Prediction of correct intermolecular interactions in host-guest systems involving cyclodextrins

Abstract

Investigations of intermolecular interactions are of great interest and many studies in this field focus on the use of theoretical computational chemistry. Commonly the systems of interest comprise molecules with hundreds of atoms, limiting the use of ab initio theoretical methods. In order to investigate the accuracy of different quantum chemical methods, a systematic study was carried out involving 15 inclusion complexes of α-cyclodextrin and 28 complexes of β-cyclodextrin. The accuracy of semiempirical methods in geometry prediction was evaluated in comparison to crystallographic data, with AM1 and PM3 showing the best results. Subsequently, the accuracy of semiempirical methods in predicting both geometry and interaction energy was studied using the results of DFT calculation as reference, with and without dispersion correction. The best method was B3LYP/6-31G(d,p) with D3 correction, followed by PM6 with D3 correction with similar accuracy. However, as the DFT method require a high computational cost for large systems, PM6-D3 is the method recommended for the systems studied here. The main conclusion is the need to develop a semiempirical method capable of correctly describing the interaction energy, which must correspond to an accurate geometry.