Reactivity of Nitric Oxide and Nitrosonium Ion with Copper(II/I) Schiff Base Complexes: Mechanistic Aspects of Imine C═N Bond Cleavage and Oxidation of Pyridine-2-aldehyde to Pyridine-2-carboxylic Acid.

Four Schiff base ligands of the general formulas [6-(R)-2-pyridyl-N-(2'-methylthiophenyl)methylenimine] (RL1) and 6-p-chlorophenyl-2-pyridyl-N-(2'-phenylthiophenyl)methylenimine (RL2), where R = H, Me, p-ClPh, and their bis-ligand copper(II) and copper(I) complexes, 1-4 and 1'-4', respectively, were synthesized and characterized. The reactivities of 1-4 with nitric oxide (NO) gas and of 1'-4' with solid NOBF4 (NO+) were examined in dry acetonitrile in the presence and absence of water (H2O). The results revealed that, in the absence of H2O, complexes 1-4 (or 1'-4') reacts with NO (or NOBF4), leading to imine C═N bond cleavage of both (or one) Schiff base(s) that generates 2 (or 1) equiv of 2-(methyl/phenyl)thiobenzenediazonium perchlorates (5/6) and the corresponding picolaldehyde (RPial) via a copper nitrosyl of a {CuNO}10-type intermediate. In the presence of H2O, the in situ formed RPial get oxidized to the corresponding picolinic acid (RPicH) via an in situ formed LCuIOH intermediate (LCuI + HO-NO → LCuIOH + NO+; L = RL1/RL2/RPic- and νO-H of CuIOH = 3650 cm-1) and subsequently produces, with the aid of NO+ oxidant, the picolinate-ligated copper(II) complexes (i) [(HPic)2Cu] (7), [(MePic)4Cu3(NO3)2]n·H2O (8·H2O), or [(ClPhPic)2Cu] (9) when NO reacts with 1-4 or (ii) [(RPic)CuII(RL1/RL2)]+ when NO+ reacts with 1'-4'. The CuII to CuI reduction of [(RPic)CuII(RL1/RL2)]+ is essential for C═N cleavage of the remaining RL1/RL2 Schiff base; excess NO can do it. The X-ray structures (1, 1', 3', 5, 7, and 8) and spectroscopic results revealed the role of CuII/I, NO, NO+, and H2O, shedding light on the mechanism of C═N bond cleavage and the oxidation of pyridine-2-aldehyde to pyridine-2-carboxylic acid. The reaction of 1 with 15NO revealed that the terminal N of the N2+ group of 5 originates from 15NO [ν14N14N- = 2248 cm-1 and ν15N14N- = 2212 cm-1].

Bis(µ-thiolato)-dicopper Containing Fully Spin Delocalized Mixed Valence Copper-Sulfur Clusters and Their Electronic Structural Properties with Relevance to the CuA Site.

With aromatic and aliphatic thiol-S donor Schiff base ligands, the copper-sulfur clusters, [(L1)8CuI6CuII2](ClO4)2·DMF·0.5CH3OH (1) and [(L2)12CuI5CuII11(µ4-S)(µ4-O)6](ClO4)·4H2O, respectively, have been reported ( Chem. Commun. 2017, 53, 3334); HL1/HL2 are 2-(((3-methylthiophen-2-yl)methylene)amino)benzene/ethanethiol). Complex 1 comprises a wheel shaped Cu8S8 framework, made up of interlinked Cu2{µ-S(R)}2 units. To understand the properties with relevance to the CuA site and to check whether self-assembly generates similar type clusters to 1, three complexes, [(L3)8CuI6CuII2](ClO4)2·(C2H5)2O·2.5H2O (2), [(L3Cl)8CuI6CuII2](ClO4)2·1.25(C2H5)2O·1.25CH3OH·2H2O (3), and [(L3CF3)8CuI6CuII2](ClO4)2·2(C2H5)2O·H2O (4) have been synthesized with supporting ligands HL3X (HL3 = 2-((furan-2-ylmethylene)amino)benzenethiol when X = -H; X = -Cl or -CF3 para to thiol-S are HL3Cl and HL3CF3 ligands, respectively). The X-ray structures of 3 and 4 feature a similar Cu8S8 architecture to 1. The spectroscopic properties and the X-ray structures revealed that 2-4 are fully spin delocalized mixed valence (MV) of class-III type clusters. The structural parameters of the N2Cu2{µ-S(R)}2 units of 3 and 4 closely resemble those of the MV binuclear CuA site. With the aid of UV-vis-NIR, EPR, and spectroelectrochemical studies, the electronic properties of these complexes have been described in comparison with the MV model complexes and CuA site.

