Reactions reductive nitrosylation

Reductive nitrosylation, on the other hand, can refer to the addition of NO to a metal center Mox with formal reduction of the metal center to yield Mred(NO +), but in the context of ligand reactions reductive nitrosylation refers to the net reactions of NO with metal-bound NO and the ensuing events. Reductive nitrosation of coordinated amines to form nitrosamines occurs through the conjugate base of the amine, and this process has been reported for reactions of NO with [Ni(tacn)2]3 +, 198 with methyl-amine coordinated to a macrocyclic Ni(III) complex,199 with triglycyl complexes of Fe(III), Ni(III), and Cu(III),200 and with Cu(II) macrocyclic complexes.201 Reductive nitrosation of [Ru(NH3)6]3+ produces [Ru(NH3)5N2]2 + with base-catalyzed kinetics the coordinated N2 is produced by hydrolysis after the nitrosation step.170... 

The coordination chemistry of NO is often compared to that of CO but, whereas carbonyls are frequently prepared by reactions involving CO at high pressures and temperatures, this route is less viable for nitrosyls because of the thermodynamic instability of NO and its propensity to disproportionate or decompose under such conditions (p. 446). Nitrosyl complexes can sometimes be made by transformations involving pre-existing NO complexes, e.g. by ligand replacement, oxidative addition, reductive elimination or condensation reactions (reductive, thermal or photolytic). Typical examples are ... 

Additional mechanistic insight into the reductive nitrosylation of ferri-heme proteins was obtained from kinetic studies carried out on aqueous solutions of Cytm, metMb, and metHb at various pH values (67). For example, Cytm undergoes reduction by NO to Cyt11 in aqueous solutions at pH values > 6.5. A hypothetical reaction mechanism is shown in Scheme 2 which would predict the rate law presented in Eq. (31) (67). 

Studies in this laboratory (69) of the water soluble ferri-heme model Fem(TPPS) in aqueous solution have shown that this species also undergoes reductive nitrosylation in solutions that are moderately acidic (pH 4-6) (Eq. (32)). The rate of this reaction includes a buffer dependent term indicating that the reaction of the Fem(TPPS)(NO) complex with H20 is subject to general base catalysis. The reaction depicted in Eq. (33) is not observable at pH values < 3, since the half-cell reduction potential for the nitrite anion (Eq. (1)) is pH dependent, and Eq. (33) is no longer thermodynamically favorable. 

It was also found that N02 accelerated the observed rates of reductive nitrosylation (kso, = 3.1 0.1 M 1 s 1 in 16mM acetate at pH 4.96) (69). Since nitrite is a product of the reductive nitrosylation reaction in aqueous solution, the system is, in principle, autocatalytic. 

Table III also shows the values of the equilibrium constants, KVAp for the conversion of iron nitrosyl complexes into the corresponding nitro derivatives. Keq decreases downwards, meaning that the conversions are obtained at a lower pH for the complexes at the top of the table. Thus, NP can be fully converted into the nitro complex only at pHs greater than 10. The NO+ N02 conversion, together with the release of N02 from the coordination sphere, are key features in some enzymatic reactions leading to oxidation of nitrogen hydrides to nitrite (14). The above conversion and release must occur under physiological conditions with the hydroxylaminoreductase enzyme (HAO), in which the substrate is seemingly oxidized through two electron paths involving HNO and NO+ as intermediates. Evidently, the mechanistic requirements are closely related to the structure of the heme sites in HAO (69). No direct evidence of bound nitrite intermediates has been reported, however, and this was also the case for the reductive nitrosylation processes associated with ferri-heme chemistry (Fig. 4) (25).

The reaction of NO with Cru(TPP) affords Cr(TPP)NO which is a red solid with v(NO) = 1700 cm-1 and an ESR spectrum typical of an S = species.595 When solutions of Cr(OMe)(TPP) in CHClj/MeOH are exposed to NO, spectroscopic changes indicative of the formation of an NO complex occur. On degassing, the original spectrum reappears. Since the electronic and ESR spectra of the NO complex are similar to those of Cr(TPP)NO, it is believed that reductive nitrosylation has taken place according to equations (67) to (69). It is not stated whether Cr(TPP)NO as the solid or redissolved loses NO. More recent work1247 shows that DMF, DMSO and py coordinate axially to Cr(TPP)NO in CH2C12 and formation constants have been determined at high concentrations some displacement of NO occurs. 

