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An NMR study of cyclodextrin complexes of the steroidal neuromuscular blocker drug Rocuronium Bromide
Author(s) -
Cameron Kenneth S.,
Fletcher Dan,
Fielding Lee
Publication year - 2002
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/mrc.1008
Subject(s) - chemistry , rocuronium bromide , cyclodextrin , bromide , rocuronium , intramolecular force , stoichiometry , titration , proton nmr , binding constant , nuclear magnetic resonance spectroscopy , stereochemistry , binding site , inorganic chemistry , organic chemistry , pharmacology , biochemistry , medicine , propofol
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 1 H 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 1 H and 13 C NMR shift changes upon complexation and from intramolecular NOE correlations. Rocuronium Bromide forms a weak complex with β‐cyclodextrin ( K a = 3.3 ± 0.5 × 10 3 M −1 ) and no clear picture of the structure of the complex emerges. The complexes with γ‐cyclodextrin ( K a = 1.8 ± 0.2 × 10 4 M −1 ) and Org 25969 ( K a > 10 5 M −1 ) are true inclusion complexes with the steroid located inside the central void of the cyclodextrin. Copyright © 2002 John Wiley & Sons, Ltd.