Redox‐Neutral S‐nitrosation Mediated by a Dicopper Center

Abstract

An unprecedented redox-neutral S-nitrosation of thiol has been achieved at dicopper(I,I) center. Treatment of dicopper (I,I) complex with excess NO • and thiol generates a dicopper (I,I) di-Snitrosothiol complex [Cu I Cu I (RSNO)2] 2+ or dicopper (I,I) mono-Snitrosothiol complex [Cu I Cu I (RSNO)] 2+ , which readily release RSNO in 88-94% yield. The S-nitrosation reaction proceeds through a mixedvalence [Cu II Cu III (-O)(-NO)] 2+ species, which deprotonates RS-H at the basic -O site and nitrosates the RS − at the -NO site. The [Cu II Cu III (-O)(-NO)] 2+ complex is also competent for O-nitrosation of MeOH, which is isoelectronic to thiol. In this case, a rare [Cu II Cu II (-NO)(OMe)] 2+ intermediate has been isolated and fully characterized, suggesting the S-nitrosation proceeds through the intermediary of analogous [Cu II Cu II (-NO)(SR)] 2+ species. The redox-and protonneutral S-nitrosation process reported here represents the first functional model of ceruloplasmin in mediating S-nitrosation of external thiols, adding further implications for biological copper sites in the interconversion of NO • /RSNO.

Redox‐Neutral S‐nitrosation Mediated by a Dicopper Center

“…Since 2 can deprotonate MeOH, it is reasonable to hypothesize that it can 4). [48] Scheme 5. Ap ossible mechanistic pathway to generate 3-PE from dicopper(II,III) m-oxo, m-nitrosyl 2.…”

“…The differences pectrum of 14 Nand 15 Nsample is shown in black. C) Solidstate structure of [LCu II Cu II (m-NO)(m-OMe)] complex 4.E llipsoids are set at 50 %p robability.T he outer-sphere triflate anion, solvent molecules, hydrogen atoms, and minor components of disordered atoms are omitted for clarity.S elected bond distances []: Cu1-N1 1.976(16), Cu2-N1 2.00(3), Cu1-O1 1.871(15), Cu2-O1 1.950(13), N1-O2 1.32-(5), N1B-O2B 1.27(4) [48].…”

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

“…Recently, we demonstrated that a synthetic dicopper complex could promote S-nitrosation without an external oxidant, which serves as a functional model of ceruloplasmin-mediated NO • storage (Scheme 1C). 32,33 A common mechanistic step in metal-mediated S-nitrosation is the insertion of NO • into metal−thiolate bonds to generate RSNO together with the reduced metal center, 16,25,26,28 reminiscent of reductive elimination in organometallic chemistry. Therefore, it is commonly proposed that the coupling of NO • with thiol occurs at a transient metal nitrosyl…”

“…To visualize the interconversion between M x (NO)(SR) and M x (RSNO), we employ our dicopper platform 33 which has successfully modeled the S-nitrosation process at ceruloplasmin. 22,23 Instead of using the previous Py 4 DMB ligand (Scheme 3 right), we prepared a new binucleating ligand L by linking four pyridines with a 2-hydroxybenzenethiol linker (Scheme 3).…”

“…The UV−vis features of species 2-BAr F 4 closely resemble those of our previously reported dicopper(I,I) di-S-nitrosothiol adduct (λ = 575 nm, ε = 2400 M −1 cm −1 ; λ = 675 nm, ε = 1450 M −1 cm −1 ). 33 To establish the ratio of Ph Me SNO to the dicopper center in 2-BAr F 4 , we performed a UV−vis titration experiment at −50 °C with dicopper(I) precursor 1-BAr F 4 and Ph Me SNO. The complete conversion of 1-BAr F 4 to 2-BAr F 4 requires 1 equiv of Ph Me SNO (Figures S26−S28), suggesting that 2-BAr F 4 is a dicopper(I,I) mono-S-nitrosothiol adduct (Figure 1A).…”