NO Photorelease Research Articles

A First Proposal on the Nitrobenzene Photorelease Mechanism of NO2 and Its Relation to NO Formation through a Roaming Mechanism.

Despite the fact that NO2 is considered to be the main photoproduct of nitrobenzene photochemistry, no mechanism has ever been proposed to rationalize its formation. NO photorelease is instead a more studied process, probably due to its application in the drug delivery sector and the study of roaming mechanisms. In this contribution, a photoinduced mechanism accounting for the formation of NO2 in nitrobenzene is theorized based on CASPT2, CASSCF, and DFT electronic structure calculations and CASSCF classical dynamics. A triplet nπ* state is shown to evolve toward C-NO2 dissociation, being, in fact, the only low-lying excited state favoring such a deformation. Along the triplet dissociation path, the possibility to decay to the singlet ground state results in the frustration of the dissociation and in the recombination of the fragments, either back to the nitro or the nitrite isomer. The thermal decomposition of the latter to NO constitutes globally a roaming mechanism of NO formation.

On the photorelease of nitric oxide by nitrobenzene derivatives: A CASPT2//CASSCF model.

Nitroaromatic compounds can photorelease nitric oxide after UV absorption. The efficiency of the photoreaction depends on the molecular structure, and two features have been pointed out as particularly important for the yield of the process: the presence of methyl groups at the ortho position with respect to the nitro group and the degree of conjugation of the molecule. In this paper, we provide a theoretical characterization at the CASPT2//CASSCF (complete active space second-order perturbation theory//complete active space self-consistent field) level of theory of the photorelease of NO for four molecules derived from nitrobenzene through the addition of ortho methyl groups and/or the elongation of the conjugation. Our previously described mechanism obtained for the photorelease of NO in nitrobenzene has been adopted as a model for the process. According to this model, the process proceeds through a reactive singlet-triplet crossing (STC) region that the system can reach from the triplet 3(πOπ*) minimum. The energy barrier that must be surmounted in order to populate the reactive STC can be associated with the efficiency of the photoreaction. Here, the obtained results display clear differences in the efficiency of the photoreaction in the studied systems and can be correlated with experimental results. Thus, the model proves its ability to highlight the differences in the photoreaction efficiency for the nitroaromatic compounds studied here.

Dissociation of Bipyridine and Coordination with Nitrosyl: Cyclometalated Ruthenium Nitrosyl Complex.

A novel family of ruthenium nitrosyl complexes [Ru(bpy)(C∧N)(MeCN)NO](PF6)2 (2a-2e, bpy = 2,2'-bipyridine, HC∧N = 2-phenylpyridine and its derivatives) has been prepared by reacting cyclometalated ruthenium complexes [Ru(bpy)2(C∧N)][PF6] (1a-1e) with NO+, which were comprehensively characterized by mass, IR, NMR, and UV-vis spectra as well as the single-crystal X-ray structure determinations. Herein, the coordination geometry of Ru atoms in 2a-2e is a distorted octahedron and {RuII-NO+}6 is present in these complexes. Theoretical calculations suggest that the reactions involving dissociation of one bipyridine and coordination with NO+ proceed spontaneously (ΔG < 0) and the transformation from 1a-1e to the intermediates is dominated by substituents (ΔGRI varies from -1.19 to -1.53 eV), which influence the binding energy between Ru(II) and NO+ in complexes 2a-2e (-89.42 to -101.17 kcal/mol) and thus control the photorelease of NO on a certain scale. The weak absorption bands in the visible region could be attributed to the contribution of dπ(RuII) → π*(NO+), which were enhanced greatly under light, indicating the possible release of NO. The photoinduced NO, as well as singlet oxygen (1O2), was then confirmed by EPR spectra, and the amount of NO released from 2a-2e was estimated via Griess reagent assay. The cytotoxicity of these complexes with or without visible light irradiation was also investigated using an MTT assay.

