A β-cyclodextrin "click cluster" decorated with seven paramagnetic chelates containing two water exchange sites

Joshua M. Bryson, Wen Jang Chu, Jing Huei Lee, Theresa M. Reineke

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

The development of novel macromolecular contrast agents that offer enhanced relaxivity profiles at high magnetic fields have the potential to greatly improve the diagnosis, understanding, and treatment of disease. To this end, we have designed a monodiperse paramagnetic β-cyclodextrin click cluster decorated with seven paramagnetic arms. A novel alkyne-functionalized diethylenetriaminetetraacetic acid (DTTA) chelate (6) has been created and coupled to a per-azido-β-cyclodextrin core (7) to yield the precursor macromolecule (8). After removal of the protecting groups and titrating with Gd3+, the final paramagnetic click cluster, Gd10, was obtained. Luminescence measurements were carried out in H2O and D2O on an analogous structure, Eu10, and indicated that at each lanthanide has an average of 1.8 water exchange sites, which is important for enhancing relaxivity and MRI resolution. This discrete paramagnetic click cluster yields a high relaxivity profile (43.4 mM-1 s-1 per molecule and 6.2 mM-1 s-1 per Gd3+ at 9.4 T) and enhanced contrast on a human MRI scanner as compared to a commercial agent, Magnevist (3.2 mM-1 s-1 at 9.4 T). Moreover, the useful inclusion properties exhibited by β-cyclodextrin also make this an excellent host scaffold to functionalize via noncovalent assembly with receptor specific targeting moieties for biomolecular imaging.

Original languageEnglish (US)
Pages (from-to)1505-1509
Number of pages5
JournalBioconjugate Chemistry
Volume19
Issue number8
DOIs
StatePublished - Aug 2008

Fingerprint Dive into the research topics of 'A β-cyclodextrin "click cluster" decorated with seven paramagnetic chelates containing two water exchange sites'. Together they form a unique fingerprint.

Cite this