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Andrey G. Kalinichev - One of the best experts on this subject based on the ideXlab platform.
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Interaction of Ions with Hydrated Clay Surfaces: Computational Molecular Modeling for Nuclear Waste Disposal Applications
Procedia Earth and Planetary Science, 2017Co-Authors: Andrey G. Kalinichev, Narasimhan Loganathan, B.f. Ngouana Wakou, Z. ChenAbstract:The Callovo-Oxfordian clay formation (COx) is the potential host rock for long term nuclear waste repository in France. The clayey component of COx consists mostly of illite, smectite and interstratified illite/smectite (I/S) clay minerals. We performed a series of Molecular dynamics (MD) computer simulations in order to quantify the Molecular scale mechanisms responsible for the adsorption and transport of ions at the hydrated surfaces of illite, smectite, and I/S clays. New structural models of illite, smectite, and I/S allowed us to identify several structurally different adsorption sites at the basal surfaces of all three clay substrates. Adsorption free energy profiles above each individual adsorption site on each clay surface for a wide range of metal cations were then calculated and the metal sorption properties for the three clay surfaces are compared in terms of the preferable sorption sites and their surface distributions, most stable adsorption distances, and free energies of adsorption. The resulting equilibrium constants for surface adsorption and ion exchange were calculated and found in general agreement with available literature data. The observed discrepancies between the exchange energies obtained in the current MD simulations and the values obtained through the interpretation of recent X-ray reflectivity measurements can be attributed to the differences in the description of the exchange reaction equilibria between the experimental conditions and the simplified conditions of our simulations.
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NMR and Computational Molecular Modeling studies of mineral surfaces and interlayer galleries: A review
American Mineralogist, 2015Co-Authors: R. James Kirkpatrick, Andrey G. Kalinichev, Geoffrey M. Bowers, A. Oezguer Yazaydin, Marimuthu Krishnan, Moumita Saharay, Christin P. MorrowAbstract:![Figure][1] This paper reviews experimental nuclear magnetic resonance (NMR) and Computational Molecular dynamics (MD) investigations of the structural and dynamical behavior of cations, anions, H2O, and CO2 on the surfaces and in the interlayer galleries of layer-structure minerals and their composites with polymers and natural organic matter (NOM). The interaction among mineral surfaces, charge-balancing cations or anions, H2O, CO2, and NOM are dominated by Coulombic, H-bond, and van der Waals interactions leading to statically and dynamically disordered systems and Molecular-scale processes with characteristic room-temperature frequencies varying from at least as small as 102 to >1012 Hz. NMR spectroscopy provides local structural information about such systems through the chemical shift and quadrupolar interactions and dynamical information at frequencies from the sub-kilohertz to gigahertz ranges through the T 1 and T 2 relaxation rates and line shape analysis. It is often difficult to associate a specific structure or dynamical process to a given NMR observation, however, and Computational Molecular Modeling is often effective in providing a much more detailed picture in this regard. The examples discussed here illustrate these capabilities of combining experimental NMR and Computational Modeling in mineralogically and geochemically important systems, including clay minerals and layered double hydroxides. [1]: pending:yes
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NMR and Computational Molecular Modeling studies of mineral surfaces and interlayer galleries: A review
American Mineralogist, 2015Co-Authors: R. James Kirkpatrick, Andrey G. Kalinichev, Geoffrey M. Bowers, A. Oezguer Yazaydin, Marimuthu Krishnan, Moumita Saharay, Christin P. MorrowAbstract:This paper reviews experimental nuclear magnetic resonance (NMR) and Computational Molecular dynamics (MD) investigations of the structural and dynamical behavior of cations, anions, H2O, and CO2 on the surfaces and in the interlayer galleries of layer-structure minerals and their composites with polymers and natural organic matter (NOM). The interaction among mineral surfaces, charge-balancing cations or anions, H2O, CO2, and NOM are dominated by Coulombic, H-bond, and van der Waals interactions leading to statically and dynamically disordered systems and Molecular-scale processes with characteristic room-temperature frequencies varying from at least as small as 10(2) to >10(12) Hz. NMR spectroscopy provides local structural information about such systems through the chemical shift and quadrupolar interactions and dynamical information at frequencies from the sub-kilohertz to gigahertz ranges through the T-1 and T-2 relaxation rates and line shape analysis. It is often difficult to associate a specific structure or dynamical process to a given NMR observation, however, and Computational Molecular Modeling is often effective in providing a much more detailed picture in this regard. The examples discussed here illustrate these capabilities of combining experimental NMR and Computational Modeling in mineralogically and geochemically important systems, including clay minerals and layered double hydroxides.
