Aromatic–Aromatic Interaction of Amitriptyline: Implication of Overdosed Drug Detoxification

The objectives of this work are to explore the π–π complexation of amitriptyline with π electron-deficient aromatic rings and demonstrate the feasibility of π–π complexation for overdosed drug detoxification. Water-soluble oligochitosan was chemically modified with dinitrobenzenesulfonyl groups to induce selective binding toward amitriptyline through π–π complexation. NMR studies showed that benzenesulfonyl and dinitrobenzenesulfonyl protons were upfield shifted by the addition of amitriptyline, indicating the formation of π–π complexes. The π–π complexation of amitriptyline is driven primarily by a desolvation driving force, whereas the magnitude of interaction is dictated by the complementrary electrostatic interaction. Isolated rat heart tests revealed that dinitrobenzenesulfonyl oligochitosan prevented the amitriptyline-induced cardiotoxicity and was itself not cardiotoxic.