Novel applications of 3:1 site-differentiated [4Fe-4S] clusters

Abstract

[4Fe-4S] clusters are one of Nature’s most ubiquitous cofactors, playing vital roles in protein structure stabilization, electron transport, catalysis, and sensing. When an enzymatic active site features a [4Fe-4S] cluster, the coordination environment of the cluster is 3:1 site-differentiated, meaning that the ligand or residue coordinated to one of the four iron atoms is markedly different from those coordinated to the other three iron atoms. To study these intriguing metallosites, biomimetic chemists prepare, study, and compare synthetic [4Fe-4S] clusters to their biological counterparts. 3:1 site differentiation in synthetic clusters is usually achieved by the use of tripodal trithiolate ligands, which chelate three of the four iron sites, leaving one iron atom free for further modification. Chapter 1 of this thesis provides an overview of natural and synthetic 3:1 site-differentiated [4Fe-4S] clusters. Chapter 2 presents a new synthetic route to the promising site-differentiating TriSH3 ligand. The route avoids the use of highly toxic reagents and results in an overall yield that is more than double that in the original procedure. TriSH3 reacts with (n-Bu4N)2[Fe4S4(SEt)4] to yield (n-Bu4N)2[Fe4S4(TriS)(SEt)], which in turn reacts with [Fe(tpySH)2](PF6)2 (tpySH = 2,2':6',2''-terpyridine-4'-thiol) to form the first [4Fe-4S] cluster dimer to be linked by a metal-containing bridge. Chapter 3 presents a series of symmetrically substituted [4Fe-4S] clusters with N-substituted indole-3-thiolate ligands, which are monodentate analogues of TriS3–. The new cluster family undergoes 2–/3– redox transitions at potentials midway between the potential ranges in which clusters fully coordinated by all-aliphatic and all-aromatic thiolates generally display redox transitions, and show electronic transitions that are among the most redshifted known in [4Fe-4S] cluster chemistry. Chapter 4 demonstrates that reaction of (n-Bu4N)2[Fe4S4(TriS)(SEt)] with 4-pyridinethiol results in a 3:1 site-differentiated [4Fe-4S] cluster with a pendant pyridyl group, which can subsequently react with the ruthenium porphyrin [Ru(TTP)(CO)(MeOH)] (TTP = 5,10,15,20-tetra(p-tolyl)porphyrinato dianion) to form a [4Fe-4S]-Ru assembly. Furthermore, 19F NMR indicates that the reaction of (n-Bu4N)2[Fe4S4(TriS)(SEt)] with p-fluorothiophenol forms minor side products stemming from decoordination of TriS3– arms, demonstrating the benefits of using 19F NMR to study the substitution behavior of [4Fe-4S] clusters. Chapter 5 presents a new model for the active site of iron-only hydrogenase. The model is the TriS3– analogue of an earlier, LS33–-based model reported by Pickett and co-workers and the change in tripodal ligand has a profound impact on the properties of the mimic as a whole. 1H NMR spectroscopy and cyclic voltammetry suggest that the [4Fe-4S] and diiron redox entities in the new model are strongly coupled, as also observed in the natural enzyme. Chapter 6 describes the immobilization of [4Fe-4S] clusters on self-assembled monolayers (SAMs). (n-Bu4N)2[Fe4S4(TriS)(SEt)] can react with the thiol groups at the surface of a mixed SAM, resulting in an immobilizing interaction strong enough to resist extensive washing. The immobilization represents a first step towards studies of [4Fe-4S] clusters at controlled solid-liquid interfaces.