title: Design and Synthesis of a γ(1)β(8)-Cyclodextrin Oligomer: A New Platform with Potential Application as a Dendrimeric Multicarrier.
abstract: We report the synthesis and characterization of a water-soluble, star-shaped macromolecular platform consisting of eight β-cyclodextrin (β-CD) units anchored to the narrower rim of a γ-CD core through bis(triazolyl)alkyl spacers. The efficient synthetic protocol is based on the microwave (MW)-promoted Cu-catalyzed 1,3-dipolar cycloaddition of CD monoazides to CD monoacetylenes. The ligand-hosting capability of the construct has been assessed by relaxometric titration and nuclear magnetic relaxation dispersion (NMRD) profiling, which showed it to be good, and this was supported by molecular dynamics simulations. To demonstrate the feasibility of obtaining supramolecular structures with high hosting ability, we designed a dimeric platform, formed by joining two nonamers through the γ-CD cores through a bis(lithocholic acid) linker. With a view to the potential biological applications, cytotoxicity and extent of binding to human serum albumin were assessed. The properties of this dendrimeric multicarrier make it suitable for pharmaceutical and diagnostic purposes, ranging from targeted drug delivery to molecular imaging.
authors.affiliation: Department of Drug Science and Technology, University of Turin, Via Pietro Giuria 9, 10125 Torino (Italy), Fax: (+39) 011-6707687.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barge
authors.forename: Marina
authors.initials: M
authors.lastname: Caporaso
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Cravotto
authors.forename: Katia
authors.initials: K
authors.lastname: Martina
authors.forename: Paolo
authors.initials: P
authors.lastname: Tosco
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Carla
authors.initials: C
authors.lastname: Carrera
authors.forename: Eliana
authors.initials: E
authors.lastname: Gianolio
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pariani
authors.forename: Davide
authors.initials: D
authors.lastname: Corpillo
mesh_terms: D061565:Cycloaddition Reaction; D016503:Drug Delivery Systems / Q000379:methods; D005682:Gadolinium / Q000737:chemistry; D006801:Humans; D008095:Lithocholic Acid / Q000737:chemistry; D046911:Macromolecular Substances / Q000138:chemical synthesis* / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D025202:Molecular Diagnostic Techniques / Q000379:methods; D012709:Serum Albumin / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D046911:Macromolecular Substances; D012709:Serum Albumin; D047392:beta-Cyclodextrins; D008095:Lithocholic Acid; D005682:Gadolinium
keywords: Gd‐based contrast agents; click chemistry; cyclodextrin oligomers; imaging agents; microwave chemistry