Solution and solid-state light-induced transformations in heterometallic vanadium-ruthenium nitrosyl complex

The work is devoted to the preparation and photochemical investigations of the novel binuclear heterometallic complex [Ru(NO)(NO2)2(μ-NO2)(μ−CH3COO)(μ-O)VO(dbbpy)]·CH3CN (dbbpy - 4,4′-di-tert-butyl-2,2′-bipyridyl), which is obtained with quantitative yield. The structure of the complex is determined by single crystal X-ray diffraction and by DFT calculations. On the one hand, irradiation at 445 nm of an acetonitrile solution of the complex leads to a NO photo-release reaction. The light excitation induces the charge transfer from NO2 and dbbpy ligands to the antibonding orbitals of ON-Ru-O-V chain, leading to the NO release, which is confirmed by the DFT. The quantum yield of the Ru-NO photo-cleavage is 0.57 ± 0.05 %. The products of the photolysis (NO and paramagnetic RuIII complex) are confirmed by the Griess test and EPR-spectroscopy. On the other hand, the irradiation of the complex in the solid phase at 10 K results in the formation of the metastable bond isomer Ru-ON (MS1), which is detected by the infrared spectroscopy. The stretching vibration of the ν(NO) band of MS1 (1750 cm−1) is shifted by 150 cm−1 to lower energy with respect to the ν(NO) band of the ground state GS (1900 cm−1). The population of the MS1 is about 5%. MS1 thermally decays at 120−140 K back to the GS. Hence, this complex represents a bifunctional platform, which can release nitric oxide in solution and reversibly switch the NO ligand coordination in the solid state. It is shown, that the presence of vanadium strongly influences the photochemical properties of ruthenium nitrosyl both in the solid phase and in solution.

CASPT2 Potential Energy Curves for NO Dissociation in a Ruthenium Nitrosyl Complex.

Ruthenium nitrosyl complexes are fascinating photoactive compounds showing complex photoreactivity, such as N→O linkage photoisomerism and NO photorelease. This dual photochemical behavior has been the subject of many experimental studies in order to optimize these systems for applications as photoswitches or therapeutic agents for NO delivery. However, despite recent experimental and computational studies along this line, the underlying photochemical mechanisms still need to be elucidated for a more efficient design of these systems. Here, we present a theoretical contribution based on the calculations of excited-state potential energy profiles for NO dissociation in the prototype trans-[RuCl(NO)(py)4]2+ complex at the complete active space second-order perturbation theory (CASPT2). The results point to a sequential two-step photon absorption photorelease mechanism coupled to partial photoisomerization to a side-on intermediate, in agreement with previous density functional theory calculations.

NO Photorelease from a Ruthenium Complex Assisted by Formation of a Supramolecular Dimer

This work presents the NO release from compound [Ru(biq)2(H2O)(NO)](PF6)3 (biq = 2,2’-biquinoline) with visible light irradiation (λirrad = 660 nm), assisted by the low-absorbing photosensitizer [Ru(biq)2Cl2]. The structure of both compounds were characterized by means of ESI-MS (electrospray ionization mass spectrometry). The NO+ stretching, ν(NO) = 1995 cm-1, is atypically shifted to higher energy. This observation, along with the E1/2 = 0.49 V (vs. Ag/AgCl) assigned to the Ru2+/3+ redox pair observed for compound [Ru(biq)2Cl2] and its photoreactivity in solution suggest that the RuII ion, when coordinated to two biquinolines, behaves as a hard Pearson acid. Molecular modelling results confirmed the typical geometry distortion of ruthenium-polypyridine complexes bearing sterically hindered ligands. They also suggest the formation of a supramolecular dimer, assembled by weak interaction between biquinoline ligands from each compound, that is claimed to be responsible for the high efficiency of the NO photorelease bimolecular sensitization.

Construction of a near-infrared responsive upconversion nanoplatform against hypoxic tumors via NO-enhanced photodynamic therapy.

