Multi-equilibrium approach to study cyclodextrins host–guest systems with GFN2-xTB quantum method: A case study of phosphorothioates included in β-cyclodextrin

Abstract

Computing equilibrium constants for cyclodextrin host–guest systems is challenging and prohibitive, depending on the quantum method chosen. We propose applying a multi-equilibrium approach to estimate stability constants for Cyclodextrin (CD) systems with the robust semiempirical GFN2-xTB method and using the User-Defined Association Parameters (UD-APARM) software. The host–guest systems formed with β-CD and some phosphorothioates were studied in the present work due to their structural diversity and reported experimental data. As a result, we obtained an excellent linear correlation with the experiment for systems formed by β-CD and diazinon (DZN), parathion (PTN), methyl parathion (MPTN), and chlorpyrifos (CPF). The obtained linear correlation was then applied to estimate the stability constants for the inclusion of chlorethoxyfos (CEF) and tebupirimfos (TPF) in β-CD, for which no experimental data is known. We discuss the applicability of the workflow adopted for sampling CD-based host–guest supramolecular space with UD-APARM and semiempirical GFN2-xTB method.