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(Aminomethylene)phosphonate Analogues as Zn II Chelators: Synthesis and Characterization
Author(s) -
Hevroni Bosmat Levi,
Jantz Thomas,
Gottlieb Hugo E.,
Fischer Bilha
Publication year - 2017
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201700210
Subject(s) - chemistry , moiety , phosphonate , potentiometric titration , titration , stability constants of complexes , chelation , stereochemistry , nuclear magnetic resonance spectroscopy , medicinal chemistry , octahedral molecular geometry , molecule , crystallography , inorganic chemistry , crystal structure , ion , organic chemistry
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/Vis spectrophotometry and by 1 H and 31 P NMR spectroscopy. Acidity and stability constants were established for each derivative by potentiometric pH titrations. ML 2 type Zn II complexes of AMP, bearing either an imidazolyl or pyridyl moiety, 8 , 10 , and 12 , exhibit high log β values (17.68, 16.92, and 16.65, respectively), while for the AMP‐thiazolyl ( 14 ) complex with Zn II , log β is 12.53. Generally, ligands 9 , 11 , and 13 , bearing two heterocyclic moieties, present higher log β values (22.25, 21.00, and 18.28, respectively) vs. analogues bearing one heterocyclic moiety. Additionally, based on 1 H, 13 C, and 31 P NMR spectroscopic data, we propose a structure of the 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 new family of water‐soluble high‐affinity Zn II chelators, in particular AMP‐(Im) 2 , which forms the most stable complex (log β 22).