Cyanide Docking and Linkage Isomerism in Models for the Artificial [FeFe]-Hydrogenase Maturation Process

Linkage
isomerization of the cyanide on the [2Fe] subsite of the
[FeFe]-H2ase active site was reported to occur during the
docking of various synthetic diiron complexes onto a carrier protein,
apo-HydF, as the initial step for the artificial maturation of the
[FeFe]-H2ase enzyme (Berggren et al., Nature, 2013, 499, 66–70). An investigation of our
triiron organometallic models (FeFe-CN/NC-Fe′) revealed that,
once a Fe-CN-Fe connection is formed, high barriers prevent such cyanide
linkage isomerization (Chem. Sci., 2016, 7, 3710–3719). To explore effects of variable oxidation
states of the receiver unit, we introduce copper­(I/II) fragments,
precedented in Holm’s models of cytochrome c oxidase to induce cyanide isomerization (Cu-CN/NC-Fe), to the diiron
synthetic analogues of [FeFe]-H2ase. For comparison, a
zinc variant of the cytochrome c oxidase model is
also examined. According to the oxidation state of copper, a cyanide
flip was induced during the formation of both Zn-NC-Cu and FeFe-CN-Cu
complexes. Density functional theory calculations are used to predict
the mechanisms for such linkage isomerization and account for optimal
conditions including oxidation states of metals, spin states, and
solvation. These results on synthetic paradigms imply a role for oxidation
state control of cyanide isomerization during hydrogenase active site
assembly.