Co-reporter:Sebastian A. Suarez, Martina Muñoz, Lucia Alvarez, Mateus F. Venâncio, Willian R. Rocha, Damian E. Bikiel, Marcelo A. Marti, and Fabio Doctorovich
Journal of the American Chemical Society October 18, 2017 Volume 139(Issue 41) pp:14483-14483
Publication Date(Web):September 19, 2017
DOI:10.1021/jacs.7b06968
Azanone (nitroxyl, HNO) is a highly reactive compound whose biological role is still a matter of debate. One possible route for its formation is NO reduction by biological reductants. These reactions have been historically discarded due to the negative redox potential for the NO,H+/HNO couple. However, the NO to HNO conversion mediated by vitamins C, E, and aromatic alcohols has been recently shown to be feasible from a chemical standpoint. Based on these precedents, we decided to study the reaction of NO with thiols as potential sources of HNO. Using two complementary approaches, trapping by a Mn porphyrin and an HNO electrochemical sensor, we found that under anaerobic conditions aliphatic and aromatic thiols (as well as selenols) are able to convert NO to HNO, albeit at different rates. Further mechanistic analysis using ab initio methods shows that the reaction between NO and the thiol produces a free radical adduct RSNOH•, which reacts with a second NO molecule to produce HNO and a nitrosothiol. The nitrosothiol intermediate reacts further with RSH to produce a second molecule of HNO and RSSR, as previously reported.
Co-reporter:Mateus F. Venâncio, Fabio Doctorovich, and Willian R. Rocha
The Journal of Physical Chemistry B July 13, 2017 Volume 121(Issue 27) pp:6618-6618
Publication Date(Web):June 16, 2017
DOI:10.1021/acs.jpcb.7b03552
In this work, quantum mechanical calculations and Monte Carlo statistical mechanical simulations were carried out to investigate the solvation properties of HNO in aqueous solution and to evaluate the proton-coupled one electron reduction potential of 2NO to 1HNO, which is essential missing information to understand the fate of 2NO in the biological medium. Our results showed that the 1HNO molecule acts mainly as a hydrogen bond donor in aqueous solution with an average energy of −5.5 ± 1.3 kcal/mol. The solvation free energy of 1HNO in aqueous solution, computed using three approaches based on the linear response theory, revealed that the current prediction of the hydration free energy of HNO is, at least, 2 times underestimated. We proposed two pathways for the production of HNO through reduction of NO. The first pathway is the direct reduction of NO through proton-coupled electron transfer to produce HNO, and the second path is the reduction of the radical anion HONO•–, which is involved in equilibrium with NO in aqueous solution. We have shown that both pathways are viable processes under physiological conditions, having reduction potentials of E°′ = −0.161 V and E°′ ≈ 1 V for the first and second pathways, respectively. The results shows that both processes can be promoted by well-known biological reductants such as NADH, ascorbate, vitamin E (tocopherol), cysteine, and glutathione, for which the reduction potential at physiological pH is around −0.3 to −0.5 V. The computed reduction potential of NO through the radical anion HONO•– can also explain the recent experimental findings on the formation of HNO through the reduction of NO, promoted by H2S, vitamin C, and aromatic alcohols. Therefore, these results contribute to shed some light into the question of whether and how HNO is produced in vivo and also for the understanding of the biochemical and physiological effects of NO.
Co-reporter:G. Carrone;J. Pellegrino;F. Doctorovich
Chemical Communications 2017 vol. 53(Issue 38) pp:5314-5317
Publication Date(Web):2017/05/09
DOI:10.1039/C7CC02186K
We present a new method for controlled generation of HNO, based on the combination of a pH photoactuator induced by visible light with an HNO donor activated by pH increase. This method avoids the use of UV light, and in the future could be extended by using an IR photoactuator.
Co-reporter:Carina Gaviglio;Juan Pellegrino;David Milstein
Dalton Transactions 2017 vol. 46(Issue 48) pp:16878-16884
Publication Date(Web):2017/12/12
DOI:10.1039/C7DT03944A
The reactivity of the {RhNO}9 complex [Rh(PCPtBu)(NO)]˙ (1˙) with NO˙ was studied. A disproportionation reaction takes place in which N2O is released quantitatively, while the complex Rh(PCPtBu)(NO)(NO2) (2), with coordinated nitrite, is formed. The new complex 2 was fully characterized by multinuclear NMR techniques, IR and X-ray diffraction. The X-ray structure reveals a square pyramidal geometry with an N-bound nitro ligand trans to the Cipso of the PCP ligand and a bent nitrosyl ligand in the apical position. IR measurement of released N2O confirms that one equivalent forms for each molecule of 1˙. Infrared spectroscopic experiments with 1˙-15NO and 14NO˙ suggest that the reaction occurs through the intermediacy of a dinitrosyl complex. In addition, DFT calculations were performed to provide more evidence on the structure of the intermediates and to support the observed reactivity.
Co-reporter:Sebastián A. Suarez; Nicolás I. Neuman; Martina Muñoz; Lucı́a Álvarez; Damián E. Bikiel; Carlos D. Brondino; Ivana Ivanović-Burmazović; Jan Lj. Miljkovic; Milos R. Filipovic; Marcelo A. Martí
Journal of the American Chemical Society 2015 Volume 137(Issue 14) pp:4720-4727
Publication Date(Web):March 15, 2015
DOI:10.1021/ja512343w
The role of NO in biology is well established. However, an increasing body of evidence suggests that azanone (HNO), could also be involved in biological processes, some of which are attributed to NO. In this context, one of the most important and yet unanswered questions is whether and how HNO is produced in vivo. A possible route concerns the chemical or enzymatic reduction of NO. In the present work, we have taken advantage of a selective HNO sensing method, to show that NO is reduced to HNO by biologically relevant alcohols with moderate reducing capacity, such as ascorbate or tyrosine. The proposed mechanism involves a nucleophilic attack to NO by the alcohol, coupled to a proton transfer (PCNA: proton-coupled nucleophilic attack) and a subsequent decomposition of the so-produced radical to yield HNO and an alkoxyl radical.
