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

BOPTA, (9R,S)-2,5,8-Tris(carboxymethyl)-12-phenyl-11-oxa-2,5,8-triazadodeca ne-1,9-dicarboxylic acid, is a chelating agent whose gadolinium complex can be used as a magnetic resonance imaging contrast agent (MRI-CA) specific f or the liver. The stepwise deprotonation constants for BOPTA were determine d from a series of C-13 NMR measurements by means of the new computer progr am HYPNMR and also from potentiometric titration data by means of the progr am HYPERQUAD. The first three stepwise protonation constants obtained by th e NMR method are in very good agreement with those determined by potentiome try. In very acidic solutions the NMR method gave more reliable results bec ause 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, in dicating that protonation occurs on amine nitrogen atoms, while the followi ng protonation steps, being athermic, involve carboxylate groups.