Photodynamic therapy (PDT) has been extensively used to treat cancer and other malignant diseases because it can offer many unique advantages over other medical treatments such as less invasive, fewer side effects, lower cost, etc. Despite great progress, the efficiency of PDT treatment, as an oxygen-dependent therapy, is still limited by the hypoxic microenvironment in the human tumor region. In this work, we have developed a near-infrared (NIR) activated theranostic nanoplatform based on upconversion nanoparticles (UCNPs), which incorporates PDT photosensitizer (curcumin) and NO donor (Roussin's black salt) in order to overcome hypoxia-associated resistance by reducing cellular respiration with NO presence in the PDT treatment. Our results suggest that the photo-released NO upon NIR illumination can greatly decrease the oxygen consumption rate and hence increase singlet oxygen generation, which ultimately leads to an increased number of cancer cell deaths, especially under hypoxic condition. It is believed that the methodology developed in this study enables to relieve the hypoxia-induced resistance in PDT treatment and also holds great potential for overcoming hypoxia challenges in other oxygen-dependent therapies.

Formation, reactivity, photorelease, and scavenging of NO in ruthenium nitrosyl complexes

The two newly designed nitrosyl complexes with Enemark–Feltham notation {RuNO}6 and {RuNO}7 configurations have been isolated as the perchlorate salts in the molecular framework [RuII(dmdptz)(phen)(NO)]n+ (dmdptz: N,N-dimethyl-4,6-di(pyridin-2-yl)-1,3,5-triazin-2-amine and phen: 1,10-phenanthroline) [RuII(dmdptz)(phen)(NO+)](ClO4)3 [4](ClO4)3 and [RuII(dmdptz)(phen)(NO)](ClO4)2 [5](ClO4)2 respectively. The single crystal X-ray structures of complexes [RuII(dmdptz)(phen)Cl](ClO4) [1](ClO4), [RuII(dmdptz)(phen)(NO2)](ClO4) [3](ClO4) and [4](ClO4)3 have been determined. The π– acceptance of the NO+ moiety in [4](ClO4)3 is reflected from the triple bond characteristic bond length 1.131(5) Å with simultaneous trans angle of 175.3(4)° as a proof of true linear coordination mode. A sizable shift in ν (NO) frequency (Δν = 361 cm−1) on moving from [4](ClO4)3 to [5](ClO4)2 are in good agreement for largely NO centered reduction with the changes in bonding {RuNO}6 [4](ClO4)3 to {RuNO}7 [5](ClO4)2. The redox properties of [4](ClO4)3 along with the precursor complexes, have been investigated. On exposure to visible light in the deoxygenated acetonitrile solution at room temperature both [4](ClO4)3 and [5](ClO4)2 spontaneously transform to their corresponding solvated derivative [RuII(dmdptz)(phen)(CH3CN)](ClO4)2 [2](ClO4)2 via the facile photocleavage of Ru–NO bond with KNO 9.26 × 10−3 min−1 (t1/2 = 74 min) and 4.03 × 10−2 min−1 (t1/2 = 17 min) respectively. The photoreleased “NO” can be scavenged by biologically relevant target molecule myoglobin as an MbNO adduct.

A calix[4]arene-based ternary supramolecular nanoassembly with improved fluoroquinolone photostability and enhanced NO photorelease.

Micellar-like nanoassemblies of a sulfonate amphiphilic calix[4]arene (1) are able to effectively co-entrap the fluoroquinolone antibacterial norfloxacin (2) and a hydrophobic nitric oxide (NO) photodonor (3), leading to a ternary supramolecular complex having a diameter of ca. 150 nm and a zeta potential of -48 mV. Outstanding photochemical stabilization of the otherwise photolabile fluoroquinolone 2 is observed under UVA excitation. Besides, visible light excitation leads to a remarkable enhancement of the NO photorelease efficiency of 3. Both the results can be explained on the basis of a "cage effect" of the micellar host that, in the case of 2, hinders the formation of the precursor complex responsible for the photodegradation, whereas in the case of 3 it provides a low polarity environment and easily abstractable hydrogens, which facilitate the radical-mediated mechanism involved in NO photorelease. Therefore, this supramolecular ternary nanoassembly simultaneously overcomes the main limitations of the free individual guests such as photolability and low photoreactivity. In view of the well-known antibacterial properties of the NO radical and the biocompatibility of the calixarene host, this nanoassembly represents a suitable bimodal system to be tested in antibacterial research.

