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Photodynamic therapy has always been an antibacterial tool for solving multi-drug resistant bacteria problem, but the side effects and the low efficiency due to the high aggregation and low solubility of photosensitizers limit its application. Due to the anti-inflammatory effect of caffeic acid, two novel photosensitizers (CA-1-TBO, CA-TBO) were synthesized by conjugating caffeic acid with toluidine blue O (TBO). The structures have been characterized by 1HNMR and high-resolution mass spectrometry. The UV–vis absorption, fluorescence spectra and the octanol-water partition coefficient of two photosensitizers were measured to evaluate their photophysical properties and hydrophilic/hydrophobic properties. Compared with parent TBO, the two modified photosensitizers have shown a higher quantum yield and kinetics constants of singlet oxygen, which has been supported by the simulation results of density functional theory. As drug-resistant representatives of gram-positive and gram-negative bacteria, respectively, S. aureus and P. aeruginosa have been used for in vitro antibacterial experiments. The sterilization efficiencies of the two modified photosensitizers far exceed that of parent TBO. The results of the octanol-water partition coefficient and fluorescence quantification showed that modified photosensitizers CA-1-TBO and CA-TBO could be more accumulated than parent TBO. Based on scanning electron microscopy images, protein gel electrophoresis, and the conductivity of the bacterial solution, the possible mechanism of improved antibacterial photodynamic efficiencies could be induced by membrane permeability due to the caffeic acid effect. The findings demonstrate the significant potential of natural phenolic compounds in the development of photosensitizer molecules with characteristics such as more efficient, biocompatible and less side effects. • Novel photosensitizers from caffeic acid and toluidine blue O have been prepared. • CA-1-TBO and CA-TBO can penetrate bacterial membranes. • CA-1-TBO and CA-TBO could accumulate efficiently into bacterial cells. • CA-1-TBO and CA-TBO showed the enhanced aPDT efficiency. • CA-1-TBO and CA-TBO could target intracellular proteins. [ABSTRACT FROM AUTHOR]

It is well established that lipid aldehydes (LAs) are able to increase the permeability of cell membranes and induce their rupture. However, it is not yet clear how LAs are distributed in phase-separated membranes (PSMs), which are responsible for the transport of selected molecules and intracellular signaling. Thus, we investigate here the distribution of LAs in a PSM by coarse-grained molecular dynamics simulations. Our results reveal that LAs derived from mono-unsaturated lipids tend to accumulate at the interface between the liquid-ordered/liquid-disordered domains, whereas those derived from poly-unsaturated lipids remain in the liquid-disordered domain. These results are important for understanding the effects caused by oxidized lipids in membrane structure, properties and organization. [Display omitted] • Liquid-ordered (Lo) and liquid-disordered (Ld) phases coexist in cell membranes (lipid rafts). • The interface between the Lo/Ld domains is more susceptible to pore formation. • Lipid aldehydes (LAs) derived from mono-unsaturated lipids tend to accumulate at the interface between the Lo/Ld domains. • LAs derived from poly-unsaturated lipids remains in the Ld domain. [ABSTRACT FROM AUTHOR]