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

The interaction of Rocuronium Bromide, and a model steroid Org 7402, with three cyclodextrins (beta-cyclodextrin, gamma-cyclodextrin and Org 25969) was studied by solution state NMR experiments. Stoichiometries and binding constants were determined from H-1 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 H-1 and C-13 NMR shift changes upon complexation and from intramolecular NOE correlations. Rocuronium Bromide forms a weak complex with beta-cyclodextrin (K-a = 3.3 +/- 0.5 X 10(3) M-1) and no clear picture of the structure of the complex emerges. The complexes with gamma-cyclodextrin (K-a = 1.8 +/- 0.2 X 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 (C) 2002 John Wiley Sons, Ltd.