A Theoretical Study of the N to O Linkage Photoisomerization Efficiency in a Series of Ruthenium Mononitrosyl Complexes.

Ruthenium nitrosyl complexes are fascinating versatile photoactive molecules that can either undergo NO linkage photoisomerization or NO photorelease. The photochromic response of three ruthenium mononitrosyl complexes, trans-[RuCl(NO)(py)4]2+, trans-[RuBr(NO)(py)4]2+, and trans-(Cl,Cl)[RuCl2(NO)(tpy)]+, has been investigated using density functional theory and time-dependent density functional theory. The N to O photoisomerization pathways and absorption properties of the various stable and metastable species have been computed, providing a simple rationalization of the photoconversion trend in this series of complexes. The dramatic decrease of the N to O photoisomerization efficiency going from the first to the last complex is mainly attributed to an increase of the photoproduct absorption at the irradiation wavelength, rather than a change in the photoisomerization pathways.

Photophysical properties and the NO photorelease mechanism of a ruthenium nitrosyl model complex investigated using the CASSCF-in-DFT embedding approach.

A complete state-averaged active space self-consistent field (SA-CASSCF) calculation by means of the SA-CASSCF(18,14)-in-BP86 Miller-Manby embedding approach was performed to explore the ground and excited electronic states of the trans-[RuCl(NO)(NH3)4]2+ complex. Insights into the NO photodissociation mechanism and Ru-NO bonding properties are provided. In addition, spin-orbit (SO) interactions were taken into account to describe and characterize the spin-forbidden transitions observed at the low-energy regions of the trans-[RuCl(NO)(NH3)4]2+ UV-Vis spectrum. The SA-CASSCF(18,14)-in-BP86 electronic spectrum is in great agreement with the experimental data of Schreiner [Schreiner et al., Inorg. Chem., 1972, 11, 880].

Is photoisomerization required for NO photorelease in ruthenium nitrosyl complexes?

The factors that explain the competition between intramolecular NO linkage photoisomerization and NO photorelease in five ruthenium nitrosyl complexes were investigated. By applying DFT-based methods, it was possible to characterize the ground states and lowest triplet potential energy surfaces of these species, and to establish that both photoisomerization and photorelease processes can occur in the lowest triplet state of each species. This work highlights the crucial role of the sideways-bonded isomer, a metastable state also known as the MS2 isomer, in the photochemical loss of NO, while the results obtained also indicate that the population of the triplet state of this isomer is compulsory for both processes and show how photoisomerization and photorelease interfere. Graphical Abstract Illustration of the crucial role of the 3MS2 state in the photoreactivities of ruthenium nitrosyl complexes.

A bactericidal calix[4]arene-based nanoconstruct with amplified NO photorelease.

A hydrophobic N-dodecyl-3-(trifluoromethyl)-4-nitrobenzenamine has been synthesized as a suitable NO photodonor and encapsulated in a nanocontainer based on a polycationic calix[4]arene derivative, leading to a supramolecular micellar-like nanoassembly ca. 45 nm in diameter. Visible light excitation of this nanoconstruct triggers NO generation with an efficiency remarkably higher than that observed for the free NO photoreleaser. This amplified NO release results in considerable antibacterial activity against Staphylococcus aureus (ATCC 6538) and Pseudomonas aeruginosa (ATCC 9027) as representative Gram positive and Gram negative bacteria, respectively.

