Water Microdroplets Promote Spontaneous Oxidation of Amino Acid- and Peptide-related Thiols to Disulfide Bonds.

Disulfide bonds (S-S) play a critical role in modern biochemistry, organic synthesis and prebiotic chemistry. Traditional methods for synthesizing disulfide bonds often rely on oxygen, alkali,  and metal catalysts. Herein, thiol groups involved in amino acids and peptides were spontaneously converted into symmetrical and unsymmetrical disulfide bonds within water microdroplets, without the need for catalysts or oxygen, and under room temperature. Water microdroplets displayed improved selectivity for disulfide bond formation, with minimal production of other oxidative species. Mechanistic investigations revealed that hydroxyl radicals (•OH) present on the water microdroplet surface facilitated the oxidation process. Thiols were firstly oxidized to thiyl radicals (RS•), which subsequently coupled to form disulfide bonds. This study highlights the potential of microdroplet chemistry as an efficient and mild approach for constructing disulfide bonds.