Parallel Partitioning Protocols

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We have developed several protocols for doing partitioning measurements in parallel by using plasticized poly(vinylchloride) films as the organic phase. Films are cast in 96-well plates. The polymer solution may contain other chemical species. Aqueous solutions, perhaps containing solutes, are introduced into the wells. Equilibrium is attained at a fixed temperature using a shaking apparatus. Aqueous solutions are then analyzed by removing the solutions to another plate, or by placing the plate in an autosampler. We have found that polymer/water partitioning is a very good surrogate for octanol water partitioning, far better, simpler, and cheaper than reversed phase HPLC (Chen 2007). Of course, it is easier to calculate log(P). However, we have found for both neutrals and ionizable species that calculations are quite poor: log(P) and log(D) by calculation do not correlate well with experiment. This method can also be used to investigate the solubilization of poorly soluble compounds like drugs - excipient effectiveness can be assess. Thus, we determined binding constants and stoichiometry for several cyclodextrins binding to econozole and miconozole, both hydrophobic drugs (Chen 2009). The method is efficient and highly reproducible. Finally, we applied it to screening for chiral selectors. The advantages are that very little selector is needed and no synthetic immobilization (e.g., to a support) is needed (Chen 2006).

Molecular Recognition in Liquids & Polymers

Growing environmental concern has demanded more selective, waste-free extractions to minimize the use of volatile organic solvents and simultaneously produce cleaner chromatograms with lower detection limits and higher accuracy. Extraction selectivity is greatly enhanced by incorporating artificial molecular receptors that interact non-covalently with a substrate in a highly selective and predictable manner (Valenta 1994, Valenta 1996). We applied this to great advantage in solid phase microextraction of barbiturates (Li 1999). Solvatochromic studies coupled with experimental measurements of receptor-enhanced extraction into solvent (in this case plasticizers for PVC) (Valenta 1997, Sun 1998) led to the realization that selectivity of an extraction depended on two things: the selectivity and efficacy of the receptor and the properties of the solvent medium. The most selective extractions will have a highly effective receptor in a very poor solvent (for the target analytes). This led us to investigate fluorocarbon solvents and polymers as partitioning/extraction media. Particularly noteworthy is the strong H-bonding-based extraction of pyridines and related compounds based on a fluorous carboxylic acid (from the Krytox family) in a fluorocarbon solvent (O'Neal 2007, O'Neal 2009). Also noteworthy is the dominating role that free volume plays in transport through films of Teflon AF, and our ability to control the fluorous selectivity of transport using well-designed additives, including fluorous nanospheres, into the films (Zhao 1995, Zhang 2010, Zhang 2012).