| Description |
Small molecule partitioning between aqueous and lipid-like phases is of importance in pharmaceutics, biology, and environmental chemistry. Measuring small-molecule partitioning has remained a challenge, however, due to the scale of current measurement techniques such as chromatographic columns and shake flasks, which require large sample volumes, long equilibration times, and ex-situ quantification steps. In the work presented in this dissertation, confocal Raman microscopy is applied to analyze, in-situ, the structure of lipid-like phases within single chromatographic support particles and their application to measuring small-molecule partitioning. The 2μm â€" 10μm diameter size of a single support particle is well-matched to the size of the confocal probe (~0.6μm diameter, 1 fL) of a 100X confocal microscope. The large (~300m2/g) surface area within the porous particle concentrates surface-associated molecular populations, providing a large enough ‘concentration’ within the particle to measure partitioning despite the small cross-sections for Raman scattering. This dissertation covers the evolution of confocal Raman microscopy measurements within individual porous particles from measuring partitioning of pyrene into surface bound C18 alkyl chains, detecting octanol-water partitioning of naphthoic acid in reverse-phase chromatographic particles, and characterizing the structure of withinparticle hybrid-phospholipid bilayers. This evolution represents a progression toward more biologically-relevant substrates for measuring small-molecule lipophilicity. |