Nickel(II)-Mediated Reversible Thiolate/Disulfide Conversion as a Mimic for a Key Step of the Catalytic Cycle of Methyl-Coenzyme†M Reductase.

According to the well-accepted mechanism, methyl-coenzyme M reductase (MCR) involves Ni-mediated thiolate-to-disulfide conversion that sustains its catalytic cycle of methane formation in the energy saving pathways of methanotrophic microbes. Model complexes that illustrate Ni-ion mediated reversible thiolate/disulfide transformation are unknown. In this paper we report the synthesis, crystal structure, spectroscopic properties and redox interconversions of a set of NiII complexes comprising a tridentate N2 S donor thiol and its analogous N4 S2 donor disulfide ligands. These complexes demonstrate reversible NiII -thiolate/NiII -disulfide (both bound and unbound disulfide-S to NiII ) transformations via thiyl and disulfide monoradical anions that resemble a primary step of MCR's catalytic cycle.

Efficient removal of Hg2+, Cd2+ and Pb2+ from aqueous solution and mixed industrial wastewater using a designed chelating ligand, 2-pyridyl-N-(2'-methylthiophenyl) methyleneimine (PMTPM).

The present study is focused on the removal of Hg2+, Cd2+ and Pb2+ ions from aqueous solution using a tridentate chelating agent, 2-pyridyl-N-(2'-methylthiophenyl) methyleneimine (PMTPM); and applicability of such removal from industrial wastewater using PMTPM is also investigated. The results showed that the metal ions removal efficiency using PMTPM was in the order of Hg2+(99.46%) > Cd2+(95.42%) > Pb2+(94.54%) under optimum reaction conditions (L:M2+ = 3:1, pH = 9, time = 24 h, temp. = 30 °C). Formed chelated complexes such as [Hg(PMTPM)Cl2] (1), [Cd(PMTPM)Cl2] (2) and [Pb(PMTPM)Cl2] (3) were characterized by numerous spectroscopic tools and X-ray structure determination of a representative complex of Hg2+. In the X-ray structure of [Hg(PMTPM)Cl2], 1, the Hg2+ adopted a distorted tetrahedral coordination geometry surrounding two N donors of PMTPM and two chloride ions. A similar coordination geometry surrounding the respective metal centres in 2 and 3 was established. The thermogravimetric analysis (TGA) revealed a stability order of [Cd(PMTPM)Cl2] > [Hg(PMTPM)Cl2] > [Pb(PMTPM)Cl2]. Further the comparative metal leaching behaviour of these chelate complexes exhibited higher stability in alkaline solution than in acidic. Moreover, PMTPM was applied in real mixed industrial wastewater with alkaline pH, and adequate removals of toxic metals were achieved.

Model Complexes for the Nip Site of Acetyl Coenzyme A Synthase/Carbon Monoxide (CO) Dehydrogenase: Structure, Electrochemistry, and CO Reactivity.

Aliphatic thiolato-S-bridged tri- and binuclear nickel(II) complexes have been synthesized and characterized as models for the Nip site of the A cluster of acetyl coenzyme A synthase (ACS)/carbon monooxide (CO) dehydrogenase. Reaction of the in situ formed N2Sthiol donor ligands with [Ni(H2O)6](ClO4)2 afforded the trinuclear complexes [Ni{(LMe(S))2Ni}2](ClO4)2·CH3CN (1·CH3CN) and [Ni{(LBr(S))2Ni}2](ClO4)2·5H2O (2·5H2O) following self-assembly. Complexes 1 and 2 react with [Ni(dppe)Cl2] and dppe [dppe = 1,2-bis(diphenylphosphino)ethane] to afford the binuclear [Ni(dppe)Ni(LMe(S))2](ClO4)2·2H2O (3·2H2O) and [Ni(dppe)Ni(LBr(S))2](ClO4)2·0.75O(C2H5)2 [4·0.75O(C2H5)2], respectively. The X-ray crystal structures of 1-4 revealed a central NiIIS4 moiety in 1 and 2 and a NiIIP2S2 moiety in 3 and 4; both moieties have a square-planar environment around Ni and may mimic the properties of the Nip site of ACS. The electrochemical reduction of both terminal NiII ions of 1 and 2 occurs simultaneously, which is further confirmed by the isolation of [Ni{(LMe(S))2Ni(NO)}2](ClO4)2 (5) and [Ni{(LBr(S))2Ni(NO)}2](ClO4)2 (6) following reductive nitrosylation of 1 and 2. Complexes 5 and 6 exhibit νNO at 1773 and 1789 cm-1, respectively. In the presence of O2, both 5 and 6 transform to nitrite-bound monomers [(LMe(S-S))Ni(NO2)](ClO4) (7) and [(LBr(S-S))Ni(NO2)](ClO4)2 (8). The nature of the ligand modification is evident from the X-ray crystal structure of 7. To understand the origin of multiple reductive responses of 1-4, complex [(LMe(SMe))2Ni](ClO4)2 (9) is considered. The central NiS4 part of 1 is labile like the Nip site of ACS and can be replaced by phenanthroline. The treatment of CO to reduce 3 generates a 3red-(CO)2 species, as confirmed by Fourier transform infrared (νCO = 1997 and 2068 cm-1) and electron paramagnetic resonance ( g1 = 2.18, g2 = 2.13, g3 = 1.95, and AP = 30-80 G) spectroscopy. The CO binding to NiI of 3red is relevant to the ACS activity.

