Reactions of site-differentiated [Fe 4S 4] 2+,1+ clusters with sulfonium cations: reactivity analogues of biotin synthase and other members of the S-adenosylmethionine enzyme family

Abstract

The first examples of reduced 3:1 site-differentiated Fe 4S 4 clusters have been synthesized as [Fe 4S 4(LS 3)(SR′)] 3− (R=Et, Ph) by chemical reduction of previously reported [Fe 4S 4(LS 3)(SR′)] 2− clusters, and isolated as NBu 4 + salts. The reduced clusters were characterized by electrochemistry and EPR, 1H NMR, and Mössbauer spectroscopies. The reaction of oxidized clusters with the sulfonium ions [PhMeSCH 2R] + (R=COPh, p-C 6H 4CN) in acetonitrile results in electrophilic attack on coordinated thiolate and production of PhSMe and R′SCH 2R 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 ∼4:1 ratio of reductive cleavage to electrophilic attack. The cleavage products are PhSMe, R′SCH 2R, and RCH 3 for both clusters, and also PhMeSCHR and RCH 2CH 2R from secondary reactions when the sulfonium cation is [PhMeSCH 2COPh] + and [PhMeSCH 2– p-C 6H 4CN] +, respectively. Reaction schemes for reductive cleavage based on product distributions are presented. These results parallel those previously reported for homoleptic [Fe 4S 4(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. {LS 3=1,3,5-tris[(4,6-dimethyl-3-mercaptophenyl)thio]-2,4,6-tris( p-tolylthio)benzene(3−)}.