A motif for reversible nitric oxide interactions in metalloenzymes.

Nitric oxide (NO) participates in numerous biological processes, such as signalling in the respiratory system and vasodilation in the cardiovascular system. Many metal-mediated processes involve direct reaction of NO to form a metal-nitrosyl (M-NO), as occurs at the Fe(2+) centres of soluble guanylate cyclase or cytochrome c oxidase. However, some copper electron-transfer proteins that bear a type 1 Cu site (His2Cu-Cys) reversibly bind NO by an unknown motif. Here, we use model complexes of type 1 Cu sites based on tris(pyrazolyl)borate copper thiolates [Cu(II)]-SR to unravel the factors involved in NO reactivity. Addition of NO provides the fully characterized S-nitrosothiol adduct [Cu(I)](κ(1)-N(O)SR), which reversibly loses NO on purging with an inert gas. Computational analysis outlines a low-barrier pathway for the capture and release of NO. These findings suggest a new motif for reversible binding of NO at bioinorganic metal centres that can interconvert NO and RSNO molecular signals at copper sites.

Copper(I) nitrosyls from reaction of copper(II) thiolates with S-nitrosothiols: mechanism of NO release from RSNOs at Cu.

S-nitrosothiols (RSNOs) serve as ready sources of biological nitric oxide activity, especially in conjunction with copper centers. We report a novel pathway for the generation of NO within the coordination sphere of copper model complexes from reaction of copper(II) thiolates with S-nitrosothiols. Reaction of tris(pyrazolyl)borate copper(II) thiolates (iPr2)TpCu-SR (R = C6F5 or CPh3) with (t)BuSNO leads to formation of (iPr2)TpCu(NO) and the unsymmetrical disulfide RS-S(t)Bu. Quantum mechanical investigations with B3LYP-D3/6-311G(d) suggest formation of a κ(1)-N-RSNO adduct (iPr2)TpCu(SR)(R'SNO) that precedes release of RSSR' to deliver (iPr2)TpCu(NO). This process is reversible; reaction of (iPr2)TpCu(NO) (but not (iPr2)TpCu(NCMe)) with C6F5S-SC6F5 forms (iPr2)TpCu-SC6F5. Coupled with the facile, reversible reaction between (iPr2)TpCu(NO) and C6F5SNO to give (iPr2)TpCu-SC6F5 and 2 equiv NO, we outline a new, detailed catalytic cycle for NO generation from RSNOs at Cu.

A copper(II) thiolate from reductive cleavage of an S-nitrosothiol.

S-Nitrosothiols RSNO represent circulating reservoirs of nitric oxide activity in the plasma and play intricate roles in protein function control in health and disease. While nitric oxide has been shown to reductively nitrosylate copper(II) centers to form copper(I) complexes and ENO species (E = R(2)N, RO), well-characterized examples of the reverse reaction are rare. Employing the copper(I) ß-diketiminate [Me(2)NN]Cu, we illustrate a clear example in which an RS-NO bond is cleaved to release NO(gas) with formation of a discrete copper(II) thiolate. The addition of Ph(3)CSNO to [Me(2)NN]Cu generates the three-coordinate copper(II) thiolate [Me(2)NN]CuSCPh(3), which is unstable toward free NO.

Reversible RS-NO bond cleavage and formation at copper(I) thiolates.

Two coordinate copper(I) thiolates IPrCu-SR undergo rapid, reversible transnitrosation with S-nitrosothiols RSNOs without catalyzing the loss of NO(gas) from these biological carriers of NO.

Reductive cleavage of O-, S-, and N-organonitroso compounds by nickel(I) beta-diketiminates.

An electron-rich nickel(I) beta-diketiminate cleaves the E-NO bond of O-, S-, and N-organonitroso species to give the nickel nitrosyl [Me 3NN]NiNO along with dimeric nickel(II) alkoxide or thiolate complexes {[Me 3NN]Ni} 2(mu-E) 2 or the mononuclear nickel(II) amide [Me 3NN]NiNPh 2. This diamagnetic three-coordinate amide exhibits temperature-dependent NMR spectra due to a low-lying triplet state.

Transient terminal Cu-nitrene intermediates from discrete dicopper nitrenes.

Reaction of the copper(I) beta-diketiminate {[Me3NN]Cu}2(mu-toluene) with the aryl azide N3Ar (Ar = 3,5-Me2C6H3) in toluene results in immediate effervescence and formation of the dicopper nitrene {[Me3NN]Cu}2(mu-NAr) (2) in 77% yield. The X-ray structure of 2 shows nearly symmetric bonding of the nitrene to two Cu centers separated by 2.911(1) A with Cu-N distances of 1.794(5) and 1.808(5) A along with a Cu-N-Cu angle of 107.8(2) degrees . This structure is conceptually related to the dicopper carbenes {[MexNN]Cu}2(mu-CPh2) (x = 2 or 3) (Dai, X.; Warren J. Am. Chem. Soc. 2004, 126, 10085. Badiei, Y. M.; Warren J. Organomet. Chem. 2005, 690, 5989.) which exhibit shorter Cu-Cu distances (2.4635(7) or 2.485(1) A) and acute Cu-C-Cu angles (79.51(14) or 80.1(2) degrees ). Addition of the Cu(I) anilidoimine {[Me2AI]Cu}2 (prepared from CuOtBu and the aniline-imine H[Me2AI] in 77% yield) to a benzene-d6 solution of 2 results in the formation of two new anilidoimine complexes {[Me2AI]Cu(mu- NAr)Cu[Me3NN] (5) and {[Me2AI]Cu}2(mu-NAr) (6) as well as [Me3NN]Cu(benzene) over 3 h. These observations are consistent with the slow dissociation of a [Me3NN]Cu fragment from 2 to generate the transient terminal nitrenes [Me3NN]Cu=NAr and [Me2AI]Cu=NAr quickly trapped by the [Me2AI]Cu fragment to form the new unsymmetrical and symmetrical dicopper nitrenes 5 and 6. Preliminary reactivity studies indicate electrophilic reactivity at the nitrene moiety. Dicopper nitrene 2 reacts with 10 equiv PMe3 and CNtBu to give ArN=PMe3 and ArN=C=NtBu in 94% and 92% yields, respectively, with concomitant formation of [Me3NN]Cu(L) (L = PMe3 and CNtBu). Reaction between 2 and 2 equiv PMe3 allows for observation of the structurally characterized Cu(I) phosphaimide [Me3NN]Cu(ArN=PMe3) (7).