Zinc(ii) complexes with intramolecular amide oxygen coordination as models of metalloamidases

Abstract

Polydentate ligands (6-R¹-2-pyridylmethyl)–R² (R¹ = NHCO^tBu, R² = bis(2-pyridylmethyl)amine L¹, bis(2-(methylthio)ethyl)amine L² and N(CH₂CH₂)₂S L³) form mononuclear zinc(II) complexes with intramolecular amide oxygen coordination and a range of coordination environments. Thus, the reaction of Zn(ClO₄)₂·6H₂O with L^1–3 in acetonitrile affords [(L)Zn](ClO₄)₂ (L = L¹, 1; L², 2) and [(L³)Zn(H₂O)(NCCH₃)](ClO₄)₂3. The simultaneous amide/water binding in 3 resembles the motif that has been proposed to be involved in the double substrate/nucleophile Lewis acidic activation and positioning mechanism of amide bond hydrolysis in metallopeptidases. X-ray diffraction, ¹H and ¹³C NMR and IR data suggests that the strength of amide oxygen coordination follows the trend 1 > 2 > 3. L^1–3 and 1–3 undergo cleavage of the tert-butylamide upon addition of Me₄NOH·5H₂O (1 equiv.) in methanol at 50(1) °C. The rate of amide cleavage follows the order 1 > 2 ≫ 3, L^1–3. The extent by which the amide cleavage reaction is accelerated in 1–3 relative to the free ligands, L^1–3, is correlated with the strength of amide oxygen binding and Lewis acidity of the zinc(II) centre in 1–3 deduced from the X-ray, NMR and IR studies.