The Experts below are selected from a list of 240 Experts worldwide ranked by ideXlab platform
Steven J Enoch - One of the best experts on this subject based on the ideXlab platform.
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A review of the Electrophilic Reaction chemistry involved in covalent protein binding relevant to toxicity
Critical Reviews in Toxicology, 2011Co-Authors: Steven J Enoch, Claire M. Ellison, T. W. Schultz, M. T.d. CroninAbstract:Several pieces of legislation have led to an increased interest in the use of in silico methods, specifically the formation of chemical categories for the assessment of toxicological endpoints. For a number of endpoints, this requires a detailed knowledge of the Electrophilic Reaction chemistry that governs the ability of an exogenous chemical to form a covalent adduct. Historically, this chemistry has been defined as compilations of structural alerts without documenting the associated Electrophilic chemistry mechanisms. To address this, this article has reviewed the literature defining the structural alerts associated with covalent protein binding and detailed the associated Electrophilic Reaction chemistry. This information is useful to both toxicologists and regulators when using the chemical category approach to fill data gaps for endpoints involving covalent protein binding. The structural alerts and associated Electrophilic Reaction chemistry outlined in this review have been incorporated into the OECD (Q)SAR Toolbox, a freely available software tool designed to fill data gaps in a regulatory environment without the need for further animal testing.
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A review of the Electrophilic Reaction chemistry involved in covalent DNA binding
Critical reviews in toxicology, 2010Co-Authors: Steven J Enoch, Mark T. D. CroninAbstract:The need to assess the ability of a chemical to act as a mutagen or a genotoxic carcinogen (collectively termed genotoxicity) is one of the primary requirements in regulatory toxicology. Several pieces of legislation have led to an increased interest in the use of in silico methods, specifically the formation of chemical categories for the assessment of toxicological endpoints. A key step in the development of chemical categories for genotoxicity is defining the organic chemistry associated with the formation of a covalent bond between DNA and an exogenous chemical. This organic chemistry is typically defined as structural alerts. To this end, this article has reviewed the literature defining the structural alerts associated with covalent DNA binding. Importantly, this review article also details the mechanistic organic chemistry associated with each of the structural alerts. This information is extremely important in terms of meeting regulatory requirements for the acceptance of the chemical category approach. The structural alerts and associated mechanistic chemistry have been incorporated into the Organisation for Economic Co-operation and Development (OECD) (Q)SAR Application Toolbox.
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Electrophilic Reaction chemistry of low molecular weight respiratory sensitizers.
Chemical research in toxicology, 2009Co-Authors: Steven J Enoch, David W. Roberts, Mark T. D. CroninAbstract:Certain types of low molecular weight chemicals have the ability to cause respiratory sensitization via haptenation of carrier proteins. It has been suggested that such chemicals must contain multiple "reactive" functional groups to elicit an immune response. In contrast to the well-developed Electrophilic Reaction chemistry ideas detailing the initial haptenation event for skin sensitization, no detailed mechanistic chemistry analysis has been performed for respiratory sensitization. The aim of this study, therefore, was to perform an Electrophilic Reaction chemistry analysis to explain the differing respiratory sensitizing potentials of 16 chemicals containing both single and multiple functional groups. The analysis has been supported by quantum chemical calculations probing the Electrophilicities of the reactive chemicals. These calculations suggest that within each mechanistic category differing "reactivity thresholds" exist that must be passed for respiratory sensitization to occur. In addition, this study highlights how such mechanistically driven category formation could be used as an in silico hazard identification tool.
Mark T. D. Cronin - One of the best experts on this subject based on the ideXlab platform.
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A review of the Electrophilic Reaction chemistry involved in covalent DNA binding
Critical reviews in toxicology, 2010Co-Authors: Steven J Enoch, Mark T. D. CroninAbstract:The need to assess the ability of a chemical to act as a mutagen or a genotoxic carcinogen (collectively termed genotoxicity) is one of the primary requirements in regulatory toxicology. Several pieces of legislation have led to an increased interest in the use of in silico methods, specifically the formation of chemical categories for the assessment of toxicological endpoints. A key step in the development of chemical categories for genotoxicity is defining the organic chemistry associated with the formation of a covalent bond between DNA and an exogenous chemical. This organic chemistry is typically defined as structural alerts. To this end, this article has reviewed the literature defining the structural alerts associated with covalent DNA binding. Importantly, this review article also details the mechanistic organic chemistry associated with each of the structural alerts. This information is extremely important in terms of meeting regulatory requirements for the acceptance of the chemical category approach. The structural alerts and associated mechanistic chemistry have been incorporated into the Organisation for Economic Co-operation and Development (OECD) (Q)SAR Application Toolbox.
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Electrophilic Reaction chemistry of low molecular weight respiratory sensitizers.
Chemical research in toxicology, 2009Co-Authors: Steven J Enoch, David W. Roberts, Mark T. D. CroninAbstract:Certain types of low molecular weight chemicals have the ability to cause respiratory sensitization via haptenation of carrier proteins. It has been suggested that such chemicals must contain multiple "reactive" functional groups to elicit an immune response. In contrast to the well-developed Electrophilic Reaction chemistry ideas detailing the initial haptenation event for skin sensitization, no detailed mechanistic chemistry analysis has been performed for respiratory sensitization. The aim of this study, therefore, was to perform an Electrophilic Reaction chemistry analysis to explain the differing respiratory sensitizing potentials of 16 chemicals containing both single and multiple functional groups. The analysis has been supported by quantum chemical calculations probing the Electrophilicities of the reactive chemicals. These calculations suggest that within each mechanistic category differing "reactivity thresholds" exist that must be passed for respiratory sensitization to occur. In addition, this study highlights how such mechanistically driven category formation could be used as an in silico hazard identification tool.
