREDICTION OF BENZOTHIAZOLE DERIVATIVES WITH THEIR BIOLOGICAL EVALUATION Drug likeliness and toxicity prediction data determined using Pre-ADMET software plays a vital role in development of newer potent compounds. Further, its outcomes help us to process their synthesis of selected compounds with their biological evaluation. Benzothiazole is one of the important heterocyclic nucleuses which coupled with number of biological activities resulting to develop the newer class of drugs. The assessment of antidiabetic activity can be done by inducing the diabetic conditions in the experimental model using streptozotocin (STZ). This research work was focused on selection of potent benzothiazole derivatives through Pre ADMET toxicity profile and further evaluating their antidiabetic activity in the streptozotocin induced diabetes rat model. Among the entire selected compounds 7d exhibited more potent anti-diabetic activity at 350 mg/kg (p. o.). Benzothiazole ; Drug ; Toxicity ; Chemistry ; Pharmacology ; Biology ; Biochemistry ; Organic chemistry Synthesis and biological activity ; Phenothiazines and Benzothiazines Synthesis and Activities ; Synthesis and Characterization of Heterocyclic Compounds
Authors: Ryan F. Landis
Source: Scholarworks (University of Massachusetts Amherst) (article, 2021-04-12)
Field: Chemistry — Organic Chemistry

HYBRIDIZED POLYMERIC NANO-ASSEMBLIES: KEY INSIGHTS INTO ADDRESSING MDR INFECTIONS Multidrug-resistant (MDR) bacteria contribute to more than 700,000 annual deaths world-wide. Millions more suffer from limb amputations or face high healthcare treatment costs where prolonged and costly therapeutic regimens are used to counter MDR infections. While there is an international push to develop novel and more powerful antimicrobials to address the impending threat, one particularly interesting approach that has re-emerged are essential oils, phytochemical extracts derived from plant sources. While their antimicrobial activity demonstrates a promising avenue, their stability in aqueous media, limits their practical use in or on mammals. Inspired by the versatility of polymer nanotechnology and the sustainability of traditional medicine, I employed a hybridization approach to improve the stability and subsequently the antimicrobial activity of phytochemical extracts. This approach was accomplished through a crosslinked Nano-emulsification templating strategy, generating a highly robust and reproducible library of potent oil-in-water Nano-assemblies. These assemblies, stabilized using synthetic or natural polymers, demonstrated long-term shelf life, high stability in serum-containing aqueous environments, and most notably, were demonstrated to penetrate highly refractory biofilm infections, eliminating a broad-spectrum of pathogenic bacteria where accumulated resistance towards these materials were not observed during the course of laboratory experiments. Taken together, the technology presented herein, offers key insight into addressing MDR-associated infections with hopes that future platforms can be built from to tackle the rising dangers of MDR infections. Key (lock) ; Nanotechnology ; Computer science ; Materials science ; Computer security Antimicrobial agents and applications ; Polydiacetylene-based materials and applications ; Antimicrobial Peptides and Activities
Authors: Peter Ertl
Source:  (preprint, 2021-10-05)
Field: Chemistry — Organic Chemistry

Substituents of life: The most common substituent patterns present in natural products Comparison of substituents present in natural products with the substituents found in average synthetic molecules revealed considerable differences between these 2 groups. The natural products substituents contain mostly oxygen atoms and very little other heteroatoms, are structurally more complex, often containing double bonds and are rich in stereocenters. Substituents found in synthetic molecules contain nitrogen and sulfur atoms, halogenes and more aromatic and particularly heteroaromatic rings. The characteristics of substituents typical for natural products identified here can be useful in the medicinal chemistry context, for example to guide the synthesis of natural product-like libraries and natural product-inspired fragment collections. The results may be used also to support compound derivatization strategies and the design of pseudo-natural natural products. Natural product ; Substituent ; Heteroatom ; Stereocenter ; Chemistry ; Context (archaeology) ; Molecule ; Derivatization ; Sulfur ; Oxygen atom ; Stereochemistry ; Combinatorial chemistry ; Organic chemistry ; Ring (chemistry) ; Catalysis ; Enantioselective synthesis ; Biology Chemical synthesis and alkaloids ; Asymmetric Synthesis and Catalysis ; Synthetic Organic Chemistry Methods
Authors: Krishnan Radhakrishnan | Senthilkumar Paratharaj | Pandy Karthik Manikandan | Uttam Kumar Ray
Source: Journal of Advanced Scientific Research (article, 2021-10-31)
Field: Chemistry — Organic Chemistry

