title: Supramolecular assembly of an amphiphilic Gd(III) chelate: tuning the reorientational correlation time and the water exchange rate.
abstract: We report the synthesis and characterization of the novel ligand H(5)EPTPA-C(16) ((hydroxymethylhexadecanoyl ester)ethylenepropylenetriaminepentaacetic acid). This ligand was designed to chelate the Gd(III) ion in a kinetically and thermodynamically stable way while ensuring an increased water exchange rate (kappa(ex)) on the Gd(III) complex owing to steric compression around the water-binding site. The attachment of a palmitic ester unit to the pendant hydroxymethyl group on the ethylenediamine bridge yields an amphiphilic conjugate that forms micelles with a long tumbling time (tau(R)) in aqueous solution. The critical micelle concentration (cmc = 0.34 mM) of the amphiphilic [Gd(eptpa-C(16))(H(2)O)](2-) chelate was determined by variable-concentration proton relaxivity measurements. A global analysis of the data obtained in variable-temperature and multiple-field (17)O NMR and (1)H NMRD measurements allowed for the determination of parameters governing relaxivity for [Gd(eptpa-C(16))(H(2)O)](2-); this is the first time that paramagnetic micelles with optimized water exchange have been investigated. The water exchange rate was found to be kappa(298)(ex) = 1.7 x 10(8) s(-1), very similar to that previously reported for the nitrobenzyl derivative [Gd(eptpa-bz-NO(2))(H(2)O)](2-) kappa(298)(ex) = 1.5 x 10(8) s(-1)). The rotational dynamics of the micelles were analysed by using the Lipari-Szabo approach. The micelles formed in aqueous solution show considerable flexibility, with a local rotational correlation time of tau(298)(l0) = 330 ps for the Gd(III) segments, which is much shorter than the global rotational correlation time of the supramolecular aggregates, tau(298)(g0) = 2100 ps. This internal flexibility of the micelles is responsible for the limited increase of the proton relaxivity observed on micelle formation (r(1) = 22.59 mM(-1) s(-1) for the micelles versus 9.11 mM(-1) s(-1) for the monomer chelate (20 MHz; 25 degrees C)).
authors.affiliation: Centro de Química, Campus de Gualtar, Universidade do Minho, Braga, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Torres
authors.forename: José A
authors.initials: JA
authors.lastname: Martins
authors.forename: João P
authors.initials: JP
authors.lastname: André
authors.forename: Carlos F G C
authors.initials: CF
authors.lastname: Geraldes
authors.forename: André E
authors.initials: AE
authors.lastname: Merbach
authors.forename: Eva
authors.initials: E
authors.lastname: Tóth
mesh_terms: D002104:Cadmium / Q000737:chemistry*; D002614:Chelating Agents / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles
chemical_list: D002614:Chelating Agents; D004952:Esters; D008823:Micelles; D002104:Cadmium