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H 2 Activation in [FeFe]‐Hydrogenase Cofactor Versus Diiron Dithiolate Models: Factors Underlying the Catalytic Success of Nature and Implications for an Improved Biomimicry
Author(s) -
Arrigoni Federica,
Bertini Luca,
Bruschi Maurizio,
Greco Claudio,
De Gioia Luca,
Zampella Giuseppe
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201804687
Subject(s) - cofactor , hydrogenase , catalysis , protonation , chemistry , hydride , biocatalysis , combinatorial chemistry , stereochemistry , photochemistry , metal , enzyme , organic chemistry , reaction mechanism , ion
Abstract Catalytic H 2 oxidation has been dissected by means of DFT into the key steps common to the Fe 2 unit of both the [FeFe]‐hydrogenase cofactor and selected biomimics. The aim was to elucidate the molecular details underlying the very different performances of the two systems. We found that the better enzyme performance is based on a single iron atom that is maintained electron‐poor, favoring H 2 binding, although embedded within a highly electron‐rich cofactor, ensuring a facile oxidation of the Fe 2 –H 2 adduct. This is due to 1) CN − coordinating to both iron atoms, due to their amphipathic Lewis acid/bas e properties, and 2) the 4Fe4S subunit further withdrawing electrons from the Fe 2 core. Preserving a moderate electron deficiency at a single iron also helps the cofactor preserve hydride affinity, which favors H 2 cleavage. Such valuable characteristics allow the biocatalyst to turnover close to equilibrium conditions. All previous biomimicry has shown, in contrast, the impossibility to properly balance the two apparently contrasting aforementioned requisites, although evident progress has been made by the H 2 ‐ase community. Disclosure of the differences identified could inspire the design of novel biomimics, for instance, reconsidering the use of CN − in the catalyst architecture. Indeed, in the presence of bases normally employed in oxidative catalysis, undesired stable protonation at coordinated CN − , which affects the opposite process (proton reduction), could be overcome.

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