SYNTHESIS, CHARACTERIZATION AND ANTIOXIDANT ACTIVITY OF NOVEL 26-MEMBER RING [2+2] MACROCYCLES FROM DIAMINE DERIVATIVE AND TEREPHTHALDEHYDE Schiff base macrocycles play a significant role in living organisms with a broad range of pharmaceutical activities. In the present study, a novel series of 26 member macrocyclic compounds were synthesized via recombination of novel diamine and terephthaldehyde. A variety of triaryl diamine derivatives react with terephthaldehyde to efficiently result in a [2+2] macrocyclic Schiff base compounds. The newly synthesized compounds were characterized by UV, IR, NMR and Mass and further confirmed by single crystal x-ray diffraction analysis. The antioxidant activity of all the synthesized compounds were tested by Reducing power activity. The compounds were screened at different concentrations from 50-250 (μg/ml) to check the absorbance of compounds. Among seven macrocycle compounds, compound 4f showed highly significant activity. The result shows that as the concentration of compound increase, the compound showed high significant activity. Diamine ; Chemistry ; Schiff base ; Ring (chemistry) ; Antioxidant ; Derivative (finance) ; Stereochemistry ; Proton NMR ; Combinatorial chemistry ; Organic chemistry ; Medicinal chemistry Synthesis and biological activity ; Synthesis and Characterization of Heterocyclic Compounds ; Synthesis of Organic Compounds
Authors: Івчук В.В.
Source: Zenodo (CERN European Organization for Nuclear Research) (article, 2021-12-24)
Field: Materials Science — Polymers and Plastics

Antypenko L. M. 2-Alkyl(aryl)-quinazolin-4(3H)-thiones, 2-R-(quinazolin-4(3H)-ylthio)carboxylic acids and amides: synthesis, molecular docking, antimicrobial and anticancer properties / L. M. Antypenko, S. I. Kovalenko, Y. Yu. Posylkina, Vl. O. Nikitin, N. S. Fedyunina, V. V. Ivchuk // J Enzyme Inhib Med Chem, Early Online. – 2015. – P. 1-13. In this study, a series of novel 2-alkyl(aryl)-quinazolin-4(3H)-thiones, 2-R-(quinazolin-4(3H)- ylthio)carboxylic acids and amides were synthesized and evaluated for antimicrobial and anticancer activities. Their structure was confirmed by elemental analysis and spectral data (FT-IR, LC-MS, 1H-NMR). Antimicrobial activity was tested in vitro against Staphylococcus aureus, Enterococcus faecalis, Enterobacter aerogenes, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, Candida albicans and NCI in vitro preliminary anticancer activity against nine different cancer types. The most active antibacterial and antifungal compounds were: 2.1, 2.2 and 2.4. The introduction of the carboxylic acid or amide residue into the fourth position of quinazolin-4(3H)-thione resulted in the absence of antimicrobial activity. Substance 3.8 inhibited renal cancer UO-31 line and 2.18 – leukemia CCRF-CEM. The results of in silico molecular docking for DHFR and CK2 kinase had no correlation with in vitro properties, proposing the presence of other biological activity pathways. Antimicrobial ; Chemistry ; Alkyl ; Aryl ; Stereochemistry ; Docking (animal) ; Medicinal chemistry ; Organic chemistry ; Medicine Polymer Synthesis and Characterization ; Veterinary medicine and infectious diseases ; Quinazolinone synthesis and applications
Authors: Lina Bouzouaid
Source:  (preprint, 2021-11-25)
Field: Materials Science — Biomaterials

Impact de petites molécules organiques sur la nucléation du silicate de calcium hydraté Les superplastifiants sont aujourd'hui couramment utilisés dans le béton pour améliorer sa mise en oeuvre et ses performances mécaniques. Ils ont généralement pour effet secondaire de retarder l'hydratation du ciment Portland, qui elle résulte de deux réactions simultanées : la dissolution des grains de ciment et la précipitation des hydrates de ciment. Les mécanismes responsables de ce retard, qui se traduit par des temps de prise plus long, restent cependant largement inexpliqués. Le présent travail vise à résoudre cette énigme du point de vue de la formation des hydrates de ciment et en utilisant quatre petites molécules organiques comme modèle de superplastifiants. En particulier, l'impact de ces composés organiques sur la nucléation homogène de l'hydrate de silicate de calcium (C-S-H) a été étudié en détail. Le travail s'est également concentré sur la détermination de la force motrice de la nucléation (et de la dissolution) et donc sur la détermination et la modélisation de la formation de complexes organiques avec les espèces aqueuses de calcium, de silicate et d'hydroxyde. Un riche éventail de complexes mono- et poly-nucléaires entre les molécules organiques et les ions calcium, hydroxyde et silicate a été trouvé. La formation de ces complexes a été modélisée avec succès avec le programme de spéciation PHREEQC. Cela a permis de comparer et de quantifier l'impact des molécules organiques sélectionnées sur la vitesse de nucléation du C-S-H. Le taux de nucléation a été corrélé au pouvoir complexant des molécules organiques. En outre, une modification du chemin de formation du C-S-H a été trouvée pour laquelle la complexation organique avec les ions silicate et calcium semble jouer un rôle crucial. Plus généralement, le pouvoir retardateur des molécules sur l'hydratation de l'alite, la principale phase minérale du ciment Portland, s'est avéré être bien corrélé avec leur impact sur la vitesse de nucléation du C-S-H. Nucleation ; Hydrate ; Silicate ; Calcium silicate hydrate ; Calcium silicate ; Calcium ; Materials science ; Chemical engineering ; Organic molecules ; Mineralogy ; Molecule ; Chemistry ; Organic chemistry ; Cement ; Metallurgy ; Engineering Calcium Carbonate Crystallization and Inhibition ; CO2 Sequestration and Geologic Interactions ; Drilling and Well Engineering
Authors: Aditya N. Bade | Howard E. Gendelman | JoEllyn McMillan | Yutong Liu
Source: bioRxiv (Cold Spring Harbor Laboratory) (preprint, 2021-02-27)
Field: Materials Science — Materials Chemistry

