Tunable amphiphilic π-systems based on isatin derivatives containing a quaternary ammonium moiety: The role of alkyl chain length in biological activity

This work deals with polyfunctional biocompatible amphiphilic isatin derivatives. Isatin-3-acylhydrazones containing a quaternary ammonium moiety (Is-Q-n) with varying hydrophobicity (R = CnH2n+1, where n = 10, 12, 14, 16, 18, 20) were synthesized. Tunable self-assembly behavior, morphology of nanostructures, and their biological activity were modulated by hydrophilic-lipophilic balance of π-amphiphiles and solvent polarity. Self-assembly of Is-Q-n was investigated by tensiometry, conductometry, IR and UV–Vis spectroscopy, fluorimetry and dynamic light scattering. The unexpected values of the physicochemical parameters at long alkyl chain length have been interpreted. The CAC of Is-Q-16 is lower than CMC of classical surfactant CTAB. Solvent-induced self-assembly for Is-Q-16 was observed. The hydrophobic dye Orange OT was solubilized in Is-Q-10 solutions twice better than in CTAB solutions. Is-Q-n self-assembled structures with size 50 nm and 100 nm in a concentration range from 0.01 mM (below CAC) to 10 mM were found. Is-Q-10 forms small associates with size 3 nm. Selective antimicrobial activity of low toxic ammonium salts against Gram-positive bacteria (S. aureus 209p and B. cereus 8035) and fungus Candida albiсans 855–653 was shown. Newly synthesized 1-dodecylisatin derivatives containing a quaternary ammonium moiety may be recommended as antimicrobial agents and for drug solubilization, in particular for drugs capable for π-π stacking interactions. [Display omitted] •Polyfunctional biocompatible π-amphiphilic isatin derivatives were synthesized.•Long alkyl chain length derivatives show unexpected physicochemical parameters.•HLB of π-amphiphiles modulate the self-assembly behavior.•Solvent induces self-assembly of amphiphilic isatin derivatives.•Dodecylisatin derivatives are antimicrobial agents and can be used for drug solubilization.