AB-INITIO MODELING OF THE INTERACTION BETWEEN GUANINE-CYTOSINE BASE-PAIR AND MUSTARD ALKYLATING-AGENTS

Interaction between the guanine-cytosine base pair and the episulfoniu m form of sulfur mustard (HD+) or the aziridinium form of nitrogen mus tard (HN2(+)) was studied using the ab initio LCAO-MO method at the HF /6-31G level. The alkylation mechanism on the guanine N7 was analyzed by using a supermolecular modeling. Our stereostructural results assoc iated with the molecular electrostatic potentials and highest occupied /lowest unoccupied molecular orbital (HOMO-LUMO) properties show that in vacuum the alkylation of the N7 of guanine by HD+ in the agressive episulfonium form is a direct process without a transition state and o f which the pathway is determined. Our study shows that interaction of guanine with the aziridinium form of HN2(+) necessitates a transition state for the N7 alkylation route. When the N7 guanine alkylation by HD+ or HN2+ is achieved, about half of a positive charge moves from th e alkylator toward the guanine in both cases. (C) 1996 John Wiley & So ns, Inc.