Biomimetic Ketone Reduction by Disulfide Radical Anion

• Main Authors: Sebastian Barata-Vallejo, Konrad Skotnicki, Carla Ferreri, Bronislaw Marciniak, Krzysztof Bobrowski, Chryssostomos Chatgilialoglu
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Molecules
• Subjects: biomimetic chemistry; cysteine; ketone reduction; free radicals; pulse radiolysis; kinetics
• Online Access: https://www.mdpi.com/1420-3049/26/18/5429

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 10⁴–10⁵ M⁻¹s⁻¹ at ~22 °C.