COMPLEXES OF GA3-BIS(BUTYLAMIDE) DERIVATIVE OF DIETHYLENETRIAMINEPENTAACETIC ACID - STABILITY-CONSTANTS AND NUCLEAR-MAGNETIC-RESONANCE STUDIES IN AQUEOUS-SOLUTION( AND IN3+ WITH THE N,N'')

Potentiometric titrations showed that the sum of the first three proto nation constants of diethylenetriaminepentaacetate N,N''-bis(butylamid e) (L(1)) decreases by 6.6 units when compared to the diethylenetriami nepentaacetate (dtpa). and that the complexes of Ga3+ and In3+ of L(1) have stability constants 6.1-6.3 log units lower than those of dtpa. The decreased basicity of the bis(amide) derivative thus correlates wi th the lower stability of its complexes. However. at pH 7.4 the lower overall basicity of L(1) compared to dtpa partly compensates the lower stability of its complexes, thus causing their conditional stability constants to be comparable to those of the dtpa complexes. The efficac y of L(1) in binding Ga3+ and In3+ under physiological conditions is d iscussed by comparing pM values at pH 7.4, showing that this compound can withstand the competition of transferrin for In3+ in biological me dia relevant to medical applications. The C-13 and H-1 NMR shifts were measured for the complexes of Al3+. Ga3+, In3+ and Y3+ with L(1) and compared with C-13 shifts for the dtpa complexes. The complexes of AP( +) and Ga3+ are hexadentate, possibly of octahedral geometry, and form various structural isomers, whereas those of ln(3+) and Y3+, With a s ingle structural isomer of eight-co-ordination, are very similar to th e lanthanide complexes. The complexes of Al3+ and Ga3+ of L(1) have co nsiderable populations of isomers with bound amide groups, whereas the single structural isomer of the complexes of In3+ and Y3+ With both a mide groups co-ordinated yield a variety of enantiomers in solution.