Molecular dynamics study of racemic mixtures. II. Temperature dependence of the separation of ibuprofen racemic mixture with beta-cyclodextrin in methanol solvent

Using a realistic united atom interaction model, molecular dynamics simulations were carried out to investigate properties of mixtures of ibuprofen and beta-cyclodextrin both in vacuo and in solution with methanol solvent. The property in focus here is the temperature dependence of the intermolecular interaction energy and the distribution of hydrogen bonds in inclusion complexes established by both the (R)- and (S)-forms of ibuprofen with beta-cyclodextrin. Temperatures were considered in the range from 260 K to 380 K with an increment of 10 K. It was found that (R)-ibuprofen is strongly bonded inside the cyclodextrin molecule, which is more pronounced in the case when the so-called DOWN complex is formed. However, this effect is diminished in the presence of methanol because methanol molecules tend to occupy the majority of possible hydrogen bonding sites. The temperature dependence is not monotonic, and for the DOWN complex in methanol it exhibits two maxima, at 260 K and 310 K. For the UP complex no significant difference was observed at any temperature within the considered range. These results may help both experimentalists and theorists to understand the process of chiral selection of ibuprofen enantiomers. (C) 2020 Elsevier B.V. All rights reserved.