Heme-Copper Assembly Mediated Reductive Coupling of Nitrogen Monoxide (·NO)

Abstract

A iron-dinitrosyl species ( 6 L)Fe(NO) 2 (2), generated from nitrogen monoxide (•NO) binding to its related iron(II)-mononitrosyl complex ( 6 L)Fe(NO) (1), efficiently effects reductive coupling of two •NO molecules to release nitrous oxide (N 2 O), when Cu + ion and two equiv acid are added; the heme/ Cu product is [( 6 While there is extensive recent activity in the design and study of discrete heme/copper synthetic complexes which resemble HCO active sites and/or effect dioxygen binding and reduction chemistry, 6,10 there are no cases where a synthetic small molecule heme/Cu complex reacts with •NO to effect reductive coupling leading to nitrous oxide. In this report, we describe such a system, employing the binucleating ligand 6 L and its iron and heme-copper derivatives which have been previously used in our investigations involving O 2 -chemistry. 10a The starting point is the reductive nitrosylation of ( 6 L)Fe III (OH) 11 to straightforwardlygive the iron(II)-nitrosyl compound ( 6 L)Fe(NO) (1) (Scheme 1), possessing the expected threeline hyperfine split EPR spectrum 12 (Fig. 1a). 13 As has been reported previously, 14 such complexes may react with additional •NO (g) to form a dinitrosyl species. This occurs here and evidence in support of this formulation, ( 6 L)Fe(NO) 2 are as follows: (a) As monitored by UVvis spectroscopy in acetone (−80 °C), 1 reversibly binds •NO (g) to form ( 6 L)Fe(NO) 2 (2); 2 is stable, but loses •NO (g) upon warming to RT. (b) With formation of 2 at −80 °C, the EPR signal due to ( 6 L)Fe-(NO) (1) disappears, as would be expected for 2, having an even number of electrons. (c) Titration of a −80 °C solution of ( 6 L)Fe(NO) 2 (2) with one equiv (F 8 )Fe II {F 8 = tetrakis(2,6-difluorophenyl)porphyrinate(2-)} leads to a clean conversion to ( 6 L)Fe(NO) (1) plus (F 8 )Fe(NO) (X-Ray structure determined); 2 possesses two equiv of bound •NO. 13The existence of ( 6 L)Fe(NO) 2 (2) . This is based on the observed UV-vis spectrum, appearing as a single species with λ max = 396, 515 nm in THF, matching that of a typical (porphyrinate)Fe III -X high-spin complex (X = a non-coordinating anion like PF 6 − or here B(C 6 F 5 ) 4 − ). Further supporting this formulation, an EPR spectrum (Fig. 1b) reveals that a high-spin heme-Fe III along with a Cu II (tetragonal complex) are both present. 13,16Wang et al.

Roles of glutamates and metal ions in a rationally designed nitric oxide reductase based on myoglobin

“…As a complementary approach, rational protein design, using small, easy-toproduce and well-characterized proteins such as myoglobin, offers a powerful method with which to gain insights into more complex native enzymes such as NOR (14). Similar to synthetic models (41,43), the metal ion at the putative Fe B site in the protein model can be substituted freely. Better yet, Glu residues can be placed at precise locations in the protein, including the secondary coordination sphere, due to its rigid network.…”

“…Despite these successes, the roles of the conserved glutamates and metal ions still remain to be fully elucidated, partly because of the difficulty in obtaining native NOR in high yield and the lack of a 3D structure. Even if these problems are resolved, it is still difficult to replace iron in the native Fe B site with other metal ions, and spectroscopic studies of native NOR are often complicated by the presence of other metal cofactors (e.g., low-spin heme).To overcome these limitations, a number of synthetic models of NOR using small organic molecules as ligands, have been made in which the nonheme Fe B site can be replaced by a copper ion (17,(38)(39)(40)(41)(42)(43)(44)(45). In addition, since these model systems lack additional metal-binding sites, spectroscopic studies are often simplified.…”

“…To overcome these limitations, a number of synthetic models of NOR using small organic molecules as ligands, have been made in which the nonheme Fe B site can be replaced by a copper ion (17,(38)(39)(40)(41)(42)(43)(44)(45). In addition, since these model systems lack additional metal-binding sites, spectroscopic studies are often simplified.…”

Reductive N–N coupling of NO molecules on transition metal complexes leading to N2O

“…The reported IR wavenumbers associated with the N 2 O 2 stretching vibrations are shown in ), but these are not clearly assigned [12b,17]. As can be seen in the IR spectra of two sodium hyponitrite [26], the trans-and ( [31]. In control experiments, the dinitrosyl complex 14 was protonated at -80 ºC and then warmed to room temperature to afford a mono nitrosyl complex ( indicates paramagnetism, although the NMR spectrum of 11 shows diamagnetism probably owing to strong antiferromagnetic spin exchange coupling via a superexchange mechanism [35].…”

Understanding the Role of Hyponitrite in Nitric Oxide Reduction

“…In biological systems, this reaction is performed by NO reductase (NOR) and flavodiiron NO reductase (FDP), [1][2][3][4][5][6][7][8][9][10][11][12] which convert two equivalents of nitric oxide, two reducing equivalents, and two protons, into N 2 O and water. The exact order of proton and electron additions during their catalytic cycles is not known, nor is the mechanism by which the N-N bond of N 2 O is formed.…”