Inclusion of paraoxon, parathion, and methyl parathion into α-cyclodextrin: a GFN2-xTB multi-equilibrium quantum study

A new theoretical approach was recently addressed to predict cyclodextrin host–guest binding constants with the GFN2-xTB semiempirical quantum method. Within such a strategy, a set of starting supramolecular arrangements is automatically obtained through the UD-APARM software, and many optimized host–guest systems are used to obtain each binding constant. In the present work, within the scope of the multi-equilibrium treatment, we carried out a theoretical study concerning the host–guest systems formed with paraoxon (PRX), methyl-parathion (MPTN), and parathion (PTN) into α-cyclodextrin (α-CD), for which experimental data were addressed. Those guests correspond to pesticides in use, and their inclusion plays a role in remediation technology. The procedure for estimating binding constants for the host–guest system is discussed in terms of the ranges for the supramolecular parameters employed in exploring the GFN2-xTB Potential Energy Surface (PES). As a result, by investigating an unprecedented number of starting systems (3,076), we identified that proper exploration of the GFN2-xTB PES gives a reliable prediction of the binding constant in solution. Furthermore, with the study of different starting associations, for PTN/α-CD, we found an excellent linear correlation (R2 = 0.987) between GFN2-xTB data and experimental information, which, as in our previous study, supports the discussed methodology for application in predicting binding constants for CD-based host–guest systems.