Computational Chemistry and Molecular Modeling
Atomic, Molecular and Optical Physics
Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
The aziridine analogues of the epoxide metabolites of carcinogenic polycyclic aromatic hydrocarbons have greater mutagenic potency than the epoxides. Like their well-studied analogues, the aziridines undergo a pH-dependent decomposition that leads to a reactive carbocation intermediate. In aqueous solution the nucleophile with which the carbocation generally reacts is water. The kinetics of this pH-dependent reaction have been experimentally characterized by others. Although the effect of DNA on this reaction has not been studied, we hypothesize that, like their epoxide analogues, the aziridine derivatives of polycyclic aromatic hydrocarbons undergo a DNA-catalyzed reaction leading through a carbocation to either a DNA-adduct or a hydrolysis product. Using Poisson-Boltzmann calculations in conjunction with Metropolis Monte Carlo simulations and energy-minimized conformations, we predict the DNA-dependence of the acidcatalyzed decomposition of the K-region aziridine, phenanthrene[9,10]imine. © 1995 John Wiley & Sons, Inc.
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