Selective Action of Antimalarial Hydroxychloroquine on the Packing of Phospholipids and Interfacial Water Associated with Lysosomal Model Membranes: A Vibrational Sum Frequency Generation Study.

Understanding the structural change of lysosomal membranes induced by hydroxychloroquine (HCQ) drug is essential as it has been considered as one of the probable mechanisms of its antimalarial action. In this context, vibrational sum frequency generation (VSFG) spectra of the O-H region of water and C-H of the hydrocarbon chain of negatively charged and zwitterionic phospholipids associated with the lysosomal membrane in the absence and presence of different concentrations of HCQ have been measured at the air/water interface. The interfacial water at the negatively charged and zwitterionic lipids gets restructured in the presence of HCQ; however, the mechanism of restructuring is different due to the charge of the head groups of lipids. Interestingly, the presence of HCQ leads to a disorder in the negatively charged lipids, irrespective of their chemical nature, mainly by creating the gauche defect in the hydrocarbon chain of the lipid. In contrast, the ordering of the zwitterionic lipid does not show any appreciable change with the addition of HCQ. The finding on the selectivity of HCQ in affecting the ordering of the lipid depending on its head group charge and restructuring of interfacial water may be useful in understanding the molecular level mechanism of the antimalarial action of HCQ.