Influence of Cu⁺ on the RS-NO bond dissociation energy of S-nitrosothiols

Density functional theory methods have been used to investigate the role and effects of Cu⁺ binding to the S and N centers of the -SNO functional group within S-nitrosothiols (RSNOs), on the lability of the NO group. The binding of Cu⁺ to the S center is found to weaken the S-N bond, while the N-O bond is concomitantly strengthened, consistent with the notion that Cu⁺ binding catalyzes NO radical release. In contrast, however, the binding of Cu⁺ to the N center is found to dramatically shorten and strengthen the S-N bond with a concomitant lengthening of the N-O bond, suggesting stabilization of the RSNOs against NO release. Upon solvation, complexes with Cu⁺ bound to the N center are stabilized relative to the corresponding S-bound complexes, though remaining slightly higher in energy. The barriers to interconversion between corresponding isomers were also investigated. Implications for biochemical regulation of NO release from RSNOs are discussed.