QSAR STUDIES BY LIPOSOME ELECTROKINETIC CHROMATOGRAPHY

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A primary goal of this project is to investigate the usefulness of Micellar Electrokinetic Capillary Chromatography (MECC) and Micellar Liquid Chromatography (MLC) for prediction of bioactivity through Quantitative Retention -Activity Relationships (QRAR) and for quantitation of lipophilic character of molecules. The development of quantitative relationships between chemical structural properties and biological activity has had a tremendous impact in the fields of drug design, toxicology, and environmental monitoring. Our aim is to achieve a better understanding of the common underlying molecular interactions that influence retention in MECC and MLC and cause biological activity, partitioning into biomembranes, or binding to proteins. These goals will be realized through parallel studies of correlating MECC / MLC retention, octanol-water partition coefficient, proteins binding, and liposomes partitioning to the Solvatochromic Parameters of solutes through Linear Solvation Energy Relationships (LSER). In order to! fully explore the multidimensional nature of these problems, we will investigate the usefulness of the factor - based, multivariate analysis chemometric techniques such as principal component regression and partial least square in QRAR modeling. This research should lead to the development of unique methodologies for characterization of physicochemical properties of biomolecules. The combination of biomimicry of micellar aggregates due to their amphiphilic and organized nature, the enormous capabilities of MECC and MLC techniques in physicochemical analysis, their flexibility and versatility for incorporation of different types of interactions, and the computional power of the mutivariate analysis techniques for treatment of a large set of data in a multidimensional space should provide exciting opportunities in structure - activity modeling. Another major goal is to explore the enormous capabilities of these two micellar mediated techniques for solving complex bioseparation problems. We will take advantage of the predictive power of the quantitatve models that have been developed in our laboratory, and will extend the range of these models in order to achieve a better understanding of migration behavior of a variety of small biomolecules in MECC and MLC. This will include systematic studies of the chromatographic parameters that influence separation of solutes of general interest in bioanalysis, specifically pharmaceutically important compounds and small peptides. We will investigate the usefulness of computer assisted modeling and, simulation in developing rapid and effective methods for optimization of MECC and MLC separations.