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

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. H-1 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)x10(5) M-1 in phosphate buffered saline (PBS) solution, thermodynamically driven by both enthalpy change (Delta H=-12.2 kJ/mol) and entropy change (T Delta S=21.1 kJ/mol). More importantly, ABX's inhibitory activity (MIC50) against bacillary strains towards Pseudomonas aeruginosa and Escherichia coli strains was decreased from (5.11 +/- 0.31)x10(-6) M-1 and (2.63 +/- 0.34)x10(-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].