@unpublished{pittir22566,
           month = {September},
           title = {PARALLEL POLYMER-BASED MICROEXTRACTION METHODS TO STUDY INTERMOLECULAR ASSOCIATION AND PHYSICOCHEMICAL PROPERTIES},
          author = {Dujuan Lu},
            year = {2014},
        keywords = {distribution coefficient, Cyclodextrin, binding constant, lipophilicity, SPME},
             url = {http://d-scholarship-dev.library.pitt.edu/22566/},
        abstract = {Lipophilicity and acid dissociation constants are important physicochemical properties that in part determine the suitability of an organic molecule as a pharmacological agent. Intermolecular associations are omnipresent in chemical and biochemical systems and particularly important in the efficacy of an excipient for a poorly soluble drug. Current standard methods to determine lipophilicity require large amounts of pure sample and have problems due to emulsion formation. This dissertation describes a method based on distribution of the solutes between a polymer phase and an aqueous phase in a 96-well format, in the presence and absence of a receptor (e.g., candidate excipient) in one of the two phases. This parallel approach uses minimal amounts of organic solvent and only requires small amounts of sample. This approach has been used to determine polymer-water distribution coefficients of solutes. In addition, by measuring polymer-water distribution coefficients at a variety of experimental conditions, such as pH and receptor concentration, acid dissociation constants and solute-receptor binding constants have been successfully determined for several chemical systems.    
This method has been applied to measure binding constants of econazole with six cyclodextrins in aqueous solutions. The acid dissociation constant of econazole was determined by measuring econazole-cyclodextrin binding constants at various pH values. Distribution coefficients and acid dissociation constants of twenty-four novel drug-like compounds have also been determined by this parallel approach and compared to the values calculated by commercially available software. The software packages did not adequately predict experimental results, especially for ionizable compounds. This emphasizes the need for laboratory separations-based measurements of distribution coefficients. The polymeric phase was poly(vinyl chloride) (PVC) plasticized by 67\% (w/w) dioctyl sebacate (DOS). Intermolecular association has also been studied in Teflon AF 2400, a fluorous polymer phase, with and without fluorous hydrogen bond donor Krytox 157 FSH in the 96-well approach. In addition, a novel fluorous receptor-doped fiber solid phase microextraction (SPME) was developed to selectively detect quinoline in aqueous solutions. }
}