An NMR study of cyclodextrin complexes of the steroidal neuromuscular blocker drug Rocuronium Bromide

• Published in: Magnetic resonance in chemistry Vol. 40; no. 4; pp. 251 - 260
• Main Authors: Cameron, Kenneth S., Fletcher, Dan, Fielding, Lee
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-04-2002
• Subjects: 13C NMR; 1H NMR; anaesthetics; cyclodextrins; host-guest chemistry; NMR; steroids
• ISSN: 0749-1581; 1097-458X
• DOI: 10.1002/mrc.1008

The interaction of Rocuronium Bromide, and a model steroid Org 7402, with three cyclodextrins (β‐cyclodextrin, γ‐cyclodextrin and Org 25969) was studied by solution state NMR experiments. Stoichiometries and binding constants were determined from 1H chemical shift titrations. All of the systems formed 1 : 1 complexes. Most of the complexes were in fast exchange with unbound species on the NMR time scale, but the most tightly bound complex (Rocuronium Bromide–Org 25969) was in the slow exchange regime. The geometry of the complexes was inferred from 1H and 13C NMR shift changes upon complexation and from intramolecular NOE correlations. Rocuronium Bromide forms a weak complex with β‐cyclodextrin (Ka = 3.3 ± 0.5 × 103 M−1) and no clear picture of the structure of the complex emerges. The complexes with γ‐cyclodextrin (Ka = 1.8 ± 0.2 × 104 M−1) and Org 25969 (Ka > 105 M−1) are true inclusion complexes with the steroid located inside the central void of the cyclodextrin. Copyright © 2002 John Wiley & Sons, Ltd.