Photochemical and Electrochemical Study of the Release of Nitric Oxide from [Ru(bpy)2L(NO)](PF6)nComplexes (L = Imidazole, 1-Methylimidazole, Sulfite and Thiourea), Toward the Development of Therapeutic Photodynamic Agents

The development of NO photoreleaser compounds has important potential applications on medicine, particularly on preventing topic infections and controlling cancers. Due to these expectations, the photochemical release of nitric oxide from complexes of [Ru(bpy)2LX]n+, where L = imidazole, 1-methylimidazole, sulphite and thiourea and X = NO+ and NO2− was investigated employing spectroscopic and electrochemical techniques. The release of NO was confirmed by chronoamperometry using a NO selective electrode, while the other product, mainly [RuIIH2O], was detected by UV-Visible spectroscopy and electrochemical techniques for all complexes except for thiourea. The amount of NO released by these complexes upon irradiation was determined using a new developed method using square wave voltammetry.

Carbon quantum dot-NO photoreleaser nanohybrids for two-photon phototherapy of hypoxic tumors.

We report a conjugate between carbon quantum dots and a NO photoreleaser able to photogenerate the anticancer NO radical via an energy transfer mechanism. This nanohybrid proved toxic to cancer cells in vitro and significantly reduced tumor volume in mice bearing human xenograft BxPC-3 pancreatic tumors upon two-photon excitation with the highly biocompatible 800 nm light.

Ruthenium–Nitrosyl Complexes Derived from Ligands Containing Two Carboxylate Functional Groups and Studies on the Photolability of Coordinated NO

AbstractRuthenium complexes [RuIII(L1)(PPh3)2(Cl)] (1) and [RuIII(L2)(PPh3)2(Cl)] (2) (in which L1H2 and L2H2 are iminodiacetic acid and pyridine‐2,6‐dicarboxylic acid, respectively, and H stands for a dissociable proton) derived from the ligands that contain two carboxylate groups were synthesized and characterized. These complexes were treated with in situ generated NO derived from acidified nitrite solution, which afforded the formation of two {Ru–NO}6 complexes [Ru(L1)(PPh3)2(NO)](ClO4) (1a) and [Ru(L2)(PPh3)2(NO)](ClO4) (2a). The molecular structure of the representative complex [Ru(L2)(PPh3)2(NO)](ClO4) (2a) was determined using X‐ray crystallography. Characterization of complexes 1a and 2a by IR and NMR spectroscopic studies revealed the presence of {Ru–NO}6 species with S = 0 ground state. ESI‐MS data also supported the formation of 1a and 2a. Exposure to UV light promoted rapid loss of NO from both ruthenium nitrosyls to generate RuIII photoproducts of the type [Ru(L)(PPh3)2(S)](ClO4) (in which S stands for solvent). The quantum yields of NO photorelease for complexes 1a and 2a were measured using a chemical actinometry study. The NO released in solution was estimated using the Griess reagent, and the results were compared with the data obtained from sodium nitroprusside (SNP). A 2,2‐diphenyl‐1‐picrylhydrazine (DPPH) radical quenching assay was performed to estimate the amount of generated reactive nitrogen species and/or reactive oxygen species under aerobic conditions during photolysis of NO.

Evidence of dexter energy transfer in NO photolability of dye-sensitized ruthenium nitrosyls

Direct attachment of light-harvesting dye molecules to the ruthenium center of designed {Ru–NO}6 nitrosyls has been shown to exhibit enhanced light-induced NO photorelease upon exposure to visible light. Theoretical studies have indicated that orbital overlap between the MOs of the dye and the nitrosyl units are key for such sensitization. In order to check whether altering the electronic conjugation between these two units causes reduction in the extent of sensitization, we have synthesized a pyridinyloxy-fluorescein dye PyFlEt and attached it to two designed ruthenium nitrosyls through the pyridine-N donor of the pyridinyloxy-end. The quantum yield values of NO photodissociation at 500nm (ϕNO) and fluorescence quantum yield values (ϕFl) of these two nitrosyl–dye conjugates namely, [(Me)2bpb)Ru(NO)(PyFlEt)]ClO4 (1-PyFlEt) and [((OMe)2IQ1)Ru(NO)(PyFlEt)]BF4 (2-PyFlEt) have been compared with those of [(Me)2bpb)Ru(NO)(FlEt)]ClO4 (1-FlEt) and [((OMe)2IQ1)Ru(NO)(FlEt)]BF4 (2-FlEt) in which the same FlEt dye is directly attached through the phenolato-O donor. This minor alteration in the linkage between the dye and the nitrosyl unit has caused significant reduction in the ϕNO values of 1-PyFlEt and 2-PyFlEt while their ϕFl values have shown moderate improvement. These results strongly suggest that the light energy absorbed by the dye unit is transferred to the Ru–NO moiety through the Dexter pathway. If the electronic overlap is disrupted, only part of the energy is used in NO photorelease and a significant portion is lost through fluorescence.

