| Abstract
| - The para and meta isomers of the dinuclear GdIII complexes, [Gd2(pX(DTTA)2)(H2O)4]2- and [Gd2(mX(DTTA)2)(H2O)4]2-, based on a xylene core functionalized with two polyaminocarboxylate chelators, exhibit high complex stability and identical water exchange rate. They have remarkable proton relaxivities (r1 = 16.8 and 15.8 mM-1 s-1, 25 °C, 20 MHz), as a consequence of two inner-sphere water molecules, a rigid linker, and a relatively slow rotational motion.
- Two novel dinuclear GdIII complexes have been synthesized, based on a xylene core substituted withdiethylenetriamine-N,N,N‘ ‘,N‘ ‘-tetraacetate (DTTA) chelators in para or meta position. The complexes[Gd2(pX(DTTA)2)(H2O)4]2- and [Gd2(mX(DTTA)2)(H2O)4]2- both exhibit high complex stability (log KGdL = 19.1 and17.0, respectively), and a good selectivity for GdIII against ZnII, the most abundant endogenous metal ion (log KZnL= 17.94 and 16.19). The water exchange rate is identical within experimental error for the two isomers: kex298 =(9.0 ± 0.4) × 106 s-1 for [Gd2(pX(DTTA)2)(H2O)4]2- and (8.9 ± 0.5) × 106 s-1 for [Gd2(mX(DTTA)2)(H2O)4]2-. It isvery similar to the kex298 of the structural analogue, bishydrated [Gd(TTAHA)(H2O)2]3-, and about twice as high asthat of the monohydrated [Gd(DTPA)(H2O)]2- (TTAHA6- = N-tris(2-aminoethyl)amine-N‘,N‘,N‘ ‘,N‘ ‘,N‘ ‘‘,N‘ ‘‘-hexaacetate; DTPA5- = diethylenetriamine-N,N,N‘,N‘ ‘,N‘ ‘-pentaacetate). This relatively fast water exchange canbe related to the presence of two inner sphere water molecules which decrease the stereorigidity of the innersphere thus facilitating the water exchange process. At all frequencies, the water proton relaxivities (r1 = 16.79and 15.84 mM-1 s-1 for the para and meta isomers, respectively; 25 °C and 20 MHz) are remarkably higher forthe two dinuclear chelates than those of mononuclear commercial contrast agents or previously reported dinuclearGdIII complexes. This is mainly the consequence of the two inner-sphere water molecules. In addition, the increasedmolecular size as compared to monomeric compounds associated with the rigid xylene linker between the two GdIIIchelating subunits also contributes to an increased relaxivity. However, proton relaxivity is still limited by fast molecularmotions which also hinder any beneficial effect of the increased water exchange rate.
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