Calcium−Phosphonate Interactions: Solution Behavior and Ca²⁺ Binding by 2-Hydroxyethylimino-bis(methylenephosphonate) Studied by Multinuclear NMR Spectroscopy

The tetra-acid 2-hydroxyethylimino-bis(methylenephosphonic acid) (HEIBPH, 1) and its ring condensation product, the triacid 2-hydroxy-2-oxo-4-phosphonemethyl-1,4,2-oxazaphosphorinane (2), were investigated for determination of protonation constants using ³¹P, ¹H, and ¹³C NMR spectroscopy in a wide pH range. As for other α-amino-phosphonic acids, the first protonation of 1 is straightforward and occurs at the nitrogen, while for 2 the first protonation occurs simultaneously at the exo phosphonate group, allowing estimation of the microscopic protonation constants. The complexation of Ca²⁺ with 1 in a 1:1 molar ratio in aqueous solutions and in the presence of a 5-fold excess Na⁺ is rationalized by the products LCaH₂, LCaH, LCaNaH, LCa, and LCa₂ (L = 1). Only the phosphonate groups are involved in Ca²⁺ binding at pH > 3, while the phosphonate, hydroxyl, and amine functionalities coordinate to Ca²⁺ at pH > 6−7, as soon as the proton at N is lost. Probable conformation states of ions of 1 and 2 are estimated by means of the dependence of vicinal coupling constants ³J_HH and ³J_PC from dihedral angles.