A Copper(II) Nitrite That Exhibits Change of Nitrite Binding Mode and Formation of Copper(II) Nitrosyl Prior to Nitric Oxide Evolution.

The proton-coupled reduction of CuII-bound nitrite (NO2-) to nitric oxide (NO2- + 2H+ + e- → NO(g) + H2O), such as occurs in the enzyme copper nitrite reductase, is investigated in this work. Our studies focus on the copper(II/I) model complexes [(L2)Cu(H2O)Cl] (1), [(L2)Cu(ONO)] (2), [(L2)Cu(CH3CO2)] (3), and [Co(Cp)2][(L2)Cu(NO2)(CH3CN] (4), where HL2 = N-[2-(methylthio)ethyl]-2'-pyridinecarboxamide. Complex 1 readily reacts with a NO2- anion to form the nitrito-O-bound copper(II) complex 2. Electrochemical reduction of CuII → CuI indicates coordination isomerization from asymmetric nitrito-κ2-O,O to nitro-κ1-N. Isolation and spectroscopic characterization of 4 support this notion of nitrite coordination isomerization (νCu-N ∼ 460 cm-1). A reduction of 2, followed by reaction with acetic acid, causes evolution of stoichiometric NO via the transient copper(II) nitrosyl species and subsequent formation of the acetate-bound complex 3. The probable copper nitrosyl intermediate [(L2)Cu(NO)(CH3CN)]+ of the {CuNO}10 type is evident from low-temperature UV-vis absorption (λmax = 722 nm) and electron paramagnetic resonance spectroscopy. A density functional theory (DFT)-optimized model of [(L2)Cu(NO)(CH3CN)]+ shows end-on NO binding to Cu with Cu-N(NO) and N-O distances of 1.989 and 1.140 Å, respectively, and a Cu-N-O angle of 119.25°, consistent with the formulation of CuII-NO•. A spin-state change that triggers NO release is observed. Considering singlet- and triplet-state electronic configurations of this model, DFT-calculated νNO values of 1802 and 1904 cm-1, respectively, are obtained. We present here important mechanistic aspects of the copper-mediated nitrite reduction pathway with the use of model complexes employing the ligand HL2 and an analogous phenyl-based ligand, N-[2-(methylthio)phenyl]-2'-pyridinecarboxamide (HL1).

Mixed valence copper-sulfur clusters of highest nuclearity: a Cu8 wheel and a Cu16 nanoball.

Fully spin delocalized mixed valence copper-sulfur clusters, 1 and 2, supported by µ4-sulfido and NSthiol donor ligands are synthesized and characterized. Wheel shaped 1 consists of Cu2S2 units. The unprecedented nanoball 2 can be described as S@Cu4(tetrahedron)@O6(octahedron)@Cu12S12(cage) consisting of both Cu2S2 and (µ4-S)Cu4 units. The Cu2S2 and (µ4-S)Cu4 units resemble biological CuA and CuZ sites respectively.

Electron transfer mechanism of catalytic superoxide dismutation via Cu(ii/i) complexes: evidence of cupric-superoxo/-hydroperoxo species.

To understand the electron transfer mechanisms (outer versus inner sphere) of catalytic superoxide dismutation via a Cu(ii/i) redox couple such as occur in the enzyme copper-zinc superoxide dismutase, the Cu(ii/i) complexes [(L1)2Cu](ClO4)2·CH3CN, (1·CH3CN) and [(L1)2Cu](ClO4), (2) supported by a bis-N2Sthioether ligand, 2-pyridyl-N-(2'-methylthiophenyl)methyleneimine (L1) have been synthesized and structurally characterised. Both 1 and 2 display the same cyclic voltammogram (CV) featuring a quasireversible response at E1/2 = +0.33 V vs. SCE that falls in the SOD potential window of -0.04 V to +0.99 V. These complexes catalytically dismutate superoxide radicals at 298 K in aqueous medium (the IC50 for 1 is 2.15 µM). Electronic absorption spectra (233 K and 298 K), FTIR, ESI mass spectra, CV (233 K and 298 K) and DFT calculations collectively indicate formation of [(L1)2Cu(O2˙(-))](+), [(L1)2Cu(O2(2-))] and [(L1)2Cu(OOH(-))](+) species and help to elucidate the electron transfer mechanism for the SOD function of 1 and 2. Once O2˙(-) binds to Cu(II) (evident at 233 K), the first step of the catalytic cycle (Cu(II) + O2˙(-)→ Cu(I) + O2) does not follow but the second step (Cu(I) + O2˙(-) + 2H(+)→ H2O2 + Cu(II)) does follow. Therefore, the catalytic disproportionation of superoxide radicals via1 and 2 at 298 K indicates that the first and second steps of the catalytic cycle proceed through outer and inner sphere electron transfer mechanisms, respectively. Feasibility of the first step to occur in pure aprotic solvent (where 18-crown-6-ether is used to solubilise KO2) was tested and also supports the same notion of the electron transfer mechanisms as stated above.

