Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation...

Cationic surfactants based on phenylalanine (C_nPC₃NH₃Cl) and tryptophan (C_nTC₃NH₃Cl) were synthesized using renewable raw materials as starting compounds and a green synthetic procedure. The synthesis, acid-base equilibrium, aggregation properties, and antibacterial activity were investigated. Conductivity and fluorescence were used to establish critical micelle concentrations. Micellization of C_nPC₃NH₃Cl and C_nTC₃NH₃Cl occurred in the ranges of 0.42-16.2 mM and 0.29-4.6 mM, respectively. Since those surfactants have some acidic character, the apparent pK_a was determined through titrations, observing increasing acidity with increasing chain length and being slightly more acidic with the phenylalanine than the tryptophan derivatives. Both families showed promising antibacterial efficacy against eight different bacterial strains. Molecular docking studies against the enzyme peptidoglycan glycosyltransferase (PDB ID:2OQO) were used to investigate the potential binding mechanism of target surfactant molecules. According to small angle X-ray scattering (SAXS) results, the surfactants incorporate into DPPC (Dipalmitoyl Phosphatidyl Choline) bilayers without strong perturbation up to high surfactant concentration. Some of the C₁₂TC₃NH₃Cl/DPPC formulations (40%/60% and 20%/80% molar ratios) exhibited good antibacterial activity, while the others were not effective against the tested bacteria. The strong affinity between DPPC and surfactant molecules, as determined by the DFT (density functional theory) method, could be one of the reasons for the loss of antibacterial activity of these cationic surfactants when they are incorporated in vesicles.