TY - JOUR
T1 - Dendrimeric β-Cyclodextrin/GdIII chelate supramolecular host-guest adducts as high-relaxivity MRI probes
AU - Martinelli, Jonathan
AU - Thangavel, Kalaivani
AU - Tei, Lorenzo
AU - Botta, Mauro
PY - 2014/8/25
Y1 - 2014/8/25
N2 - We have synthesized a new macromolecular architecture, (PAMAM)-CD 8, 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 GdIII chelates functionalized with hydrophobic groups, thus leading to well-defined supramolecular adducts. 1H NMR relaxometric investigations were carried out to follow the formation of adducts with three GdIII 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. 106 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.
AB - We have synthesized a new macromolecular architecture, (PAMAM)-CD 8, 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 GdIII chelates functionalized with hydrophobic groups, thus leading to well-defined supramolecular adducts. 1H NMR relaxometric investigations were carried out to follow the formation of adducts with three GdIII 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. 106 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.
KW - cyclodextrin units
KW - magnetic resonance imaging
KW - relaxivity
KW - responsive systems
KW - supramolecular chemistry
UR - http://www.scopus.com/inward/record.url?scp=84906498285&partnerID=8YFLogxK
U2 - 10.1002/chem.201402418
DO - 10.1002/chem.201402418
M3 - Article
SN - 0947-6539
VL - 20
SP - 10944
EP - 10952
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 35
ER -