Synthesis, biological evaluation and structure-activity relationships of self-assembled and solubilization properties of amphiphilic quaternary ammonium derivatives of quinuclidine

Abstract

© 2018 Elsevier B.V. This work deals with development of polyfunctional biocompatible cationic surfactant systems based on bioactive saturated bicyclic alkaloid quinuclidine. It is focused on the effect of the chemical structure of surfactants on their aggregation behavior, their physicochemical estimation of solubility of model water insoluble dye Orange OT and drugs, quercetin and rutin, microbiology and cytotoxicity. Quaternary ammonium derivatives of quinuclidine (Q-Nuc-n) with different hydrophobicity (R = CnH2n+1, where n = 14, 16, 18) were synthesized. Self-assembly of Q-Nuc-n was investigated by tensiometry, conductometry, spectrophotometry, fluorimetry and dynamic light scattering. The critical micelle concentration, thermodynamic and adsorption parameters at water-air interface, size and aggregation numbers of Q-Nuc-n micelles were determined. The looser packing of surfactant molecules in Q-Nuc-n micelles compared to its analogues, quaternized derivatives of 1,4‑diazabicyclo[2.2.2]octane (DABCO-n), was established. The hydrophobic dye Orange OT and drugs quercetin and rutin were solubilized in micellar Q-Nuc-n solutions better than in solutions of classical surfactant CTAB and its analogue DABCO-n. Solubilization capacity of Q-Nuc-18 is 5 times higher than that of classical surfactant CTAB. Q-Nuc-18 1.95 μg·mL−1 has also bactericidal and fungicidal activity 2 times (against S. aureus 209P) and 8 times (against B. cereus 8035) higher than antibiotics Norfloxacin and antifungal Ketoconazole. Q-Nuc-16 has the highest bactericidal activity. It is 6 times (against S. aureus 209P) and 15 times (against B. cereus 8035) higher than the bactericidal activity value of Norfloxacin. Synthesized cationic surfactants based on quinuclidine are new multifunctional biocompatible compounds with high potential in nanomedicine and biotechnology.