Synthesis, characterization and photochemical properties of some ruthenium nitrosyl complexes

Synthesis of new nitrosyl complexes [RuCl3(CNPy)2(NO)] (1), [RuCl3(AMPy)2(NO)] (2), [RuCl3(CPI)2(NO)] (3), [RuCl3(NOPI)2(NO)] (4), and [RuCl3(HPI)2(NO)] (5) [CNPy=4-cyanopyridine; AMPy=4-aminopyridine; CPI=1-(4-cyanophenyl)-imidazole; NOPI=1-(4-nitrophenyl)-imidazole; HPI=1-(4-hydroxyphenyl)-imidazole] has been described. The complexes 1–5 have been characterized by satisfactory elemental analyses, spectral (ESI-MS, FT-IR 1H, 13C NMR, UV–Vis) and electrochemical studies. Linear nitrosyl group and S0 state in these complexes have been supported by IR, 1H NMR spectral studies and X-ray single crystal analyses on representaive complex 1. Photorelease of NO and its trapping by myoglobin have been monitored by UV–Vis studies. Structure of the complexes under investigation has also been supported by theoretical studies. The geometrical parameters of 1–5 are comparable to those obtained from single crystal X-ray diffraction studies on 1.

Influence of nitrosyl coordination on the binding mode of quinaldate in selective ruthenium frameworks. Electronic structure and reactivity aspects

The nitrosyl complexes, [RuII(trpy)(L)(NO+)Cl]BF4, [1]BF4, and [RuII(trpy)(L)(NO+)](BF4)2, [2](BF4)2, (trpy = 2,2′:6′,2′′-terpyridine, L− = deprotonated form of unsymmetrical quinaldic acid) have been synthesized. Single crystal X-ray structures of [1]BF4 and [2](BF4)2 reveal that in the former L− binds to the ruthenium ion selectively in a monodentate fashion through the O− donor whereas the usual bidentate mode of L− (O−, N donors) has been retained in [2](BF4)2 with the same meridional configuration of trpy being seen in both. The Ru–NO group in [1]BF4 or [2](BF4)2, exhibits almost linear (sp-hybridized form of NO+) geometry. The difference in bonding mode of the unsymmetrical quinaldate in [1]BF4 and [2](BF4)2 has been reflected in their corresponding ν(NO)/ν(CO) frequencies as well as in their NO based two-step reduction processes, {RuII–NO+} → {RuII–NO•} and {RuII–NO•}→{RuII–NO−}. The close to bent geometry (sp2-hybridized form of NO•) of the one-electron reduced 1 or [2]+ is been reflected in their DFT optimized structures. The spin density plot of the reduced species reveals that NO is the primary spin-bearing center with slight delocalization onto the metal ion which has been reflected in its radical EPR spectrum. [1]+ and [2]2+ undergo facile photorelease of NO with significantly different kNO (s−1) and t1/2 (s) values which eventually lead to the concomitant formation of the corresponding solvent species. The photoreleased NO• can be trapped as an Mb–NO adduct. The reduced species 1 selectively reacts with the molecular oxygen (O2) at pH ∼ 1 to yield the corresponding nitro species, [RuII(trpy)(L)(NO2)Cl]−.

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.