Growth and Nucleation Modifiers of Calcium Oxalate Mineralization



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Crystallization is a ubiquitous process essential in chemical, biological, physical and geological phenomena. The kinetics and thermodynamics facilitating crystallization are important metrics that allow understanding of the underlying mechanisms in determining the structure and property of the crystal. Insights from such fundamental studies of growth establish rules or heuristics useful to tune the structure and property of the crystals to transition into functional materials that find applications in energy, environment, and health. This dissertation focuses on the mineralization of calcium oxalate monohydrate (COM), the most common constituent of human kidney stones, and the mechanisms by which various modifiers alter the rate of COM formation with concomitant changes in crystal properties (e.g., size and shape). Specifically, we investigated modifiers that can inhibit nucleation and growth of COM, which can be potential candidates for new therapeutics of pathological calcification in humans. In certain cases, promoters of growth and intergrowth formation have been identified, which can be insightful in understanding COM formation in plants. We employed macroscopic and molecular scale approaches to investigate the influence of divalent ions (Zn2+, Sr2+, and Mg2+) and polyphosphates (hexametaphosphate, linear tripolyphosphate, and cyclic trimetaphosphate) on COM mineralization. These ions and molecules interact with the crystal through mechanisms dominated by thermodynamic and/or kinetic processes. We examined the impact of these modifiers on the morphology and kinetics of COM crystallization. In these studies, we have uncovered unique modes of action for several modifiers where ions (e.g., Zn2+ and Sr2+) can have dual modes of action in modulating COM crystallization. Cyclic polyphosphates (HMP), on the other hand, can be effective nucleation inhibitors, but only moderately effective growth inhibitors, while linear polyphosphates (LTPP) are only effective growth inhibitors. Some modifiers (e.g., Mg2+ and CTMP) do not impact the overall crystallization rate, which cannot be easily explained from our experiments. Overall, our understanding of modifier-crystal interactions that mediate COM crystallization can be useful in obtaining guidelines or heuristics in designing processes to regulate materials assembly. Specifically, the combination of bulk and interfacial approaches in deciphering modifier-crystal interactions may find use in screening preventative drug candidates that are capable of inhibiting pathological calcification.



Crystallization, Modifiers