Chemical exchange saturation transfer for detection of antiretroviral drugs in brain tissue Abstract Human immunodeficiency virus type-1 (HIV-1) antiretroviral drug (ARV) theranostics facilitates biodistribution and efficacy of therapies designed to target viral reservoirs. To this end, we have now deployed intrinsic drug chemical exchange saturation transfer (CEST) contrast to detect ARV distribution within the central nervous system (CNS). Methods CEST effects for lamivudine (3TC) and emtricitabine (FTC) were measured by asymmetric magnetization transfer ratio analyses in solutions. CEST magnetic resonance imaging (MRI) was performed on 3TC-treated mice with analysis made by Lorentzian fitting. Results CEST effects of 3TC and FTC hydroxyl and amino protons linearly correlated to drug concentrations. 3TC was successfully detected in brain sub-regions by MRI. The imaging results were validated by measurements of CNS drug concentrations. Conclusion CEST contrasts can be used to detect ARVs using MRI. Such detection can be used to assess spatial-temporal drug biodistribution. This is most notable within the CNS where drug biodistribution may be more limited with the final goal of better understanding ARV-associated efficacy and potential toxicity. Biodistribution ; Emtricitabine ; Magnetic resonance imaging ; Magnetization transfer ; Lamivudine ; Drug ; Chemistry ; Antiretroviral therapy ; Antiretroviral drug ; Nuclear magnetic resonance ; Human immunodeficiency virus (HIV) ; Pharmacology ; Medicine ; Virology ; Viral load ; Virus ; Radiology ; Biochemistry ; Physics Lanthanide and Transition Metal Complexes ; Advanced MRI Techniques and Applications ; MRI in cancer diagnosis
Authors: Kartik Sau | Tamio Ikeshoji | Godwill Mbiti Kanyolo | Titus Masese
Source: ChemRxiv (preprint, 2021-05-21)
Field: Chemistry — Inorganic Chemistry

Modelling Cationic Diffusion in Nickel-Based Honeycomb Layered Tellurates using Vashishta-Rahman Interatomic Potential and Relevant Insights Although the fascinatingly rich crystal chemistry of honeycomb layered oxides has been accredited as the propelling force behind their remarkable electrochemistry, the atomistic mechanisms surrounding their operations remain unexplored. Thus, herein, we present an extensive molecular dynamics study performed systematically using a reliable set of inter-atomic potential parameters of A2Ni2TeO6 (where A = Li, Na, and K). We demonstrate the effectiveness of the Vashishta-Rahman form of the inter-atomic potential in reproducing various structural and transport properties of this promising class of materials and predict an exponential increase in cationic diffusion with larger inter-layer distances. The simulations demonstrate the correlation between broadened inter-layer (inter-slab) distances associated with the larger ionic radii of K and Na compared to Li and the enhanced cationic conduction exhibited in K2Ni2TeO6 and Na2Ni2TeO6 relative to Li2Ni2TeO6. Whence, our findings connect lower potential energy barriers, favourable cationic paths and wider bottleneck size along the cationic diffusion channel within frameworks (comprised of larger mobile cations) to the improved cationic diffusion experimentally observed in honeycomb layered oxides. Furthermore, we elucidate the role of inter-layer distance and cationic size in cationic diffusion. Our theoretical studies reveal the dominance of inter-layer distance over cationic size, a crucial insight into the further performance enhancement of honeycomb layered oxides. Cationic polymerization ; Materials science ; Nickel ; Honeycomb ; Diffusion ; Chemical physics ; Ionic conductivity ; Chemistry ; Physical chemistry ; Thermodynamics ; Composite material ; Physics ; Metallurgy ; Electrolyte Zeolite Catalysis and Synthesis ; Advanced Battery Materials and Technologies ; Advanced Condensed Matter Physics