**Electrophoretic Light Scattering and Electrochemical Impedance Spectroscopy Studies of Lipid Bilayers Modified by Cinnamic Acid and Its Hydroxyl Derivatives**

#### **Monika Naumowicz 1, \* , Marcin Zaj ˛ac 2 , Magdalena Kusaczuk 3 , Miroslav Gál 4 and Joanna Koty ´nska 1**


Received: 23 October 2020; Accepted: 13 November 2020; Published: 15 November 2020

**Abstract:** Pharmacological efficiency of active compounds is largely determined by their membrane permeability. Thus, identification of drug-membrane interactions seems to be a crucial element determining drug-like properties of chemical agents. Yet, knowledge of this issue is still lacking. Since chemoprevention based on natural compounds such as cinnamic acid (CinA), *p*-coumaric acid (*p*-CoA) and ferulic (FA) is becoming a strong trend in modern oncopharmacology, determination of physicochemical properties of these anticancer compounds is highly important. Here, electrophoretic light scattering and impedance spectroscopy were applied to study the effects of these phenolic acids on electrical properties of bilayers formed from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-diacyl-sn-glycero-3-phospho-l-serine (PS) or DOPC-PS mixture. After phenolic acid treatment, the negative charge of membranes increased in alkaline pH solutions, but not in acidic ones. The impedance data showed elevated values of both the electrical capacitance and the electrical resistance. We concluded that at acidic pH all tested compounds were able to solubilize into the membrane and permeate it. At neutral and alkaline pH, the CinA could be partially inserted into the bilayers, whereas *p*-CoA and FA could be anchored at the bilayer surface. Our results indicate that the electrochemical methods might be crucial for predicting pharmacological activity and bioavailability of phenolic acids.

**Keywords:** cinnamic acid; *p*-coumaric acid; ferulic acid; phenolic compound; electrophoretic light scattering; electrochemical impedance spectroscopy; phospholipid bilayers; liposomes; drug-membrane interaction; membrane biophysical study
