New Biomimetic Analogues of Functional [2Fe-2S] Proteins

Abstract

Iron-sulfur proteins are ubiquitous natural cofactors of prime importance in biological systems. While electron transfer is regarded as their main role, iron-sulfur clusters also feature increasingly recognized new functionalities, e.g. in catalysis, sensing of small molecules, radical-based processes and gene regulation. Accordingly, iron-sulfur proteins are nowadays viewed as nature"s modular multipurpose structures, involved in crucial biological processes - most likely since the beginning of terrestrial life. The understanding of their structural and electronic properties has benefited significantly from investigations on synthetic model compounds over the last decades. A variety of synthetic challenges however remained to inorganic chemists even for the smallest [2Fe-2S] clusters. In the present work, novel biomimetic [2Fe-2S] clusters were synthesized and comprehensively examined in order to gain further insights into the fundamental characteristics of their biological counterparts. At first, a ligand exchange pathway starting from a homoleptic indolate-ligated [2Fe-2S] precursor was developed affording the thiophenolate-coordinated ferredoxin analogues via a convenient experimental procedure. In addition to various differently substituted thiophenols, heteroaromatic thiols and chelating biphenols were successfully applied as reagents in the latter exchange reaction, indicating that the conversion is of general use in synthetic [2Fe-2S] chemistry. Ligand effects on prominent spectroscopic characteristics of all-thiolate-ligated clusters were studied by introduction of electron-withdrawing and electron-donating substituents into chelating dithiobiphenyl-based ligand scaffolds. The anticipated ligand-mediated control over the redox potentials of those cluster compounds has been ascertained by electrochemical measurements. In order to provide models for the interaction of additional donor atoms with the iron atoms in biological [2Fe-2S] sites, a series of synthetic clusters with terminal thiophenolateligands and tethered ether or thioether moieties has been prepared. Secondary interactions do occur in those clusters if the additional Lewis-bases are suitably positioned in proximity to the cluster core. Significant structural distortions of the usually rigid cluster core geometries were observed with the iron atoms approaching trigonal bipyramidal coordination polyhedra. The detected effects are clearly more pronounced for thioether compared to ether donor groups. DFT calculations are in agreement with the experimental implications. The potential relevance of these findings for biological iron-sulfur sites, e.g. for the unique arginine-ligated [2Fe-2S] cluster in biotin synthase is considered. Beyond those studies, the synthesis of a model compound for mixed-valent [2Fe-2S] ferredoxins is generally considered as pending task to be achieved by synthetic iron-sulfur chemists. In order to tackle this challenge, {N}-homoleptic clusters with terminal dipyrromethanate and 1,2-benzene-bis-benzimidazolate coordination were synthesized and examined with respect to one-electron reduction. The chelating nature of those terminal ligands imparts a relatively high stability that permitted the coulometric generation and EPR characterization of a [2Fe-2S]+ species ligated by 1,2-benzene-bis-benzimidazolate. Finally, asymmetrically coordinate [2Fe-2S] clusters were approached synthetically. After an extensive ligand screening, a chelating diskatyl-{N2}-ligand was discovered that allows the isolation of a heteroleptic {N2Cl2}-ligated cluster with both exchangeable chlorine substituents located on the same iron atom. A first accurate {N2S2}-coordinate analogue of Rieske-type clusters could then be synthesized by consecutive replacement of both remaining halides for the chelating o-xylen-α,α -dithiolate. This Rieske-type cluster accurately emulates structural and spectroscopic features (inter alia the typical Mössbauer parameters) of the natural protein sites, including the characteristic low gav value in the EPR spectra of the reduced [2Fe-2S]+ species.