ИСТИНА

Antiseptics are antimicrobial compounds used in a clinical setting. Positively charged cationic antiseptics bind strongly to the cell walls and membranes of bacteria because of their opposite negative charge. The plasma cell membrane of a bacterial cell is supposed to be the main target of antiseptic action. We created molecular dynamics coarse-grained models of four cationic antiseptics: miramistin, chlorhexidine, octenidine, picloxydine and carried out molecular dynamics simulations during one microsecond for each model. It was found that at the concentrations used in medical preparations (0.05-0.15\%), chlorhexidine and picloxydine exist in water solution in monomeric form, while miramistin and octenidine form micelle-like aggregates at concentrations three times higher. The model plasma membrane consisted of 180 POPE and 60 POPG molecules. To study the molecular mechanism of action of antiseptics at different concentrations, we designed molecular models of membrane with antiseptic molecules, with antiseptic to lipid ratio of 1/24, 1/ 8 and 1/ 4. The systems with 1/24, 1/ 8 antiseptic/lipid ratio were simulated for 3 microseconds, the system with 1/4 antiseptic/lipid ratio was simulated for 30 microseconds. The area per lipid, the density profiles, order parameters, and bilayer thickness were calculated for all systems. It was shown that cationic antiseptic molecules effectively penetrate into the bacterial plasma membrane, and their positively charged beads are located in the region of phosphate residues, while the terminal beads of the antiseptics molecules are located in the area of lipid fatty acids. It was demonstrated that octenidine has the most pronounced disintegrating effect on the bacterial plasma membrane by the significant change in the area of lipid and bilayer thickness. The reported study was funded by RFBR, project number 19-34-90045.