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Molecular structure and dynamics of nano confined water computer simulations of aqueous species in clay cement and polymer membranes
2014Co-Authors: Andrey G. KalinichevAbstract:Molecular-level knowledge of the thermodynamic, structural, and transport properties of water confined by interfaces and nanopores of various materials is crucial for quantitative understanding and prediction of many natural and technological processes, including carbon sequestration, water desalination, nuclear waste storage, cement chemistry, fuel cell technology, etc. Computational Molecular Modeling is capable to significantly complement the experimental investigations of such systems by providing invaluable atomic-scale information leading to improved understanding of the specific effects of the substrate structure and composition on the structure, dynamics and reactivity of interfacial and nano-confined aqueous solutions. This paper offers a brief overview of recent efforts to quantify some of these effects for individual H2O molecules and hydrated ions confined at the interfaces and in nanopores of several typical hydrophilic and hydrophobic materials. The first Molecular layer of aqueous solution at all substrates is often highly ordered, indicating reduced translational and orientational mobility of the H2O molecules. This ordering cannot be simply described as “ice-like”, but rather resembles the behavior of supercooled water or amorphous ice, although with very significant substrate-specific variations.
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Chapter 9. Molecular Structure and Dynamics of Nano-Confined Water: Computer Simulations of Aqueous Species in Clay, Cement, and Polymer Membranes
2014Co-Authors: Andrey G. KalinichevAbstract:Molecular-level knowledge of the thermodynamic, structural, and transport properties of water confined by interfaces and nanopores of various materials is crucial for quantitative understanding and prediction of many natural and technological processes, including carbon sequestration, water desalination, nuclear waste storage, cement chemistry, fuel cell technology, etc. Computational Molecular Modeling is capable to significantly complement the experimental investigations of such systems by providing invaluable atomic-scale information leading to improved understanding of the specific effects of the substrate structure and composition on the structure, dynamics and reactivity of interfacial and nano-confined aqueous solutions. This paper offers a brief overview of recent efforts to quantify some of these effects for individual H2O molecules and hydrated ions confined at the interfaces and in nanopores of several typical hydrophilic and hydrophobic materials. The first Molecular layer of aqueous solution at all substrates is often highly ordered, indicating reduced translational and orientational mobility of the H2O molecules. This ordering cannot be simply described as “ice-like”, but rather resembles the behavior of supercooled water or amorphous ice, although with very significant substrate-specific variations.
Christopher C. Marvin - One of the best experts on this subject based on the ideXlab platform.
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Novel Lavendamycin Analogues as Antitumor Agents: Synthesis, in Vitro Cytotoxicity, Structure−Metabolism, and Computational Molecular Modeling Studies with NAD(P)H:Quinone Oxidoreductase 1
Journal of medicinal chemistry, 2005Co-Authors: Mary Hassani, Wen Cai, David C. Holley, Jayana P. Lineswala, Babu R. Maharjan, G. Reza Ebrahimian, Hassan Seradj, Mark G. Stocksdale, Farahnaz Mohammadi, Christopher C. MarvinAbstract:Novel lavendamycin analogues with various substituents were synthesized and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. Pictet−Spengler condensation of quinoline- or quninoline-5,8-dione aldehydes with tryptamine or tryptophans yielded the lavendamycins. Metabolism studies with recombinant human NQO1 revealed that addition of NH2 and CH2OH groups at the quinolinedione-7-position and indolopyridine-2‘-position had the greatest positive impact on substrate specificity. The best and poorest substrates were 37 (2‘-CH2OH-7-NH2 derivative) and 31 (2‘-CONH2-7-NHCOC3H7-n derivative) with reduction rates of 263 ± 30 and 0.1 ± 0.1 μmol/min/mg NQO1, respectively. Cytotoxicity toward human colon adenocarcinoma cells was determined for the lavendamycins. The best substrates for NQO1 were also the most selectively toxic to the NQO1-rich BE-NQ cells compared to NQO1-deficient BE-WT cells with 37 as the most selective. Molecular docking supported a model in which the best subst...
