Mutual induced fit in cyclodextrin-rocuronium complexes

Org Biomol Chem. 2005 May 21;3(10):1863-71. doi: 10.1039/b415903a. Epub 2005 Mar 23.

Abstract

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.

MeSH terms

  • Androstanols / chemistry*
  • Calorimetry
  • Crystallography
  • Cyclodextrins / chemistry*
  • Magnetic Resonance Spectroscopy
  • Neuromuscular Blocking Agents / chemistry*
  • Rocuronium
  • Spectrometry, Fluorescence
  • Spectrophotometry, Ultraviolet

Substances

  • Androstanols
  • Cyclodextrins
  • Neuromuscular Blocking Agents
  • Rocuronium