A Water Molecule Triggers Guest Exchange at a Mono-Zinc Centre Confined in a Biomimetic Calixarene Pocket: a Model for Understanding Ligand Stability in Zn Proteins

In this study, the ligand exchange mechanism at a biomimetic Zn^II centre, embedded in a pocket mimicking the possible constrains induced by a proteic structure, is explored. The residence time of different guest ligands (dimethylformamide, acetonitrile and ethanol) inside the cavity of a calix[6]arene-based tris(imidazole) tetrahedral zinc complex was probed using 1D EXchange SpectroscopY NMR experiments. A strong dependence of residence time on water content was observed with no exchange occurring under anhydrous conditions, even in the presence of a large excess of guest ligand. These results advocate for an associative exchange mechanism involving the transient exo-coordination of a water molecule, giving rise to 5-coordinate Zn^II intermediates, and inversion of the pyramid at the Zn^II centre. Theoretical modelling by DFT confirmed that the associative mechanism is at stake. These results are particularly relevant in the context of the understanding of kinetic stability/lability in Zn proteins and highlight the key role that a single water molecule can play in catalysing ligand exchange and controlling the lability of Zn^II in proteins.     

Understanding the Deactivation Pathways of Iridium(III) Pyridine-Carboxiamide Catalysts for Formic Acid Dehydrogenation

The degradation pathways of highly active [Cp*Ir(κ²-N,N-R-pica)Cl] catalysts (pica=picolinamidate; 1 R=H, 2 R=Me) for formic acid (FA) dehydrogenation were investigated by NMR spectroscopy and DFT calculations. Under acidic conditions (1 equiv. of HNO₃), 2 undergoes partial protonation of the amide moiety, inducing rapid κ²-N,N to κ²-N,O ligand isomerization. Consistently, DFT modeling on the simpler complex 1 showed that the κ²-N,N key intermediate of FA dehydrogenation ( I_NH ), bearing a N-protonated pica, can easily transform into the κ²-N,O analogue ( I_NH2 ; ΔG^≠≈11 kcal mol⁻¹, ΔG ≈−5 kcal mol⁻¹). Intramolecular hydrogen liberation from I_NH2 is predicted to be rather prohibitive (ΔG^≠≈26 kcal mol⁻¹, ΔG≈23 kcal mol⁻¹), indicating that FA dehydrogenation should involve mostly κ²-N,N intermediates, at least at relatively high pH. Under FA dehydrogenation conditions, 2 was progressively consumed, and the vast majority of the Ir centers (58 %) were eventually found in the form of Cp*-complexes with a pyridine-amine ligand. This likely derived from hydrogenation of the pyridine-carboxiamide via a hemiaminal intermediate, which could also be detected. Clear evidence for ligand hydrogenation being the main degradation pathway also for 1 was obtained, as further confirmed by spectroscopic and catalytic tests on the independently synthesized degradation product 1 c . DFT calculations confirmed that this side reaction is kinetically and thermodynamically accessible.