Formation Pathway of Roussin’s Red Ester (RRE) via the Reaction of a {Fe(NO)₂}¹⁰ Dinitrosyliron Complex (DNIC) and Thiol: Facile Synthetic Route for Synthesizing Cysteine-Containing DNIC

Transformation of {Fe­(NO)₂}¹⁰ dinitrosyliron complex (DNIC) Fe­(CO)₂(NO)₂ into [{Fe­(NO)₂}⁹]₂ Roussin’s red ester (RRE) [(μ-S­(CH₂)₂NH₂)­Fe­(NO)₂]₂ (3) triggered by cysteamine via the reaction pathway (intermediates) [{Fe­(NO)₂}¹⁰]₂­[(NO)₂­Fe­(μ-CO)­(μ-S­(CH₂)₂­NH₃)­Fe­(NO)₂] (1) → {Fe­(NO)₂}⁹­{Fe­(NO)₂}¹⁰­[(NO)₂Fe­(μ-S­(CH₂)₂­NH₂)­(μ-S­(CH₂)₂­NH₃)­Fe­(NO)₂] (2) → RRE 3 is demonstrated. The 1-to-2-to-3 conversion is promoted by proton transfer followed by O₂ oxidation and deprotonation. Additionally, a study on facile conversion of complex 3 to complexes [(SR)­(S­(CH₂)₂NH₃)­Fe­(NO)₂] [SR = 2-aminoethanethiolate (4), benzenethiolate (5)] and [(CysS))­(S­(CH₂)₂NH₃)­Fe­(NO)₂] (6) via reaction with thiols and the further utility of complex 5 as a template for synthesizing mixed-thiolate-containing reduced RRE (rRRE) [(μ-SC₆H₅)­(μ-S­(CH₂)₂NH₃)­Fe₂(NO)₄] (7) provide the methodology for the synthesis and isolation of neutral, pure cysteine-/mixed-thiolate-containing DNIC/RRE. Compared to the conversion of complex 2 to complex 3 via reaction with O₂, diphenyl disulfide triggers oxidation of complex 2 to lead to formation of the neutral {Fe­(NO)₂}⁹ DNIC 5 and RRE 3. S–S bond activation of diphenyl disulfide by rRRE 2 may support the decay (oxidation) of rRRE species in ToMOC via the reduction of adjacent protein residues such as cystins, proposed by Lippard.