Influences of 7-alkyl substitution on the reversible binding of the proximate carcinogen trans-3,4-dihydroxy-3,4-dihydrobenz[a]anthracene to DNA

The effects of 7-alkyl substitution on the reversible intercalation of the proximate carcinogen trans-3,4-dihydroxy-3,4-dihydrobenz[a]anthracene (BAD) to calf thymus DNA have been examined using time-resolved fluorescence spectroscopy. The results indicate that in 10(-3) M sodium cacodylate the binding constant of BAD is 1.8 x 10(3) M-1. 7-Ethyl substitution decreases the binding constant 1.6 times, while 7-methyl substitution increases the binding constant 1.7 times. UV Photoelectron data and results from ab initio molecular orbital calculations suggest that an increase in polarizability contributes to the increased binding accompanying methyl substitution. The decreased binding accompanying ethyl substitution arises from steric inhibition. The physical binding data correlates with the decrease in carcinogenic activity which occurs with 7-ethyl substitution of benz[a]anthracene metabolites.