Redox-Neutral S-nitrosation Mediated by a Dicopper Center

Area of Science:

• Bioinorganic Chemistry
• Coordination Chemistry
• Nitric Oxide Chemistry

Background:

• Nitric oxide (NO) plays crucial roles in biological signaling.
• S-nitrosothiols (RSNO) are important NO carriers.
• Ceruloplasmin is a copper-containing protein involved in NO metabolism.

Purpose of the Study:

• To develop a functional model for ceruloplasmin's S-nitrosation activity.
• To investigate a novel redox-neutral S-nitrosation pathway using a dicopper complex.
• To explore the mechanism of S-nitrosothiol formation and release.

Main Methods:

• Synthesis and characterization of a dicopper(I,I) complex.
• Reaction of the dicopper complex with nitric oxide (NO) and thiols.
• Isolation and structural determination of key intermediates, including a rare [CuII CuII(μ-NO)(OMe)]2+ species.

Main Results:

• Achieved efficient S-nitrosation of thiols using the dicopper complex under redox-neutral conditions.
• Generated dicopper di-S-nitrosothiol and mono-S-nitrosothiol complexes with high yields (88-94%).
• Identified a mixed-valence [CuII CuIII(μ-O)(μ-NO)]2+ species as the active nitrosating agent.

Conclusions:

• The developed dicopper system serves as the first functional model of ceruloplasmin for external thiol S-nitrosation.
• The mechanism involves deprotonation of thiol by a μ-oxo ligand and nitrosation by a μ-nitrosyl ligand.
• Provides insights into the biological roles of copper sites in NO/RSNO interconversion.