Supramolecular Modulation of Antibacterial Activity of Ambroxol by Cucurbit[7]uril

Graphical Antibacterial switch : The capability of cucurbit[7]uril (CB[7]) in modulating the antibacterial activity of ambroxol hydrochloride (ABX) was successfully demonstrated by using two strains of Pseudomonas aeruginosa and Escherichia coli . The antibacterial activity of ABX was “turned off” upon encapsulation by CB[7] and “turned on” after ABX was released from the CB[7]-ABX host–guest complex upon addition of a competitive guest amantadine hydrochloride. Supramolecular encapsulation by cucurbit[7]uril (CB[7]) was recently demonstrated to provide a simple and efficient method for antibacterial activity regulation of antibiotics. In this work, CB[7] was shown to form binary host-guest complex with ambroxol hydrochloride (ABX), a clinical mucokinetic and expectorant drug, which was reported to exhibit certain antibacterial activity. 1 H NMR titration and isothermal titration calorimetry experiment results suggested that the 4-hydroxyl cyclohexylamine group of ABX was included inside the CB[7] cavity, with a binding constant K a of (6.69±0.11)×10 5 M −1 in phosphate buffered saline (PBS) solution, thermodynamically driven by both enthalpy change (ΔH=−12.2 kJ/mol) and entropy change (TΔS=21.1 kJ/mol). More importantly, ABX's inhibitory activity (MIC 50 ) against bacillary strains towards Pseudomonas aeruginosa and Escherichia coli strains was decreased from (5.11±0.31)×10 −6 M −1 and (2.63±0.34)×10 −5 M −1 to zero upon encapsulation by CB[7], and was subsequently recovered to almost its original activity when a competitive guest, amantadine hydrochloride, for disassembling CB[7]-ABX complex, was added, suggesting that the antibacterial activity of ABX could be readily “turned off/on” upon its complexation and decomplexation with CB[7].