Modeling Acid and Cationic Catalysis on the Reactivity of Duocarmycins

Several catalyzed alkylation reactions of 9-methyladenine by a model [CPI, cyclopropa[c]pyrrolo-[3,2-e]indol-4(5H)-one] of duocarmycin anticancer drugs have been compared to the uncatalyzed reaction in gas phase and in water solvent bulk, using density functional theory at the B3LYP level with the 6-31+G(d,p) basis set and C-PCM solvation model. The effect on the CPI reactivity induced by water, formic and phosphoric acids (general acid catalysis), H3O+ (specific acid catalysis), sodium, and ammonium cation complexation (cationic catalysis) has been investigated.