Mutual induced fit in cyclodextrin-rocuronium complexes.
The binding of rocuronium bromide to 6-perdeoxy-6-per(4-carboxyphenyl)thio-gamma-cyclodextrin sodium salt, displays biphasic behaviour characteristic of the formation of a binary and 2 : 1 ternary guest-host complex in aqueous solution. Thermodynamic and structural data on this sequential complexation process can be rationalised within a single model involving switching of the conformational equilibria of both the rocuronium bromide and cyclodextrin molecules. Isothermal titration calorimetry (ITC), NMR and fluorescence experiments in solution, together with X-ray crystallography and molecular modelling, suggest that in order to induce encapsulation both rocuronium bromide and the modified cyclodextrin undergo conformational changes. Ring A of rocuronium bromide 'switches' from the more sterically encumbered chair to the sterically less demanding twist-boat, whilst the modified cyclodextrin "opens" its cavity to allow the steroid to enter. The recognition and mutual induced fit between cyclodextrin and steroid represents a classic example of dynamic host-guest chemistry.
Cooper
Alan
A
Department of Chemistry, Glasgow University, Scotland, UK.
Nutley
Margaret
M
MacLean
Elizabeth J
EJ
Cameron
Ken
K
Fielding
Lee
L
Mestres
Jordi
J
Palin
Ronald
R
D000732:Androstanols / Q000737:chemistry*; D002151:Calorimetry; D003461:Crystallography; D003505:Cyclodextrins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009466:Neuromuscular Blocking Agents / Q000737:chemistry*; D000077123:Rocuronium; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
D000732:Androstanols; D003505:Cyclodextrins; D009466:Neuromuscular Blocking Agents; D000077123:Rocuronium