Reactions of site-differentiated [Fe4S4]2+,1+ clusters with sulfonium cations:: reactivity analogues of biotin synthase and other members of the S-adenosylmethionine enzyme family

The first examples of reduced 3:1 site-differentiated Fe4S4 clusters have been synthesized as [Fe4S4(LS3)(SR')](3-) (R=Et, Ph) by chemical reduction of previously reported [Fe4S4(LS3)(SR')](2-) clusters, and isolated as NBu4+ salts. The reduced clusters were characterized by electrochemistry and EPR, H-1 NMR, and Mossbauer spectroscopies. The reaction of oxidized clusters with the sulfonium ions [PhMeSCH2R](+) (R=COPh, p-C6H4CN) in acetonitrile results in electrophilic attack on coordinated thiolate and production of PhSMe and R'SCH2R when the reaction occurs at the unique cluster site. The reactions of reduced clusters with these substrates were examined in relation to the reductive cleavage of the cofactor S-adenosylmethionine, the first step in the catalytic cycle of biotin synthase. Product analysis indicated a similar to4:1 ratio of reductive cleavage to electrophilic attack. The cleavage products are PhSMe, R'SCH2R, and RCH3 for both clusters, and also PhMeS=CHR and RCH2CH2R from secondary reactions when the sulfonium cation is [PhMeSCH2COPh](+) and [PhMeSCH2-p-C6H4CN](+), respectively. Reaction schemes for reductive cleavage based on product distributions are presented. These results parallel those previously reported for homoleptic [Fe4S4(SR')(4)](2-,3-) clusters and demonstrate that site-differentiated clusters sustain a high percentage of reductive cleavage, a necessary result in the context of biotin synthase activity preceding an investigation of the mode of binding Of sulfonium substrates and inhibitors at the unique iron site. {LS3=1,3,5-tris[(4,6-dimethyl-3-mercaptophenyl)thio]-2,4,6-tris(p-tolylthio)benzene(3-)}. (C) 2003 Elsevier Inc. All rights reserved.