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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 β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM), 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.

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)).

Two new manganese complexes derived from the pentadentate ligand N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-quinoline-2-carboxamide, PaPy2QH, where H is dissociable proton), namely, [Mn(PaPy2Q)(NO)]ClO4 (2) and [Mn(PaPy2Q)(OH)]ClO4 (3), have been synthesized and structurally characterized. The Mn(III) complex [Mn(PaPy2Q)(OH)]ClO4 (3), though insensitive to dioxygen, reacts with nitric oxide (NO) to afford the nitrosyl complex [Mn(PaPy2Q)(NO)]ClO4 (2) via reductive nitrosylation. This diamagnetic {Mn-NO}6 nitrosyl exhibits nuNO at 1725 cm-1 and is highly soluble in water, with lambdamax at 500 and 670 nm. Exposure of solutions of 2 to near-infrared (NIR) light (810 nm, 4 mW) results in bleaching of the maroon solution and detection of free NO by an NO-sensitive electrode. The quantum yield of 2 (Phi = 0.694 +/- 0.010, lambdairr = 550 nm, H2O) is much enhanced over the first generation {Mn-NO}6 nitrosyl derived from analogous polypyridine ligand, namely, [Mn(PaPy3)(NO)]ClO4 (1, Phi = 0.385 +/- 0.010, lambdairr = 550 nm, H2O), reported by this group in a previous account. Although quite active in the visible range (500-600 nm), 1 exhibits very little photoactivity under NIR light. Both 1 and 2 have been incorporated into sol-gel (SG) matrices to obtain nitrosyl-polymer composites 1.SG and 2.SG. The NO-donating capacities of the polyurethane-coated hybrid materials 1.HM and 2.HM have been determined. 2.HM has been used to transfer NO to reduced myoglobin with 780 nm light. The various strategies for synthesizing photosensitive metal nitrosyls have been discussed to establish the merits of the present approach. The results of the present study confirm that proper ligand design is a very effective way to isolate photoactive manganese nitrosyls that could be used to deliver NO to biological targets under the control of NIR light.

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.

An Fe(III) nitro complex [(bpb)Fe(NO2)(py)] (2) of the tetradentate ligand 1,2-bis(pyridine-2-carboxamido)benzene (H2bpb, H is the dissociable amide proton) has been synthesized via addition of NaNO2 to [(bpb)Fe(py)2](ClO4) (1) in MeCN or DMF. This structurally characterized Fe(III) nitro complex exhibits its nuNO2 at 1384 cm(-1). The reaction of 1 with 2 equiv of Et4NX (X = Cl-, Br-) affords the high-spin complexes (Et4N)[(bpb)Fe(Cl2)] (3) and (Et4N)[(bpb)Fe(Br)2] (4), respectively. The structure of 4 has been determined. The addition of an equimolar amount of Et4NCl, Et4NBr, or Et4NCN to a solution of 2 affords the mixed-ligand complexes (Et4N)[(bpb)Fe(NO2)(Cl)] (5), (Et4N)[(bpb)Fe(NO2)(Br)] (6), and (Et4N)[(bpb)Fe(NO2)(CN)] (7), respectively. These complexes are all low spin with isotropic g values of 2.15. Under anaerobic conditions, the reactions of 5-7 with Ph3P in MeCN afford the five-coordinate {Fe-NO}7 nitrosyl [(bpb)Fe(NO)] (and Ph3PO) via secondary oxygen-atom (O-atom) transfer. The O-atom transfer to Ph3P by 5-7 becomes catalytic in the presence of dioxygen with transfer rates in the range of 1.70-13.59 x 10-3 min(-1). The O-atom transfer rates and turnover numbers (5 > 6 > 7) are reflective of the strength of the axial donors (Cl- > Br- > CN-). The catalytic efficiencies of complexes 5-7 are limited due to formation of the thermodynamic end products [(bpb)Fe(X)2]- (where X = Cl- for 5, Br- for 6, and CN- for 7).

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.

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.

