Membrane fluidization & eryptotic properties of hesperidin–copper complex

Metal–flavonoid complexes have elicited much attention in recent years due to their enhanced pharmacological activities when compared with their parent flavonoid and hence have the potential to be used as therapeutic agents. The membrane interactions and localization of these molecules will determine their role as a clinically relevant therapeutic molecule. Hesperidin is a flavone glycoside present in citrus plants. In the present work, a room temperature synthesis of hesperidin–copper complex was carried out and its interactions with membranes were investigated on a self-assembled nano-dimensional lipid bilayer membrane using electrochemical techniques. The results reveal that the copper complex interacts strongly at the membrane–electrolyte interface and localizes in the outer bilayer leaflet in a dose-dependent manner causing extensive membrane fluidization. When incubated with erythrocytes, hesperidin–copper complex initiated eryptosis and triggered formation of echinocytes by disrupting the actin cytoskeletal network because of its surface interaction. The parent flavonoid did not show such extensive membrane perturbation effects which may be attributed to their deeper penetration. The hesperidin–copper complex exhibits lower anti-oxidant activity when compared with hesperidin. These alterations in the mode of interaction of hesperidin–copper complex compared with their parent flavonoid may influence their pharmacological activities.