POTENTIOMETRIC AND NMR SPECTROSCOPIC STUDY OF PROTONATIONS AND AMIDE HYDROGEN-EXCHANGE RATES OF DTPA-BIS(BUTYLAMIDE), DTPA-BIS(GLUCAMIDE), AND THEIR LANTHANIDE(III) COMPLEXES

The macroscopic and microscopic protonations of DTPA-GlucA(2) (DTPA-bi s(glucamide)) have been investigated using potentiometry, H-1 and C-13 NMR. The protonation behavior appears to be similar to that of the co rresponding bis(alkylamides), showing that it is not affected by the p resence of the polyhydroxy side chains. Consideration of the various p ossible protonation pathways leads to the conclusion that the differen ces in basicity of the amino functions in DTPA and DTPA-bis( amides) r esult in different protonation sequences of these ligands, which is re flected in the macroscopic protonation constants. The significance for the design of DTPA-based contrast agents for MRI is discussed. Exchan ge rates of the amide NH of this compound and that of DTPA-bis(butylam ide) (DTPA-BuA(2)) were determined via longitudinal relaxation rate me asurements of the amide H-1 resonances in H2O-D2O (9:1) as solvent. Th e reaction is strongly base catalyzed and the rate increases substanti ally upon coordination of the DTPA-bis(amide) by La(III). (C) 1998 Els evier Science S.A. All rights reserved.