Iron (II/III) Halide Complexes Promote the Interconversion of Nitric Oxide and S-nitrosothiols through Reversible Fe-S Interaction

Heme and non-heme iron in biology mediate the storage/release of NO^• from <i>S</i>-nitrosothiols as a means to control the biological concentration of NO^•. Despite their importance in many physiological processes, the mechanisms of N-S bond formation/cleavage at Fe centers have been controversial. Herein, we report the interconversion of NO^• and <i>S</i>-nitrosothiols mediated by Fe^II/Fe^III chloride complexes. The reaction of two equivalents of <i>S</i>-nitrosothiol (Ph₃CSNO) with [Cl₆Fe^II₂]²^- results in facile release of NO^• and formation of iron(III) halothiolate. Detailed spectroscopic studies, including in situ UV-vis, IR, and Mössbauer spectroscopy, support the interaction of the S−atom with the Fe^II center. This is in contrast to the proposed mechanism of NO^• release from the well-studied “red product” <i>k</i>¹-N bound <i>S</i>-nitrosothiol Fe^II complex, [(CN)₅Fe(<i>k</i>¹-N-RSNO)]³^-. Additionally, Fe^III chloride can mediate NO^• storage through the formation of <i>S</i>-nitrosothiols. Treatment of iron(III) halothiolate with two equivalents of NO^• regenerates Ph₃CSNO with the Fe^II source trapped as the <i>S</i> = 3/2 {FeNO}⁷ species [Cl₃FeNO]^-, which is inert towards further coordination and activation of <i>S</i>-nitrosothiols. Our work demonstrates how labile iron can mediate the interconversion of NO^•/thiolate and <i>S</i>-nitrosothiol, which has important implications for how Nature manages the biological concentration of free NO^•.