Elucidating Secondary Coordination Sphere Effects on the Electronic Structure and Redox Properties of Biomimetic Iron–Sulfur Cubanes
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.
Related
- Modulating the Electronic Properties of Conductive Conjugated Coordination Polymers with Atomic-Level Precision.
- Electrochemical Properties and Changes of Crystal and Electronic Structures of Spinel-Type Mg1.33– y V1.67– x + y Mn x O4 ( x = 0.15, 0.06 ≤ y ≤ 0.13) for Magnesium Secondary Batteries
- Trace H2O2-triggered Fenton-like reaction by secondary coordination sphere in iron-based metal-organic frameworks
- Elucidating the Acidic and Textural Properties of ZMQ-1, a 28-membered Ring Mesoporous Aluminosilicate Zeolite
- From Rim to Core: Nitrile Coordination Creates an Electronic Gradient across Cu12 Nanocluster Nodes for CO2-to-Formate Electrosynthesis
BibTeX
@misc{davis2026elucidating,
title = {{Elucidating Secondary Coordination Sphere Effects on the Electronic Structure and Redox Properties of Biomimetic Iron–Sulfur Cubanes}},
author = {Shelby T. Davis and Jan-Niklas Boyn},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15008641/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008641/v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Elucidating Secondary Coordination Sphere Effects on the Electronic Structure and Redox Properties of Biomimetic Iron–Sulfur Cubanes
AU - Shelby T. Davis
AU - Jan-Niklas Boyn
PY - 2026
DA - 2026/09/10
PB - ChemRxiv
DO - 10.26434/chemrxiv.15008641/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008641/v1
AB - 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.
ER -