High-relaxivity contrast agents for magnetic resonance imaging based on multisite interactions between a β-cyclodextrin oligomer and suitably functionalized Gd^III chelates

The results reported in this work show that tightly assembled adducts formed by trisubstituted Gd^III complexes and a β-CD multimer (Poly-β-CD, d.p. ca. 12) may represent very interesting candidates for novel MRI applications wherein a high number of paramagnetic ions endowed with high relaxivity (per Gd^III ion) are necessary. The relaxivities found for the paramagnetic adducts represent a remarkable step forward on the relaxivity scale. However, a detailed investigation of the determinants of the relaxation enhancement in these systems shows that their relaxivities are still limited by a nonoptimal τ_R and a relatively long exchange lifetime of the coordinated water(s). Moreover, the exchange rate of the water molecule(s) coordinated to the Gd^III ion further decreases upon binding to the Poly-β-CD. It is suggested that this finding is related to the structural properties of the supramolecule, which brings a high density of hydroxyl groups into the proximity of the "guest" complexes, and this yields an overall reinforcement of the hydrogen-bonding network involving the coordinated water(s). On the other hand, such a tight arrangement appears responsible for an enhanced contribution to the observed relaxivity arising from water molecules in the second coordination sphere of the metal center.