Mechanostereoselective One-Pot Synthesis of Functionalized Head-to-Head Cyclodextrin [3]Rotaxanes and Their Application as Magnetic Resonance Imaging Contrast Agents

• Published in: Organic letters Vol. 19; no. 5; pp. 1136 - 1139
• Main Authors: Fredy, Jean Wilfried, Scelle, Jérémy, Ramniceanu, Gregory, Doan, Bich-Thuy, Bonnet, Célia S, Tóth, Éva, Ménand, Mickaël, Sollogoub, Matthieu, Vives, Guillaume, Hasenknopf, Bernold
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 03-03-2017
• Subjects: Chemical Sciences
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.7b00153

A versatile, five-component, one-pot synthesis of cyclodextrin (CD) [3]­rotaxanes using copper-catalyzed azide–alkyne cycloaddition has been developed. Head-to-head [3]­rotaxanes of α-CD selectively functionalized by one or two gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid monoamide complexes were obtained mechanostereoselectively. The magnetic resonance imaging efficiency, expressed by the longitudinal proton relaxivity of the rotaxanes, was significantly improved as compared to the functionalized CD. In vitro and in vivo preclinical studies showed a higher contrast and retention in the kidney than gadolinium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex, demonstrating the potential of these rotaxanes as MRI contrast agent.