Reaction of a Co(III)-peroxo complex with nitric oxide: putative formation of a peroxynitrite intermediate.

A Co(II) complex, [CoII(L)2(H2O)2](ClO4)2, 1, having a bidentate ligand L [L = bis(3,5-dimethylpyrazolyl)methane] has been synthesized. Complex 1 in acetonitrile solution at -40 °C, in the presence of H2O2 and NEt3, afforded the corresponding Co(III)-peroxo species, [CoIII(L)2(O22-)]+, as the transient intermediate 1a. Thermal instability precluded its isolation and further characterization. The addition of nitric oxide (NO) gas into the freshly prepared [CoIII(L)2(O22-)]+ in acetonitrile at -40 °C resulted in the corresponding Co(II)-nitrato complex, [CoII(L)2(NO3)](ClO4) (2). The reaction is proposed to proceed through a putative Co(II)-peroxynitrite intermediate 1b. It was evidenced by the characteristic phenol ring nitration reaction.

Sixth Ligand Induced HNO/NO- Release by a Five-Coordinated Cobalt(II) Nitrosyl Complex Having a {CoNO}8 Configuration.

Nitroxyl (HNO) and nitroxide (NO-) anion, the one-electron-reduced form of nitric oxide (NO), have been shown to have distinct advantages over NO from pharmacological and therapeutic points of view. However, the role of nitroxyl in chemical biology has not yet been studied as extensively as that of NO. Consequently, only a few examples of HNO donors such as Angeli's salt, Piloty's acid, or acyl- and acyloxynitroso derivatives are known. However, the intrinsic limitations of all of these hinder their widespread utility. Metal nitrosyl complexes, although few examples, could serve as an efficient HNO donor. Here, a cobalt nitrosyl complex of the {CoNO}8 (1) configuration has been reported. This complex in the presence of a sixth ligand [BF4-, DTC- (diethyldithiocarbamate anion), or imidazole] releases/donates HNO/NO-. This has been confirmed using well-known HNO/NO- acceptors like [Fe(TPP)Cl] and [Fe(DTC)3]. The HNO release has been authenticated further by the detection and estimation of N2O using gas chromatography-mass spectroscopy as well as its reaction with PPh3.

Modulation of iron spin states in highly distorted iron(III) porphyrins: H-bonding interactions and implications in hemoproteins.

A family of five- and six-coordinated Fe-porphyrins which enable us to scrutinize the effects of non-covalent interactions on the out-of-plane displacement of iron and its spin-states and axial ligand orientation in a single distorted macrocyclic environment has been reported. Combined analysis using single-crystal X-ray structure determination and EPR spectral investigation revealed the stabilization of the high-spin state of iron in the five-coordinate complex FeIII(TPPBr8)(OCHMe2), while six-coordinate complexes [FeIII(TPPBr8)(MeOH)2]ClO4, [FeIII(TPPBr8)(H2O)2]ClO4 and [FeIII(TPPBr8)(1-MeIm)2]ClO4 stabilize admixed-high, admixed-intermediate and low-spin states, respectively. The H-bonding interactions between the weak axial H2O/MeOH and perchlorate anion resulted in an elongation of the Fe-O bond which eventually shortened the Fe-N(por) distances leading to the stabilization of the admixed spin state of iron which, otherwise, stabilizes the high-spin (S = 5/2) state only. In addition, the iron atom in [FeIII(TPPBr8)(H2O)2]ClO4 is displaced by 0.02 Å towards one of the water molecules engaged in the H-bonding interactions leading to two different Fe-O (H2O) distances of 2.098(8) and 2.122(9) Å. In contrast, iron in [FeIII(TPPBr8)(MeOH)2]ClO4 sits on the plane of the porphyrin since both the axial methanol units are engaged in similar H-bonding interactions with the ClO4- ion. Moreover, the X-ray structure of low-spin FeII(TPPBr8)(1-MeIm)2 revealed a dihedral angle of 63.0° between two imidazoles which deviates largely from the expected angle of 90° (perpendicular orientations) since the axial imidazole protons are engaged in strong intermolecular C-H⋯π interactions which thereby restrict the axial ligand movement. The complex also displays the shortest Fe-N(1-MeIm) bond along with smallest dihedral angles of 7.8° and 22.4° between the axial imidazole ring and the closest Fe-Np axis due to strong π-interactions between iron and the axial imidazole ligand. Our work highlights the influence of non-covalent interactions on the out-of-plane displacement and spin state of iron and axial ligand orientations which are indeed important steps in the functioning of various hemoproteins.

Reaction of a nitrosyl complex of Mn(II)-porphyrinate with superoxide: NOD activity is favoured over SOD activity.

A five-coordinated {Mn(NO)}6 complex of Mn(II)-porphyrinate, [Mn(TMPP2-)(NO)], 1 {TMPPH2 = 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin}, upon reaction with two equivalents of superoxide (O2-) in THF at -40 °C results in the corresponding MnIII-OH complex [MnIII(TMPP2-)(OH)], 2, via the formation of a putative MnIII-peroxynitrite intermediate. Spectral studies and chemical analysis suggest that one equivalent of superoxide ion is consumed to oxidize the metal center of complex 1 leading to [MnIII(TMPP2-)(NO)]+, while the subsequent equivalent reacts with [MnIII(TMPP2-)(NO)]+ to form the corresponding peroxynitrite intermediate. UV-visible and X-band EPR spectroscopic studies suggest the involvement of a MnIV-oxo species in the reaction, which forms through the O-O bond cleavage of the peroxynitrite moiety with concomitant release of NO2. The formation of MnIII-peroxynitrite is further supported by the well-established phenol ring nitration experiment. The released NO2 has been trapped using TEMPO. It should be noted that in cases of MnII-porphyrin complexes, the reaction with superoxide generally proceeds through a SOD-like pathway where the first equivalent of superoxide ion oxidizes the MnII center and itself is reduced to peroxide (O22-), while the subsequent equivalent of superoxide reduces the MnIII center with the release of O2. In contrast, here the second equivalent of superoxide reacts with the MnIII-nitrosyl complex and follows a NOD-like pathway.

