Reductive nitrosylation and proton-assisted bridge splitting of a (mu-oxo)dimanganese(III) complex derived from a polypyridine ligand with one carboxamide group

Aerobic oxidation of the Mn(II) complex [Mn(Papy3)(H2O)](ClO4) (1, PaPy3- is the anion of the designed ligand N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide) in acetonitrile affords the (mu-oxo)dimanganese(III) complex [(Mn(PaPy3))2(mu-O)](ClO4)2 (3) in high yield. The unsupported single oxo bridge between the two high-spin Mn(III) centers in 3 is readily cleaved upon addition of proton sources such as phenol, acetic acid, and benzoic acid, and complexes of the type [Mn(PaPy3)(L)](ClO4) (5, L = PhO-; 6, L = AcO-; 7, L = BzO-) are formed. The basicity of the bridge is evident by the fact that simple addition of methanol to a solution of 3 in acetonitrile affords the methoxide complex [Mn(PaPy3)(OMe)](ClO4) (4). The structures of 3-5 and 7 have been determined. Passage of NO through a solution of 3 in acetonitrile produces the [Mn-NO]6 nitrosyl [Mn(PaPy3)(NO)](ClO4) (2) via reductive nitrosylation. Complexes 4-7 also afford the [Mn-NO]6 nitrosyl 2 upon reaction with NO. In the latter case, the anionic O-based ligands (such as MeO- and PhO-) act as built-in bases and promote reductive nitrosylation of the Mn(III) complexes.     

Formation of a triply bridged mu-oxo diiron(III) core stabilized by two deprotonated carboxamide groups upon photorelease of NO from a [Fe-NO]6 iron nitrosyl

The iron nitrosyl [(PaPy2Q)Fe(NO)](ClO4)2 (2), derived from the quinoline-based ligand PaPy2QH (N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-quinoline-2-carboxamide, where H is dissociable proton) has been characterized by spectroscopy and X-ray diffraction techniques. The 1H NMR spectrum (S = 0 ground state) and v(NO) value of 1885 cm(-1) indicate that 2 is a [Fe-NO]6 nitrosyl. Although 2 is stable in the dark, exposure of an acetonitrile solution of 2 (lambdamax = 510 nm) to light in the visible range causes rapid release of NO and formation of the solvato species [(PaPy2Q)Fe(MeCN)](ClO4)2 (6). Quantum yield (Phi) measurements indicate that 2 is a more efficient NO donor (Phi = 0.258) than [(PaPy3)Fe(NO)](ClO4)2 (1, Phi = 0.185), a complex derived from a similar but pyridine-based ligand. Interestingly, when the photoproduct 6 is exposed to water or a small amount of base, the triply bridged diiron(III) species [(PaPy2Q)FeOFe(PaPy2Q)](ClO4)2 (3) forms in good yield. This species can be independently synthesized from aerobic oxidation of the Fe(II) species [(PaPy2Q)Fe(MeCN)](ClO4) in acetonitrile. The structure of 3 reveals a unique Fe(III)-O-Fe(III) link supported by two (eta2,mu2)mu-NCO bridges derived from the carboxamido groups of the two (PaPy2Q)Fe(III) moieties.     

Release of nitric oxide from a sol-gel hybrid material containing a photoactive manganese nitrosyl upon illumination with visible light

A polyurethane-coated sol-gel material containing the photoactive Mn nitrosyl [Mn(PaPy3)(NO)]ClO4 rapidly releases NO with high quantum efficiency when exposed to visible light of low intensity. This rigid and strongly colored hybrid material is a convenient point source of NO that can only be triggered with light. Successful delivery of NO to biological targets, such as proteins, by this material has also been demonstrated.     

