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

Marie Bergner†, Sebastian Dechert†, Serhiy Demeshko†, Claudia Kupper†, James M. Mayer*‡, and Franc Meyer*† 

† Institute of Inorganic Chemistry, Georg-August-University Göttingen, Tammannstraße 4, D-37077 Göttingen, Germany

‡ Yale University, 225 Prospect Street, New Haven, Connecticut 06511, United States

J. Am. Chem. Soc., 2017, 139 (2), pp 701–707

DOI: 10.1021/jacs.6b09180

Publication Date (Web): January 5, 2017

Copyright © 2017 American Chemical Society

*james.mayer@yale.edu, *franc.meyer@chemie.uni-goettingen.de

Abstract

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.

[Question]

先行研究研究のCluster(Rieske model)と、今回の研究のCluster(mitoNEET model)において、 ΔG°PCET の値の違いは何によるものか。

(Previous work(Rieske model): 3b, 2, This work(mitoNEET model): 4, 5)

[Answer]

Rieske model clusterの3bや2ではプロトン化された種において、N原子上のプロトンが共鳴安定化されるため、そのような共鳴安定化がされないmito NEET model clusterのほうが ΔG°PCET が負に大きくなると考えられる。

 ΔG°PCET で比較した場合、Rieske model cluster(3b, 2)よりもmito NEET model(4, 5)の方が負に大きいため、PCETが熱力学的には起こりやすいと考えられる。しかし、実際の速度定数kを比較すると、mitoNEET model(5)が最も遅い反応であった。これは5において、{SN}で配位されたFe部位で電子密度の局在化がより起こり、電子移動に伴うFe－S中心の構造変化が起こりにくいためであると考えられる。したがって、再配列エネルギー（λ）（マーカス理論：ΔG‡= (ΔG° + λ) /4λ）が大きくなり、したがって活性化エネルギーΔG‡も大きくなるため、mitoNEET model cluster（5）において最も小さな速度定数が得られた。