Molecular, crystal and solution structure of a β-cyclodextrin complex with the bromide salt of 2-(3-dimethylaminopropyl)tricyclo[3.3.1.1 3,7]decan-2-ol, a potent antimicrobial drug

• Published in: Carbohydrate research 1999-04, Vol.317 (1), p.19-28
• Main Authors: Perrakis, Anastassis, Antoniadou-Vyza, Ekaterini, Tsitsa, Polyxeni, S. Lamzin, Victor, S. Wilson, Keith, J. Hamodrakas, Stavros
• Format: Article
• Language: English
• Subjects: Ab initio structure solution; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial drug; Bacteria - drug effects; beta-Cyclodextrins; Bromides; Carbohydrate Conformation; Crystallography, X-Ray; Cyclodextrins - chemistry; Fatty Alcohols - chemical synthesis; Fatty Alcohols - chemistry; Fatty Alcohols - pharmacology; Models, Molecular; NMR; Nuclear Magnetic Resonance, Biomolecular; Synchrotron radiation; X-ray crystallography; β-Cyclodextrin
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/S0008-6215(99)00021-X

The pharmacological properties of a cyclomaltoheptaose (β-cyclodextrin) series of adamantane-group-bearing compounds that exhibit potent antibacterial activity have been studied, both isolated and in complex with β-cyclodextrins (βCDs). In this work, the structure of the bromide salt of 2-(3-dimethylaminopropyl)tricyclo[3.3.1.1 3,7]decan-2-ol (ADM-10) complexed with βCD 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 βCD cavity. Chemical shifts in NMR experiments can be explained on the basis of the crystal structure of the complex.