Computer-Aided Molecular Designs of the Enediyne Model Compounds

Abstract

Recently we have developed several enediyne model compounds which posses DNA damaging abilities. In the course of our studies, we often encountered the loss of the DNA damaging abilities of these models in buffer solutions, while the cycloaromatization reaction of them were proceeded via biradical pathway in non-polar media. To overcom this problem, we designed enediyne model compounds which have an electron-withdrawing group on the benzylic radical forming centers (p-radical center).These models cycloaromatized to gave products derived from the biradical, not the zwitterion, in both polar and non-polar media and showed potent DNA cleaving ability. Intuitively, the effect of introducing electron-withdrawing groups may be rationalized that a p-acceptor group destabilizes the benzylic cation to diminish the contribution of the zwitterionic mesomer and therefore enhance the radical character. In this paper, we report the theoretical aspects of this type of bieadicals in detail.