Controlling the Direction of S-Nitrosation versus Denitrosation: Reversible Cleavage and Formation of an S-N Bond within a Dicopper Center

Abstract

Iron and copper enzymes are known to promote reversible S-nitrosation/denitrosation in biology. However, it is unclear how the direction of S-N bond formation/scission is controlled. Herein, we demonstrate the interconversion of metal-S-nitrosothiol adduct M(RSNO) and metal nitrosyl thiolate complex M(NO)(SR), which may regulate the direction of reversible S-(de)nitrosation. Treatment of a dicopper(I,I) complex with RSNO leads to a mixture of two structural isomers: dicopper(I,I) S-nitrosothiol [Cu^ICu^I(RSNO)]²⁺ and dicopper(II,II) nitrosyl thiolate [Cu^IICu^II(NO)(SR)]²⁺. The K_eq between these two structural isomers is sensitive to temperature, the solvent coordination ability, and counterions. Our study illustrates how copper centers can modulate the direction of RS-NO bond formation and cleavage through a minor perturbation of the local environment.