A model for sequential threading of alpha-cyclodextrin onto a guest: A complete thermodynamic and kinetic study in water

The first variable-temperature and variable-pressure stopped-flow spectroph otometric study of the sequential threading of alpha -cyclodextrin (alpha - CD) onto the guest dye Mordant Orange 10, S, is reported. Complementary H-1 one-dimensional (1D) variable-temperature kinetic studies and two-dimensio nal (2D) rotating-frame nuclear Overhauser effect spectroscopy (ROESY) and EXSY NMR studies are also reported. In aqueous solution at 298.2 K, the fir st alpha -CD threads onto S to form a 1:1 complex S.alpha -CD* with a forwa rd rate constant k(1,f) = 15 200 +/- 200 M-1 s(-1) and dethreads with a rev erse rate constant k(1,r) = 4.4 +/- 0.3 s(-1). Subsequently, S.alpha -CD* i somerizes to S.a-CD (k(3,f) = 0.158 +/- 0.006 s(-1), k(3,f) = 0.148 +/- 0.0 06 s(-1)). This process can be viewed as a thermodynamically controlled mol ecular shuttle. A second a-CD threads onto S.alpha -CD* to form a 1:2 compl ex, S.(alpha -CD)(2)*, with k(2,f) = 98 +/- 2 M-1 s(-1) and k(2,r) = 0.032 +/- 0.002 s(-1).(.)A second alpha -CD also threads onto S.alpha -CD to form another 1:2 complex, S.(alpha -CD)(2), characterized by k(4,f) = 9640 +/- 1800 M-1 s(-1) and k(4,r) = 61 +/- 6 s(-1). Direct interconvertion between S.(alpha -CD)(2)* and S.(alpha -CD)(2) was not detected; instead, they inte rconvert by dethreading the second alpha -CD and through the isomerization equilibrium between S.alpha -CD* and S.alpha -CD. The reaction volumes, Del taV(o), were found to be negative for the first three equilibria and positi ve for the fourth equilibrium. For the first three forward and reverse reac tions, the volumes of activation are substantially more negative, indicatin g a compression of the transition state in comparison with the ground state s. These data were used in conjunction with DeltaH double dagger, DeltaH(o) , DeltaS double dagger, and DeltaS(o) data to deduce the dominant mechanist ic threading processes, which appear to be largely controlled by changes in hydration and van der Waals interactions, and possibly by conformational c hanges in both S and alpha -CD. The structure of the four complexes were de duced from H-1 2D ROESY NMR studies.