Generation of HS from Thiol-Dependent NO Reactivity of Model [4Fe-4S] Cluster and Roussin's Black Anion.

Iron-sulfur clusters (Fe-S) have been well established as a target for nitric oxide (NO) in biological systems. Complementary to protein-bound studies, synthetic models have provided a platform to study what iron nitrosylated products and byproducts are produced depending on a controlled reaction environment. We have previously shown a model [2Fe-2S] system that produced a dinitrosyl iron complex (DNIC) upon nitrosylation along with hydrogen sulfide (HS), another important gasotransmitter, in the presence of thiol, and hypothesized a similar reactivity pattern with [4Fe-4S] clusters which have largely produced inconsistent reaction products across biological and synthetic systems. Roussin's black anion (RBA), [Fe(μ-S)(NO)], is a previously established reaction product from synthetic [4Fe-4S] clusters with NO. Here, we present a new reactivity for the nitrosylation of a synthetic [4Fe-4S] cluster in the presence of thiol and thiolate. [EtN][FeS(SPh)] () was nitrosylated in the presence of excess PhSH to generate HS and an "RBA-like" intermediate that when further reacted with [NEt][SPh] produced a {Fe(NO)} DNIC, [EtN][Fe(NO)(SPh)] (). This "RBA-like" intermediate proved difficult to isolate but shares striking similarities to RBA in the presence of thiol based on IR υ stretching frequencies. Surprisingly, the same reaction products were produced when the reaction started with RBA and thiol. Similar to /NO, RBA in the presence of thiol and thiolate generates stoichiometric amounts of DNIC while releasing its bridging sulfides as HS. These results suggest not only that RBA may not be the final product of [4Fe-4S] + NO but also that RBA has unprecedented reactivity with thiols and thiolates which may explain current challenges around identifying biological nitrosylated Fe-S clusters.