Mechanism of NO photodissociation in photolabile manganese-NO complexes with pentadentate N5 ligands

The Mn-nitrosyl complexes [Mn(PaPy(3))(NO)](ClO(4)) (1; PaPy(3)(-) = N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide) and [Mn(PaPy(2)Q)(NO)](ClO(4)) (2, PaPy(2)Q(-) = N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-quinoline-2-carboxamide) show a remarkable photolability of the NO ligand upon irradiation of the complexes with UV-vis-NIR light [Eroy-Reveles, A. A.; Leung, Y.; Beavers, C. M.; Olmstead, M. M.; Mascharak, P. K. J. Am. Chem. Soc. 2008, 130, 4447]. Here we report detailed spectroscopic and theoretical studies on complexes 1 and 2 that provide key insight into the mechanism of NO photolabilization in these compounds. IR- and FT-Raman spectroscopy show N-O and Mn-NO stretching frequencies in the 1720-1750 and 630-650 cm(-1) range, respectively, for these Mn-nitrosyls. The latter value for ν(Mn-NO) is one of the highest transition-metal-NO stretching frequencies reported to this date, indicating that the Mn-NO bond is very strong in these complexes. The electronic structure of 1 and 2 is best described as Mn(I)-NO(+), where the Mn(I) center is in the diamagnetic low-spin state and the NO(+) ligand forms two very strong π backbonds with the d(xz) and d(yz) orbitals of the metal. This explains the very strong Mn-NO bonds observed in these complexes, which even supersede the strengths of the Fe- and Ru-NO bonds in analogous (isoelectronic) Fe/Ru(II)-NO(+) complexes. Using time-dependent density functional theory (TD-DFT) calculations, we were able to assign the electronic spectra of 1 and 2, and to gain key insight into the mechanism of NO photorelease in these complexes. Upon irradiation in the UV region, NO is released because of the direct excitation of d(π)_π* → π*_d(π) charge transfer (CT) states (direct mechanism), which is similar to analogous NO adducts of Ru(III) and Fe(III) complexes. These are transitions from the Mn-NO bonding (d(π)_π*) into the Mn-NO antibonding (π*_d(π)) orbitals within the Mn-NO π backbond. Since these transitions lead to the population of Mn-NO antibonding orbitals, they promote the photorelease of NO. In the case of 1 and 2, further transitions with distinct d(π)_π* → π*_d(π) CT character are observed in the 450-500 nm spectral range, again promoting photorelease of NO. This is confirmed by resonance Raman spectroscopy, showing strong resonance enhancement of the Mn-NO stretch at 450-500 nm excitation. The extraordinary photolability of the Mn-nitrosyls upon irradiation in the vis-NIR region is due to the presence of low-lying d(xy) → π*_d(π) singlet and triplet excited states. These have zero oscillator strengths, but can be populated by initial excitation into d(xy) → L(Py/Q_π*) CT transitions between Mn and the coligand, followed by interconversion into the d(xy) → π*_d(π) singlet excited states. These show strong spin-orbit coupling with the analogous d(xy) → π*_d(π) triplet excited states, which promotes intersystem crossing. TD-DFT shows that the d(xy) → π*_d(π) triplet excited states are indeed found at very low energy. These states are strongly Mn-NO antibonding in nature, and hence, promote dissociation of the NO ligand (indirect mechanism). The Mn-nitrosyls therefore show the long sought-after potential for easy tunability of the NO photorelease properties by simple changes in the coligand.     

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.     

A new approach for studying fast biological reactions involving nitric oxide: generation of NO using photolabile ruthenium and manganese NO donors

