Controlling Substrate Binding to Fe4S4 Clusters through Remote Steric Effects.

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 [Fe4S4] clusters ligated by N -heterocyclic carbene (NHC) ligands with variable steric profiles: IMes (1,3-dimesitylimidazol-2-ylidene) and I iPrMe (1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene). Treatment of (IMes)3Fe4S4Cl with NaBArF4 in ethereal solvents (Et2O and THF) leads to the formation of an ether adduct, [(IMes)3Fe4S4(solv)][BArF4]; solvent can be displaced by addition of tBuNC to form the unusual monoisocyanide adduct [(IMes)3Fe4S4(CN tBu)][BArF4]. Carrying out the same reactions with the less sterically encumbered cluster (I iPrMe)3Fe4S4Cl results in more typical reactivity: undesired ligand redistribution to form the homoleptic cluster [(I iPrMe)4Fe4S4][BArF4] and generation of the triisocyanide adduct [(I iPrMe)3Fe4S4(CN tBu)3][BArF4]. 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.