Elucidating Secondary Coordination Sphere Effects on the Electronic Structure and Redox Properties of Biomimetic Iron–Sulfur Cubanes
Year: 2026
Type: preprint
Abstract: Nature readily employs iron–sulfur (Fe–S) clusters to perform a wide range of essential biological processes involving long-range electron transport and catalysis for kinetically challenging redox chemistry. Notably, the structure of Fe–S cubane ([Fe4S4]) metalloclusters that serve as electron transfer mediators are highly conserved, where ligand coordination to four cysteine residues anchors the cofactor within metalloproteins such as ferredoxins (Fds) and high-potential iron-sulfur protein (HiPIPs). Despite sharing the same primary coordination environment, the [Fe4S4] cofactors within Fds and HiPIPs operate with discrete redox couples and potential windows that afford distinct electrochemical properties depending on the Fe–S secondary coordination sphere and protein environment. This enables [Fe4S4] clusters to serve as versatile coupling partners for kinetically challenging redox reactions spanning the full range of biologically accessible reduction potentials. The electrochemical properties of [Fe4S4] clusters are tuned through the cooperative interplay between its strongly-correlated electronic structure and the noncovalent interactions within its secondary-sphere and protein environments. Significant experimental and computational efforts have been made to identify the structure-function relationships driving selective modulation of cluster electrochemical features; however, disentangling this complex interplay remains a significant challenge. Here, we employ a low-scaling, multi-reference computational approach to elucidate how secondary-sphere interactions, namely hydrogen bonding (H-bonding) and solvent electrostatics, tune the electronic structure of biomimetic [Fe4S4] clusters and give rise to the diverging redox properties observed across different protein scaffolds in biological systems.
Source: ChemRxiv
Authors: Shelby T. Davis, Jan-Niklas Boyn
Institution: University of Minnesota
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7212176616