Reaction of a {Co(NO)}8 complex with superoxide: Formation of a six coordinated [CoII(NO)(O2-)] species followed by peroxynitrite intermediate.

A nitrosyl complex of cobalt(II) porphyrinate, [Co(F20TPP2-)(NO)], (F20TPPH2 = 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin) having {Co(NO)}8 configuration was synthesized and characterized by means of spectroscopic and structural analyses. Single crystal X-ray structure of the complex revealed the square pyramidal geometry around the cobalt center with a bent nitrosyl group. It reacts with superoxide (O2-) ion in CH2Cl2 at -40 °C to result in the corresponding nitrite (NO2-) complex. Involvement of a cobalt(II)-peroxynitrite intermediate is proposed in the course of the reaction. Moreover, spectroscopic studies suggested the formation of a transient six-coordinated [CoII(NO)(O2-)] species.

Can a Nitrosyl of a Mn(II)-Porphyrin Complex Release Nitroxyl/HNO?

In general, the nitrosyl complexes of Mn(II)-porphyrinate having the {Mn(NO)}6 configuration are not considered as HNO or nitroxyl (NO-) donors because of [MnI-NO+] nature. A nitrosyl complex of Mn(II)-porphyrin, [Mn(TMPP2-)(NO)], 1 [TMPPH2 = 5,10,15,20-tetrakis-4-methoxyphenylporphyrin], is shown to release HNO in the presence of HBF4. It is evidenced from the characteristic reaction of HNO with triphenylphosphine and isolation of the [(TMPP2-)MnIII(H2O)2](BF4), 2. This is attributed to the fact that H+ from HBF4 polarizes the NO group whereas the BF4- interacts with metal ion to stabilize the Mn(III) form. These two effects cooperatively result in the release of HNO from complex 1. In addition, complex 1 behaves as a nitroxyl (NO-) donor in the presence of [Fe(dtc)3] (dtc = diethyldithiocarbamate anion) and [Fe(TPP)(Cl)] (TPP = 5,10,15,20-tetraphenylporphyrinate) to result in [Fe(dtc)2(NO)] and [Fe(TPP)(NO)], respectively.

Nitric Oxide Dioxygenase Activity of a Nitrosyl Complex of Mn(II)-Porphyrinate in the Presence of Superoxide: Formation of a Mn(IV)-oxo Species through a Putative Peroxynitrite Intermediate.

A nitrosyl complex of MnII-porphyrinate, [(F20TPP)MnII(NO)], 1 (F20TPPH2 = 5,10,15,20 tetrakis(pentafluorophenyl)porphyrin), was synthesized and characterized. Spectroscopic and structural characterization revealed complex 1 as a penta-coordinated MnII-nitrosyl with a linear Mn-N-O (180.0°) moiety. Complex 1 does not react with O2. However, it reacts with superoxide (O2-) in THF at -80 °C to result in the corresponding nitrate (NO3-) complex, 2, via the formation of a presumed MnIII-peroxynitrite intermediate. ESI-mass spectrometry and UV-visible and X-band EPR spectroscopic studies suggest the generation of MnIV-oxo species in the reaction through homolytic cleavage of the O-O bond of the peroxynitrite ligand as proposed in NOD activity. The intermediate formation of the MnIII-peroxynitrite was further supported by the well accepted phenol ring nitration which resembles the biologically well-established tyrosine nitration.

Nitric Oxide Dioxygenase Activity of a Nitrosyl Complex of Cobalt(II) Porphyrinate in the Presence of Hydrogen Peroxide via Putative Peroxynitrite Intermediate.

The reaction of a cobalt porphyrin complex, [(F8TPP)Co], 1 {F8TPP = 5,10,15,20- tetrakis(2,6-difluorophenyl)porphyrinate dianion} in dichloromethane with nitric oxide (NO) led to the nitrosyl complex, [(F8TPP)Co(NO)], 2. Spectroscopic studies and structural characterization revealed it as a bent nitrosyl of {CoNO}8 description. It was stable in the presence of dioxygen. However, it reacts with H2O2 in acetonitrile (or THF) solution at -40 °C (or -80 °C) to result in the corresponding Co(III)-nitrate complex, [(F8TPP)Co(NO3)], 3. The reaction presumably proceeds via the formation of a Co-peroxynitrite intermediate. X-Band electron paramagnetic resonance and electrospray ionization-mass spectroscopic studies suggest the intermediate formation of the [(porphyrin)Co(III)-O•] radical, which in turn supports the generation of the corresponding Co(IV)-oxo species during the reaction. This is in accord with the homolytic cleavage of the O-O bond in heme-peroxynitrite proposed in the nitric oxide dioxygenases activity. In addition, the characteristic peroxynitrite-induced phenol ring reaction was also observed.