As an approach to explore the amide cleavage reaction, we designed, synthesised, fully characterised and investigated different model systems resembling the catalytic zinc sites of peptidases. The models are mononuclear zinc(II) complexes containing the unit (6-NHR-2-pyridylmethyl)amine (R = CO^tBut, H) as a common feature. This unit supplies an N2 coordination motif and an intramolecular amide oxygen capable of binding the metal ion (Zn^…O=C(amide)); such event has been proposed to be crucial for the cleavage of peptide bonds in peptidases. Besides, these models offer different types and numbers of metal binding sites, which affect electronically and sterically the zinc(II) ion as well as its Lewis acidity. Indeed, the effect of the first coordination sphere seems to influence drastically the cleavage of the intramolecular amide bond leading to an overall change in the stability of the amide bond of ca. 300-fold. The unit (6-NHR-2-pyridylmethyl)amine also provides amide/amine groups that can hydrogen bond other zinc-bound ligands. Some of these complexes were, therefore, used to explore strategies to induce and manipulate hydrogen bond interactions, and to investigate the factors that influence their strength. These hydrogen bond interactions occur both in solution and in the solid state and their strength was determined by IR spectroscopy and correlated with the X-ray crystal structures. We also report two strategies to position NH groups in the proximity of a zinc(II)-bound amide oxygen N-H^…O=C(amide), and we investigate their effect on the stability of the amide group.