SEMIEMPIRICAL MOLECULAR-ORBITAL THEORY IN CARCINOGENESIS RESEARCH

It is generally believed that most chemical carcinogens exert their ef fects through covalent modification of the nucleic acid base sites. Si gnificant clarification of the underlying chemistry involved in these early and critical events is available through the techniques of compu tational chemistry. The role of semiempirical molecular orbital theory in this area is reviewed using examples focusing on (i) the conversio n of precarcinogens to reactive electrophiles, (ii) the regiochemistry of nucleic acid adduct formation, (iii) the chemical and physical con sequences of nucleic acid base modification, and (iv) empirical struct ure activity relationships. The symbiotic relationship that can exist between the semiempirical and ab initio molecular orbital procedures i s emphasized, as is the continuing niche for the semiempirical methodo logy in the study of systems that are too large, or in situations that are insufficiently cost effective, for the application of ab initio m ethods. (C) 1997 Elsevier Science B.V.