Title

Controlled Protonation of [2Fe–2S] Leading to MitoNEET Analogues and Concurrent Cluster Modification

Document Type

Article

Publication Date

11-1-2021

Abstract

MitoNEET, a key regulatory protein in mitochondrial energy metabolism, exhibits a uniquely ligated [2Fe–2S] cluster with one histidine and three cysteines. This unique cluster has been postulated to sense the redox environment and release Fe–S cofactors under acidic pH. Reported herein is a synthetic system that shows how [2Fe–2S] clusters react with protons and rearrange their coordination geometry. The low-temperature stable, site-differentiated clusters [Fe2S2(SPh)3(CF3COO)]2– and [Fe2S2(SPh)3(py)] have been prepared via controlled protonation below −35 °C and characterized by NMR, UV–vis, and X-ray absorption spectroscopy. Both complexes exhibit anodically shifted redox potentials compared to [Fe2S2(SPh)4]2– and convert to [Fe4S4(SPh)4]2– upon warming to room temperature. The current study provides insight into how mitoNEET releases its [2Fe–2S] in response to highly tuned acidic conditions, the chemistry of which may have further implications in Fe–S biogenesis.

Identifier

PMID: 34672568

DOI

10.1021/acs.inorgchem.1c02622

Publisher

American Chemical Society

Publication Information

Inorganic Chemistry

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