Inclusion Complexation of Oxymetazoline Hydrochloride and Xylometazoline Hydrochloride with Cucurbit[n]urils ( <i>N</i> = 7, 8): Experimental and Theoretical Study

This paper reports the preparation and analysis of inclusion complexes of oxymetazoline (OXY) and xylometazoline (XYL) with two cucurbit-[n]-uril (<i>n</i> = 7, 8) (CB-[n]) hosts. Using electrospray ionization mass spectrometry (ESI-MS) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS), the formation of 1:1 guest:host complexes was confirmed. The solid complexes were characterized for their thermal stability using thermogravimetry/differential scanning calorimetry (TGA/DSC) analysis and their crystallinity by powder X-ray diffraction (PXRD) analysis. ¹H NMR spectroscopy and diffusion-ordered spectroscopy (DOSY) analysis were used to study and compare the behavior of the guests, hosts, and inclusion complexes in aqueous media. Molecular dynamics (MD) simulations and density functional theory (DFT) calculations employing the ωB97X-D/6-31G-(d) method were performed to elucidate the interaction mechanism between the guests and hosts and to evaluate the factors that influence complex formation. The results indicate that OXY and XYL form stable complexes with CB[7] and CB[8]. The formation of these complexes is spontaneous and enthalpy-driven, as suggested by the calculated thermodynamic properties. van der Waals forces mainly stabilize these complexes, along with weak to moderate hydrogen bonding interactions and ion-dipole interactions.