Zinc Thiolate Reactivity toward Nitrogen Oxides: Insights into the Interaction of Zn[superscript 2+] with S- Nitrosothiols and Implications for Nitric Oxide Synthase

Zinc thiolate complexes containing N2S tridentate ligands were prepared to investigate their reactivity toward reactive nitrogen species, chemistry proposed to occur at the zinc tetracysteine thiolate site of nitric oxide synthase (NOS). The complexes are unreactive toward nitric oxide in the absence of dioxygen, strongly indicating that NO cannot be the species directly responsible for S-nitrosothiol formation and loss of Zn2+ at the NOS dimer interface in vivo. S-Nitrosothiol formation does occur upon exposure of zinc thiolate solutions to NO in the presence of air, however, or to NO2 or NOBF4, indicating that these reactive nitrogen/oxygen species are capable of liberating zinc from the enzyme, possibly through generation of the S-nitrosothiol. Interaction between simple Zn2+ salts and pre-formed S-nitrosothiols leads to decomposition of the –SNO moiety, resulting in release of gaseous NO and N2O. The potential biological relevance of this chemistry is discussed.