2 research outputs found

    Local Electrophilicity Predicts the Toxicity-Relevant Reactivity of Michael Acceptors

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    Electrophilic substances can form covalent bonds to proteins and DNA, resulting in reactive toxicity and according diseases such as dermal or respiratory sensitization and mutagenicity. Employing site-specific quantum chemical parameters for quantifying the energy change associated with the gain or loss of electronic charge, two new local electrophilicity parameters are derived. Application to a set of 31 α,β-unsaturated carbonyl compounds and their experimental rates of reaction toward glutathione as a model nucleophile yields <i>r</i><sup>2</sup> values up to 0.95, outperforming both the global electrophilicity and its earlier introduced local variant based on the condensed-to-atom Fukui function. A second data set demonstrates the suitability of the new reactivity parameters to also model Mayr’s electrophilicity parameter, again superior to existing approaches. The results indicate the suitability of the new parameters to screen, without experimental investigation, organic compounds for their electrophilic reactivity in general, and for their potential to exert reactive toxicity in particular

    Anaerobic Microbial Transformation of Halogenated Aromatics and Fate Prediction Using Electron Density Modeling

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    Halogenated homo- and heterocyclic aromatics including disinfectants, pesticides and pharmaceuticals raise concern as persistent and toxic contaminants with often unknown fate. Remediation strategies and natural attenuation in anaerobic environments often build on microbial reductive dehalogenation. Here we describe the transformation of halogenated anilines, benzonitriles, phenols, methoxylated, or hydroxylated benzoic acids, pyridines, thiophenes, furoic acids, and benzenes by <i>Dehalococcoides mccartyi</i> strain CBDB1 and environmental fate modeling of the dehalogenation pathways. The compounds were chosen based on structural considerations to investigate the influence of functional groups present in a multitude of commercially used halogenated aromatics. Experimentally obtained growth yields were 0.1 to 5 × 10<sup>14</sup> cells mol<sup>–1</sup> of halogen released (corresponding to 0.3–15.3 g protein mol<sup>–1</sup> halogen), and specific enzyme activities ranged from 4.5 to 87.4 nkat mg<sup>–1</sup> protein. Chlorinated electron-poor pyridines were not dechlorinated in contrast to electron-rich thiophenes. Three different partial charge models demonstrated that the regioselective removal of halogens is governed by the least negative partial charge of the halogen. Microbial reaction pathways combined with computational chemistry and pertinent literature findings on Co<sup>I</sup> chemistry suggest that halide expulsion during reductive dehalogenation is initiated through single electron transfer from B<sub>12</sub>Co<sup>I</sup> to the apical halogen site
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