Supramolecular assembly of an amphiphilic GdIII chelate : tuning the reorientat...

• Author(s): Torres, Susana ; Martins, J. A. R. ; André, João P. ; Geraldes, Carlos F. G. C. ; Merbach, André E. ; Tóth, Éva
• Date: 2006
• Persistent ID: http://hdl.handle.net/1822/4469
• Origin: RepositóriUM - Universidade do Minho
• Subject(s): Gadolinium; Imaging agents; Micelles; Steric compression; Water exchange; MRI; CMC
• Document Type: Article
• Language: English

Description

In this paper we report the synthesis and the characterization of the novel ligand H5EPTPA-C16 ((hydroxymethylhexadecanoyl ester)ethylenepropylenetriaminepentaacetic acid). This ligand was designed to chelate the GdIII ion in a kinetically and thermodynamically stable way while ensuring an increased water exchange rate (kex) on the GdIII complex due 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 in aqueous solution with a long tumbling time (R). The critical micelle concentration (CMC = 0.34 mM) of the amphiphilic [Gd(EPTPA-C16)(H2O)]2- chelate was determined by variable concentration proton relaxivity measurements. A global analysis of the data obtained in variable temperature and multiple field 17O NMR, and 1H NMRD measurements allowed the determination of parameters governing relaxivity for [Gd(EPTPA-C16)(H2O)]2-; this is the first time that paramagnetic micelles with optimized water exchange are investigated. The water exchange rate was found to be kex298 = 1.7×108 s-1, very similar to that previously reported for the nitrobenzyl derivative [Gd(EPTPA-bz-NO2)(H2O)]2- (kex298 = 1.5×108 s-1). The rotational dynamics of the micelles was analysed using the Lipari-Szabo approach. The micelles formed in aqueous solution show a considerable flexibility, with a local rotational correlation time of the GdIII segments, lO298 = 330 ps, being much shorter than the global rotational correlation time of the supramolecular aggregates, gO298 = 2100 ps. This internal flexibility of the micelles is responsible for the only limited increase of the proton relaxivity observed on micelle formation (r1 = 22.59 mM-1s-1 for the micelles vs. 9.11 mM-1s-1 for the monomer chelate (20 MHz; 25°C)).