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A model has been developed to predict the kinetic rate constants (k(GSH)) of α,β-unsaturated Michael acceptor compounds for their reaction with glutathione (GSH). The model uses the local charge-limited electrophilicity index ω(q) [Wondrousch, D., et al. (2010) J. Phys. Chem. Lett. 1, 1605-1610] at the β-carbon atom as a descriptor of reactivity, a(More)
Chemotypes are a new approach for representing molecules, chemical substructures and patterns, reaction rules, and reactions. Chemotypes are capable of integrating types of information beyond what is possible using current representation methods (e.g., SMARTS patterns) or reaction transformations (e.g., SMIRKS, reaction SMILES). Chemotypes are expressed in(More)
Measurement and Estimation of Electrophilic Reactivity for Predictive Toxicology Johannes A. H. Schw€obel, Yana K. Koleva, Steven J. Enoch, Fania Bajot,MarkHewitt, Judith C.Madden, David W. Roberts, Terry W. Schultz, and Mark T. D. Cronin* School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, England College of(More)
Kinetic rate constants (k(GSH)) for the reaction of compounds acting as Michael acceptors with glutathione (GSH) were modelled by quantum chemical transition-state calculations at the B3LYP/6-31G** and B3LYP/TZVP level. The data set included α, β-unsaturated aldehydes, ketones and esters, with double bonds and triple bonds, linear and cyclic systems, both(More)
Hydrogen bonding affects the partitioning of organic compounds between environmental and biological compartments as well as the three-dimensional shape of macromolecules. Using the semiempirical quantum chemical AM1 level of calculation, we have developed a model to predict the site-specific hydrogen bond (HB) acceptor strength from ground-state properties(More)
A number of toxic effects are brought about by the covalent interaction between the toxicant and biological macromolecules. In chemico assays are available that attempt to identify reactive compounds. These approaches have been developed independently for pharmaceuticals and for other nonpharmaceutical compounds. The assays vary widely in terms of the(More)
Quantitative structure-activity relationships (QSARs) provide a useful tool to define a relationship between chemical structure and toxicity and allow for the prediction of the toxicity of untested chemicals. QSAR models based upon an anaesthetic or narcosis mechanism represent a baseline, or minimum, toxicity, i.e. unless a chemical acts by another, more(More)
A computational model to predict acute aquatic toxicity to the ciliate Tetrahymena pyriformis has been developed. A general prediction of toxicity can be based on three consecutive steps: 1. Identification of a potential reactive mechanism via structural alerts; 2. Confirmation and quantification of (bio)chemical reactivity; 3. Establishing a relationship(More)
A quantum chemical model has been developed for predicting the hydrogen bond (HB) acceptor strength of monofunctional organic compounds from electronic ground-state properties of the single molecules. Local molecular parameters are used to quantify electrostatic, polarizability, and charge transfer components to hydrogen bonding, employing the ab initio and(More)
A quantum chemical model is introduced to predict the H-bond donor strength of monofunctional organic compounds from their ground-state electronic properties. The model covers -OH, -NH, and -CH as H-bond donor sites and was calibrated with experimental values for the Abraham H-bond donor strength parameter A using the ab initio and density functional theory(More)