Co-reporter:Ana Foi;Florencia Di Salvo;Tapashi G. Roy;Kathrin Stirnat;Christian Biewer;Axel Klein
European Journal of Inorganic Chemistry 2015 Volume 2015( Issue 6) pp:1033-1040
Publication Date(Web):
DOI:10.1002/ejic.201403145
Abstract
The previously reported complex [Ph4P][Fe(bpy)(CN)3(NO)] (bpy = 2,2′-bipyridine) was synthesised and characterised in detail using UV/Vis absorption and IR spectroscopy, cyclic voltammetry, and single-crystal XRD. Detailed spectroelectrochemical (UV/Vis, IR and EPR) insight adds perfectly to the previous electrochemical characterisation of this complex. The description of this {Fe(NO)}7 complex as a low-spin FeII–NO· system based on the spectroscopic results is supported by DFT calculations. Reversible oxidation leads to the corresponding {Fe(NO)}6 (FeII–NO+) complex, whereas the reduction to the formal {Fe(NO)}8 species [presumably (FeII–NO–)] occurs irreversibly. When trying to synthesise further derivatives that contain other α-diimine ligands, only for the 1,10-phenanthroline (phen) derivative were some results obtained. For other ligands the obtained materials were too reactive. The reasons for such behaviour are also discussed.
Co-reporter:Miguel A. Morales Vásquez, Sebastián A. Suárez, Fabio Doctorovich
Materials Chemistry and Physics 2015 Volume 159() pp:159-166
Publication Date(Web):1 June 2015
DOI:10.1016/j.matchemphys.2015.03.065
•A Co porphyrin attached to a gold electrode is a robust system to obtain H2 from H2O.•The redox potential for both oxidation and reduction of water is decreased by 200 mV.•In aqueous buffers, the current increases with decreasing pH.•Efficient electrocatalyst for water split, focused H2 production.In natural photosynthesis, the energy in sunlight is used to rearrange the bonds present in water to produce oxygen and hydrogen. Artificial systems that perform water splitting require catalysts that assist the production of hydrogen from water without excessive reduction potential.Consequently a cobalt porphyrin({cobaltII-5,10,15,20-tetrakis[3-(p-acetylthiopropoxy) phenyl]porphyrin}[Co–P]) covalently bound to gold or silver has been tested as a catalyst for reduction and oxidation of H2O to H2 and O2, respectively. In the cyclic voltammogram CoIII/CoII and CoII/CoI reversible waves were observed at potentials close to the expected values. The addition of water increased the cathodic peak for the CoII/CoI wave, consistent with the electrocatalytic reduction of water. In aqueous buffers the current increased for catalytic [Co–P] with decreasing pH. Similar results are obtained by changing the solvent or metal electrode to which the porphyrin is adsorbed. This leads to a reduction in the redox potential for the H+/H2 couple by 200 mV.The material (Au°–[Co–P]) shows good efficiency and robustness for the electrochemical production of H2 in different solvents and buffers in contrast to results previously seen for other porphyrins in solutions. The modified electrode Au°–[Co–P] shows high stability, and it is not damaged after several cycles. It can be stored in a CH2Cl2 solution and reused several times.
Co-reporter:Fabio Doctorovich, Damian E. Bikiel, Juan Pellegrino, Sebastián A. Suárez, and Marcelo A. Martí
Accounts of Chemical Research 2014 Volume 47(Issue 10) pp:2907
Publication Date(Web):September 19, 2014
DOI:10.1021/ar500153c
Azanone (1HNO, nitroxyl) shows interesting yet poorly understood chemical and biological effects. HNO has some overlapping properties with nitric oxide (NO), sharing its biological reactivity toward heme proteins, thiols, and oxygen. Despite this similarity, HNO and NO show significantly different pharmacological effects. The high reactivity of HNO means that studies must rely on the use of donor molecules such as trioxodinitrate (Angeli’s salt). It has been suggested that azanone could be an intermediate in several reactions and that it may be an enzymatically produced signaling molecule. The inherent difficulty in detecting its presence unequivocally prevents evidence from yielding definite answers. On the other hand, metalloporphyrins are widely used as chemical models of heme proteins, providing us with invaluable tools for the study of the coordination chemistry of small molecules, like NO, CO, and O2. Studies with transition metal porphyrins have shown diverse mechanistic, kinetic, structural, and reactive aspects related to the formation of nitrosyl complexes. Porphyrins are also widely used in technical applications, especially when coupled to a surface, where they can be used as electrochemical gas sensors. Given their versatility, they have not escaped their role as key players in chemical studies involving HNO.This Account presents the research performed during the last 10 years in our group concerning azanone reactions with iron, manganese, and cobalt porphyrins. We begin by describing their HNO trapping capabilities, which result in formation of the corresponding nitrosyl complexes. Kinetic and mechanistic studies of these reactions show two alternative operating mechanisms: reaction of the metal center with HNO or with the donor. Moreover, we have also shown that azanone can be stabilized by coordination to iron porphyrins using electron-attracting substituents attached to the porphyrin ring, which balance the negatively charged NO¯.Second, we describe an electrochemical HNO sensing device based on the covalent attachment of a cobalt porphyrin to gold. A surface effect affects the redox potentials and allows discrimination between HNO and NO. The reaction with the former is fast, efficient, and selective, lacking spurious signals due to the presence of reactive nitrogen and oxygen species. The sensor is both biologically compatible and highly sensitive (nanomolar). This time-resolved detection allows kinetic analysis of reactions producing HNO. The sensor thus offers excellent opportunities to be used in experiments looking for HNO. As examples, we present studies concerning (a) HNO donation capabilities of new HNO donors as assessed by the sensor, (b) HNO detection as an intermediate in O atom abstraction to nitrite by phosphines, and (c) NO to HNO interconversion mediated by alcohols and thiols.Finally, we briefly discuss the key experiments required to demonstrate endogenous HNO formation to be done in the near future, involving the in vivo use of the HNO sensing device.