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novel lavendamycin analogues as antitumor agents synthesis in vitro cytotoxicity structure metabolism and Computational Molecular Modeling studies with nad p h quinone oxidoreductase 1
Journal of Medicinal Chemistry, 2005Co-Authors: Mary Hassani, Wen Cai, David C. Holley, Jayana P. Lineswala, Babu R. Maharjan, Hassan Seradj, Mark G. Stocksdale, Farahnaz Mohammadi, Reza G Ebrahimian, Christopher C. MarvinAbstract:Novel lavendamycin analogues with various substituents were synthesized and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. Pictet−Spengler condensation of quinoline- or quninoline-5,8-dione aldehydes with tryptamine or tryptophans yielded the lavendamycins. Metabolism studies with recombinant human NQO1 revealed that addition of NH2 and CH2OH groups at the quinolinedione-7-position and indolopyridine-2‘-position had the greatest positive impact on substrate specificity. The best and poorest substrates were 37 (2‘-CH2OH-7-NH2 derivative) and 31 (2‘-CONH2-7-NHCOC3H7-n derivative) with reduction rates of 263 ± 30 and 0.1 ± 0.1 μmol/min/mg NQO1, respectively. Cytotoxicity toward human colon adenocarcinoma cells was determined for the lavendamycins. The best substrates for NQO1 were also the most selectively toxic to the NQO1-rich BE-NQ cells compared to NQO1-deficient BE-WT cells with 37 as the most selective. Molecular docking supported a model in which the best subst...
Song Ja Kim - One of the best experts on this subject based on the ideXlab platform.
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Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and Computational Molecular Modeling
Drug design development and therapy, 2016Co-Authors: Zaman Ashraf, Alamgeer, Munazza Kanwal, Mubashir Hassan, Sahar Abdullah, Mamuna Waheed, Haseeb Ahsan, Song Ja KimAbstract:Flurbiprofen-antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (-COOH) was temporarily masked by esterification with phenolic -OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P
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flurbiprofen antioxidant mutual prodrugs as safer nonsteroidal anti inflammatory drugs synthesis pharmacological investigation and Computational Molecular Modeling
Drug Design Development and Therapy, 2016Co-Authors: Zaman Ashraf, Munazza Kanwal, Mubashir Hassan, Sahar Abdullah, Mamuna Waheed, Haseeb Ahsan, Song Ja KimAbstract:Flurbiprofen-antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (-COOH) was temporarily masked by esterification with phenolic -OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (4b) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer's yeast-induced pyrexia model, and significant (P<0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug.
Zaman Ashraf - One of the best experts on this subject based on the ideXlab platform.
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flurbiprofen antioxidant mutual prodrugs as safer nonsteroidal anti inflammatory drugs synthesis pharmacological investigation and Computational Molecular Modeling
Drug Design Development and Therapy, 2016Co-Authors: Zaman Ashraf, Munazza Kanwal, Mubashir Hassan, Sahar Abdullah, Mamuna Waheed, Haseeb Ahsan, Song Ja KimAbstract:Flurbiprofen-antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (-COOH) was temporarily masked by esterification with phenolic -OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (4b) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer's yeast-induced pyrexia model, and significant (P<0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities with reduced GI adverse effects than the parent drug.
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Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and Computational Molecular Modeling
Drug design development and therapy, 2016Co-Authors: Zaman Ashraf, Alamgeer, Munazza Kanwal, Mubashir Hassan, Sahar Abdullah, Mamuna Waheed, Haseeb Ahsan, Song Ja KimAbstract:Flurbiprofen-antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (-COOH) was temporarily masked by esterification with phenolic -OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P
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Iminothiazoline-Sulfonamide Hybrids as Jack Bean Urease Inhibitors; Synthesis, Kinetic Mechanism and Computational Molecular Modeling.
