In this proposal, the molecular level crystallization and phase transformation phenomena of assorted uric acid phases will be investigated. Uric acid is known to precipitate under physiological conditions in its protonated state as either an anhydrous material (UA) or as a less stable dihydrate (UAD), and as a number of different urate salts, including monosodium urate monohydrate (MSU) and ammonium acid urate (AAU). The studies proposed address the following four specific aims: (1) To elucidate molecular-level changes in the UA surface topology and step kinetics when growth occurs in the presence of impurities (e.g., molecular dye probes and model urine components) with in situ atomic force microscopy (AFM), (2) To establish baseline growth kinetics and mechanisms on UAD and MSU single crystal surfaces in model solutions as a function of fundamental solution parameters such as pH, super-saturation, and temperature using in situ AFM, (3) To study the phase transformation of metastable UAD and UA both in air and in solution, and, in doing so, elucidate the effects of particle size, shape, temperature, pH, impurity composition and concentration on this process, and (4) To explore hydrothermal methods as a means to map out the conditions (e.g., pH, temperature, cooling rate) under which uric acid phases grow individually or simultaneously and to generate diffraction quality crystals of AAU as well as other metal-urate complexes. The insights gained from the proposed studies will help to elucidate pathological crystallization events in a direct sense and molecular crystal growth processes in general. This research program provides solid interdisciplinary training for PhD students and an excellent opportunity for undergraduates and high school students to gain experience with research methods. Educational impact will also be realized in the ongoing development of lectures/exercises which are used in graduate and undergraduate professional development workshops.