Copper coordinated ligand thioether-S and NO2(-) oxidation: relevance to the CuM site of hydroxylases.

In order to gain insight into the coordination site and oxidative activity of the CuM site of hydroxylases such as peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine ß-monooxygenase (DßM), and tyramine ß-monooxygenase (TßM), we have synthesized, characterized and studied the oxidation chemistry of copper complexes chelated by tridentate N2Sthioether, N2Osulfoxide or N2Osulfone donor sets. The ligands are those of N-2-methylthiophenyl-2'-pyridinecarboxamide (HL1), and the oxidized variants, N-2-methylsulfenatophenyl-2'-pyridinecarboxamide (HL1(SO)), and N-2-methylsulfinatophenyl-2'-pyridinecarboxamide (HL1(SO2)). Our studies afforded the complexes [(L1)Cu(II)(H2O)](ClO4)·H2O (1·H2O), {[(L1(SO))Cu(II)(CH3CN)](ClO4)}n (2), [(L1)Cu(II)(ONO)] (3), [(L1(SO))Cu(II)(ONO)]n (4), [(L1)Cu(II)(NO3)]n (5), [(L1(SO))Cu(II)(NO3)]n (6) and [(L1(SO2))Cu(II)(NO3)] (7). Complexes 1 and 3 were described in a previous publication (Inorg. Chem., 2013, 52, 11084). The X-ray crystal structures revealed either distorted octahedral (in 2, 4-6) or square-pyramidal (in 1, 3) coordination geometry around Cu(II) ions of the complexes. In the presence of H2O2, conversion of 1→2, 3-5→6 and 6→7 occurs quantitatively via oxidation of thioether-S and/or Cu(ii) coordinated NO2(-) ions. Thioether-S oxidation of L1 also occurs when [L1](-) is reacted with [Cu(I)(CH3CN)4](ClO4) in DMF under O2, albeit low in yield (20%). Oxidations of thioether-S and NO2(-) were monitored by UV-Vis spectroscopy. Recovery of the sulfur oxidized ligands from their metal complexes allowed for their characterization by elemental analysis, (1)H NMR, FTIR and mass spectrometry.

Hexacoordinate nickel(II)/(III) complexes that mimic the catalytic cycle of nickel superoxide dismutase.

A functional model complex of nickel superoxide dismutase (NiSOD) with a non-peptide ligand which mimics the full catalytic cycle of NiSOD is unknown. Similarly, it has not been fully elucidated whether NiSOD activity is a result of an outer- or inner-sphere electron-transfer mechanism. With this in mind, two octahedral nickel(II)/(III) complexes of a bis-tridentate N2 S donor carboxamide ligand, N-2-phenylthiophenyl-2'-pyridinecarboxamide (HL(Ph)), have been synthesized, structurally characterized, and their SOD activities examined. These complexes mimic the full catalytic cycle of NiSOD. Electrochemical experiments support an outer-sphere electron-transfer mechanism for their SOD activity.

Copper complexes relevant to the catalytic cycle of copper nitrite reductase: electrochemical detection of NO(g) evolution and flipping of NO2 binding mode upon Cu(II) → Cu(I) reduction.

