Negative solubility coefficient of methylated cyclodextrins in water: A theoretical study

Molecular dynamics and Monte Carlo simulations of β-cyclodextrin and its per-dimethylated derivative heptakis(2,6-di-O-methyl)-β-cyclodextrin have been carried out in water solutions at two temperatures, 25°C and 70°C. The structure of the hydration shells, as well as the solute–solvent and solvent–solvent correlations have been analyzed. The negative solubility coefficient of heptakis(2,6-di-O-methyl)-β-cyclodextrin is conditioned first of all by progressive destruction of the hydration shells around its methyl groups with temperature increase, whereas for β-cyclodextrin with positive temperature coefficient, solution is comparable at 25°C and 70°C.