Solvent effects of flavin electron transfer reactions.

The effects of solvent environment on the rates of several flavin redox reactions have been studied by using laser flash photolysis. These include electron transfer to the flavin triplet state (a measure of oxidized flavin electrophilicity) and the oxidation of flavin semiquinone by oxidized flavin radical, oxidized phenol radical, and quinone. The rate constant for triplet quenching by 2,6-dimethylphenol was found to be proportional to the inverse of solvent viscosity, as would be expected for a diffusional process. The flavin semiquinone yield due to flavin reduction during the quenching reaction was linearly dependent on the solvent dielectric constant. This implies the existence of a polar or charged intermediate along the reaction pathway. A similar effect of solvent dielectric was found for the self-quenching reaction, which produces semiquinone and an oxidized flavin radical. The rate constants for all three of the semiquinone oxidation reactions studied were found to exhibit a biphasic dependence on solvent dielectric, being virtually independent of dielectric at low values and sharply increasing at high values. This is interpreted in terms of a change in mechanism with solvent polarity. Specifically, we propose a neutral transition state and hydrogen atom transfer in low dielectric media and a dipolar transition state and electron transfer in high dielectric media. No specific effects of hydrogen-bonding interaction between flavin and solvent were observed for any of the processes studied. The mechanistic implications of these results for flavoenzyme catalysts are discussed.