An Assessment of the Potential Relationship between the Charge of Gd-DTPA Complexes and the Exchange Rate of the Water Coordinated to the Metal

The residence time of coordinated water (tau(M)), a parameter of paramount importance for relaxivity, is compared in a series of Gd-DTPA derivatives carrying different global charges. The importance of the charge in the first coordination sphere of the metal and in its vicinity is reported. Neutral bisester and bisamide complexes have significantly different tau(M) values. The paradoxical similarity of the exchange rates of bisester complexes and Gd-DTPA, on the one hand, and the large difference between neutral bisester and bisamide complexes, on the other hand, suggest that the charge inside the first coordination sphere is not the factor dominating the water exchange rate, which seems therefore more sensitive to the steric congestion. The study of Gd-(S)-N-6-carboxymethyl-DTPA, Gd-DTPA-BHydroxamide at basic pH, and Gd-DTPA-BAlaA clearly shows that anionic groups located outside the first coordination sphere have a beneficial influence on the value of tau(M), but that this effect strongly decreases with an increasing distance between the anionic group and the coordinated water. These conclusions underline the influence of steric hindrance and of the charged groups present in close proximity of the first coordination sphere on the exchange rate of the coordinated water. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)