Nitric oxide (NO) is recognized as one of the major players in various biochemical processes, including blood pressure, neurotransmission and immune responses. However, experimental studies involving NO are often limited by difficulties associated with the use of NO gas, including its toxicity and precise control over NO concentration. Moreover, the reactions of NO with biological molecules, which frequently occur on time scales of microseconds or faster, are limited by the millisecond time scale of conventional stopped-flow techniques. Here we present a new approach for studying rapid biological reactions involving NO. The method is based on designed ruthenium and manganese nitrosyls, [Ru(PaPy3)(NO)](BF4)2 and [Mn(PaPy3)(NO)](ClO4) (PaPy3H = N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide), which upon photolysis produce NO on a fast time scale. The kinetics of the binding of the photogenerated NO to reduced cytochrome c oxidase (CcO) and myoglobin (Mb) was investigated using time-resolved optical absorption spectroscopy. The NO was found to bind to reduced CcO with an apparent lifetime of 77 micros using the [Mn(PaPy3)(NO)]+ complex; the corresponding rate is 10-20 times faster than can be detected by conventional stopped-flow methods. Second-order rate constants of approximately 1 x 10(8) M(-1) s(-1) and approximately 3 x 10(7) M(-1) s(-1) were determined for NO binding to reduced CcO and Mb, respectively. The generation of NO by photolysis of these complexes circumvents the rate limitation of stopped-flow techniques and offers a novel alternative to study other fast biological reactions involving NO.     

Light-triggered eradication of Acinetobacter baumannii by means of NO delivery from a porous material with an entrapped metal nitrosyl

A photoactive manganese nitrosyl, namely [Mn(PaPy(3))(NO)](ClO(4)) ({Mn-NO}), has been loaded into the columnar pores of an MCM-41 host. Strong interaction between the polar nitrosyl and the -OH groups on the host wall leads to excellent entrapment of the NO donor within the porous host. With the aluminosilicate-based host (Al-MCM-41), the loading is further enhanced due to electrostatic interaction of the cationic species with the aluminum sites. The extent of loading has been determined via analytical techniques including N(2) adsorption/desorption isometry. Powder X-ray diffraction studies on the loaded materials afford patterns typical of an ordered mesoporous silicate consisting of a hexagonal array of unidimensional channels (with slight loss of crystallinity). Elemental mapping of the loaded particles confirms the incorporation of {Mn-NO} into the porous MCM-41 structure and attests to the homogeneity of the guest molecule distribution throughout individual particles. When suspensions of the loaded materials in saline solution are exposed to low-power (10-100 mW) visible light, rapid release of NO is observed. With continuous exposure, a steady release of 50-80 μM of NO is attained with 5 mg of material/mL buffer within 5 min, and the NO flux is maintained for a period of ~60 min. Rapid bursts of 5-10 μM NO are noted with short light pulses. Loss of either the nitrosyl or its photoproduct(s) from these materials in biological media is minimal over long periods of time. The NO release profiles suggest potential use of these powdery biocompatible materials as NO donors where the delivery of NO (a strong antibiotic) could be controlled via the exposure of light. Such prediction has been confirmed with the successful eradication of both drug-susceptible and drug-resistant Acinetobacter baumannii in a soft-tissue infection model through light-triggered NO delivery.     

Iron nitrosyls of a pentadentate ligand containing a single carboxamide group: syntheses, structures, electronic properties, and photolability of NO

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. M?ssbauer 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.     

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.     

Sensitization of ruthenium nitrosyls to visible light via direct coordination of the dye resorufin: trackable NO donors for light-triggered NO delivery to cellular targets

