Synthesis, Variable Temperature and Pressure 17O NMR Study of Bis(alkylamide) Derivatives of [(Gd-DTPA)(H2O)]2 − An Assessment of the Substitution Effect on Water Exchange Kinetics

Abstract

In this work, primary, secondary and tertiary bis(amide) derivatives of DTPA have been synthesized and the residence time of the water molecule coordinated to their gadolinium complexes has been measured by variable temperature 17O NMR spectroscopy. The influence of substituent characteristics (molecular mass, hydrophobicity, volume) has been studied. For the primary and secondary bis(amide) complexes, increasing the length of the lateral chains decreases the water residence time. It varies from 1171±38 ns for [Gd(DTPA-BA)(H2O)] to 673±32 ns for [Gd(DTPA-BHeptA)(H2O)]. The activation volumes of 5 bis(amide) complexes {[Gd(DTPA-BA)(H2O)], [Gd(DTPA-BEA)(H2O)], [Gd(DTPA-BnBA)(H2O)], [Gd(DTPA-BAA)(H2O)], and [Gd(DTPA-BHA)(H2O)]} have been measured by a variable pressure 17O NMR spectroscopic study. No change in the activation volume is observed when the substituent size is increased. The inner sphere is therefore not disturbed by the substitution on the amide groups. The slight decrease in water residence time can be attributed to the hydrophobicity increase of the complexes which, in turn, leads to a hydrophobic environment favorable to water molecule exchange. The water residence time of tertiary bis(amide) complexes is similar to the fastest secondary bis(amide) complex. For the tertiary bis(amide) complexes, a length increase by the substituent does not change the residence time. According to these results, we suspect that a disruption of the hydration shell of the complexes by amide substituents occurs that can influence coordinated water exchange by a factor of two, at most. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)