Premium
Insights into the elimination mechanisms employed for the degradation of different hexachlorocyclohexane isomers using kinetic isotope effects and docking studies
Author(s) -
Manna Rabindra Nath,
DybalaDefratyka Agnieszka
Publication year - 2013
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.3163
Subject(s) - chemistry , kinetic isotope effect , transition state , aqueous solution , hexachlorocyclohexane , computational chemistry , hydrogen bond , chlorine , docking (animal) , catalysis , organic chemistry , molecule , deuterium , medicine , physics , nursing , quantum mechanics , pesticide , agronomy , biology
Modern DFT functional as well as the continuum solvation model have been applied in order to theoretically predict carbon, chlorine and hydrogen kinetic isotope effects (KIEs) during aerobic degradation of four hexachlorocyclohexane isomers (α, β, δ and γ). A small model of the hexachlorocyclohexane dehydrochlorinase (LinA) active site comprising its catalytic dyad has been constructed based on the receptor–ligand complexes suggested by docking studies and compared to the respective reaction modeled in aqueous solution. In‐depth analysis of chlorine and hydrogen KIEs patterns clearly indicates different transition states in aqueous solution and in the model mimicking the protein active site. Although all isomers seem to undergo a concerted E2 mechanism, the contribution of proton transfer and carbon–chlorine leaving group bond stretch in the transition states differs for the different isomers giving rise to totally different magnitudes of predicted isotope effects. Copyright © 2013 John Wiley & Sons, Ltd.