Stabilization of Calcium− and Terbium−Carboxylate Bonds by NH···O Hydrogen Bonds in a Mononuclear Complex: A Functional Model of the Active Site of Calcium-Binding Proteins

Novel benzoic acid ligands with bulky amide groups at the ortho position, 2,6-(MeCONH)2C6H3CO2H (1) and 2,6-(t-BuCONH)2C6H3CO2H (2), and their tris- and tetrakis(carboxylate) complexes with Ca(II) and Tb(III) ions, (NEt4)2[CaII{O2C-2,6-(t-BuCONH)2C6H3}4] (4), [Tb{O2C-2,6-(t-BuNHCO)2C6H3}3(H2O)3}] (5), and (NMe)4[Tb{O2C-2,6-(t-BuNHCO)2C6H3}4(thf)] (6), were synthesized. The formation of the NH···O hydrogen bonds between the amide
NH and carboxylate for 2, (NEt4){2,6-(t-BuCONH)2C6H3CO2} (3), and 4 was determined by 1H NMR spectroscopy
in solution and in the solid state (CRAMPS, IR). The ligand exchange reactions were attempted between 4 and a
large excess of 2,4,6- Me3C6H3CO2H in chloroform-d solution; however, exchange reaction did not take place,
indicating that the Ca(II) ions bound strongly to the carboxylate in 4. The Ca(II) ion binding properties with the
benzoate derivatives were also examined using Tb(III) ion as a fluorescence probe. These results indicate that the
NH···O hydrogen bonding between the amide NH and the oxygen atom of the carboxylate contributes to strong
Ca(II) binding and prevents the dissociation of the calcium−carboxylate bond. The X-ray structural analyses of
these complexes revealed that the NH···O hydrogen-bonded carboxylate ligands prefer the chelate-type coordination
and create a mononuclear {Ca(O2CR)4}2- or {Tb(O2CR)4}- core with anionic charge, which is known only in the
active site of calcium-binding proteins.