Copper complexes of the deprotonated tridentate ligand, N-2-methylthiophenyl-2'-pyridinecarboxamide (HL1), were synthesized and characterized as part of our investigation into the reduction of copper(II) o-nitrito complexes into the related copper nitric oxide complexes and subsequent evolution of NO(g) such as occurs in the enzyme copper nitrite reductase. Our studies afforded the complexes [(L1)Cu(II)Cl]n (1), [(L1)Cu(II)(ONO)] (2), [(L1)Cu(II)(H2O)](ClO4)·H2O (3·H2O), [(L1)Cu(II)(CH3OH)](ClO4) (4), [(L1)Cu(II)(CH3CO2)]·H2O (5·H2O), and [Co(Cp)2][(L1)Cu(I)(NO2)(CH3CN)] (6). X-ray crystal structure determinations revealed distorted square-pyramidal coordination geometry around Cu(II) ion in 1-5. Substitution of the H2O of 3 by nitrite quantitatively forms 2, featuring the κ(2)-O,O binding mode of NO2(-) to Cu(II). Reduction of 2 generates two Cu(I) species, one with κ(1)-O and other with the κ(1)-N bonded NO2(-) group. The Cu(I) analogue of 2, compound 6, was synthesized. The FTIR spectrum of 6 reveals the presence of κ(1)-N bonded NO2(-). Constant potential electrolysis corresponding to Cu(II) → Cu(I) reduction of a CH3CN solution of 2 followed by reaction with acids, CH3CO2H or HClO4 generates 5 or 3, and NO(g), identified electrochemically. The isolated Cu(I) complex 6 independently evolves one equivalent of NO(g) upon reaction with acids. Production of NO(g) was confirmed by forming [Co(TPP)NO] in CH2Cl2 (λ(max) in CH2Cl2: 414 and 536 nm, ν(NO) = 1693 cm(-1)).

Shuttling of nickel oxidation states in N4S2 coordination geometry versus donor strength of tridentate N2S donor ligands.

Seven bis-Ni(II) complexes of a N(2)S donor set ligand have been synthesized and examined for their ability to stabilize Ni(0), Ni(I), Ni(II) and Ni(III) oxidation states. Compounds 1-5 consist of modifications of the pyridine ring of the tridentate Schiff base ligand, 2-pyridyl-N-(2'-methylthiophenyl)methyleneimine ((X)L1), where X = 6-H, 6-Me, 6-p-ClPh, 6-Br, 5-Br; compound 6 is the reduced amine form (L2); compound 7 is the amide analog (L3). The compounds are perchlorate salts except for 7, which is neutral. Complexes 1 and 3-7 have been structurally characterized. Their coordination geometry is distorted octahedral. In the case of 6, the tridentate ligand coordinates in a facial manner, whereas the remaining complexes display meridional coordination. Due to substitution of the pyridine ring of (X)L1, the Ni-N(py) distances for 1~5 < 3 < 4 increase and UV-vis λ(max) values corresponding to the (3)A(2g)(F)→(3)T(2g)(F) transition show an increasing trend 1~5 < 2 < 3 < 4. Cyclic voltammetry of 1-5 reveals two quasi-reversible reduction waves that correspond to Ni(II)→Ni(I) and Ni(I)→Ni(0) reduction. The E(1/2) for the Ni(II)/Ni(I) couple decreases as 1 > 2 > 3 > 4. Replacement of the central imine N donor in 1 by amine 6 or amide 7 N donors reveals that complex 6 in CH(3)CN exhibits an irreversible reductive response at E(pc) = -1.28 V, E(pa) = +0.25 V vs saturated calomel electrode (SCE). In contrast, complex 7 shows a reversible oxidation wave at E(1/2) = +0.84 V (ΔE(p) = 60 mV) that corresponds to Ni(II)→Ni(III). The electrochemically generated Ni(III) species, [(L3)(2)Ni(III)](+) is stable, showing a new UV-vis band at 470 nm. EPR measurements have also been carried out.

First structural example of a metal uncoordinated mesoionic imidazo[1,5-a]pyridine and its precursor intermediate copper complex: an insight to the catalytic cycle.

Four copper complexes of a tridentate Schiff base ligand, 2-pyridyl-N-(2'-methylthiophenyl) methyleneimine, L(1) have been synthesized. All theses species, namely, [L(1)Cu(2)(SCN)(3)](n) (1), [Cu(SCN)(CH(3)CN)](n) (3), [(L(1))Cu(N(3))(Cl)] (4) and [(L(1))Cu(N(3))(SCN)] (5) have been structurally characterized. Complex 1 in acetonitrile promotes cycloaddition of a Cu(II) bound SCN(-) ion to L(1) that exclusively and stoichiometrically forms a mesoionic imidazo[1,5-a]pyridine, namely, 3-(imino-N'-2-methylthiophenyl)imidazo[1,5-a]pyridinium-1-thiolate (2) and a thiocyanato bridged Cu(i) complex, [Cu(SCN)(CH(3)CN)](n) (3). The X-ray crystal structure of 1 confirms the presence of square-pyramidal Cu(II) and tetrahedral Cu(I) ions in N(3)S(2) and N(2)S(2) coordination environments, respectively, bridged to each other via thiocyanate anion. The Cu(II) ions are bonded to a tridentate ligand L(1) and two SCN(-) ions occupy the remaining equatorial and an axial coordination site to adopt a square-pyramidal coordination geometry. To investigate which SCN(-) ion, axially or equatorially bound to Cu(II) center, underwent cycloaddition to L(1) to form 2, two mononuclear Cu(II) complexes 4 and 5 have been synthesized and their reactivity towards externally added KSCN was studied. The molecular structures of 4 and 5 feature a meridionally bound L(1) and an azide ion (N(3)(-)) in the square plane, while a Cl(-) or SCN(-) ion are occupying the axial site, respectively, to fulfill square-pyramidal coordination geometry. Complex 4 reacts with SCN(-) ion to form 5. That an MeCN solution of 5 itself, or of 5 in the presence of KSCN, does not produce 2, supports that possibly the Cu(II) bound equatorial SCN(-) ion is responsible for cycloaddition to L(1). Dark purple solid 2 has also been prepared (turnover number ~4 or 41% yield) efficiently following an alternative and easier one-pot synthesis procedure, that is from a mixture of KSCN and L(1) in the presence of a catalytic amount of anhydrous CuCl(2) (10 mol%) in MeCN in air. The X-ray crystal structure, (1)H NMR spectrum and solution conductivity measurements strongly support that 2 is mesoionic. An MeCN solution of 2 fluoresces at room temperature upon excitation at 240 nm with an emission maximum λ(em) at 470 nm, associated with a quantum yield of 0.16 with respect to a standard Rhodamine-6G fluorophore.

