Copper(II) Activation of Nitrite: Nitrosation of Nucleophiles and Generation of NO by Thiols

Abstract

Nitrite (NO) and nitroso compounds (E-NO, E = RS, RO, and RN) in mammalian plasma and cells serve important roles in nitric oxide (NO) dependent as well as NO independent signaling. Employing an electron deficient β-diketiminato copper(II) nitrito complex [ClNN]Cu(κ-ON)·THF, thiols mediate reduction of nitrite to NO. In contrast to NO generation upon reaction of thiols at iron nitrite species, at copper this conversion proceeds through nucleophilic attack of thiol RSH on the bound nitrite in [Cu](κ-ON) that leads to S-nitrosation to give the S-nitrosothiol RSNO and copper(II) hydroxide [Cu]-OH. This nitrosation pathway is general and results in the nitrosation of the amine PhNH and alcohol BuOH to give PhNNO and BuONO, respectively. NO formation from thiols occurs from the reaction of RSNO and a copper(II) thiolate [Cu]-SR intermediate formed upon reaction of an additional equiv thiol with [Cu]-OH.

The Unusual Role of Aromatic Solvent in Single‐Site AluminumI Chemistry: Insights from Theory

“…The mechanism for s-bond activation of the HÀH, HÀNa nd HÀPb onds by the NacNacAl I complex, as experimentally reported, [15] was carefullyi nvestigated with DFT.I tw as observed that the solventw as far from as pectator in this chemistry:i t actively and explicitly participated in the s-bond activation process and had as ignificant effect on the efficiency.T he current work therefore reveals that aluminum I chemistry,f or the cases studied, is richer and more complex than had been realized, andi sa ctually an example of metal-solventc ooperativity. Althought here are examples of solvent bindinga saligand in transition-metal complexes, [46,47] to the best of our knowledge, this is the first example of its kind in main-group chemistry, not only of solvent binding as al igand,b ut also of metal-solvent cooperativity.I ndeed, as shown in Figure 13, we had to Figure 9. The free energy profile (DG in kcalmol À1 )for the formationo fh' (hexane-NacNacAl III complex)b yactivationoft he terminalC ÀHb ond.…”

“…The current work therefore reveals that aluminum I chemistry, for the cases studied, is richer and more complex than had been realized, and is actually an example of metal–solvent cooperativity. Although there are examples of solvent binding as a ligand in transition‐metal complexes, to the best of our knowledge, this is the first example of its kind in main‐group chemistry, not only of solvent binding as a ligand, but also of metal–solvent cooperativity. Indeed, as shown in Figure , we had to take the log plot of the relative efficiencies, with and without the explicit assistance of the solvent, to fit the relative efficiency values for different cases of σ‐bond activation by the aluminum I complex into a single graph.…”

Four‐Coordinate Copper Halonitrosyl {CuNO}10 Complexes

“…[37] Additionally,t he isoelectronic and isostructural [Br 3 CuNO] À analog performs similar N-, O-, and S-nitrosylation in 93 %, 91 %, 18 %yields,respectively.The low yield of [Br 3 CuNO] À promoted S-nitrosylation is perhaps due to its weak NOC binding affinity. Consistent with the NO-based LUNO,w ef ound that [Cl 3 CuNO] À performs reductive nitrosylation of N-, O-, and S-based nucleophiles, producing N-, O-, S-nitroso compounds in 93 %, 95 %, and 77 %y ield, respectively (Scheme 3).…”

“…The reactivity of [Cl 3 CuNO] À compounds mirrors that of the copper(II) nitrite complex [Cl 2 NN F6 ]Cu II (k 2 -O 2 N), adding further implications for nitrite-derived nitrosative reactivity. [37] Additionally,t he isoelectronic and isostructural [Br 3 CuNO] À analog performs similar N-, O-, and S-nitrosylation in 93 %, 91 %, 18 %yields,respectively.The low yield of [Br 3 CuNO] À promoted S-nitrosylation is perhaps due to its weak NOC binding affinity.…”

Four‐Coordinate Copper Halonitrosyl {CuNO}10 Complexes

“…The S ‐nitrosylation reactivity of [Cl 3 CuNO] − represents the first example of such occurring via a discrete copper nitrosyl complex. The reactivity of [Cl 3 CuNO] − compounds mirrors that of the copper(II) nitrite complex [Cl 2 NN F6 ]Cu II (κ 2 ‐O 2 N), adding further implications for nitrite‐derived nitrosative reactivity . Additionally, the isoelectronic and isostructural [Br 3 CuNO] − analog performs similar N ‐, O ‐, and S ‐nitrosylation in 93 %, 91 %, 18 % yields, respectively.…”