Three nitrosyl-dye conjugates, namely, [(Me 2bpb)Ru(NO)(Resf)] ( 1-Resf), [(Me 2bQb)Ru(NO)(Resf)] ( 2-Resf), and [((OMe) 2bQb)Ru(NO)(Resf)] ( 3-Resf) have been synthesized via direct replacement of the chloride ligand of the parent {Ru-NO} (6) nitrosyls of the type [(R 2byb)Ru(NO)(L)] with the anionic tricyclic dye resorufin (Resf). The structures of 1-Resf- 3-Resf have been determined by X-ray crystallography. The dye is coordinated to the ruthenium centers of these conjugates via the phenolato-O atom and is trans to NO. Systematic red shift of the d pi(Ru) --> pi*(NO) transition of the parent nitrosyls [(R 2byb)Ru(NO)(L)] due to changes in R and y in the equatorial tetradentate ligand R 2byb (2-) results in its eventual merge with the intense absorption band of the dye around 500 nm in 3-Resf. Unlike the UV-sensitive parent [(R 2byb)Ru(NO)(L)] nitrosyls, these dye-sensitized nitrosyls rapidly release NO when exposed to visible light (lambda >/= 465 nm). Comparison of the photochemical parameters reveals that direct coordination of the light-harvesting chromophore to the ruthenium center in the present nitrosyls results in a significantly greater extent of sensitization to visible light compared to nitrosyls with appended chromophore (linked via alkyl chains). 1-Resf has been employed as a "trackable" NO donor to promote NO-induced apoptosis in MDA-MB-231 human breast cancer cells under the control of light. The results of this work demonstrate that (a) the d pi(Ru) --> pi*(NO) transition (photoband) of {Ru-NO} (6) nitrosyls can be tuned into visible range via careful alteration of the ligand frame(s) and (b) such nitrosyls can be significantly sensitized to visible light by directly ligating a light-harvesting chromophore to the ruthenium center. The potential of these photosensitive nitrosyl-dye conjugates as (i) biological tools to study the effects of NO in cellular environments and (ii) "trackable" NO donors in photodynamic therapy of malignancies (such as skin cancer) has been discussed.     

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.     

Syntheses, structures, and reactivities of mono- and dinuclear iridium thiolato complexes containing nitrosyl ligands

Reactions of the iridium(III) nitrosyl complex [Ir(NO)Cl2(PPh3)2] (1) with hydrosulfide and arenethiolate anions afforded the square-pyramidal iridium(III) complex [Ir(NO)(SH)2(PPh3)2] (2) with a bent nitrosyl ligand and a series of the square-planar iridium(I) complexes [Ir(NO)(SAr)2(PPh3)] (3a, Ar = C6H2Me3-2,4,6 (Mes); 3b, Ar = C6H3Me2-2,6 (Xy); 3c, Ar = C6H2Pri3-2,4,6) containing a linear nitrosyl ligand, respectively. Complex 1 also reacted with alkanethiolate anions or alkanethiols to give the thiolato-bridged diiridium complexes [Ir(NO)(mu-SPri)(SPri)(PPh3)]2 (4) and [Ir(NO)(mu-SBut)(PPh3)]2 (5). Complex 4 contains two square-pyramidal iridium(III) centers with a bent nitrosyl ligand, whereas 5 contains two tetrahedral iridium(0) centers with a linear nitrosyl ligand and has an Ir-Ir bond. Upon treatment with benzoyl chloride, 3a and 3b were converted into the (diaryl disulfide)- and thiolato-bridged dichlorodiiridium(III) complexes [[IrCl(mu-SC6HnMe4-nCH2)(PPh3)]2(mu-ArSSAr)] (6a, Ar = Mes, n = 2; 6b, Ar = Xy, n = 3) accompanied by a loss of the nitrosyl ligands and cleavage of a C-H bond in an ortho methyl group of the thiolato ligands. Similar treatment of 4 gave the dichlorodiiridium complex [Ir(NO)(PPh3)(mu-SPri)3IrCl2(PPh3)] (7), which has an octahedral dichloroiridium(III) center and a distorted trigonal-bipyramidal Ir(I) atom with a linear nitrosyl ligand. The detailed structures of 3a, 4, 5, 6a, and 7 have been determined by X-ray crystallography.     

Dye-tethered ruthenium nitrosyls containing planar dicarboxamide tetradentate N4 ligands: effects of in-plane ligand twist on NO photolability

