Model systems for flavoenzyme activity. The role of N(3)-H hydrogen bonding in flavin redox processes

Computational and experimental studies were performed to determine the role of N(3)H hydrogen bonding in controlling flavin redox chemistry. B3LYP cal culations of a lumiflavin-DMF complex indicate that hydrogen bonding to N(3 )H is redox state dependent: hydrogen bonds to this position are formed in the oxidized state, and released in the flavin radical anion system due to increased electron density in the reduced species. Electrochemical studies of flavin and N(3)-methyl flavin in hydrogen bonding and non-hydrogen bondi ng solvents confirm this prediction, demonstrating that N(3)H hydrogen bond ing modulates the potential of flavin reduction to the corresponding radica l anion by 80 mV (1.8 kcal/mol). Variable-temperature electrochemical studi es were also performed to establish the enthalpic and entropic effects of N (3)H hydrogen bonding on flavin reduction.