Co-reporter:Lucía Álvarez, Sebastián A. Suarez, Damian E. Bikiel, Julio S. Reboucas, Ines Batinić-Haberle, Marcelo A. Martí, and Fabio Doctorovich
Inorganic Chemistry 2014 Volume 53(Issue 14) pp:7351-7360
Publication Date(Web):July 8, 2014
DOI:10.1021/ic5007082
Azanone (1HNO, nitroxyl) is a highly reactive molecule with interesting chemical and biological properties. Like nitric oxide (NO), its main biologically related targets are oxygen, thiols, and metalloproteins, particularly heme proteins. As HNO dimerizes with a rate constant between 106 and 107 M–1 s–1, reactive studies are performed using donors, which are compounds that spontaneously release HNO in solution. In the present work, we studied the reaction mechanism and kinetics of two azanone donors Angelís Salt and toluene sulfohydroxamic acid (TSHA) with eight different Mn porphyrins as trapping agents. These porphyrins differ in their total peripheral charge (positively or negatively charged) and in their MnIII/MnII reduction potential, showing for each case positive (oxidizing) and negative (reducing) values. Our results show that the reduction potential determines the azanone donor reaction mechanism. While oxidizing porphyrins accelerate decomposition of the donor, reducing porphyrins react with free HNO. Our results also shed light into the donor decomposition mechanism using ab initio methods and provide a thorough analysis of which MnP are the best candidates for azanone trapping and quantification experiments.
Co-reporter:Fernando Godoy, Alejandra Gómez, Rodrigo Segura, Fabio Doctorovich, Juan Pellegrino, Carina Gaviglio, Paulina Guerrero, A. Hugo Klahn, Mauricio Fuentealba, María Teresa Garland
Journal of Organometallic Chemistry 2014 Volume 765() pp:8-16
Publication Date(Web):15 August 2014
DOI:10.1016/j.jorganchem.2014.04.019
•The dimethylamino group is easily displaced by two electron donor ligands.•Re(III) complexes exhibited a trans stereochemistry, the NMe2 remained coordinated.•The assignment of the NO stretching band was confirmed by 15N enriched compound.•The new {ReNO}6 was prepared and characterized and the redox behavior was studied.The UV irradiation of a hexane solution of the complex (η5-C5Me4(CH2)2NMe2)Re(CO)3 (1) afforded the chelated species (η5:η1-C5Me4(CH2)2NMe2)Re(CO)2 (2). The molecular structure of 2 has been determined by X-ray crystallography. The reaction of 2 with two-electron donor ligands yields (η5-C5Me4(CH2)2NMe2)Re(CO)2(L) (1, L = CO; 3, L = PMe3). The chelated species 2 also reacts with MeOTf, HBF4, and I2 to form the cationic compounds trans-[(η5-C5Me4(CH2)2NMe2)Re(CO)2X]+ ([4]+, X = Me; [5]+, X = H; [6]+, X = I). The trans stereochemistry of 4–6 have been assigned on the basis of ν(CO) IR intensities and 13C NMR spectroscopy. Also, complex 2 reacts with nitrosyl tetrafluoroborate to yield [(η5-C5Me4(CH2)2NMe2NO)Re(CO)2(NO)]BF4 ([7]2+). The redox behavior of the {ReNO}6 complex [7]2+ was studied and the products obtained after two-electron reduction were characterized by IR. DFT calculations were done to optimize the structure of [7]2+ and to study the effect of the sidearm coordination on the electronic structure of a cyclopentadienyl {ReNO}8 complex.The NMe2 group in the complex (η5:-2 (2) is easily displaced by two electron donor. However, the cationic species Re(III) with a trans stereochemistry, in which the NMe2 sidearm remained coordinated. The redox behaviour of the nitrosyl derivative was studied and the DFT calculations were done to optimize the structure.
Co-reporter:Sebastián A. Suárez, Damian E. Bikiel, Diana E. Wetzler, Marcelo A. Martí, and Fabio Doctorovich
Analytical Chemistry 2013 Volume 85(Issue 21) pp:10262
Publication Date(Web):August 19, 2013
DOI:10.1021/ac402134b
Azanone (HNO, nitroxyl) is a highly reactive and short-lived compound with intriguing and highly relevant properties. It has been proposed to be a reaction intermediate in several chemical reactions and an in vivo, endogenously produced key metabolite and/or signaling molecule. In addition, its donors have important pharmacological properties. Therefore, given its relevance and elusive nature (it reacts with itself very quickly), the development of reliable analytical methods for quantitative HNO detection is in high demand for the advancement of future research in this area. During the past few years, several methods were developed that rely on chemical reactions followed by mass spectrometry, high-performance liquid chromatography, UV–vis, or fluorescence-trapping-based methodologies. In this work, our recently developed HNO-sensing electrode, based on the covalent attachment of cobalt(II) 5,10,15,20-tetrakis[3-(p-acetylthiopropoxy)phenyl] porphyrin [Co(P)] to a gold electrode, has been thoroughly characterized in terms of sensibility, accuracy, time-resolved detection, and compatibility with complex biologically compatible media. Our results show that the Co(P) electrode: (i) allows time-resolved detection and kinetic analysis of the electrode response (the underlying HNO-producing reactions can be characterized) (ii) is able to selectively detect and reliably quantify HNO in the 1–1000 nM range, and (iii) has good biological media compatibility (including cell culture), displaying a lack of spurious signals due to the presence of O2, NO, and other reactive nitrogen and oxygen species. In summary, the Co(P) electrode is to our knowledge the best prospect for use in studies investigating HNO-related chemical and biological reactions.
