IR analyses of rate processes in lipid – antibiotic 4 monomolecular films 5

9 10 Abstract 11 12 Polarization modulation infrared reflection spectra of a 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid (DPPA) monolayer on a subphase 13 containing 5 mM tetracycline hydrochloride (TC) were collected under varying surface pressures at the air–water interface. Statistical 14 correlation spectroscopy using 2D IR, bn and kn correlation analyses were performed on these spectra to gain a better understanding of the 15 surface pressure-induced effects on the interaction between the phospholipid and antibiotic. Conventional 2D IR correlation maps revealed 16 strong correlation behavior between the vibrational modes of the lipid and antibiotic. bn correlation plots provided information about the 17 relative rates of occurrence of the coupled responses noted in the conventional 2D IR plots. These calculations indicated that molecular 18 reorientation occurs at lower surface pressures for the modes in Ring A than for the modes in Ring C. A new model-dependent two19 dimensional correlation method, exponential kn correlation analysis, confirmed the results from the previous correlation methods and 20 confirmed that the lipid–antibiotic interactions occurred in a bimodal fashion, depending upon surface pressure. The conclusions of the 21 correlation analysis of the surface-pressure induced changes in the DPPA–TC monolayer system lead to the following model for lipid– 22 antibiotic interaction. Initial interaction between the tetracycline molecule and the DPPA molecule occurs at low surface pressures primarily 23 between Ring A of the tetracycline molecule and the lipid headgroup region. However, with increasing surface pressure, the mode of 24 interaction changes, and the strongest interaction at high surface pressures occurs between Ring C of tetracycline and the DPPA headgroup. 25 # 2004 Published by Elsevier B.V. 26 27