Biomimetic Ketone Reduction by Disulfide Radical Anion

The conversion of ribonucleosides to 2′-deoxyribonucleosides is catalyzed by ribonucleoside reductase enzymes in nature. One of the key steps in this complex radical mechanism is the reduction of the 3′-ketodeoxynucleotide by a pair of cysteine residues, providing the electrons via a disulfide radical anion (RSSR(•−)) in the active site of the enzyme. In the present study, the bioinspired conversion of ketones to corresponding alcohols was achieved by the intermediacy of disulfide radical anion of cysteine (CysSSCys)(•−) in water. High concentration of cysteine and pH 10.6 are necessary for high-yielding reactions. The photoinitiated radical chain reaction includes the one-electron reduction of carbonyl moiety by disulfide radical anion, protonation of the resulting ketyl radical anion by water, and H-atom abstraction from CysSH. The (CysSSCys)(•−) transient species generated by ionizing radiation in aqueous solutions allowed the measurement of kinetic data with ketones by pulse radiolysis. By measuring the rate of the decay of (CysSSCys)(•−) at λ(max) = 420 nm at various concentrations of ketones, we found the rate constants of three cyclic ketones to be in the range of 10(4)–10(5) M(−1)s(−1) at ~22 °C.