Co-reporter:Kiran Sirsalmath, Sebastián A. Suárez, Damián E. Bikiel, Fabio Doctorovich
Journal of Inorganic Biochemistry 2013 Volume 118() pp:134-139
Publication Date(Web):January 2013
DOI:10.1016/j.jinorgbio.2012.10.008
A group of Piloty's acid (N-hydroxybenzenesulfonamide) derivatives were synthesized and fully characterized in order to assess the rates and pH of HNO (azanone, nitroxyl) donation in aqueous media. The derivatives, with electron-withdrawing and -donating substituents include methyl, nitro, fluoro, tri-isopropyl, trifluoromethyl and methoxy groups. The most interesting modulation observed is the change in pH range in which the compounds are able to donate HNO. UV–visible kinetic measurements at different pH values were used to evaluate the decomposition rate of the donors. A novel technique based on electrochemical measurements using a Co-porphyrin sensor was used to assess the release of HNO as a function of pH, by direct measurement of [HNO]. The results were contrasted with DFT calculations in order to understand the electronic effects exerted by the ring substituents, which drastically modify the pH range of donation. For example, while Piloty's acid donates HNO from pH 9.3, the corresponding fluoro derivative starts donating at pH 4.0.A group of Piloty's acid (N-hydroxybenzenesulfonamide) derivatives were synthesized and characterized. A Co-porphyrin sensor was used to assess the release of HNO as a function of pH, by direct measurement of [HNO], showing a large change in the pH range at which the compounds start to donate HNO.Highlights► The decomposition rate of PA derivatives at different pH values is ca 10– 3–10– 4 s– 1. ► Novel electrochemical measurements were used to determine the pH of HNO donation. ► The pH of donation starts at − 1 to 10 depending on the substitution. ► DFT calculations allowed to understand the effects exerted by the ring substituents.
Co-reporter:Juan Pellegrino, Carina Gaviglio, David Milstein, and Fabio Doctorovich
Organometallics 2013 Volume 32(Issue 21) pp:6555-6564
Publication Date(Web):October 31, 2013
DOI:10.1021/om4008746
The electrochemistry of the {RhNO}8 complexes [Rh(PCPtBu)(NO)][BF4] (1+), [Rh(PCPtBuCH2)(NO)][BF4] (2+), and Rh(PCPtBu)(NO)Cl (3) was studied. Both four-coordinate complexes 1+ and 2+ exhibit a reversible reduction within the CH2Cl2 solvent window. Nevertheless, the chemical or electrochemical reduction of 1+ and 2+ in CH2Cl2 led to the formation of the five-coordinate {RhNO}8 complexes 3 and Rh(PCPtBuCH2)(NO)Cl (4), respectively, through chloride abstraction from CH2Cl2 by the one-electron-reduced {RhNO}9 species [Rh(PCPtBu)(NO)]• (1•) and [Rh(PCPtBuCH2)(NO)]• (2•), as has been observed for many other 17-electron paramagnetic complexes. The new complex 4 was fully characterized by multinuclear NMR techniques, IR, X-ray diffraction, CV, UV–vis, and elemental analysis. On the other hand, the five-coordinate complexes 3 and 4 show only one irreversible oxidation in CH2Cl2 and two irreversible reductions in THF. The {RhNO}9 complex 1• could be obtained quantitatively by one-electron reduction of 1+ with cobaltocene in nonchlorinated solvents and was characterized by IR, EPR, and 1H NMR in solution. Activation of carbon–halogen bonds by complex 1• was observed by studying the reactivity of 1• with some aryl halides, giving in all cases the {RhNO}8 Rh(PCPtBu)(NO)X (X = Cl–, 3, or X = I–, 6) as the only rhodium complex, while a complex with coordination of the aryl moiety was not observed as a stable final product in any case. The fate of the aryl organic radicals could be determined in some cases. In addition, DFT calculations were performed to elucidate the electronic structure of 1• and to support the observed reactivity.
Co-reporter:Fabio Doctorovich, Damian Bikiel, Juan Pellegrino, Sebastián A. Suárez, Anna Larsen, Marcelo A. Martí
Coordination Chemistry Reviews 2011 Volume 255(23–24) pp:2764-2784
Publication Date(Web):December 2011
DOI:10.1016/j.ccr.2011.04.012
The present review starts describing nitroxyl (azanone, 1HNO) biological relevance, in relation with NO physiology, from a chemical reactivity perspective. After a description of commonly used azanone donors and their characteristics, the overlapping molecular targets of HNO and NO are presented with an emphasis on heme models and proteins. We present also a brief description of metalloporphyrins and the main characteristics of their nitrosyl complexes, and then describe the reactivity of azanone towards Fe, Ru, Mn and Co porphyrins, briefly mentioning heme proteins, and focusing on 1HNO trapping and its discrimination from NO. A comparison of reaction kinetics and/or nitrosyl product stability with non-heme models is also described. We illustrate the promiscuity of iron porphyrins, the stabilization properties of Ru and the discriminating behavior of Mn and Co porphyrins, which allows the design of optical and electrochemical selective 1HNO sensors. Finally, a comparative analysis and future perspectives are presented, focusing on the in vivo reactivity of azanone and its putative endogenous production.Highlights► Azanone 1HNO biological relevance from a chemical reactivity perspective. ► A description of its donors and their characteristics. ► The overlapping targets of HNO and NO with emphasis on heme models and proteins. ► Reactivity towards Fe, Ru, Mn and Co porphyrins. ► The design of an electrochemical Co(P) selective 1HNO sensors.
