Substituent effects on electrophilicity of flavins: an experimental and semi-empirical molecular orbital study

The reactivities of the triplet excited states of several flavins with different N(10)-phenyl substituents have been found to be very similar. There is a good correlation between semi-empirical molecular orbital calculations at the MINDO/AM1 level and observed redox potentials. However, the most interesting observation is that the substituent effects are very small; this suggests that the N(10)-phenyl substituents are nearly perpendicular to the plane of the main ring due to their steric interactions with the main isoalloxazine system. Computed calculations as well as the fact that similar absorption maxima are obtained for 3-methyl-10-phenylisoalloxazine and 3-methyl-10-methylisoalloxazine are in agreement with this prediction.