title: Molecular, crystal and solution structure of a beta-cyclodextrin complex with the bromide salt of 2-(3-dimethylaminopropyl)tricyclo[3.3.1.1(3,7)]decan-2-ol, a potent antimicrobial drug.
abstract: The pharmacological properties of a cyclomaltoheptaose (beta-cyclodextrin) series of adamantane-group-bearing compounds that exhibit potent antibacterial activity have been studied, both isolated and in complex with beta-cyclodextrins (betaCDs). In this work, the structure of the bromide salt of 2-(3-dimethylaminopropyl)-tricyclo[3.3.1.1(3,7)]decan-2-ol(A DM-10) complexed with betaCD and ten water molecules was studied in the solid state by X-ray crystallography and in solution by NMR spectroscopy. X-ray crystallographic studies of the complex were performed both at room and cryogenic temperatures. The long aliphatic chain of ADM-10 adopts a single conformation at low temperature in contrast to what is observed at room temperature, where two side chain conformations are seen. Both NMR and X-ray crystallography studies indicate that the adamantane moiety of ADM-10 is buried in the betaCD cavity. Chemical shifts in NMR experiments can be explained on the basis of the crystal structure of the complex.
authors.affiliation: European Molecular Biology Laboratory (EMBL), Grenoble, France.
authors.forename: A
authors.initials: A
authors.lastname: Perrakis
authors.forename: E
authors.initials: E
authors.lastname: Antoniadou-Vyza
authors.forename: P
authors.initials: P
authors.lastname: Tsitsa
authors.forename: V S
authors.initials: VS
authors.lastname: Lamzin
authors.forename: K S
authors.initials: KS
authors.lastname: Wilson
authors.forename: S J
authors.initials: SJ
authors.lastname: Hamodrakas
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001965:Bromides; D002236:Carbohydrate Conformation; D018360:Crystallography, X-Ray; D003505:Cyclodextrins / Q000737:chemistry*; D005233:Fatty Alcohols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D047392:beta-Cyclodextrins
chemical_list: C121202:ADM 10; D000900:Anti-Bacterial Agents; D001965:Bromides; D003505:Cyclodextrins; D005233:Fatty Alcohols; D047392:beta-Cyclodextrins; C031215:betadex