Dissertation Defense: Victoria Hall
Candidate Name: Victoria Hall
Advisor: Jennifer A. Swift, Ph.D.
Title: Uric Acid Crystals
Uric acid is a crystalline component in kidney stones and gout deposits. In the work described herein, a variety of approaches are adopted to (1) create more soluble forms of uric acid, (2) examine the effects of additives on the crystallization of uric acid, and (3) compare the properties of urine-grown and water-grown samples.
Cocrystallization studies with pyridine and pyrimidine derivatives generated six new phases with hydrogen-bonding patterns inspired by DNA base pairing. Most of the new phases showed a modest increase in solubility compared to pure uric acid, though cocrystals with 2-
aminopyridine had > 2X higher solubility. Cocrystallization studies also yielded some unexpected results, including a gel and an amorphous film. New polymorphs of 2-amino- 5,6-dimethyl-4- hydroxypyrimidine and 2,6-diaminopyridine were additionally identified.
Growth studies in the presence of both a urinary pigment, urorosein (Ur) and 2,4-diaminopyridine (24-DAP) were performed. The structure of Ur was determined from synchrotron X-ray diffraction. This helped to complete our understanding of how Ur can include in anhydrous uric acid (UA) and uric acid dihydrate (UAD) crystal matrices during growth. Solutions containing 4:1 ratios of uric acid:24-DAP yielded pyramidal UAD crystals with thin anhydrous UA layers in their centers. Over time the UAD to UA transformation in solution resulted in an unusual kind of “inside-out” epitaxial growth. AFM revealed dramatic topological differences in the UA (100) surface when exposed to acetate buffer and in buffered solutions containing 24-DAP.
Finally, prior work suggested that UAD crystals grown from urine (UAD-U) and water (UAD-W) have different levels of molecular disorder. Quasi-Elastic Neutron Scattering performed at NIST-NCNR enabled the water dynamics in both samples to be measured. UAD-U was found to have a small but statistically significant higher diffusion rate, which is consistent with a higher degree of molecular disorder in the solid.
Wednesday, May 16 at 11:00am to 1:00pm
Reiss Science Building, 238
37th and O St., N.W., Washington