The HNO donor ability of hydroxamic acids upon oxidation with cyanoferrates(III)

Abstract

The hydroxamic acids (RC(O)NHOH, HA) exhibit diverse biological activity, including hypotensive properties associated with formation of nitroxyl (HNO) or nitric oxide (NO). Oxidation of two HA's, benzohydroxamic and acetohydroxamic acids (BHA, AHA) by [Fe(CN) 5 NH 3 ] 2− or [Fe(CN) 6 ] 3− was analyzed by spectroscopic, mass spectrometric techniques, and flow EPR measurements. Mixing BHA with both Fe(III) reactants at pH 11 allowed detecting the hydroxamate radical, (C 6 H 5 )C(O)NO • − , as a 1-electron oxidation product, as well as N 2 O as a final product. Successive UV-vis spectra of mixtures containing [Fe(CN) 5 NH 3 ] 2− (though not [Fe(CN) 6 ] 3− ) at pH 11 and 7 revealed an intermediate acylnitroso-complex, [Fe(CN) 5 (NOC(O)(C 6 H 5 )] 3− (λ max , 465 nm, very stable at pH 7), formed through ligandinterchange in the initially formed reduction product, [Fe(CN) 5 NH 3 ] 3− , and characterized by FTIR spectra through the stretching vibrations ν (CN − ) , ν (CO) and ν (NO) . Free acylnitroso derivatives, formed by alternative reaction paths of the hydroxamate radicals, hydrolyze forming RC(O)OH and HNO, postulated as precursor of N 2 O. Minor quantities of NO are formed only with an excess of oxidant. The intermediacy of HNO was confirmed through its identification as [Fe(CN) 5 (HNO)] 3− (λ max , 445 nm) as a result of hydrolysis of [Fe(CN) 5 (NOC(O)(C 6 H 5 )] 3− at pH 11. The results demonstrate that hydroxamic acids behave predominantly as HNO-donors.

Nitrogen Dioxide Reaction with Nitroxide Radical Derived from Hydroxamic Acids: The Intermediacy of Acyl Nitroso and Nitroxyl (HNO)

“…Hydroxamic acids (RC­(O)­NHOH, HXs) form a class of compounds that display interesting chemical and biological properties. , Recent studies have highlighted HXs’ biological activities, some of which are associated with their ability under oxidative stress to generate nitroxyl (HNO) and nitric oxide (NO). − The chemistry of HXs is associated with one- and two-electron oxidations forming the respective nitroxide radical (RC­(O)­NHO • ) and acyl nitroso (RC­(O)­NO), respectively, which are relatively unstable species. Hydrolysis of acyl nitroso (denoted also nitrosocarbonyl) and its reaction with nucleophiles generates HNO, ,− which readily undergoes dimerization followed by dehydration to give N 2 O .…”

Generation and Trapping of Nitrosocarbonyl Intermediates

“…Nitrosocarbonyls are found in studies devoted to the biological applications of their starting materials , or as generators of HNO through their dimerization and hydrolysis …”

“…380,381 Nitrosocarbonyls are found in studies devoted to the biological applications of their starting materials 382,383 or as generators of HNO through their dimerization and hydrolysis. 384 The natural product synthesis was also extensively performed and reviewed, 385,386 as well as the catalytic enantioselective C−N and/or C−O bond formation. 386 In these fields the chiral version of the NC chemistry found large applications.…”

Synthesis of Pyrrolo[1,2-a]pyrimidine Enantiomers via Domino Ring-Closure followed by Retro Diels-Alder Protocol

“…Their pharmacological properties are related to their ability to scavenge metal ions [ 3 ]. In addition, they are able to generate nitric oxide [ 3 , 4 , 5 ] in living systems. In this way, they can act as antimicrobial [ 6 , 7 , 8 , 9 ], antitumour [ 6 , 10 ], antihypertensive [ 11 ], anti-inflammatory [ 6 , 12 ], and neuroleptic agents, among others [ 3 , 13 ].…”