In this reaction the nitrosyl ligand bends, undergoing a 2 e reduction, rather than form a 20 e complex. This reaction can also serve to activate the nitrosyl ligand. Whereas the linear nitrosyl may be unreactive if vNO is sufficiently low, the bent nitrosyl is reactive to electrophiles. 

In contrast, complexation of HNO tends to result in reductive nitrosylation. Doyle et al. (39, 170) first demonstrated the experimental utility of this reaction with iron proteins such as methemoglobin (metHb) and metmyoglobin (metMb). 

Oxidized proteins including peroxidases, catalases, and Cu, Zn or Mn SOD (84, 147, 170, 192) as well as synthetic iron porphyrins (193) can be reductively nitrosylated by HNO. The reaction of HNO with peroxidases results in activity inhibition (data not shown). Additionally, HNO inhibits oxidation by cytochrome P450 (69), suggesting an antiinflammatory role for HNO. 

The reductive nitrosylation of a synthetic iron porphyrin by HNO (193) proceeds with a reported rate constant of 1 x 107 A/-1 s However, this value was estimated based on a HNO dimerization rate constant of 8 x 109 M-1 s-1 (210), which is now considered to be 1000-fold lower [(8 x 106 A/-1 s-1 (106)]. The recalculated constant for the reaction of HNO with the porphyrin (3 x 10s AT V1) is similar to the estimated value of HNO addition to metMb. Synthetic porphyrins generally react 30-fold faster with NO (1 x 109M 1 s-1) than ferrous Mb [for a recent, thorough review see (44)] due to rate-limiting diffusion of NO through the protein. The similarity in rate constants for HNO with metMb and the ferric porphyrin suggests that the rate-limiting step in reductive nitrosylation is likely addition of HNO to the ferric metal, with little influence from the protein structure. 

This reaction is a reductive nitrosylation of a [MoIV(S4)] complex. (Throughout this contribution, NO ligands are considered as neutral 3e donor ligands.)... 

As part of the work on model heme FeNO complexes, mechanistic studies on the reversible binding of nitric oxide to metmyoglobin and water soluble Fe, Co and Fe porphyrin complexes in aqueous solution, ligand-promoted rapid NO or NO2 dissociation from Fe porphyrins, reductive nitrosylation of water-soluble iron porphyrins, activation of nitrite ions to carry out O-atom transfer by Fe porphyrins, demonstration of the role of scission of the proximal histidine-iron bond in the activation of soluble guanylyl cyclase through metalloporphyrin substitution studies, reactions of peroxynitrite with iron porphyrins, and the first observation of photoinduced nitrosyl linkage isomers of FeNO heme complexes have been reported. 

NO reacts with both ferric and ferrous centers in hemoproteins to form the respective iron(II) and iron(III) nitrosyl adducts, whose structural features are similar to those observed for iron (II) and iron(III) porphyrin nitrosyls. These analogies are also reflected in similar chemical reactivity observed for nitrosylated ferri- and ferroproteins and their respective porphyrin models. For example, NO-adducts of Fe(III) undergo reductive nitrosylation in the presence of an excess of NO, and a similar process is commonly observed for synthetic Fe(III) porphyrins. The first step of this reaction involves nucleophilic attack of OH on the nitrosyl ligand coordinated to the iron center, as presented in reaction (13) (33,60) ... 

Hoshino M, Maeda M, Konishi R, Seki H, Ford PC. Studies on the reaction mechanism for reductive nitrosylation of ferrihemopro-teins in buffer solutions. J. Am. Chem. Soc. 1996 118 5702-5707. Weichsel A, Maes EM, Andersen JF, Valenzuela JG, Shokhireva T, Walker FA, Montfort WR. Heme-assisted S-nitrosation of a proximal thiolate in a nitric oxide transport protein. Proc. Natl. Acad. Sci. U. S. A. 2005 102 594-599. 

Reductive nitrosylation also occurs on reaction of hydroxylamine with transition metal oxo- compounds (33-35) ... 

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