Ruthenium nitrosyls derived from polypyridine ligands with carboxamide or imine nitrogen donor(s): isoelectronic complexes with different NO photolability.

As part of our search for photoactive ruthenium nitrosyls, a set of {RuNO}6 nitrosyls has been synthesized and structurally characterized. In this set, the first nitrosyl [(SBPy3)Ru(NO)](BF4)3 (1) is derived from a polypyridine Schiff base ligand SBPy3, while the remaining three nitrosyls are derived from analogous polypyridine ligands containing either one ([(PaPy3)Ru(NO)](BF4)2 (2)) or two ([(Py3P)Ru(NO)]BF4 (3) and [(Py3P)Ru(NO)(Cl)] (4)) carboxamide group(s). The coordination structures of 1 and 2 are very similar except that in 2, a carboxamido nitrogen is coordinated to the ruthenium center in place of an imine nitrogen in case of 1. In 3 and 4, the ruthenium center is coordinated to two carboxamido nitrogens in the equatorial plane and the bound NO is trans to a pyridine nitrogen (in 3) and chloride (in 4), respectively. Complexes 1-3 contain N6 donor set, and the NO stretching frequencies (nuNO) correlate well with the N-O bond distances. All four diamagnetic {RuNO}(6) nitrosyls are photoactive and release NO rapidly upon illumination with low-intensity (5-10 mW) UV light. Interestingly, photolysis of 1 generates the diamagnetic Ru(II) photoproduct [(SBPy3)Ru(MeCN)](2+) while 2-4 afford paramagnetic Ru(III) species in MeCN solution. The quantum yield values of NO release under UV illumination (lambda(max) = 302 nm) lie in the range 0.06-0.17. Complexes 3 and 4 also exhibit considerable photoactivity under visible light. The efficiency of NO release increases in the order 2 < 3 < 4, indicating that photorelease of NO is facilitated by (a) the increase in the number of coordinated carboxamido nitrogen(s) and (b) the presence of negatively charged ligands (like chloride) trans to the bound NO.

Biological activity of designed photolabile metal nitrosyls: light-dependent activation of soluble guanylate cyclase and vasorelaxant properties in rat aorta.

The biological and pharmacological utility of nitric oxide (NO) has led to the development of many classes of NO-donor compounds as both research tools and therapeutic agents. Many donors currently in use rely on thermal decomposition or bioactivation for the release of NO. We have developed several photolabile metal-nitrosyl donors that release NO when exposed to either visible or UV light. Herein, we show that these donors are capable of activating the primary "NO receptor", soluble guanylate cyclase (sGC), in a light-dependent fashion leading to increases in cGMP. Moreover, we demonstrate that these donors are capable of eliciting light-dependent increases of cGMP in smooth muscle cells and vasorelaxation of rat aortic smooth muscle tissue, all effects that are attributed to activation of sGC. The potential utility of these compounds as drugs and/or research tools is discussed.

Electronic structure of mononuclear bis(1,2-diaryl-1,2-ethylenedithiolato)iron complexes containing a fifth cyanide or phosphite ligand: a combined experimental and computational study.

