Two-electron transfer reactions in proteins: bridge-mediated and proton-assisted processes.

Nonadiabatic two-electron transfer (TET) reactions through donor-bridge-acceptor (DBA) systems is investigated within the approximation of fast vibrational relaxation. For TET reactions in which the population of bridging states remains small (less than 10(-2)) it is demonstrated that a multiexponential transition process reduces to three-state kinetics. The transfer starts at the state with two excess electrons at the D center (D(2-)BA), goes through the intermediate (transient) state with one electron at the D center and one at the A center (D-BA-), and ends up with the two electrons at the A center (DBA2-). Furthermore, if the population of the intermediate state becomes also small the two-exponential kinetics can be transformed with high accuracy to single-exponential D-A TET kinetics. The related overall transfer rate contains contributions from stepwise and from concerted TET. The latter process is determined by a specific two-electron superexchange coupling incorporating the bridging states (D-B-A and DB-A-) as well as the intermediate state (D-BA-). As an example, the reduction of micothione reductase by nicotinamide adenine dinucleotide phosphate is analyzed. Existing experimental data can be explained if one assumes that the proton-assisted reduction of the enzyme is realized by the concerted TET mechanism.