Biomimetic Ketone Reduction by Disulfide Radical Anion

Abstract

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 λmax = 420 nm at various concentrations of ketones, we found the rate constants of three cyclic ketones to be in the range of 104–105 M−1s−1 at ~22 °C.

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

“…Such a reducing potential is attained by CysS-SCysc − , thus supporting the feasibility of reducing the furanone intermediate by the disulde radical anion of C 225 and C 462 within the active site of RNR. Consistent with the thermodynamic values determined herein, recent pulse radiolysis results show that the cysteine disulde radical anion is able to reduce model ketone substrates under aqueous conditions 38.…”

“…Consistent with the thermodynamic values determined herein, recent pulse radiolysis results show that the cysteine disulfide radical anion is able to reduce model ketone substrates under aqueous conditions. 38 …”

Low Energy Photoionization of Phosphorothioate DNA-Oligomers and Ensuing Hole Transfer

“…It is known that the RS∴SR radical usually has characteristic broad absorption maxima ranging from 400 to 500 nm with a high extinction coefficient (∼10 4 M –1 cm –1 ), while the corresponding RS • exhibits absorption maximum below 350 nm with a much smaller extinction coefficient (<10 3 M –1 cm –1 ) . For example, transient absorption maximum of the disulfide radical resulting from two cysteines (Cys-S∴S-Cys) was observed to be 420 nm (ε ≥ 8.8 × 10 3 M –1 cm –1 ) while the Cys-S • showed maximum at 330 nm (ε ∼ 290 M –1 cm –1 ). , Second, the oxidized RS • with an unpaired electron is usually highly reactive and has strong tendency to be stabilized by a second sulfide molecule RS with a diffusion-control rate . In fact, we calculated the Gibbs free energy (Δ G ) at 298 K for reaction (PS • + PS → -P-S∴S-P-) to be −25.4 kJ/mol at the M062x/6-31++G ** level (see Table S1), showing that the association of PS • with PS to form -P-S∴S-P- is a thermodynamically favorable process at room temperature.…”

Biomimetic Radical Chemistry and Applications

“…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 [ 36 ]. Experimental conditions were found to obtain the bioinspired conversion of ketones to corresponding alcohols with high-yield by the intermediacy of disulfide radical anion of cysteine (CysSSCys) •− in water [ 37 ].…”