To examine the steric effects of the in-plane ligands in dye-sensitized {RuNO}(6) nitrosyls on their NO photolability, two new ligands, namely, 1,2-Bis(pyridine-2-carboxamido)-4,5-dimethoxybenzene (H(2)(OMe)(2)bpb) and 1,2-Bis(Isoquinoline-1-carboxamido)-4,5-dimethoxybenzene (H(2)(OMe)(2)IQ1, H's are dissociable carboxamide protons) have been designed and synthesized. The syntheses and spectroscopic properties of {RuNO}(6) nitrosyls derived from these two ligands, namely, [((OMe)(2)bpb)Ru(NO)(Cl)] (4-Cl), [((OMe)(2)IQ1)Ru(NO)(Cl)] (5-Cl), [((OMe)(2)bpb)Ru(NO)(Resf)] (4-Resf), and [((OMe)(2)IQ1)Ru(NO)(Resf)] (5-Resf), are reported. The structures of 5-Cl, 4-Resf, and 5-Resf have been determined by X-ray crystallography. Removal of the in-plane ligand twist in the quinoline-based R(2)bQb(2-) ligand frame (because of steric interactions between the extended quinoline ring systems) in both R(2)bpb(2-) and R(2)IQ1(2-) (pyridine and 1-isoquinoline rings, respectively, instead of quinoline rings in the equatorial plane) results in enhanced solution stability, as well as higher quantum yield values for NO photorelease upon exposure to 500 nm light. Both dye-tethered {RuNO}(6) nitrosyls 4-Resf and 5-Resf exhibit greater sensitivity to visible light compared to the chloro-bound species 4-Cl and 5-Cl. In addition, the dye-tethered nitrosyls are fluorescent and hence can be used as trackable NO donors in cellular studies.     

Nitrosyliron(III) porphyrinates: porphyrin core conformation and FeNO geometry. Any correlation?

The synthesis, structural, and spectroscopic characterization of (nitrosyl)iron(III) porphyrinate complexes designed to have strongly nonplanar porphyrin core conformations is reported. The species have a nitrogen-donor axial ligand trans to the nitrosyl ligand and display planar as well as highly nonplanar porphyrin core conformations. The systems were designed to test the idea, expressly discussed for the heme protein nitrophorin (Roberts, et al. Biochemistry 2001, 40, 11327), that porphyrin core distortions could lead to an unexpected, bent geometry for the FeNO group. For [Fe(OETPP)(1-MeIm)(NO)]ClO(4).C(6)H(5)Cl (H(2)OETPP = octaethyltetraphenylporphyrin), the porphyrin core is found to be severely saddled. However, this distortion has little or no effect on the geometric parameters of the coordination group: Fe-N(p) = 1.990(9) A, Fe-N(NO) = 1.650(2) A, Fe-N(L) = 1.983(2) A, and Fe-N-O = 177.0(3) degrees. For the complex [Fe(OEP)(2-MeHIm)(NO)]ClO(4).0.5CH(2)Cl(2) (H(2)OEP = octaethylporphyrin), there are two independent molecules in the asymmetric unit. The cation denoted [Fe(OEP)(2-MeHIm)(NO)](+)(pla) has a close-to-planar porphyrin core. For this cation, Fe-N(p) = 2.014(8) A, Fe-N(NO) = 1.649(2) A, Fe-N(L) = 2.053(2) A, and Fe-N-O = 175.6(2) degrees. The second cation, [Fe(OEP)(2-MeHIm)(NO)](+)(ruf), has a ruffled core: Fe-N(p) = 2.003(7) A, Fe-N(NO) = 1.648(2) A, Fe-N(L) = 2.032(2) A, and Fe-N-O = 177.4(2) degrees. Thus, there is no effect on the coordination group geometry caused by either type of nonplanar core deformation; it is unlikely that a protein engendered core deformation would cause FeNO bending either. The solid-state nitrosyl stretching frequencies of 1917 cm(-)(1) for [Fe(OEP)(2-MeHIm)(NO)]ClO(4) and 1871 cm(-)(1) for [Fe(OETPP)(1-MeIm)(NO)]ClO(4) are well within the range seen for linear Fe-N-O groups. M?ssbauer data for [Fe(OEP)(2-MeHIm)(NO)]ClO(4) confirm that the ground state is diamagnetic. In addition, the quadrupole splitting value of 1.88 mm/s and isomer shift (0.05 mm/s) at 4.2 K are similar to other (nitrosyl)iron(III) porphyrin complexes with linear Fe-N-O groups. Crystal data: [Fe(OETPP)(1-MeIm)(NO)]ClO(4).C(6)H(5)Cl, monoclinic, space group P2(1)/c, Z = 4, with a = 12.9829(6) A, b = 36.305(2) A, c = 14.0126(6) A, beta = 108.087(1) degrees; [Fe(OEP)(2-MeHIm)(NO)]ClO(4).0.5CH(2)Cl(2), triclinic, space group Ponemacr;, Z = 4, with a = 14.062(2) A, b = 16.175(3) A, c = 19.948(3) A, alpha = 69.427(3) degrees, beta = 71.504(3) degrees, gamma = 89.054(3) degrees.     

