Thermodynamics of the acid dissociation of BOPTA.: Determination of equilibrium constants by means of 13C NMR spectroscopy

BOPTA, (9R,S)-2,5,8-Tris(carboxymethyl)-12-phenyl-11-oxa-2,5,8-triazadodecane-1,9-dicarboxylic acid, is a chelating agent whose gadolinium complex can be used as a magnetic resonance imaging contrast agent (MRI-CA) specific for the liver. The stepwise deprotonation constants for BOPTA were determined from a series of C-13 NMR measurements by means of the new computer program HYPNMR and also from potentiometric titration data by means of the program HYPERQUAD. The first three stepwise protonation constants obtained by the NMR method are in very good agreement with those determined by potentiometry. In very acidic solutions the NMR method gave more reliable results because the glass electrode is susceptible to interference at low pH. The enthalpy changes for the protonation reactions have also been measured by microcalorimetry. The first two protonation reactions are exothermic, indicating that protonation occurs on amine nitrogen atoms, while the following protonation steps, being athermic, involve carboxylate groups.