Controlling Substrate Binding to Fe4S4 Clusters through Remote Steric Effects

Abstract

The extraordinary reactivity exhibited by many Fe-S enzymes is due in large part to the influence of the protein scaffold on substrate binding and activation. In principle, the coordination chemistry of synthetic Fe-S clusters could similarly be controlled through remote steric effects. Toward this end, we report the synthesis of 3:1 site-differentiated [Fe 4 S 4 ] clusters ligated by N-heterocyclic carbene (NHC) ligands with variable steric profiles: IMes (1,3-dimesitylimidazol-2-ylidene) and I i Pr Me (1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene). Treatment of (IMes) 3 Fe 4 S 4 Cl with NaBAr F4 in ethereal solvents (Et 2 O and THF) leads to the formation of an ether adduct, [(IMes) 3 Fe 4 S 4 (solv)][BAr F4 ]; solvent can be displaced by addition of t BuNC to form the unusual monoisocyanide adduct [(IMes) 3 Fe 4 S 4 (CN t Bu)][BAr F4 ]. Carrying out the same reactions with the less sterically encumbered cluster (I i Pr Me ) 3 Fe 4 S 4 Cl results in more typical reactivity: undesired ligand redistribution to form the homoleptic cluster [(I i Pr Me ) 4 Fe 4 S 4 ][BAr F4 ] and generation of the triisocyanide adduct [(I i Pr Me ) 3 Fe 4 S 4 (CN t Bu) 3 ][BAr F4 ]. The increased steric profile of the IMes ligands disfavors ligand redistribution and defines a binding pocket at the apical Fe, thereby enabling the generation of a coordinatively unsaturated and substitutionally labile Fe site. This method of controlling the coordination chemistry at the apical Fe site by modifying the sterics of ligands bound to adjacent Fe sites complements existing strategies for generating site-differentiated Fe-S clusters and provides new opportunities to direct reactivity at cuboidal metalloclusters.