The effect of side group on the dynamic behavior of anthracyclines on DOPG lipid membranes revealed by second harmonic generation and fluorescence

In this work we use two-photon fluorescence (TPF) and surface-sensitive second harmonic generation (SHG) techniques to investigate the interaction of the lipid membrane with anthracyclines of different side groups including DOX (Doxorubicin), DNR (Daunorubicin), IDA (Idarubicin) and MIT (Mitoxantrone). It is observed that DOX, DNR and IDA molecules which are with one charged side group behave similarly. They lean on the lipid membrane in the adsorption and then embed in it with the dipole orientation pointing to the same direction. On contrary, MIT molecules with two charged side groups firstly adsorb at the lipid surface with the anthracene part pointing to the water phase, then flip and embed in the lipid membrane. It is revealed that most of the anthracyclines on the lipid surface are close to the head group of the lipid molecules in the membrane. It is also observed that although a higher hydrophobicity of the anthracyclines results in a higher tendency for them to penetrate across the lipid bilayer, it may not necessarily result in a faster embedding of the drug molecules in the lipid membrane.