Figure 4.

PAINS-like polyphenols and their C-glucosides affect differently the membrane dipole potential. This schematic illustration represents a pictorial view of a ternary lipid mixture with l_d/l_o phase coexistent, in the absence (top) and in the presence of genistein (middle) or 8-glucosylgenistein (8G) (bottom). These compounds are placed in the membrane with the polyphenol at different depth and orientation, inspired in previously reported theoretical and experimental work^89–92. The C-glucosyl polyphenol has, indeed, a more superficial location due to the sugar moiety. Together with the H-bonding pattern of the sugar, the location and the orientation of the C-glucosyl polyphenol contribute to its performance as a non-dipole modifier.