A series of mononuclear square-based pyramidal complexes of iron containing two 1,2-diaryl-ethylene-1,2-dithiolate ligands in various oxidation levels has been synthesized. The reaction of the dinuclear species [Fe(III)2(1L*)2(1L)2]0, where (1L)2- is the closed shell di-(4-tert-butylphenyl)-1,2-ethylenedithiolate dianion and (1L*)1- is its one-electron-oxidized pi-radical monoanion, with [N(n-Bu)4]CN in toluene yields dark green crystals of mononuclear [N(n-Bu)4][Fe(II)(1L*)2(CN)] (1). The oxidation of 1 with ferrocenium hexafluorophosphate yields blue [Fe(III)(1L*)2(CN)] (1ox), and analogously, a reduction with [Cp2Co] yields [Cp2Co][N(n-Bu)4][Fe(II)(1L*)(1L)(CN)] (1red); oxidation of the neutral dimer with iodine gives [Fe(III)(1L*)2I] (2). The dimer reacts with the phosphite P(OCH3)3 to yield [Fe(II)(1L*)2{P(OCH3)3}] (3), and [Fe(III)2(3L*)2(3L)2] reacts with P(OC6H5)3 to give [Fe(II)(3L*)2{P(OC6H5)3}] (4), where (3L)2- represents 1,2-diphenyl-1,2-ethylenedithiolate(2-). Both 3 and 4 were electrochemically one-electron oxidized to the monocations 3ox and 4ox and reduced to the monoanions 3red and 4red. The structures of 1 and 4 have been determined by X-ray crystallography. All compounds have been studied by magnetic susceptibility measurements, X-band EPR, UV-vis, IR, and Mössbauer spectroscopies. The following five-coordinate chromophores have been identified: (a) [Fe(III)(L*)2X]n, X = CN-, I- (n = 0) (1ox, 2); X = P(OR)3 (n = 1+) )3ox, 4ox) with St = 1/2, SFe = 3/2; (b) [Fe(II)(L*)2X]n, X = CN-, (n = 1-) (1); X = P(OR)3 (n = 0) (3, 4) with St = SFe = 0; (c) [Fe(II)(L*)(L)X]n <--> [Fe(II)(L)(L*)X]n, X = CN- (n = 2-) (1red); X = P(OR)3 (n = 1-) (3red, 4red) with St = 1/2, SFe = 0 (or 1). Complex 1ox displays spin crossover behavior: St = 1/2 <--> St = 3/2 with intrinsic spin-state change SFe = 3/2 <--> SFe = 5/2. The electronic structures of 1 and 1(ox) have been established by density functional theoretical calculations: [Fe(II)(1L*)2(CN)]1- (SFe = 0, St = 0) and [Fe(III)(1L*)2(CN)]0 (SFe = 3/2, St = 1/2).

Dinuclear Bis(1,2-diaryl-1,2-ethylenedithiolato)iron complexes: [FeIII2(L)4]n (n = 2-, 1-, 0, 1+).

The electronic structures of four members of the electron-transfer series [Fe2(1L)4]n (n = 2-, 1-, 0, 1+) have been elucidated in some detail by electronic absorption, IR, X-band electron paramagnetic resonance (EPR), and Mössbauer spectroscopies where (1L)(2-) represents the ligand 1,2-bis(4-tert-butylphenyl)-1,2-ethylenedithiolate(2-) and (1L*)- is its pi-radical monoanion. It is conclusively shown that all redox processes are ligand-centered and that high-valent iron(IV) is not accessible. The following complexes have been synthesized: [FeIII2(1L*)2(1L)2]0 (1), [FeIII2(2L*)2(2L)2].2CH2Cl2 (1') where (2L)(2-) is 1,2-bis(p-tolyl)-1,2-ethylenedithiolate(2-) and (2L*)- represents its pi-radical monoanion, [Cp2Co][FeIII2(1L*))(1L)3].4(toluene).0.5Et2O (2), and [Cp2Co]2[FeIII2(1L)4].2(toluene) (3). The crystal structures of 1' and 2 have been determined by single-crystal X-ray crystallography at 100 K. The ground states of complexes have been determined by temperature-dependent magnetic susceptibility measurements and EPR spectroscopy: 1' and 1 are diamagnetic (S(t) = 0); 2 (S(t) = 1/2); 3 (S(t) = 0); the monocation [Fe(III)2(1L*)3(1L)]+ possesses an S(t) = 1/2 ground state (S(t) = total spin ground state of dinuclear species). All species contain pairs of intermediate-spin ferric ions (S(Fe) = 3/2), which are strongly antiferromagnetically coupled (H = -2JS(1).S(2), where S1 = S2 = 3/2 and J = approximately -250 cm(-1)).

Synthesis, structure, and properties of an Fe(II) carbonyl [(PaPy3)Fe(CO)](ClO4): insight into the reactivity of Fe(II)-CO and Fe(II)-NO moieties in non-heme iron chelates of N-donor ligands.

