Substituents modulate biphenyl penetration into lipid membranes

Electrochemical impedance techniques and fluorescence spectroscopic methods have been applied to the study of the interaction of ortho (o)-, meta (m)- and para (p)-Cl-, o-, m- and p-HO-, p-H3CO-, p-H3C-, p-NC- and p-O3−S- substituted biphenyls (BPs) with Hg supported dioleoyl phosphatidylcholine (DOPC) monolayers and DOPC vesicles. Non-planar o-substituted BPs exhibit the weakest interactions whereas planar p-substituted BPs interact to the greatest extent with the DOPC layers. The substituted BP/DOPC monolayer and bilayer interaction depends on the effect of the substituent on the aromatic electron density, which is related to the substituents' mesomeric Hammetts constants. Substituted BPs with increased ring electron density do not increase the DOPC monolayer thickness on Hg and penetrate the DOPC vesicle membranes to the greatest extent. Substituted BPs with lower ring electron density can cause an increase in the monolayer's thickness on Hg depending on their location and they remain in the interfacial and superficial layer of the free standing DOPC membranes. Quantum mechanical calculations correlate the binding energy between the substituted BP rings and methyl acetate, as a model for the –CH2-(CO)O-CH2- fragment of a DOPC molecule, with the location of BPs within the DOPC monolayer. [Display omitted] •Substituted biphenyls (BP) interact with DOPC membranes in the order p->m->o-.•Substituents modulate the penetration of BPs into DOPC membranes.•BP substituent position and ring polarizability influence BP/membrane interaction.•Monolayer/bilayer experiments give consistent results for BP/membrane interaction.