Xian Huang - One of the best experts on this subject based on the ideXlab platform.
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cis-Carbocuperation of acetylenic sulfoxides and corresponding applications in the regio- and stereoselective synthesis of polysubstituted vinyl sulfoxides
Tetrahedron Letters, 2004Co-Authors: Xian HuangAbstract:cis-Carbocuperation Reaction of monoorganocopper reagent with acetylenic sulfoxides, followed by Electrophilic Reaction with a variety of electrophiles, provided a regio- and stereoselective method to prepare the versatile polysubstituted vinyl sulfoxides. Sonogashira cross-coupling Reaction of the obtained α-iodovinyl sulfoxides with terminal acetylenes was also investigated to afford the versatile conjugate sulfinyl enynes.
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Hydrotelluration and carbotelluration of acetylenic sulfoxides: regio- and stereoselective preparation of α- and β-organotellurovinyl sulfoxides
Tetrahedron Letters, 2004Co-Authors: Xian HuangAbstract:(Z)-β-Organotellurovinyl sulfoxides were synthesized via a highly regio- and stereoselective anti-hydrotelluration of acetylenic sulfoxides. α-Organotellurovinyl sulfoxides were obtained from a three component syn-carbotelluration Reaction of acetylenic sulfoxides, that is, syn-addition of monoorganocopper reagents to acetylenic sulfoxides followed by the Electrophilic Reaction of the vinyl copper intermediates with benzenetellurenyl iodide at low temperature. Synthetic applications of the organotellurovinyl sulfoxides have been investigated.
M. T.d. Cronin - One of the best experts on this subject based on the ideXlab platform.
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A review of the Electrophilic Reaction chemistry involved in covalent protein binding relevant to toxicity
Critical Reviews in Toxicology, 2011Co-Authors: Steven J Enoch, Claire M. Ellison, T. W. Schultz, M. T.d. CroninAbstract:Several pieces of legislation have led to an increased interest in the use of in silico methods, specifically the formation of chemical categories for the assessment of toxicological endpoints. For a number of endpoints, this requires a detailed knowledge of the Electrophilic Reaction chemistry that governs the ability of an exogenous chemical to form a covalent adduct. Historically, this chemistry has been defined as compilations of structural alerts without documenting the associated Electrophilic chemistry mechanisms. To address this, this article has reviewed the literature defining the structural alerts associated with covalent protein binding and detailed the associated Electrophilic Reaction chemistry. This information is useful to both toxicologists and regulators when using the chemical category approach to fill data gaps for endpoints involving covalent protein binding. The structural alerts and associated Electrophilic Reaction chemistry outlined in this review have been incorporated into the OECD (Q)SAR Toolbox, a freely available software tool designed to fill data gaps in a regulatory environment without the need for further animal testing.
David W. Roberts - One of the best experts on this subject based on the ideXlab platform.
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Electrophilic Reaction chemistry of low molecular weight respiratory sensitizers.
Chemical research in toxicology, 2009Co-Authors: Steven J Enoch, David W. Roberts, Mark T. D. CroninAbstract:Certain types of low molecular weight chemicals have the ability to cause respiratory sensitization via haptenation of carrier proteins. It has been suggested that such chemicals must contain multiple "reactive" functional groups to elicit an immune response. In contrast to the well-developed Electrophilic Reaction chemistry ideas detailing the initial haptenation event for skin sensitization, no detailed mechanistic chemistry analysis has been performed for respiratory sensitization. The aim of this study, therefore, was to perform an Electrophilic Reaction chemistry analysis to explain the differing respiratory sensitizing potentials of 16 chemicals containing both single and multiple functional groups. The analysis has been supported by quantum chemical calculations probing the Electrophilicities of the reactive chemicals. These calculations suggest that within each mechanistic category differing "reactivity thresholds" exist that must be passed for respiratory sensitization to occur. In addition, this study highlights how such mechanistically driven category formation could be used as an in silico hazard identification tool.
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Electrophilic chemistry related to skin sensitization. Reaction mechanistic applicability domain classification for a published data set of 106 chemicals tested in the mouse local lymph node assay.
Chemical research in toxicology, 2007Co-Authors: David W. Roberts, And Aynur O. Aptula, Grace PatlewiczAbstract:This article presents an overview of Electrophilic Reaction mechanisms relevant to skin sensitization, with reference to a published skin sensitization test data set for 106 chemicals. Where appropriate to aid the interpretation, additional data on a small number of further compounds are also discussed. It is shown that there is a close correspondence in the way differences and similarities in skin sensitization potency of chemicals relate to differences and similarities in their physical organic chemistry and Electrophilic Reaction mechanistic chemistry. The 106 chemicals are classified into their Reaction mechanistic applicability domains, and reactivity−sensitization trends are analyzed for each domain: the Michael acceptor and pro-Michael acceptor electrophile domain; the SNAr electrophile domain; the SN2 electrophile domain; the Schiff base electrophile domain; the acyl transfer electrophile domain; and the non-Electrophilic non-pro-Electrophilic domain. The last of these domains should be populated...