Disulfide radical anion as a super-reductant in biology and photoredox chemistry

Abstract

Disulfides are involved in a broad range of radical-based synthetic organic and biochemical transformations. In particular, the reduction of a disulfide to the corresponding radical anion, followed by S–S bond cleavage to yield a thiyl radical and a thiolate anion plays critical roles in radical-based photoredox transformations and the disulfide radical anion in conjunction with a proton donor, mediates the enzymatic synthesis of deoxynucleotides from nucleotides within the active site of the enzyme, ribonucleotide reductase (RNR). To gain fundamental thermodynamic insight into these reactions, we have performed experimental measurements to furnish the transfer coefficient from which the standard E⁰(RSSR/RSSR˙⁻) reduction potential has been determined for a homologous series of disulfides. The electrochemical potentials are found to be strongly dependent on the structures and electronic properties of the substituents of the disulfides. In the case of cysteine, a standard potential of E⁰(RSSR/RSSR˙⁻) = −1.38 V vs. NHE is determined, making the disulfide radical anion of cysteine one of the most reducing cofactors in biology.