Redox conversions of dinitrosyl iron complexes with natural thiol-containing ligands

Using the electron paramagnetic resonance (EPR) and optical spectrophotometric methods, it has been established that biologically active, water-soluble dinitrosyl iron complexes (DNIC) with glutathione are predominantly represented by the diamagnetic binuclear form (B-DNIC) even in the presence of a 10-fold excess of glutathione non-incorporated into DNIC at neutral pH. With the increase in pH to 10-11, B-DNIC are fully converted into the paramagnetic mononuclear form (M-DNIC) with a characteristic EPR signal at g(perpendicular to) = 2.04, g(parallel to) = 2.014 and g(aver). = 2.03. After treatment with a strong reducing agent sodium dithionite, both M- and B-DNIC are converted into the paramagnetic form with a characteristic EPR signal at g(perpendicular to) = 2.01, g(parallel to) = 1.97 and g(aver). = 2.0. Both forms display similar absorption spectra with absorption bands at 960 and 640 nm and a bend at 450 nm. After oxidation by atmospheric oxygen, this situation is reversed, which manifests itself in the disappearance of the EPR signal at g(aver). = 2.0 and complete regeneration of initial absorption spectra of M- or B-DNIC with characteristic absorption bands at 390 or 360 and 310 nm, respectively. Treatment of bovine serum albumin (BSA) solutions with gaseous NO in the presence of Fe2+ and cysteine yields BSA-bound M-DNIC (M-DNIC-BSA). After treatment with sodium dithionite, the latter undergo transformations similar to those established for low-molecular M-DNIC with glutathione. Based on the complete coincidence of the optical and the EPR characteristics of sodium dithionite-treated M- and B-DNIC and other findings, it is suggested that sodium dithionite-reduced B-DNIC are subject to reversible decomposition into M-DNIC. The reduction and subsequent oxidation of M- and B-DNIC are interpreted in the paradigm of the current concepts of the initial electronic configurations of M- and B-DNIC (d(7) ({Fe(NO)(2)}(7)) and d(7)-d(7) ({Fe(NO)(2)}(7)-{Fe(NO)(2)}(7)), respectively). (C) 2013 Elsevier Inc. All rights reserved.