Microencapsulation thermodynamics of methylated β-cyclodextrins with bile salt: enthalpy, entropy, and solvent effect

The interactions between bile salts and modified cyclodextrins (CD) have aroused intensive interest because of their influence on the in vivo drug release within the small intestine. We use a recently proposed molecular dynamics/quantum mechanics/continuum solvent model (Ye et al. in Chem Phys Lett 648:170, 2016) to investigate the microscopic binding mechanisms of the natural, dimethylated (M200), randomly methylated (M214), and trimethylated (M300) $$\beta$$ -CDs, with glycocholate (GC). The computed binding free energies of the four CDs with GC decrease in the following order: natural $$\beta$$ -CD > M200 > M214 > M300, which is in accord with the experimental data. As suggested by the computed thermodynamic quantities, the relative stabilities of the four CD/GC complexes are determined by both the host–guest interactions (enthalpy plus entropy) and the solvent effects. Moreover, the former favors M200, while the latter favors natural $$\beta$$ -CD. For M300, both factors are in disadvantage.