Growth & Transformation of Uric Acid Crystal Phases

本文研究了不同尿酸相在分子水平上的结晶和相变现象。已知尿酸在生理条件下以质子化状态沉淀为无水物质（UA）或不太稳定的二水物质（UAD），以及许多不同的尿酸盐，包括一水尿酸钠（MSU）和尿酸铵（AAU）。拟议的研究涉及以下四个具体目标：(1)利用原位原子力显微镜（AFM）阐明在杂质（如分子染料探针和模型尿液成分）存在下生长时UA表面拓扑结构和步骤动力学的分子水平变化；(2)利用原位原子力显微镜（AFM）建立模型溶液中UAD和MSU单晶表面的基线生长动力学和机制，并将其作为基本溶液参数（如pH、过饱和度和温度）的函数。(3)研究亚稳态UAD和UA在空气和溶液中的相变，并阐明粒径、形状、温度、pH、杂质组成和浓度对这一过程的影响；(4)探索水热法作为绘制条件(如pH、温度、冷却速率)，在此条件下尿酸相单独或同时生长，并产生AAU以及其他金属-尿酸复合物的衍射质量晶体。从提出的研究中获得的见解将有助于阐明直接意义上的病理结晶事件和一般的分子晶体生长过程。该研究项目为博士生提供了坚实的跨学科培训，为本科生和高中生提供了获得研究方法经验的绝佳机会。在研究生和本科生专业发展讲习班中使用的正在发展的讲座/练习也将实现教育影响。

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.