Co-reporter:Natalia Escola, Damián E. Bikiel, Ricardo Baggio, Florencia Di Salvo, Fabio Doctorovich
Inorganica Chimica Acta 2011 Volume 374(Issue 1) pp:528-539
Publication Date(Web):1 August 2011
DOI:10.1016/j.ica.2011.02.063
Pentachloronitrosyliridate(III) ([IrCl5(NO)]−), the most electrophilic NO+ known to date, can be reduced chemically and/or electrochemically by one or two electrons to produce the NO and HNO/NO− forms. The nitroxyl complex can be formed either by hydride attack to the NO+ in organic solvent, or by decomposition of iridium-coordinated nitrosothiols in aqueous solutions, while NO is produced electrochemically or by reduction of [IrCl5(NO)]− with H2O2. Both NO and HNO/NO− complexes are stable under certain conditions but tend to labilize the trans chloride and even the cis ones after long periods of time. As expected, the NO+ is practically linear, although the IrNO moiety is affected by the counterions due to dramatic changes in the solid state arrangement. The other two nitrosyl redox states comprise bent structures.Graphical abstractPentachloronitrosyliridate(III) ([IrCl5(NO)]−), the most electrophilic NO+ known to date, can be reduced chemically and/or electrochemically to produce the NO and HNO/NO− forms. The NO+ is practically linear but, its structural parameters are affected by counterions in the solid state. The other two nitrosyl redox states comprise bent structures.Highlights► The highly reactive pentachloronitrosyliridate(III) and related NO species. ► The whole NO family of [IrCl5(NO)]−: NO+, NO and HNO/NO−. ► The whole NO family forms of [IrCl5(NO)]−. ► [IrCl5(NO)]− and NO related species.
Co-reporter:Daniel Kazhdan, Laura L. Perissinotti, Bernardo Watanabe, Marcos N. Eberlin, Humberto M.S. Milagre, Boniek G. Vaz, Dario A. Estrin, Fabio Doctorovich
Inorganica Chimica Acta 2011 Volume 366(Issue 1) pp:85-90
Publication Date(Web):30 January 2011
DOI:10.1016/j.ica.2010.10.013
The aqueous decomposition of the iridium coordinated nitrosothiols (RSNOs) trans-K[IrCl4(CH3CN)NOSPh] (1), and K2[IrCl5(NOECyS)] (2, ECyS = cysteine ethyl ester), was studied by MS analysis of the gaseous products, ESI-MS, NMR, and UV–Vis spectroscopy. Bent NO (NO−, nitroxyl anion), sulfenic acids and nitrite were observed as coordinated products in solution, while nitrous oxide (N2O) and nitrogen were detected in the gas phase. The formation of coordinated NO− and N2O, a nitroxyl dimerization product, allows us to propose the formation of free nitroxyl (HNO) as an intermediate. Complex 1 decomposes 300 times slower than free PhSNO does. In both cases (1 and 2) kinetic results show a first order decomposition behavior and a very negative ΔS≠ΔS≠, which strongly indicates an associative rate-determining step. A proposed decomposition mechanism, supported by the experimental data and DFT calculations, involves, as the first step, nucleophilic attack of H2O on to the sulfur atom of the coordinated RSNO, producing an NO− complex and free sulfenic acid, followed by two competing reactions: a ligand exchange reaction of this NO− with the sulfenic acid or, to a minor extent, coordination of N2O to produce an NO−/N2O complex which finally renders free N2 and coordinated NO2−. Some of the produced NO− is likely to be released from the metal center producing nitroxyl by protonation and finally N2O by dimerization and loss of H2O. In conclusion, the decomposition of these coordinated RSNOs occurs through a different mechanism than for the decomposition of free RSNOs. It involves the formation of sulfenic acids and coordinated NO−, which is released from the complexes and protonated at the reaction pH producing nitroxyl (HNO), and ultimately N2O.Graphical abstractThe aqueous decomposition of the iridium coordinated nitrosothiols trans-K[IrCl4(CH3CN)NOSPh] (1), and K2[IrCl5(NOECyS)] (2, ECyS = cysteine ethyl ester), produces nitroxyl and sulfenic acids in solution, plus nitrous oxide and nitrogen in the gas phase. Complex 1 decomposes more than 300 times slower than free PhSNO. In both cases (1 and 2) a negative ΔS≠ indicates an associative rate-determining step. A mechanism involving the observed products is proposed and supported by DFT calculations.Research highlights► The decomposition of Ir-nitrosothiol complexes produces NO−, sulfenic acids and NO2−. ► Nitrous oxide (N2O) and nitrogen were detected in the gas phase. ► Free nitroxyl (HNO) is proposed as an intermediate. ► The decomposition involves attack of H2O on the S atom of the coordinated nitrosothiol. ► The decomposition occurs through a different mechanism than for free nitrosothiols.
Co-reporter:Damián E. Bikiel, José M. Ramallo-López, Felix G. Requejo, Ofelia B. Oña, Marta B. Ferraro, Julio C. Facelli, Fabio Doctorovich
Polyhedron 2011 30(2) pp: 221-227
Publication Date(Web):
DOI:10.1016/j.poly.2010.10.005
Co-reporter:Juan Pellegrino;Dipl.-Chem. Ralph Hübner;Dr. Fabio Doctorovich;Dr. Wolfgang Kaim
Chemistry - A European Journal 2011 Volume 17( Issue 28) pp:7868-7874
Publication Date(Web):
DOI:10.1002/chem.201003516
Abstract
Experimental and computational results for the electron-deficient porphyrin complex [Fe(NO)(TFPPBr8)] (1; TFPPBr8=2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(pentafluorophenyl)porphyrin) are reported with respect to its electron-transfer behavior. Complex 1 undergoes three one-electron processes: two reversible reductions and one irreversible oxidation. Spectroelectrochemical measurements (IR and UV/Vis/NIR spectroscopy) of 14NO- and 15NO-containing material indicate that the first reduction to 1− occurs largely on the NO ligand to produce nitroxyl anion (NO−) character, as evident from the considerable change in νNO from 1715 to around 1550 cm−1. The second reduction to 12− does not result in a further shift of νNO to lower frequencies, but to a surprising high-energy shift to 1590 cm−1. This and the notable changes of the characteristic porphyrin vibrations as well as significant changes of the UV/Vis absorptions indicate a porphyrin-centered process; DFT calculations predict the shift of νNO to higher frequencies for the intermediate- and high-spin states of 12−. The oxidation of 1 is irreversible on the voltammetry timescale, but chemically reversible in spectroelectrochemical experiments, suggesting that the cationic form dissociates to the corresponding ferric porphyrin and NO. DFT calculations support the interpretation of the experimental results.
