Receptor-Based Sensor Design with Fluorous Matrixes for Enhanced Robustness and Selectivity

University of Minnesota Ph.D. dissertation. June, 2008. Major: Chemistry. Advisor: Philippe Bühlmann. 1 computer file (PDF); xxii, 150 pages.The receptor-based membrane sensors in use today are characterized by wide ranges of linear response, high selectivities, and low detection limits. However, when these sensors are used directly in environmental or biological samples, they exhibit drift and loss of selectivity over time, which both limits their ability to measure ions and their life expectancy. Previous work has shown that this sort of sensor biofouling is primarily caused by the extraction of hydrophobic, nonionic lipids into the sensing membrane, which is usually made of lipophilic materials. In this research, a new class of ion-selective electrodes incorporating perfluorinated sensor matrixes was developed with a view to eliminate sensor biofouling. Perfluorinated phases are the most nonpolar compounds known. In fact, they have such low polarity that just as water and oil separate when mixed together due to the high polarity of water, octane and perfluorooctane do not mix precisely because octane is too polar. These highly nonpolar materials form a third class of solubility preference in addition to those of "aqueous" and "organic", termed “fluorous”. Along with the improved biofouling characteristics expected of ISEs containing fluorous matrixes, they also exhibit enhanced selectivity and wider measuring ranges. Sodium tetrakis[3,5-bis(perfluorohexyl)phenyl]borate and the new salt tris{3,5- bis[(perfluorooctyl)propyl]phenyl}methylphosphonium methyl sulfate were used as fluorophilic anionic and cationic sites in fluorous receptor-free ISE membranes. The fluorous sensors, usually consisting of the fluorous solvent perfluoro(perhydrophenanthrene) as the membrane matrix, demonstrated exceptional selectivities; the fluorous cation-exchanger demonstrated a selectivity range that was 8 orders of magnitude greater than an analogous non-fluorous sensor. Fluorous receptor-doped membranes were constructed using fluorophilic trialkylamines as H+ receptors. The selectivities of a fluorous sensor containing the receptor tris[(perfluorooctyl)pentyl]amine were among the highest ever reported for a pH ISE while the measuring range was 2.5 orders of magnitude wider than for an analogous non-fluorous electrode. Using the fluorous ISE system developed in this work, binding constants were directly measured in fluorous solvents for the first time. The pKa of tris[(perfluoro- octyl)pentyl]amine in perfluoro(perhydrophenanthrene) was measured to be 15.4 ± 0.4, which is 2-3 units higher than would be expected for the same amine in a typical organic solvent of low polarity. In addition, the weak binding character of representative fluorous solvents (neat) containing heteroatoms was measured. The pKa of perfluorotripentylamine was measured to be < –0.5, while the 1:1 formal association constants for 2H-perfluoro-5,8,11-trimethyl-3,6,9,12-tetraoxapentadecane binding to Na+ and Li+ were measured to be 2.3 and 1.5 M–1, respectively. In addition to demonstrating potentiometry in a fluorous solvent, a new fluorophilic electrolyte salt, tetrabutylammonium tetrakis[3,5-bis(perfluorohexyl)phenyl]- borate, was used to perform voltammetry in a fluorous solvent for the first time. Cyclic voltammograms of ferrocene were obtained from a 10 μm Pt microelectrode in an 80.5 mM solution of a fluorophilic electrolyte salt in perfluoro(methylcyclohexane)