Synthesis, spectroscopic analysis and photolabilization of water-soluble ruthenium(III)-nitrosyl complexes

In this paper, the synthesis, structural and spectroscopic characterization of a series of new Ru(III)-nitrosyls of {RuNO}(6) type with the coligand TPA (tris(2-pyridylmethyl)amine) are presented. The complex [Ru(TPA)Cl(2)(NO)]ClO(4) (2) was prepared from the Ru(III) precursor [Ru(TPA)Cl(2)]ClO(4) (1) by simple reaction with NO gas. This led to the surprising displacement of one of the pyridine (py) arms of TPA by NO (instead of the substitution of a chloride anion by NO), as confirmed by X-ray crystallography. NO complexes where TPA serves as a tetradentate ligand were obtained by reacting the new Ru(II) precursor [Ru(TPA)(NO(2))(2)] (3) with a strong acid. This leads to the dehydration of nitrite to NO(+), and the formation of the {RuNO}(6) complex [Ru(TPA)(ONO)(NO)](PF(6))(2) (4), which was also structurally characterized. Derivatives of 4 where nitrite is replaced by urea (5) or water (6) were also obtained. The nitrosyl complexes obtained this way were then further investigated using IR and FT-Raman spectroscopy. Complex 2 with the two anionic chloride coligands shows the lowest N-O and highest Ru-NO stretching frequencies of 1903 and 619 cm(-1) of all the complexes investigated here. Complexes 5 and 6 where TPA serves as a tetradentate ligand show ν(N-O) at higher energy, 1930 and 1917 cm(-1), respectively, and ν(Ru-NO) at lower energy, 577 and 579 cm(-1), respectively, compared to 2. These vibrational energies, as well as the inverse correlation of ν(N-O) and ν(Ru-NO) observed along this series of complexes, again support the Ru(II)-NO(+) type electronic structure previously proposed for {RuNO}(6) complexes. Finally, we investigated the photolability of the Ru-NO bond upon irradiation with UV light to determine the quantum yields (φ) for NO photorelease in complexes 2, 4, 5, and additional water-soluble complexes [Ru(H(2)edta)(Cl)(NO)] (7) and [Ru(Hedta)(NO)] (8). Although {RuNO}(6) complexes are frequently proposed as NO delivery agents in vivo, studies that investigate how φ is affected by the solvent water are lacking. Our results indicate that neutral water is not a solvent that promotes the photodissociation of NO, which would present a major obstacle to the goal of designing {RuNO}(6) complexes as photolabile NO delivery agents in vivo.     

Syntheses, structures, and reactivity of low spin iron(III) complexes containing a single carboxamido nitrogen in a [FeN5L] chromophore