En este trabajo se estudia el comportamiento redox del complejo {FeNO}7 con sustituyentes atractores de electrones, [Fe(NO)(TFPPBr8)]=1 (TFPPBr8=2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(pentafluorofenil)porfirina) mediante experimentos de espectroelectroquímica y cálculos computacionales. El complejo 1 presenta tres procesos electroquímicos de un electrón: dos reducciones reversibles y una oxidación irreversible. El considerable cambio de νNO de 1715 cm−1 a ≈ 1550 cm−1 indica que la primera reducción a 1− involucra en gran medida al ligando NO. Para la segunda reducción a 12− se observa, sorprendentemente, un cambio de νNO a ≈ 1590 cm−1. Este pequeño corrimiento de νNO y los cambios notables de las vibraciones asociadas a modos de la porfirina, así como los cambios significativos en la banda UV/Vis de Soret, indican un proceso centrado en la porfirina; los cálculos DFT predicen el corrimiento de νNO a mayores frecuencias para los estados de spin intermedio y alto de 12−. En cuanto a la oxidación de 1, la onda irreversible en la voltametría cíclica sugiere que la forma catiónica 1+ se disocia dando la porfirina de hierro(III) y NO; sin embargo, en el experimento espectroelectroquímico el proceso resulta reversible, recuperándose la νNO de 1 al reducir. Los cálculos DFT apoyan la interpretación de los resultados experimentales.
Co-reporter:Sebastián A. Suárez ; Mariano H. Fonticelli ; Aldo A. Rubert ; Ezequiel de la Llave ; Damián Scherlis ; Roberto C. Salvarezza ; Marcelo A. Martí
Inorganic Chemistry 2010 Volume 49(Issue 15) pp:6955-6966
Publication Date(Web):July 6, 2010
DOI:10.1021/ic1007022
Nitroxyl (HNO) is a small short-lived molecule for which it has been suggested that it could be produced, under certain cofactors conditions, by nitric oxide (NO) synthases. Biologically relevant targets of HNO are heme proteins, thiols, molecular oxygen, NO, and HNO itself. Given the overlap of the targets and reactivity between NO and HNO, it is very difficult to discriminate their physiopathological role conclusively, and accurate discrimination between them still remains critical for interpretation of the ongoing research in this field. The high reactivity and stability of cobalt(II) porphyrins toward NO and the easy and efficient way of covalently joining porphyrins to electrodes through S−Au bonds prompted us to test cobalt(II) 5,10,15,20-tetrakis[3-(p-acetylthiopropoxy)phenyl]porphyrin [Co(P)], as a possible candidate for the electrochemical discrimination of both species. For this purpose, first, we studied the reaction between NO, NO donors, and commonly used HNO donors, with CoII(P) and CoIII(P). Second, we covalently attached CoII(P) to gold electrodes and characterized its redox and structural properties by electrochemical techniques as well as scanning tunneling microscopy, X-ray photoelectron spectroscopy, and solid-state density functional theory calculations. Finally, we studied electrochemically the NO and HNO donor reactions with the electrode-bound Co(P). Our results show that Co(P) is positioned over the gold surface in a lying-down configuration, and a surface effect is observed that decreases the CoIII(P) (but not CoIII(P)NO−) redox potential by 0.4 V. Using this information and when the potential is fixed to values that oxidize CoIII(P)NO− (0.8 V vs SCE), HNO can be detected by amperometric techniques. Under these conditions, Co(P) is able to discriminate between HNO and NO donors, reacting with the former in a fast, efficient, and selective manner with concomitant formation of the CoIII(P)NO− complex, while it is inert or reacts very slowly with NO donors.
Co-reporter:Sara E. Bari, Valentín T. Amorebieta, María M. Gutiérrez, José A. Olabe, Fabio Doctorovich
Journal of Inorganic Biochemistry 2010 Volume 104(Issue 1) pp:30-36
Publication Date(Web):January 2010
DOI:10.1016/j.jinorgbio.2009.09.024
The reactions of hydroxylamine (HA) with several water-soluble iron(III) porphyrinate compounds, namely iron(III) meso-tetrakis-(N-ethylpyridinium-2yl)-porphyrinate ([FeIII(TEPyP)]5+), iron(III) meso-tetrakis-(4-sulphonatophenyl)-porphyrinate ([FeIII(TPPS)]3−), and microperoxidase 11 ([FeIII(MP11)]) were studied for different [FeIII(Porph)]/[HA] ratios, under anaerobic conditions at neutral pH. Efficient catalytic processes leading to the disproportionation of HA by these iron(III) porphyrinates were evidenced for the first time. As a common feature, only N2 and N2O were found as gaseous, nitrogen-containing oxidation products, while NH3 was the unique reduced species detected. Different N2/N2O ratios obtained with these three porphyrinates strongly suggest distinctive mechanistic scenarios: while [FeIII(TEPyP)]5+ and [FeIII(MP11)] formed unknown steady-state porphyrinic intermediates in the presence of HA, [FeIII(TPPS)]3− led to the well characterized soluble intermediate, [FeII(TPPS)NO]4−. Free-radical formation was only evidenced for [FeIII(TEPyP)]5+, as a consequence of a metal centered reduction. We discuss the catalytic pathways of HA disproportionation on the basis of the distribution of gaseous products, free radicals formation, the nature of porphyrinic intermediates, the FeII/FeIII redox potential, the coordinating capabilities of each complex, and the kinetic analysis. The absence of NO2- revealed either that no HAO-like activity was operative under our reaction conditions, or that NO2-, if formed, was consumed in the reaction milieu.
