Reactivity of [Fe4S4(SR)4]2-,3- clusters with sulfonium cations:: Analogue reaction systems for the initial step in biotin synthase catalysis

The first step in catalysis by a class of iron-sulfur enzymes that includes biotin synthase is the one-electron reductive cleavage of the obligatory cofactor S-adenosylmethionine by an [Fe4S4](+) cluster to afford methionine and the deoxyadenosyl radical (DOA.). To provide detailed information about the reactions of sulfonium ions with [Fe4S4](2+,+) clusters, the analogue reaction systems [Fe4S4(SR ')(4)](2-,3-)/[PhMeSCH2R](+) (R ' = Et (4, 6), Ph (5, 7); R = H (8), COPh (9), p-C6H4CN (10)) were examined by H-1 NMR spectroscopy. Sulfonium ions 8-10 react completely with oxidized clusters 4 and 5 to afford PhSMe and R ' SCH2R in equimolar amounts as a result of electrophilic attack by the sulfonium ion on cluster thiolate ligands. Reactions are also complete with reduced clusters 6 and 7 but afford, depending on the substrate, the additional products RCH3 (R = PhCO, p-C6H4CN) and the ylid PhMeS=CHR or (P-NCC6H4CH2)(2) Redox potentials of 9 and 10 allow electron transfer from 6 or 7. The reaction systems 6/9,10 and 7/9,10 exhibit two reaction pathways, reductive cleavage and electrophilic attack, in an ca. 4:1 ratio inferred from product distribution. Cleavage is a two-electron process and, for example in the system 6/9, is described by the overall reaction 2[Fe4S4(SR ')(4)](3-) + 2[PhMeSCH2R](+) --> 2[Fe4S4(SR ')(4)](2-) + PhSMe + RCH3 + PhMeS=CHR. This and other reactions may be summarized as [PhMeSCH2R](+) + 2e(-) + H+ --> PhSMe + RCH3; proposed reaction sequences parallel those for electrochemical reduction of sulfonium ions. This work demonstrates the intrinsic ability of [Fe4S4](+) clusters with appropriate redox potentials to reductively cleave sulfonium substrates in overall two-electron reactions. The analogue systems differ from the enzymes in that DOA is generated in a one-electron reduction and is sufficiently stabilized within the protein matrix to abstract a hydrogen atom from substrate or an amino acid residue in a succeeding step. In the present systems, the radical produced in the initial step of the reaction sequence, [Fe4S4(SR ')(4)](3-) + [PhMeSCH2R](+) --> [Fe4S4(SR ')(4)](2-) + PhSMe + RCH2., is not stabilized and is quenched by reduction and protonation.