Gd(3+) Complexes Conjugated to Cyclodextrins

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In the search for improvement in the properties of gadolinium-based contrast agents, cyclodextrins (CDs) are interesting hydrophilic scaffolds with high molecular weight. The impact of the hydrophilicity of these systems on the MRI efficacy has been studied using five b-CDs substituted with DOTA (1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid) or TTHA ((3,6,9,12-tetrakis(carboxymethyl)-3,6,9,12-tetraazatetradecane-1,14-dioic acid) ligands which, respectively, allow for one (q = 1) or no water molecule (q = 0) in the inner coordination sphere of the Gd3+ ion. Original synthetic pathways were developed to immobilize the ligands at C-6 position of various hydroxylated and permethylated -CDs via an amide bond. To describe the influence of alcohol and ether oxide functions of the CD macrocycle on the relaxation properties of the Gd3+ complexes, 1H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles, and 17O transverse relaxation rates have been measured at various temperatures. The differences observed between the hydroxylated and permethylated -CDs bearing non-hydrated GdTTHA complexes can be rationalized by a second sphere contribution to the relaxivity in the case of the hydroxylated derivatives, induced by hydrogen-bound water molecules around the hydroxyl groups. In contrast, for the DOTA analogs the exchange rate of the water molecule directly coordinated to the Gd3+ is clearly influenced by the number of hydroxyl groups present on the CD, which in turn influences the relaxivity and gives rise to a very complex behavior of these hydrophilic systems.

Biscotti, A.; Estour, F.; Sembo-Backonly, B.-S.; Balieu, S.; Bosco, M.; Barbot, C.; Pallier, A.; Tóth, É.; Bonnet, C.S.; Gouhier, G. Gd3+ Complexes Conjugated to Cyclodextrins: Hydroxyl Functions Influence the Relaxation Properties. Processes 2021, 9, 269.


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