A computational study of some isomerization equilibria and their possible relation to vinyl chloride carcinogenicity

There is considerable evidence indicating that the primary in vivo DNA alkylation product of vinyl chloride, believed to be responsible for its carcinogenicity, is the 7-N-(2-oxoethyl) derivative of guanine. Using a representative keto-enol system, we have studied computationally two possible equilibria involving this adduct. The first is between the 2-oxoethyl derivatives of the keto and enol forms of the representative system, whereas the second is between the 2-oxoethyl derivative of the keto form and the corresponding hemiacetal. In the case of the analogous guanine derivatives, such equilibria could lead to disruption of the hydrogen bonding between guanine and cytosine in DNA and could cause miscoding and replicational and transcriptional errors. An ab initio self-consistent field molecular orbital study has been carried out using the GAUSSIAN 82 system of programs. Optimized structures and energies have been calculated at the 2-21G level for the representative keto-enol system and its 2-oxoethyl and hemiacetal forms. The formation of the 2-oxoethyl adduct was found to have no significant effect upon this keto-enol equilibrium, which strongly favors the keto form. Our calculations further show hemiacetal formation to be an unlikely possibility for this system. On the basis of these results and recent data on guanine tautomers, we speculate about the analogous equilibria involving the guanine derivatives.