An Fe(II) carbonyl complex [(PaPy3)Fe(CO)](ClO4) (1) of the pentadentate ligand N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide (PaPy3H, H is the dissociable amide proton) has been synthesized and structurally characterized. This Fe(II) carbonyl exhibits its nu(CO) at 1972 cm(-1), and its 1H NMR spectrum in degassed CD3CN confirms its S = 0 ground state. The bound CO in 1 is not photolabile. Reaction of 1 with an equimolar amount of NO results in the formation of the {Fe-NO}7 nitrosyl [(PaPy3)Fe(NO)](ClO4) (2), while excess NO affords the iron(III) nitro complex [(PaPy3)Fe(NO2)](ClO4) (5). In the presence of [Fe(Cp)2]+ and excess NO, 1 forms the {Fe-NO}6 nitrosyl [(PaPy3)Fe(NO)](ClO4)2 (3). Complex 1 also reacts with dioxygen to afford the iron(III) mu-oxo species [{(PaPy3)Fe}2O](ClO4)2 (4). Comparison of the metric and spectral parameters of 1 with those of the previously reported {Fe-NO}6,7 nitrosyls 3 and 2 provides insight into the electronic distributions in the Fe(II)-CO, Fe(II)-NO, and Fe(II)-NO+ bonds in the isostructural series of complexes 1-3 derived from a non-heme polypyridine ligand with one carboxamide group.

Light-induced inhibition of papain by a {Mn-NO}6 nitrosyl: identification of papain-SNO adduct by mass spectrometry.

Modification of Cys25 at the active site of the cysteine protease papain by S-nitrosylation inhibits its hydrolytic ability. Previous studies have demonstrated that NO donors N-nitrosoanilines inhibit papain activity via formation of S-NO bond formation at the active site while NO donors such as S-nitroso-N-acetyl-penicillamine (SNAP), N-nitrosoaniline derivatives, and S-nitroso-glutathione (GSNO) inhibit the enzyme via S-thiolation by thiyl radicals generated from the S-nitrosothiols. In this study, we report papain inactivation by a photosensitive {Mn-NO}(6) nitrosyl [(PaPy(3))Mn(NO)](ClO(4)) (1) where PaPy(3)(-) is the anion of the designed ligand N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide. This nitrosyl releases NO upon exposure to visible light of low intensity (50W tungsten lamp). With N(alpha)-benzoyl-l-arginine-p-nitroanilide (l-BApNA) as the substrate, the dissociation constant for the breakdown of the enzyme-inactivator complex (K(I)) and the overall inactivation rate constant (k(i)) were calculated to be 2.46mM and 64.8min(-1), respectively. The papainS-NO adduct has been identified using electrospray mass spectrometry (ESI-MS). The results demonstrate that controlled inactivation of papain can be achieved with the {Mn-NO}(6) nitrosyl 1 and light. The reaction is clean and the extent of inactivation is directly proportional to the exposure time.

Syntheses, structures, and reactivities of (Fe-NO)6 nitrosyls derived from polypyridine-carboxamide ligands: photoactive NO-donors and reagents for S-nitrosylation of alkyl thiols.

Two new iron nitrosyls derived from two designed pentadentate ligands N,N-bis(2-pyridylmethyl)-amine-N'-(2-pyridylmethyl)acetamide and N,N-bis(2-pyridylmethyl)-amine-N'-[1-(2-pyridinyl)ethyl]acetamide (PcPy(3)H and MePcPy(3)H, respectively, where H is the dissociable amide proton) have been structurally characterized. These complexes are similar to a previously reported (Fe-NO)6 complex, [(PaPy(3))Fe(NO)](ClO(4))(2) (1) that releases NO under mild conditions. The present nitrosyls, namely [(PcPy(3))Fe(NO)](ClO(4))(2) (2) and [(MePcPy(3))Fe(NO)](ClO(4))(2) (3), belong to the same (Fe-NO)6 family and exhibit (a) clean (1)H NMR spectra in CD(3)CN indicating S = 0 ground state, (b) almost linear Fe-N-O angles (177.3(5) degrees and 177.6(4) degrees for 2 and 3, respectively), and (c) N-O stretching frequencies (nu(NO)) in the range 1900-1925 cm(-)(1). The binding of NO at the non-heme iron centers of 1-3 is completely reversible and all three nitrosyls rapidly release NO when exposed to light (50 W tungsten bulb). In addition to acting as photoactive NO-donors, these complexes also nitrosylate thiols such as N-acetylpenicillamine, 3-mercaptopropionic acid, and N-acetyl-cysteine-methyl-ester in yields that range from 30 to 90% in the absence of light. The addition of alkyl or aryl thiolate (RS(-)) to the (Fe-NO)6 complexes in the absence of dioxygen results in the reduction of the iron metal center to afford the corresponding (Fe-NO)7 species.