Molecular structure and interactions of the flavonols, quercetin, fisetin, kaempferol, and myricetin, with liposomal membranes

Abstract The interactions of flavonols with biological membranes underlie their beneficial biochemical effects. In the present work, we performed quantum chemical modeling of the molecular structure and electronic characteristics of some flavonols such as fisetin, kaempferol, and myricetin and compared our findings with those for quercetin obtained earlier. We considered the effects of the flavonols on liposomal membranes, using the methods of fluorescence probe spectroscopy, an electric-kinetical method and differential scanning calorimetry. The AC and B rings in the molecules of all the flavonols studied were located in the same plane. All the flavonols (5–25µM) increased the lipid bilayer order both in the surface zone and the hydrophobic area of the membrane. Quercetin was more effective in changing the liposomal membrane mobility and fisetin modulated markedly the thermotropic behavior of the membrane. Myricetin was located predominantly in the surface zone, whereas quercetin penetrated into the deeper zone of the bilayer. Using the fluorescent probe Laurdan we showed that all the flavonols studied increased the hydration of the lipid bilayer. The incorporation of effector molecules into the liposomal membrane bilayer resulted in an increase in the absolute value of zeta potential and induced an increase in the liposomal diameter. Destabilization and enhanced heterogeneity of liposomal membranes in the presence of all the flavonols studied were revealed.