Four ruthenium nitrosyls, namely [(bpb)Ru(NO)(Cl)] (1), [(Me(2)bpb)Ru(NO)(Cl)] (2), [(Me(2)bpb)Ru(NO)(py)](BF(4)) (3), and [(Me(2)bqb)Ru(NO)(Cl)] (4) (H(2)bpb = 1,2-bis(pyridine-2-carboxamido)benzene, H(2)Me(2)bpb = 1,2-bis(pyridine-2-carboxamido)-4,5-dimethylbenzene, H(2)Me(2)bqb = 1,2-bis(quinaldine-2-carboxamido)-4,5-dimethylbenzene; H is the dissociable amide proton), have been synthesized and characterized by spectroscopy and X-ray diffraction analysis. All four complexes exhibit nu(NO) in the range 1830-1870 cm(-)(1) indicating the [Ru-NO](6) configuration. Clean (1)H NMR spectra in CD(3)CN (or (CD(3))(2)SO) confirm the S = 0 ground state for all four complexes. Although the complexes are thermally stable, they release NO upon illumination. Rapid NO dissociation occurs when solutions of 1-3 in acetonitrile (MeCN) or DMF are exposed to low-intensity (7 mW) UV light (lambda(max) = 302 nm). Electron paramagnetic resonance (EPR) spectra of the photolyzed solutions display anisotropic signals at g approximately 2.00 that confirm the formation of solvated low-spin Ru(III) species upon NO release. The ligand trans to bound NO namely, anionic Cl(-) and neutral pyridine, has significant effect on the electronic and NO releasing properties of these complexes. Change in the in-plane ligand strength also has effects on the rate of NO release. The absorption maximum (lambda(max)) of 4 is significantly red shifted (455 nm in DMF) compared to the lambda(max) values of 1-3 (380-395 nm in DMF) due to the extension of conjugation on the in-plane ligand frame. As a consequence, 4 is also sensitive to visible light and release NO (albeit at a slower rate) upon illumination to low-intensity visible light (lambda > 465 nm). Collectively, the photosensitivity of the present series of ruthenium nitrosyls demonstrates that the extent of NO release and their wavelength dependence can be modulated by changes of either the in-plane or the axial ligand (trans to bound NO) field strength.

The Mn(II) and Mn(III) complexes of the pentadentate ligand N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide (PaPy3H; H is the dissociable carboxamide H), namely, [Mn(PaPy3)(H2O)]ClO4 (1) and [Mn(PaPy3)(Cl)]ClO4 (2), with bound carboxamido nitrogen have been isolated and characterized. The high-spin Mn(II) center in 1 is very sensitive to dioxygen, and this complex is rapidly converted into 2 upon reaction with Cl- in air. The bound carboxamido nitrogen in 1 is responsible for this sensitivity toward oxidation since the analogous Schiff base complex [Mn(SBPy3)Cl]ClO4 (4) is very resistant to oxidation. Reaction of NO with 1 affords the diamagnetic [Mn-NO]6 nitrosyl [Mn(PaPy3)(NO)]ClO4 (5). Complexes with no bound carboxamido nitrogen such as 4 and [Mn(PaPy3H)(Cl)2] (3) do not react with NO. No reaction with NO is observed with the Mn(III) complexes 2 and [Mn(PaPy3)(MeCN)]2+ either. Collectively these reactions indicate that NO reacts only with the Mn(II) center ligated to at least one carboxamido nitrogen. Both the carbonyl and N-O stretching frequencies (nu(CO) and nu(NO)) of the present and related complexes strongly suggest a [low-spin Mn(II)-NO*] formulation for 5. The alternative description [low-spin Mn(I)-NO+] is not supported by the spectroscopic and redox behavior of 5. Complex 5 is the first example of a [Mn-NO]6 nitrosyl that exhibits photolability of NO upon illumination with low-intensity tungsten lamps in solvents such as MeCN and H2O. The rapid NO loss from 5 leads to the formation of the corresponding solvato species [Mn(PaPy3)(MeCN)]2+ under aerobic conditions. Oxidation of 5 with (NH4)2[Ce(NO3)6] in MeCN affords the highly reactive paramagnetic (S = 1/2) [MnNO]5 nitrosyl [Mn(PaPy3)(NO)](NO3)2 (6) in high yield. Spectroscopic and magnetic studies confirm a [low-spin Mn(II)-NO+] formulation for 6. The N-O stretching frequencies (nu(NO)) of 5, 6, and analogous nitrosyls reported by other groups collectively suggest that nu(NO) is a better indicator of the oxidation state of NO (NO+, NO*, or NO-) in non-heme iron and other transition-metal complexes with bound NO.

