Model of the MitoNEET [2Fe−2S] Cluster Shows Proton Coupled Electron Transfer

MitoNEET is an outer membrane protein
whose exact function remains
unclear, though a role of this protein in redox and iron sensing as
well as in controlling maximum mitochondrial respiratory rates has
been discussed. It was shown to contain a redox active and acid labile
[2Fe–2S] cluster which is ligated by one histidine and three
cysteine residues. Herein we present the first synthetic analogue
with biomimetic {SN/S2} ligation which could be structurally
characterized in its diferric form, 52–. In addition to being a high fidelity structural model for
the biological cofactor, the complex is shown to mediate proton coupled
electron transfer (PCET) at the {SN} ligated site, pointing at a potential
functional role of the enzyme’s unique His ligand. Full PCET
thermodynamic square schemes for the mitoNEET model 52– and a related homoleptic {SN/SN}
capped [2Fe–2S] cluster 42– are
established, and kinetics of PCET reactivity are investigated by double-mixing
stopped-flow experiments for both complexes. While the NH
bond dissociation free energy (BDFE) of 5H2– (230 ± 4 kJ mol–1)
and the free energy ΔG°PCET for the reaction with TEMPO (−48.4 kJ mol–1) are very similar to values for the homoleptic cluster 4H2– (232 ± 4 kJ mol–1, –46.3 kJ mol–1) the latter
is found to react significantly faster than the mitoNEET model (data
for 5H2–: k = 135 ± 27 M–1 s–1, ΔH‡ = 17.6 ± 3.0 kJ mol–1, ΔS‡ = −143 ±
11 J mol–1 K–1, and ΔG‡ = 59.8 kJ mol–1 at
293 K). Comparison of the PCET efficiency of these clusters emphasizes
the relevance of reorganization energy in this process.