Chemical biology & drug design, 2015Co-Authors: Aamer Saeed, Shams-ul Mahmood, Muhammad Rafiq, Zaman Ashraf, Farukh Jabeen, Sung-yum SeoAbstract:The present work reports the synthesis of several 2-iminothiazoline derivatives of sulfanilamide (3a-j) as inhibitors of jack bean ureases. The title compounds were synthesized by the heterocyclization of sulfanilamide thioureas with propragyl bromide in dry ethanol in the presence of 1,8-Diazabicyclo[5.4.0]undec-7-ene as a base. All of the compounds showed higher urease inhibitory activity than the standard thiourea. The compounds (3h) and (3i) exhibited excellent enzyme inhibitory activity with IC50 0.064 and 0.058 μm, respectively, while IC50 of thiourea is 20.9 μm. The kinetic mechanism analyzed by Dixon plot showed that compound (3h) is a mixed-type inhibitor while (3i) is a competitive one. Docking studies suggested that Asp633, Ala636, His492, Ala440, Lue523, Asp494 and Arg439 are the major interacting residues in the binding site of the protein and may have an instrumental role in the inhibition of enzyme's function. 2-iminothiazoline analogues (3a-j) showed good docking score (-10.6466 to -8.7215 Kcal/mol) and binding energy (London dG ranging from -14.4825 to -10.4087 Kcal/mol) which is far better than the standard thiourea (binding score in S field -4.5790 Kcal/mol London dG -4.7726 Kcal/mol). Our results inferred compound (3i) may serve as a structural model for the design of most potent urease inhibitors.
Curtis C. Dary - One of the best experts on this subject based on the ideXlab platform.
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Informing mechanistic toxicology with Computational Molecular models.
Methods in molecular biology (Clifton N.J.), 2012Co-Authors: Michael R. Goldsmith, Shane D. Peterson, Daniel T. Chang, Thomas R. Transue, Rogelio Tornero-velez, Yu-mei Tan, Curtis C. DaryAbstract:Computational Molecular models of chemicals interacting with bioMolecular targets provides toxicologists a valuable, affordable, and sustainable source of in silico Molecular level information that augments, enriches, and complements in vitro and in vivo efforts. From a Molecular biophysical ansatz, we describe how 3D Molecular Modeling methods used to numerically evaluate the classical pair-wise potential at the chemical/biological interface can inform mechanism of action and the dose-response paradigm of modern toxicology. With an emphasis on Molecular docking, 3D-QSAR and pharmacophore/toxicophore approaches, we demonstrate how these methods can be integrated with chemoinformatic and toxicogenomic efforts into a tiered Computational toxicology workflow. We describe generalized protocols in which 3D Computational Molecular Modeling is used to enhance our ability to predict and model the most relevant toxicokinetic, metabolic, and Molecular toxicological endpoints, thereby accelerating the Computational toxicology-driven basis of modern risk assessment while providing a starting point for rational sustainable Molecular design.
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Computational toxicology: application in environmental chemicals.
Methods in molecular biology (Clifton N.J.), 2012Co-Authors: Yu-mei Tan, Michael R. Goldsmith, Shane D. Peterson, Daniel T. Chang, Rogelio Tornero-velez, Rory B. Conolly, Curtis C. DaryAbstract:This chapter provides an overview of Computational models that describe various aspects of the source-to-health effect continuum. Fate and transport models describe the release, transportation, and transformation of chemicals from sources of emission throughout the general environment. Exposure models integrate the microenvironmental concentrations with the amount of time an individual spends in these microenvironments to estimate the intensity, frequency, and duration of contact with environmental chemicals. Physiologically based pharmacokinetic (PBPK) models incorporate mechanistic biological information to predict chemical-specific absorption, distribution, metabolism, and excretion. Values of parameters in PBPK models can be measured in vitro, in vivo, or estimated using Computational Molecular Modeling. Computational Modeling is also used to predict the respiratory tract dosimetry of inhaled gases and particulates [Computational fluid dynamics (CFD) models], to describe the normal and xenobiotic-perturbed behaviors of signaling pathways, and to analyze the growth kinetics of preneoplastic lesions and predict tumor incidence (clonal growth models).