Co-reporter:Juan Pellegrino ; Sara E. Bari ; Damián E. Bikiel
Journal of the American Chemical Society 2009 Volume 132(Issue 3) pp:989-995
Publication Date(Web):December 31, 2009
DOI:10.1021/ja905062w
Nitroxyl (HNO/NO−) heme-adducts have been postulated as intermediates in a variety of catalytic processes carried out by different metalloenzymes. Hence, there is growing interest in obtaining and characterizing heme model nitroxyl complexes. The one-electron chemical reduction of the {FeNO}7 nitrosyl derivative of FeIII(TFPPBr8)Cl, FeII(TFPPBr8)NO (1) (TFPPBr8 = 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-[Tetrakis-(pentafluorophenyl)]porphyrin) with cobaltocene yields the significantly stable {FeNO}8 complex, [Co(C5H5)2]+[Fe(TFPPBr8)NO]− (2). Complex 2 was isolated and characterized by UV−vis, FTIR, 1H and 15N NMR spectroscopies. In addition, DFT calculations were performed to get more insight into the structure of 2. According to the spectroscopic and DFT results, we can state unequivocally that the surprisingly stable complex 2 is the elusive {FeNO}8 species. Both experimental and computational data allow to assign the electronic structure of 2 as intermediate between FeIINO− and FeINO, which is contrasted with the predominant FeIINO− character of known nonheme {FeNO}8 complexes. The enhanced stability achieved for a heme model {FeNO}8 is expected to allow further studies related to the reactivity of this elusive species.
Co-reporter:Laura L. Perissinotti ; Gregory Leitus ; Linda Shimon ; Dario Estrin
Inorganic Chemistry 2008 Volume 47(Issue 11) pp:4723-4733
Publication Date(Web):May 9, 2008
DOI:10.1021/ic7024999
In this work, we present a complete and detailed experimental characterization and theoretical study of a variety of coordinated S-nitrosothiols (RSNOs), such as cysteine derivatives, mercaptosuccinic acid, benzyl thiol, and phenyl thiol. Some of them are extremely unstable and sensitive in free form. Strikingly, in contrast with free S-nitrosothiols, we found that, upon coordination to iridium, they become very stable even in aqueous solutions. The study of these coordinated complexes provides further insight on the elucidation of structural aspects dealing with the nature of the S−N bond in RSNOs, a fact which still remains a matter of controversy.
Co-reporter:Florencia Di Salvo ; Darío A. Estrin ; Gregory Leitus
Organometallics 2008 Volume 27(Issue 9) pp:1985-1995
Publication Date(Web):April 5, 2008
DOI:10.1021/om700985h
In the present work the formation of several primary aliphatic coordinated nitrosamines by reaction of the extremely reactive K[IrCl5(NO)] in acetonitrile solution with the corresponding amine is described. Complete characterization, including X-ray diffraction determinations for some examples, are reported, and experimental evidence of their stability. Density functional theory calculations (DFT) helped to understand the role of the coordination environment of these complexes and to support, with excellent correlation with the experimental data, the proposed reaction pathways and stability studies. Complexes containing the highly unstable primary nitrosamines as ligands are generally scarce, and moreover, to our knowledge, our group has recently reported the first examples of isolated primary nitrosamines coordinated to the metal center only through the NO moiety.
Co-reporter:Fabio Doctorovich and Florencia Di Salvo
Accounts of Chemical Research 2007 Volume 40(Issue 10) pp:985
Publication Date(Web):September 6, 2007
DOI:10.1021/ar6000457
The inorganic nitrosyl (NO+) complexes [Fe(CN)5NO]2−, [Ru(bpy)2(NO)Cl]2+, and [IrCl5(NO)]− are useful reagents for the nitrosation of a variety of organic compounds, ranging from amines to the relatively inert alkenes. Regarding [IrCl5(NO)]−, its high electrophilicity and inertness define it as a unique reagent and provide a powerful synthetic route for the isolation and stabilization of coordinated nitroso compounds that are unstable in free form, such as S-nitrosothiols and primary nitrosamines. Related to the high electrophilicity of [IrCl5(NO)]−, an unusual behavior is described for its PPh4+ salt in the solid state, showing an electronic distribution represented by IrIV–NO• instead of IrIII–NO+ (as for the K+ and Na+ salts).
Co-reporter:Florencia Di Salvo;Natalia Escola Dr.;Damián A. Scherlis Dr.;Darío A. Estrin ;Carlos Bondía Dr.;Daniel Murgida Dr.;José M. Ramallo-López Dr.;Félix G. Requejo Dr.;Linda Shimon Dr.
Chemistry - A European Journal 2007 Volume 13(Issue 30) pp:
Publication Date(Web):18 JUL 2007
DOI:10.1002/chem.200601761
The nitrosyl in [IrCl5(NO)]− is probably the most electrophilic known to date. This fact is reflected by its extremely high IR frequency in the solid state, electrochemical behavior, and remarkable reactivity in solution. PPh4[IrCl5(NO)] forms a crystal in which the [IrCl5(NO)]− anions are in a curious wire-like linear arrangement, in which the distance between the NO moiety of one anion and the trans chloride of the upper one nearby is only 2.8 Å. For the same complex [IrCl5(NO)]− but with a different counterion, Na[IrCl5(NO)], the anions are stacked one over the other in a side-by-side arrangement. In this case the electronic distribution can be depicted as the closed-shell electronic structure IrIIINO+, as expected for any d6 third-row transition metal complex. However, in PPh4[IrCl5(NO)] an unprecedented electronic perturbation takes place, probably due to NO.–Cl− acceptor–donor interactions among a large number of [IrCl5(NO)]− units, favoring a different electronic distribution, namely the open-shell electronic structure IrIVNO.. This conclusion is based on XANES experimental evidence, which demonstrates that the formal oxidation state for iridium in PPh4[IrCl5(NO)] is +4, as compared with +3 in K[IrCl5(NO)]. In agreement, solid-state DFT calculations show that the ground state for [IrCl5(NO)]− in the PPh4+ salt comprises an open-shell singlet with an electronic structure which encompasses half of the spin density mainly localized on a metal-centered orbital, and the other half on an NO-based orbital. The electronic perturbation could be seen as an electron promotion from a metal–chloride to a metal–NO orbital, due to the small HOMO–LUMO gap in PPh4[IrCl5(NO)]. This is probably induced by electrostatic interactions acting as a result of the closeness and wire-like spatial arrangement of the Ir metal centers, imposed by lattice forces due to π–π stacking interactions among the phenyl rings in PPh4+. Experimental and theoretical data indicate that in PPh4[IrCl5(NO)] the IrNO moiety is partially bent and tilted.
