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Dendrimeric β‐Cyclodextrin/Gd III Chelate Supramolecular Host–Guest Adducts as High‐Relaxivity MRI Probes
Author(s) -
Martinelli Jonathan,
Thangavel Kalaivani,
Tei Lorenzo,
Botta Mauro
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201402418
Subject(s) - dendrimer , chemistry , supramolecular chemistry , chelation , macromolecule , adduct , cucurbituril , human serum albumin , dota , ligand (biochemistry) , stereochemistry , crystallography , polymer chemistry , molecule , organic chemistry , biochemistry , receptor
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 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.