The objective of this study is to develop the use of high performance liquid chromatography for physico-chemical measurements concerning the properties of biological substances, particularly the anti-cancer drugs. The main thrust of the project is the establishment of a hydrophobicity scale for drugs and their structural elements from appropriate retention data obtained in reversed phase chromatography over a wide range of conditions as far as the composition of the hydro-organic elements is concerned. The proposed hydrophobic index is based on linear free energy relationships (LFER) which we have found to govern retention in liquid chromatographic systems employing non-polar stationary phases. In turn, results will be used to develop LFER between biological response and physico-chemical properties of drugs. In order to model drug-receptor interactions, non-polar stationary phases having different surface geometries will be employed and an attempt will be made to gain quantitative insight into the binding process. HPLC will be employed to develop simple and accurate methods to measure pKa values, solubilities and octanol-water partition coefficients of drugs using minute quantities of material which do not have to be pure. Retention data together with the above molecular parameters will be used to attempt the development of a simple chromatographic approach to a quantitative study of drug conformation in solution as well as to evaluate binding and transport properties of selected anti-cancer drugs.
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