Mutual induced fit in cyclodextrin–rocuronium complexes

Abstract

The binding of rocuronium bromide to 6-perdeoxy-6-per(4-carboxyphenyl)thio-γ-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.