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 HAs, benzohydroxamic and acetohydroxamic acids (BHA, AHA) by [Fe(CN)₅NH₃]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, (C₆H₅)C(O)NO˙⁻, as a one-electron oxidation product, as well as N₂O as a final product. Successive UV–vis spectra of mixtures containing [Fe(CN)₅NH₃]²⁻ (though not [Fe(CN)₆]³⁻) at pH 11 and 7 revealed an intermediate acylnitroso-complex, [Fe(CN)₅NOC(O)(C₆H₅)]³⁻ (λ_max, 465 nm, very stable at pH 7), formed through ligand interchange in the initially formed reduction product, [Fe(CN)₅NH₃]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 N₂O. 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)(C₆H₅)]³⁻ at pH 11. The results demonstrate that hydroxamic acids behave predominantly as HNO donors.

Graphical abstract

Keywords:

• Hydroxamic acids
• Pentacyano(L)ferrate(III) oxidants
• Acylnitroso species
• Nitroxyl
• Nitroxyl donor

Acknowledgements

We thank the Universities of Mar del Plata and Buenos Aires for support. This work benefited from grants of CONICET and the University of Buenos Aires. SEB, JAO, and VTA are members of the research staff of CONICET.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes

¹ Values of νNO in the range 1300–1400 cm⁻¹ indicate that the nitrosyl group is in a reduced state, comprising a bond order close to 2, and this is observed for many members of the series [Fe^II(CN)₅NOX]ⁿ⁻, with X = thiolates, H, alkyls, etc. [22].

² Transient absorptions in the visible region (cf. figure 3), and the rising weak absorptions at ~1000 nm can be assigned to cyano-bridged dinuclear species containing [Fe^III, Fe^III] and [Fe^II, Fe^III] chromophores. They are generated under the initial oxidative conditions (associated with Fe(III) concentrations greater than ~10⁻⁴ M) and decay in a dissociative way under an excess of AH [23, 24].

Additional information

Funding

This work was supported by the Consejo Nacional de Investigaciones Científicas y Técnicas [grant number PIP 112–200801–02817]; Universidad de Buenos Aires [grant number 01/W391].