A new pentacoordinate ligand based on TPA (tris-(2-pyridylmethyl)amine), namely, N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide (PaPy(3)H), has been synthesized. The iron(III) complexes of this ligand, namely, [Fe(PaPy(3))(CH(3)CN)](ClO(4))(2) (1), [Fe(PaPy(3))(Cl)]ClO(4) (2), [Fe(PaPy(3))(CN)]ClO(4) (3), and [Fe(PaPy(3))(N(3))]ClO(4) (4), have been isolated and complexes 1-3 have been structurally characterized. These complexes are the first examples of monomeric iron(III) complexes with one carboxamido nitrogen in the first coordination sphere. All four complexes are low spin and exhibit rhombic EPR signals around g = 2. The solvent bound species [Fe(PaPy(3))(CH(3)CN)](ClO(4))(2) reacts with H(2)O(2) in acetonitrile at low temperature to afford [Fe(PaPy(3))(OOH)](+) (g = 2.24, 2.14, 1.96). When cyclohexene is allowed to react with 1/H(2)O(2) at room temperature, a significant amount of cyclohexene oxide is produced along with the allylic oxidation products. Analysis of the oxidation products indicates that the allylic oxidation products arise from a radical-driven autoxidation process while the epoxidation is carried out by a distinctly different oxidant. No epoxidation of cyclohexene is observed with 1/TBHP.     

Complex series [Ru(tpy)(dpk)(X)]n+ (tpy = 2,2':6',2''-terpyridine; dpk = 2,2'-dipyridyl ketone; X = Cl-, CH3CN, NO2(-), NO+, NO*, NO-): substitution and electron transfer, structure, and spectroscopy

The complex framework [Ru(tpy)(dpk)]2+ has been used to study the generation and reactivity of the nitrosyl complex [Ru(tpy)(dpk)(NO)]3+ ([4]3+). Stepwise conversion of the chloro complex [Ru(tpy)(dpk)(Cl)]+ ([1]+) via [Ru(tpy)(dpk)(CH3CN)]2+ ([2]2+) and the nitro compound [Ru(tpy)(dpk)(NO2)]+ ([3]+) yielded [4]3+; all four complexes were structurally characterized as perchlorates. Electrochemical oxidation and reduction was investigated as a function of the monodentate ligand as was the IR and UV-vis spectroscopic response (absorption/emission). The kinetics of the conversion [4]3+/[3]+ in aqueous environment were also studied. Two-step reduction of [4]3+ was monitored via EPR, UV-vis, and IR (nu(NO), nu(CO)) spectroelectrochemistry to confirm the {RuNO}7 configuration of [4]2+ and to exhibit a relatively intense band at 505 nm for [4]+, attributed to a ligand-to-ligand transition originating from bound NO-.     

Triggered dye release via photodissociation of nitric oxide from designed ruthenium nitrosyls: turn-ON fluorescence signaling of nitric oxide delivery

Two new fluorescein-tethered nitrosyls derived from designed tetradentate ligands with carboxamido-N donors have been synthesized and characterized by spectroscopic techniques. These two diamagnetic {Ru-NO}(6) nitrosyls, namely, [(Me(2)bpb)Ru(NO)(FlEt)] (1-FlEt, Me(2)bpb = 1,2-bis(pyridine-2-carboxamido)5-dimethylbenzene, FlEt = fluorescein ethyl ester) and [((OMe)(2)IQ1)Ru(NO)(FlEt)] (2-FlEt, (OMe)(2)IQ1 = 1,2-bis(isoquinoline-1-carboxamido)-4,5-dimethoxybenzene), display NO stretching frequencies (ν(NO)) at 1846 and 1832 cm(-1) in addition to their FlEt carbonyl stretching frequencies (ν(CO)) at 1715 and 1712 cm(-1), respectively. Coordination of the dye ligand enhances the absorptivity and NO photolability of these two nitrosyls in the visible region (450-600 nm) of light. Exposure to visible light promotes rapid loss of NO from both {Ru-NO}(6) nitrosyls to generate Ru(III) photoproducts in dry aprotic solvents, such as MeCN and DMF. The FlEt(-) moiety remains bound to the paramagnetic Ru(III) center in such cases, and hence, the photoproducts exhibit very weak fluorescence from the dye unit. In the presence of water, the Ru(III) photoproducts undergo further aquation and loss of the FlEt(-) moiety via protonation. These steps lead to turn-ON fluorescence (from the free FlEt unit) and provide a visual signal of the NO photorelease from 1-FlEt and 2-FlEt in aqueous media.