Dynamics of the interaction of tetracycline with a monolayer of model cell membrane using VSFG spectroscopy.

The knowledge of interaction of a drug with the membrane phospholipids is crucial to decipher its penetration mechanism inside the cell. Tetracycline is a widely used antibiotic effective against various classes of bacteria. In this work, we have employed vibrational sum-frequency generation (VSFG) spectroscopy to understand the molecular-level interaction of tetracycline with a model phospholipid monolayer, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), at the air–water interface. Results suggest that tetracycline molecules are not present on the topmost surface of the water and remain mostly in the bulk aqueous phase. However, due to charge–dipole interaction, the orientation of water molecules in the subphase immediately beneath the topmost layer gets randomized due to its presence. Due to their long hydrophobic aliphatic chains, DPPC molecules are surface active and replace the topmost water layer and increase the polar orientation of interfacial water molecules by generating electric field across the interface. In the presence of the DPPC monolayer, tetracycline molecules get adsorbed from the bulk water to the interface due to electrostatic interactions with the ionic headgroups of DPPC. This interaction also results in the ordering of hydrophobic chains as confirmed by an increase in the VSFG intensity of CH₃ groups of the hydrocarbon chains. We have been successful in unraveling the changes induced in the hydrocarbon backbone of DPPC as a result of such interaction. The water molecules associated with the DPPC monolayer also get randomized in presence of tetracycline molecules. We, for the first time, have studied the dynamics of interfacial water molecules in presence of tetracycline and tetracycline-DPPC environment. [ABSTRACT FROM AUTHOR]