El nitrosilo presente en el anión [IrCl5(NO)]−es probablemente el más electrofílico que se conoce hasta la fecha. Este hecho se refleja claramente en su altísima frecuencia en el espectro infrarrojo del sólido, su comportamiento electroquímico y su sorprendente reactividad en solución. La estructura cristalina del complejo PPh4[IrCl5(NO)] presenta una disposición peculiar de los aniones [IrCl5(NO)]−. Estos se encuentran ubicados de forma lineal, semejando un cable, y manteniendo una distancia corta (2.8 Å) entre el NO de uno de los aniones y el cloro trans del siguiente. Para el mismo anión [IrCl5(NO)]−pero con diferente contraión, Na[IrCl5(NO)], los aniones se ubican uno al lado del otro (lateralmente), y no uno sobre el otro, como en el caso mencionado anteriormente. La distribución electrónica correspondiente al cristal de sodio, se puede describir como un singulete de capa cerrada IrIIINO+, situación esperable para un complejo que posee un metal de la tercera serie de transición y d6. Sin embargo, para el complejo PPh4[IrCl5(NO)] se observa una llamativa perturbación electrónica. Probablemente, son las interacciones donor–aceptor NO.Cl−a lo largo de un gran número de unidades de [IrCl5(NO)]−las que favorecen una distribución electrónica diferente, la de singulete de capa cerrada IrIVNO.. Esta conclusión está basada en evidencias experimentales obtenidas por XANES que demuestran que el estado de oxidación formal para el iridio en PPh4[IrCl5(NO)] es +4, en comparación con el valor de +3 encontrado para el mismo metal en el complejo K[IrCl5(NO)]. Los resultados de cálculos de DFT de estado sólido concuerdan con lo planteado anteriormente. Se ha encontrado que el estado fundamental para el [IrCl5(NO)]−en el cristal de PPh4+está descripto por un singulete de capa abierta con la mitad de la densidad de spin mayoritariamente localizada en un orbital centrado en el metal, y la otra mitad en uno correspondiente al NO. Esta perturbación podría verse como una promoción electrónica desde un orbital mixto metalcloro hacia otro orbital metalNO, debido a la pequeña diferencia que existe entre el HOMO–LUMO en el caso de PPh4[IrCl5(NO)]. Esto puede estar originado por interacciones electrostáticas que resultan de la cercanía y la particular disposición de cable que presentan los centros metalicos de Ir. Se considera que las fuertes interacciones de tipo π–π entre los anillos bencénicos son las responsables de que el anión adopte esta disposición en el cristal. Con respecto a la geometría de la unidad IrNO, los resultados experimentales y teóricos indican que se encuentra parcialmente angular y que el nitrógeno está ligeramente desplazado respecto al eje Cl(trans)Ir.
Co-reporter:Mariana Hamer; Sebastian A. Suarez; Nicolás I. Neuman; Lucía Alvarez; Martina Muñoz; Marcelo A. Marti
Inorganic Chemistry () pp:
Publication Date(Web):
DOI:10.1021/acs.inorgchem.5b01347
The reduction of NO• to HNO/NO– under biologically compatible conditions has always been thought as unlikely, mostly because of the negative reduction potential: E°(NO•,H+/HNO) = −0.55 V vs NHE at physiological pH. Nonetheless, during the past decade, several works hinted at the possible NO-to-HNO conversion mediated by moderate biological reductants. Very recently, we have shown that the reaction of NO• with ascorbate and aromatic alcohols occurs through a proton-coupled nucleophilic attack (PCNA) of the alcohol to NO•, yielding an intermediate RO–N(H)O• species, which further decomposes to release HNO. For the present work, we decided to inspect whether other common biological aromatic alcohols obtained from foods, such as Vitamin E, or used as over-the-counter drugs, like aspirin, are able to undergo the reaction. The positive results suggest that the conversion of NO to HNO could occur far more commonly than previously expected. Taking these as the starting point, we set to review our and other groups’ previous reports on the possible NO-to-HNO conversion mediated by biological compounds including phenolic drugs and vitamins, as well as several thiol-bearing compounds. Analysis of revised data prompted us to ask ourselves the following key questions: What are the most likely physio/pathological conditions for NO•-to-HNO conversion to take place? Which effects usually attributed to NO• are indeed mediated by HNO? These inquiries are discussed in the context of 2 decades of NO and HNO research.
Co-reporter:Damian E. Bikiel ; Estefanía González Solveyra ; Florencia Di Salvo ; Humberto M. S. Milagre ; Marcos N. Eberlin ; Rodrigo S. Corrêa ; Javier Ellena ; Darío A. Estrin
Inorganic Chemistry () pp:
Publication Date(Web):February 15, 2011
DOI:10.1021/ic102038v
A new family of compounds is presented as potential carbon monoxide releasing molecules (CORMs). These compounds, based on tetrachlorocarbonyliridate(III) derivatives, were synthesized and fully characterized by X-ray diffraction, electrospray mass spectrometry, IR, NMR, and density functional theory calculations. The rate of CO release was studied via the myoglobin assay. The results showed that the rate depends on the nature of the sixth ligand, trans to CO, and that a significant modulation on the release rate can be produced by changing the ligand. The reported compounds are soluble in aqueous media, and the rates of CO release are comparable with those for known CORMs, releasing CO at a rate of 0.03−0.58 μM min−1 in a 10 μM solution of myoglobin and 10 μM of the complexes.
Co-reporter:G. Carrone, J. Pellegrino and F. Doctorovich
Chemical Communications 2017 - vol. 53(Issue 38) pp:NaN5317-5317
Publication Date(Web):2017/04/18
DOI:10.1039/C7CC02186K
We present a new method for controlled generation of HNO, based on the combination of a pH photoactuator induced by visible light with an HNO donor activated by pH increase. This method avoids the use of UV light, and in the future could be extended by using an IR photoactuator.