Reaction of excess NO with the non-heme Fe(III) complex [(bpb)Fe(py)2]ClO4 in MeCN under strictly anaerobic conditions affords the {Fe-NO}6(nitro)(nitrosyl) complex [(bpb)Fe(NO)(NO2)] (1) via metal-promoted NO disproportionation, while in a MeOH/MeCN mixture, the same reaction leads to reductive nitrosylation and generation of the {Fe-NO}7 species [(bpb)Fe(NO)] (2). Exposure of a solution of 1 in DMF to dioxygen leads to formation of the ring-nitrosylated product [(bpb-NO2)Fe(NO3)(DMF)] (3). The present system therefore exhibits all the NO reactivities reported so far with the iron-porphyrins.

Three iron complexes of a pentadentate ligand N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide (PaPy(3)H, H is the dissociable amide proton) have been synthesized. All three species, namely, two nitrosyls [(PaPy(3))Fe(NO)](ClO(4))(2) (2) and [(PaPy(3))Fe(NO)](ClO(4)) (3) and one nitro complex [(PaPy(3))Fe(NO(2))](ClO(4)) (4), have been structurally characterized. These complexes provide the opportunity to compare the structural and spectral properties of a set of isostructural [Fe-NO](6,7) complexes (2 and 3, respectively) and an analogous genuine Fe(III) complex with an "innocent" sixth ligand ([(PaPy(3))Fe(NO(2))](ClO(4)), 4). The most striking difference in the structural features of 2 and 3 is the Fe-N-O angle (Fe-N-O = 173.1(2) degrees in the case of 2 and 141.29(15) degrees in the case of 3). The clean (1)H NMR spectrum of 2 in CD(3)CN reveals its S = 0 ground state and confirms its [Fe-NO](6) configuration. The binding of NO at the non-heme iron center in 2 is completely reversible and the bound NO is photolabile. Mössbauer data, electron paramagnetic resonance signal at g approximately 2.00, and variable temperature magnetic susceptibility measurements indicate the S = (1)/(2) spin state of the [Fe-NO](7) complex 3. Analysis of the spectroscopic data suggests Fe(II)-NO(+) and Fe(II)-NO(*) formulations for 2 and 3, respectively. The bound NO in 3 does not show any photolability. However, in MeCN solution, it reacts rapidly with dioxygen to afford the nitro complex 4, which has also been synthesized independently from [(PaPy(3))Fe(MeCN)](2+) and NO(2)(-). Nucleophilic attack of hydroxide ion to the N atom of the NO ligand in 2 in MeCN in the dark gives rise to 4 in high yield.

Exposure of a pyridine solution of (py)2Fe(OEPO) (1) (OEPO is the trianion of octaethyloxophlorin, py is pyridine) at 22 degrees C to nitric oxide under the strict exclusion of dioxygen results in a color change from green to red-brown and the formation of {(py)(ON)Fe(OEPO)}2 (2). Monitoring the reaction by 1H NMR spectroscopy shows that the reaction is reversible. The air-sensitive product {(py)(ON)Fe(OEPO)}2 has been isolated and characterized by X-ray crystallography. NO binding is accompanied by association of two hemes through the formation of a new C-C bond between two meso carbon atoms on the porphyrin periphery. The macrocyclic ligand has a ruffled distortion that positions the C5-O1 group with its short C=O bond distance (1.237(3) A) in close proximity to the NO ligand. Since further attack upon 1 by O2 during heme degradation involves reaction in the vicinity of the oxygenated meso position, the positioning of the NO ligand so that the O2...C5 distance is only 3.100(3) A presents a highly suggestive model for the next stage of attack upon the heme periphery.