Transformation of the {Fe(NO)₂}⁹ Dinitrosyl Iron Complexes (DNICs) into S‐Nitrosothiols (RSNOs) Triggered by Acid–Base Pairs

Abstract

S-nitrosation of the coordinated thiolate of dinitrosyl iron complexes (DNICs) to generate S-nitrosothiols (RSNOs) was demonstrated. Transformation of [{(NO)(2)Fe(μ-StBu)}(2)] (1-tBuS) into the {Fe(NO)(2)}(9) DNIC [(NO)(2)Fe(StBu)(MeIm)] (2-MeIm) occurs under addition of 20 equiv of 1-methylimidazole (MeIm) into a solution of 1-tBuS in THF. The dynamic interconversion between {Fe(NO)(2)}(9) [(NO)(2)Fe(S-NAP)(dmso)] (2-dmso) (NAP = N-acetyl-D-penicillamine) and [{(NO)(2)Fe(μ-S-NAP)}(2)] (1-NAP) was also observed in a solution of complex 1-NAP in DMSO. In contrast to the reaction of complex 2-MeIm and bis(dimethylthiocarbamoyl) disulfide ((DTC)(2)) to yield {Fe(NO)}(7)[(NO)Fe(DTC)(2)] (3) (DTC = S(2)CNMe(2)) accompanied by (tBuS)(2) and NO(g), transformation of {Fe(NO)(2)}(9) 2-MeIm (2-dmso) into RSNOs (RS = tBuS, NAP-S) along with complex 3 induced by the Brønsted acid solution of (DTC)(2) demonstrated that Brønsted acid may play a critical role in triggering S-nitrosation of the coordinated thiolate of DNICs 2-MeIm (or 2-dmso) to produce RSNOs. That is, DNIC-mediated S-nitrosation requires a Brønsted acid-Lewis base pair to produce RSNO. Transformation of DNICs into RSNOs may only occur on the one-thiolate-containing {Fe(NO)(2)}(9) DNICs, in contrast to protonation of the two-thiolate-containing DNICs [(NO)(2)Fe(SR)(2)](-) by Brønsted acid to yield [{(NO)(2)Fe(μ-SR)}(2)]. These results might rationalize that the known protein-Cys-SNO sites derived from DNICs were located adjacent to acid and base motifs, and no protein-bound SNO characterized to date has been directly derived from [protein-(cysteine)(2)Fe(NO)(2)] in biology.

Thiolate-based dinitrosyl iron complexes: Decomposition and detection and differentiation from S-nitrosothiols

“…As an alternative, it has also been proposed that DNIC are in equilibrium with Fe(II), NO, thiolate, and S-nitrosothiol [1, 10]. Our observations do not support either hypothesis, but at least partially support the work of Tsou and Liaw [29] who showed that one, but not two, thiol-containing DNIC can produce S-nitrosothiol, but only under acidic conditions. These authors did not consider that this could occur through the intermediacy of nitrite/nitrous acid.…”

Theoretical Investigations on the Mechanistic Aspects of O2 Activation by a Biomimetic Dinitrosyl Iron Complex

“…Several examples of DNICs have been experimentally isolated and studied and includes the more common cysteine‐bound (S‐bound) DNICs and the rarer N‐bound, O‐bound DNICs . {Fe(NO) 2 } 9 or {Fe(NO) 2 } 10 have also been shown to interconvert into each other via a reversible redox reaction –. The formation of DNICs from the action of NO in biological systems has been reported by experimental studies for both non‐heme iron species and heme iron species .…”

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

“…In their opinion, it must be defined as d 9 ({Fe(NO) 2 } 9 in the Feltham-Enemark presentation) [9][10][11][12][13]. As regards the nature of DNIC responsible for the EPR signal at g aver.…”