(609g) Interaction of Amphiphilic Coumarin with DPPC/Dpps Using DSC and MD Simulations: Effects of Concentration and Chain Length

Amphiphilic molecules have better cell penetration properties. Interactions between novel amphiphilic amino methyl coumarin with DPPC/DPPS liposomes were investigated by combining experimental (zeta potential, fluorescence spectroscopy, DSC) and theoretical MD simulations studies. Alkyl chains comprising of 5, 9 and 12 carbon atoms were conjugated to amino methyl coumarin via single step process. Our results indicate that C5 and C12 associate with lipid membrane via flip-flop mechanism. At higher concentrations, C5 aggregate resulting in continuous insertion and ejection from the outer leaflet of the lipid bilayer causing thinning of the membrane. On the contrary, C12 lacked the ejection-reinsertion behavior suggesting they were associated with the inner leaflet of the bilayer and flip-flop occurred between the outer and inner leaflets resulting in membrane destabilization. This was further confirmed by the DSC studies that showed disappreance of phase separation and a well-mixed lipid system in the bilayer with subsequent annealing. The presence of broader transition peak also indicated increased melting cooperativity or associated with increased number of lipid molecules. The efficacy of C12 coumarin for potential biomedical applications were further demonstrated via preliminary cellular uptake, toxicity and photodynamic activity in cancer cells.