Solution properties of the LnIII complexes of a novel octadentate chelator with rigidified iminodiacetate arms

Abstract

A novel octadentate ligand derived from the core structure of EGTA (ethyleneglycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid) with two piperidine-cis-dicarboxylic acid moieties spaced by a triethylenedioxy chain (L1) has been synthesised with the aim to assess the effect of the structural rigidity on the thermodynamic and kinetic stabilities of its Ln(III) complexes. The stability constants of [Ln(L1)](-) complexes show a weaker binding affinity for Ln(3+) ions of L1 than EGTA. On the other hand, the selectivity of L1 for Ca(2+) over Mg(2+) is one of the highest ever reported. The kinetic inertness has been also investigated and faster rates of both acid catalysed and metal assisted decomplexation have been measured for [Gd(L1)](-) as compared to [Gd(EGTA)](-). The (1)H- and (13)C NMR spectra of the diamagnetic La(3+), Y(3+) and Lu(3+) complexes in aqueous media show pronounced stereochemical rigidity and the occurrence of a structural change across the lanthanide series. Finally, a complete (1)H and (17)O NMR relaxometric study indicates that [Gd(L1)](-) possesses a nine-coordinate ground state with one inner coordination sphere water molecule characterized by a fast rate of exchange ((298)k(ex) = 59 × 10(6) s(-1)).

Strategies for Optimizing Water-Exchange Rates of Lanthanide-Based Contrast Agents for Magnetic Resonance Imaging

“…Representative Gd III -containing complexes 43 – 65 that relate the influence of steric hindrance at the water-coordination site to water-exchange rate [10,50,51,52,53,54,55,56,57,58,59,60,61,62]. …”

“…Rigidifying the backbone of polyaminopolycarboxylate-based ligands is another strategy that often results in faster water-exchange rates, possibly due to enhanced steric crowding caused by substituents used to rigidify the ligand backbone. For example, backbone rigidification in complex 63 using two piperidine moieties led to a 1.9-fold faster water-exchange rate than non-rigid complex 52 [60]. In another example, complex 64 with a cyclohexylene-bridge-containing rigidified macrocycle led to a water-exchange rate that was 2.4-fold faster than that of non-rigid 25 [61].…”