Interaction of phloretin with membranes: on the mode of action of phloretin at the water-lipid interface

The interaction of phloretin with single lipid bilayers on a spherical supp ort and with multilamellar vesicles was studied by differential scanning ca lorimetry (DSC) and nuclear magnetic resonance (NMR). The results indicated that phloretin interacts with the lipid layer and changes its structural p arameters. In DSC experiments, phloretin in its neutral form strongly decre ased the lipid phase transition temperature and slightly reduced the cooper ativity of the phase transition within the lipid layer. In NMR measurements . phloretin led to an increase of the transverse relaxation time constant b ut had no effect on the spin-lattice relaxation time constant. The overall dipole moment of phloretin was experimentally determined and was found to b e roughly 40% lower than has been published previously. This result suggest ed that the size of the dipole moment of phloretin does not provide such a high contribution to the effect of phloretin on the dipole potential of mon olayers and bilayers as has been published previously. To understand the di screpancy between phloretin adsorption and dipole potential change, we perf ormed computational conformational analysis of phloretin in the gas phase. The results showed that a wide distribution of the dipole moments of phlore tin conformers exists. which mainly depends on the orientation of the OH mo ieties. The adsorption of phloretin as determined from its binding to solid supported bilayers differed from the one determined from dipole potential measurements on black lipid membranes. The difference between the phloretin dissociation constants of both types of experiments suggested a change of its dipole moment normal to the membrane surface in a concentration-depende nt manner. which was in agreement with the results of the computational con formational analysis.