Nov 1
Chemistry Department Seminar: Tenure-Track Candidate
Thermodynamic Studies of Drug-Lipid Interactions
Small molecule pharmaceutical drugs may adsorb to and perturb the physical structure of lipids in the mammalian plasma membrane. Using the laser-based analytical method, second harmonic generation (SHG), we directly monitored adsorption of aqueous solutions of the small-molecule antipsychotic drug, clozapine, to supported lipid bilayers (SLBs) without the use of extrinsic labels. Equilibrium binding constants were determined from fits to the Langmuir model. Experiments were conducted at several physiologically-relevant temperatures to quantify enthalpies and entropies of adsorption. Comparisons of the thermodynamic forces that drive drug adsorption provided molecular-level insight into binding mechanisms. We also determined membrane binding affinities of other antipsychotic drugs, such as olanzapine and chlorpromazine, which have similar physical size and aromaticity, but differ in hydrophobicity, charge, and functional group identities. Our studies provided insight into how chemical structure alters membrane interactions.
*This seminar counts toward the chemistry major requirement.
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