How to Find an HNO Needle in a (Bio)‐Chemical Haystack

Doctorovich, Fabio; Bikiel, Damián E.; Pellegrino, Juan; Suárez, Sebastián; Martí, Marcelo A.

doi:10.1002/9781118792797.ch02

Cited by 9 publications

(9 citation statements)

References 88 publications

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“…Conversely, HNO-positive inotropic and lusitropic actions in vivo have been observed with low (nM range) concentrations (Paolocci et al, 2003;Tocchetti et al, 2007) and reported to be reversible (Paolocci et al, 2003;Tocchetti et al, 2007;Irvine et al, 2013;Kemp-Harper et al, 2016). Given the few viable methodologies able to detect HNO in biological systems, it is difficult to determine HNO concentrations accurately in vivo (Kemp-Harper, 2011;Doctorovich et al, 2014;Rivera-Fuentes and Lippard, 2015). However, similar to the concentrations employed in the present and previous studies (at low HNO/thiol ratios), in vivo HNO concentrations are not expected to be in excess of PLN (Paolocci et al, 2001(Paolocci et al, , 2003Tocchetti et al, 2007Tocchetti et al, , 2011Gao et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Nitroxyl (HNO) targets phospholamban cysteines 41 and 46 to enhance cardiac function

Keceli

Majumdar

Thorpe

et al. 2019

Journal of General Physiology

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Section: Discussionmentioning

confidence: 99%

Nitroxyl (HNO) targets phospholamban cysteines 41 and 46 to enhance cardiac function

Keceli

Majumdar

Thorpe

et al. 2019

Journal of General Physiology

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“…44 Comparing ArNO with O 2 complexes would be interesting, but so far there is no reported redox data for monocopper superoxo species that would be similar in structure to 3 H . The exception is the recent work by Reinaud et al, which showed by spectroelectrochemistry that an in situ generated calix [6]amino-tren endon superoxo complex could not be reduced above −0.90 V versus Fc at −60 °C (113 K) in acetone. 73 On the other hand, a few dicopper peroxo and superoxo species have been well characterized by electrochemistry with the help of lowtemperature approaches (entries 4−7).…”

Section: ■ Introductionmentioning

confidence: 93%

“…The interaction of nitrosoarenes (ArNO) with metal centers has drawn much attention because of its relevance to biological pathways − and catalytic C–N bond formation processes. − Chemists now have a good understanding of the geometric structure of transition metal/nitrosoarene complexes. , In addition, ArNO species are redox-noninnocent ligands, − which portends a large landscape of electronic structures and reactivity types upon interaction with redox-active metal ions.…”

Section: Introductionmentioning

confidence: 99%

Tuning Inner-Sphere Electron Transfer in a Series of Copper/Nitrosoarene Adducts

et al. 2020

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A series of copper/nitrosoarene complexes were created that mimic several steps in biomimetic O 2 activation by copper(I). The reaction of the copper(I) complex of N,N,N′,N′tetramethypropylenediamine with a series of para-substituted nitrosobenzene derivatives leads to adducts in which the nitrosoarene (ArNO) is reduced by zero, one, or two electrons, akin to the isovalent species dioxygen, superoxide, and peroxide, respectively. The geometric and electronic structures of these adducts were characterized by means of X-ray diffraction, vibrational analysis, ultraviolet−visible spectroscopy, NMR, electrochemistry, and density functional theory (DFT) calculations. The bonding mode of the NO moiety depends on the oxidation state of the ArNO moiety: κN for ArNO, mononuclear η 2-NO and dinuclear μ-η 2 :η 1 for ArNO •− , and dinuclear μ-η 2 :η 2 for ArNO 2−. 15 N isotopic labeling confirms the reduction state by measuring the NO stretching frequency (1392 cm −1 for κN-ArNO, 1226 cm −1 for η 2-ArNO •− , 1133 cm −1 for dinuclear μ-η 2 :η 1-ArNO •− , and 875 cm −1 for dinuclear μ-η 2 :η 2 for ArNO 2−). The 15 N NMR signal disappears for the ArNO •− species, establishing a unique diagnostic for the radical state. Electrochemical studies indicate reduction waves that are consistent with one-electron reduction of the adducts and are compared with studies performed on Cu-O 2 analogues. DFT calculations were undertaken to confirm our experimental findings, notably to establish the nature of the charge-transfer transitions responsible for the intense green color of the complexes. In fine, this family of complexes is unique in that it walks through three redox states of the ArNO moiety while keeping the metal and its supporting ligand the same. This work provides snapshots of the reactivity of the toxic nitrosoarene molecules with the biologically relevant Cu(I) ion. 47 usually too oxidative to be stable above −60°C.

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“…The second aspect, and most relevant in the present case, concerns the possibility of its endogenous production. 19,21 Enzymatic proposed physiological relevant routes to HNO concern oxidation of arginine 21−23 or the reaction of NO 21 or nitrosyl species 24 with H 2 S. 25 Although they make a strong point for enzymatic HNO production, it should be stressed that none of them has been confirmed in vivo. 19 The chemical (nonenzymatic) and biological compatible routes to HNO have been much less pursued.…”

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confidence: 99%

HNO Is Produced by the Reaction of NO with Thiols

et al. 2017

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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.

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How to Find an HNO Needle in a (Bio)‐Chemical Haystack

Cited by 9 publications

References 88 publications

Nitroxyl (HNO) targets phospholamban cysteines 41 and 46 to enhance cardiac function

Nitroxyl (HNO) targets phospholamban cysteines 41 and 46 to enhance cardiac function

Tuning Inner-Sphere Electron Transfer in a Series of Copper/Nitrosoarene Adducts

HNO Is Produced by the Reaction of NO with Thiols

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