A series of aminomethylene-phosphonate (AMP) analogues, 8-14, bearing one or two heterocyclic moieties (imidazolyl, pyridyl, and thiazolyl) on the aminomethylene group, were synthesized as potential Zn(II)-chelators. The complexes of analogues 8-14 with Zn(II)-ions were characterized by their stoichiometry, geometry, coordination-sites, acid-base equilibria, and stability constants. Analogues 8-14 form stable water-soluble 2:1 L:Zn(II) complexes, as established by Zn(II)-titration, monitored by UV and by ¹H- and ³¹P-NMR spectroscopy. Acidity and stability constants were established for each derivative by potentiometric pH-titrations. ML₂-type Zn(II)-complexes of AMP, bearing either an imidazolyl or pyridyl moiety, 8, 10 and, 12, exhibit high logβ values - 17.68, 16.92, and 16.65, respectively, while for the AMP-thiazolyl, 14, -Zn(II) complex, logβ is 12.53. Generally, ligands 9, 11, and 13, bearing two heterocyclic moieties, present higher logβ values (22.25, 21.00, and 18.28, respectively) vs. analogues bearing one heterocyclic moiety. Additionally, based on ¹H-,¹³C-, and ³¹P-NMR data, we propose a structure of AMP-(Im)₂-Zn(II) complex in solution, where the Zn(II)-coordination sites involve the phosphonate moiety and both imidazolyl rings of the two binding molecules, forming an octahedral geometry around the Zn(II)-ion. In summary, we propose a novel family of water-soluble high-affinity Zn(II)-chelators, in particular AMP-(Im)₂, forming the most stable complex (logβ 22).
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