Ab initio MO investigation on the reactivity for electrophilic substitution of phenolics with oxirane and aziridine, as the model compounds of binding site of mutagen

The reaction of electrophilic model compounds of mutagens (ethylene oxide (EO) and aziridine (AZ)) with phenoxides were investigated by ab initio molecular orbital calculations. Model electrophiles (EO and AZ) are the parent compounds having three-membered oxirane and aziridine ring, respectively. This ring is considered to be the reactive site of mutagens with electron-rich site of phenolics, such as flavonoids. and biomolecules, such as DNA bases. This reaction is also classified in S(N)2 type nucleophilic substitution on the carbon atom in three-membered ring, in which C-C bond forming and C-X bond breaking (X = O and N) occurs concertedly. Geometrical parameters of transition structures (TSs) and activation energies (DeltaE(not equal)) for rate-determining C-C bond forming step were used as the indicators of reactivity. The calculation clarified the following points: (1) the oxirane ring is predicted to be much more reactive with phenolics than the aziridine ring: (2) the oxirane ring is able to react with phenolics in a living body but the aziridine ring is not: (3) the ortho- and para-position of -O(-) group has almost the same reactivity and their reactivities are remarkably larger than that at the meta-position: (4) the nucleophilic reactivity of the carbon atom on phenoxides is moderately affected by the increase of the -OH group substituted on it. (C) 2001 Elsevier science B.V. All rights reserved.