Dendrimeric β-cyclodextrin/Gd(III) chelate supramolecular host-guest adducts as high-relaxivity MRI probes.
We have synthesized a new macromolecular architecture, (PAMAM)-CD8 , which consists of eight β-cyclodextrin units (β-CD) attached to a generation 1 poly(amidoamine) (PAMAM) dendrimer through a disulfide bond, which can be cleaved under reducing conditions. This system shows a pronounced hosting capability towards Gd(III) chelates functionalized with hydrophobic groups, thus leading to well-defined supramolecular adducts. (1)H NMR relaxometric investigations were carried out to follow the formation of adducts with three Gd(III) chelates based on the ligand architectures of 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid (AAZTA) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) suitably functionalized with benzyl or adamantyl (Ad) pendant groups. In particular, the ditopic complex composed of two AAZTA chelating units connected to a central aromatic ring that bears an adamantyl group showed a strong affinity (ca. 10(6)  M(-1)) for the CD units of the dendrimer, which is two orders of magnitude higher than toward human serum albumin (HSA). Remarkable relaxivity enhancements (i.e., up to 71% at 1 T and 25 °C) were observed upon the formation of the macromolecular host-guest adducts due to a decrease in the molecular tumbling rate and fast water-exchange. Reduction experiments and competition studies between the paramagnetic dendrimer and HSA were carried out by relaxometric techniques. The results show that the metal complexes are not displaced by the protein, thus suggesting that this novel macromolecular probe is potentially suitable for applications in vivo.
Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale "Amedeo Avogadro", Viale T. Michel 11, 15121 Alessandria (Italy).
Jonathan
J
Martinelli
Kalaivani
K
Thangavel
Lorenzo
L
Tei
Mauro
M
Botta
D002614:Chelating Agents / Q000737:chemistry*; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D015335:Molecular Probes / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry
D002614:Chelating Agents; D050091:Dendrimers; D015335:Molecular Probes; D047392:beta-Cyclodextrins; D005682:Gadolinium
cyclodextrin units; magnetic resonance imaging; relaxivity; responsive systems; supramolecular chemistry