NMR, potentiometric and ESI-MS combined studies on the zinc(II) magnesium(II) and calcium(II) complexation by (morpholin-1-yl)methane-1,1-diphosphonic acid and its thio-analog

The crystal structures of the two derivatives of aminomethane-1,1-diphosphonic acid with morpholinyl- (1) and thiomorpholinyl- (2) side chains were determined by single crystal X-ray diffraction and discussed with respect to molecular geometry and solid state organization. The protonation equilibria, solution behavior and complex-formation equilibria in solutions of 1 and 2 with the Zn(II), Mg(II) and Ca(II) ions were studied by means of NMR, pH-potentiometry and ESI-MS methods.As the pK_(NH⁺) protonation constants of 1 and 2 are high (11.65 and 11.91, respectively) two different approaches were used to evaluate the pH-potentiometric data. The first approach disregarded the proton-dissociation from the NH⁺ group. In the second one, all the pK_a values were considered in the M(II):ligand formation equilibria. For 1, the accuracy of the pK_(NH⁺) determination was shown to be sufficient to calculate reliable stability constants of metal complexes with the use of both approaches. For 2, only approach neglecting the pK_(NH⁺) protonation constant was shown to be correct.The studied acids form dinuclear, [M₂L₃H_x], [M₂L₂H_x] and mononuclear MLH_x and ML₂H_x complexes with different degree of ligand protonation. Tendency to undergo some oligomerization with the increase in the metal and ligand concentration was demonstrated for the [CaLH] complex of 1 and 2. As far as 1 and 2 remain protonated, the Zn(II), Mg(II) and Ca(II) ions are coordinated exclusively through oxygen atoms of the phosphonate groups. The metal promoted proton dissociation from the NH⁺ ring atom takes place in alkaline pH.