Molecular recognition properties of water-soluble Prism[5]arene towards drugs of abuse

The binding of WPr[5] towards a panel of 11 drugs by 1H NMR spectroscopy, isothermal titration calorimetry, and molecular modelling is reported. 1H NMR spectroscopy showed that the narrower drugs (fentanyl, methamphetamine, MDMA, mephedrone) exhibited dramatic upfield shifts (Δδ up to −4.8 ppm) upon complexation due to the naphthalene walls of WPr[5]. Analysis of the Δδ values , backed up by molecular modelling, showed that WPr[5] encircles the ammonium ion region to engage in cation-π interactions. The larger drugs do not undergo cavity inclusion binding. ITC was used to determine the binding constants and enthalpies of complexation in PBS which range up to 1.11 × 107 M−1 for WPr[5]•fentanyl and −9.26 ± 0.04 kcal mol−1 for WPr[5]•MDMA. In vitro assays using HEK293 and Hep G2 cells establish good cytocompatibility up to 33 μM. Finally, an in vivo maximum tolerated dose study using (mice) showed that WPr[5] is well tolerated at 45 mg/kg.