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 Fe(4)S(4) cluster to afford methionine and the deoxyadenosyl radical (DOA*). To provide detailed information about the reactions of sulfonium ions with Fe(4)S(4) clusters, the analogue reaction systems Fe(4)S(4)(SR')(4)(-)(,3)(-)/PhMeSCH(2)R (R' = Et (4, 6), Ph (5, 7); R = H (8), COPh (9), p-C(6)H(4)CN (10)) were examined by (1)H NMR spectroscopy. Sulfonium ions 8-10 react completely with oxidized clusters 4 and 5 to afford PhSMe and R'SCH(2)R 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 RCH(3) (R = PhCO, p-C(6)H(4)CN) and the ylid PhMeS=CHR or (p-NCC(6)H(4)CH(2))(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 2Fe(4)S(4)(SR')(4)(-) + 2PhMeSCH(2)R --> 2Fe(4)S(4)(SR')(4)(-) + PhSMe + RCH(3) + PhMeS=CHR. This and other reactions may be summarized as PhMeSCH(2)R + 2e(-) + H(+) --> PhSMe + RCH(3); proposed reaction sequences parallel those for electrochemical reduction of sulfonium ions. This work demonstrates the intrinsic ability of Fe(4)S(4) 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, Fe(4)S(4)(SR')(4)(-) + PhMeSCH(2)R --> Fe(4)S(4)(SR')(4)(-) + PhSMe + RCH(2)*, is not stabilized and is quenched by reduction and protonation.