(178g) Controlling Calcium Oxalate Monohydrate Crystal Growth: Investigating the Synergistic Effects of Cooperative Modifiers

In this presentation we will discuss methods of controlling the crystallization of calcium oxalate monohydrate (COM), which is a principal component of human kidney stones. This disease affects 12-14% of the global population, with a recurrence rate exceeding 50% within the first five years.¹ The role of (macro)molecular additives as crystal growth modifiers is instrumental in regulating pathological conditions that either promote or inhibit the formation of COM crystals. Prior studies have shown that COM crystals grow by classical layer-by-layer mechanisms through monomer addition to surface sites (e.g., kinks, steps, terraces).² It has been demonstrated for a range of modifiers spanning from ions and small organic molecules to macromolecules (e.g., proteins), that interactions between modifiers and COM crystal surfaces leads to different mechanisms of growth inhibition.^3-4

Here we will discuss the use of multiple modifiers acting cooperatively to control COM crystallization. These experimental studies involve a combination of techniques that probe growth (or dissolution) at both macroscopic and microscopic length scales. Microfluidics is used to caption time-resolved changes in bulk crystal size and morphology, while in situ atomic force microscopy (AFM) is used to visualize the dynamics of surface growth. Modifiers acting by one of three mechanisms – kink blocking, step pinning, and lattice strain inducing – are paired to quantify their cooperative effects on COM crystallization. Our findings reveal conditions leading to both synergism and antagonism. Overall, we have identified highly efficient combinations of modifiers capable of inhibiting COM crystal growth and enhancing dissolution under varying environmental conditions, well beyond the capability of any single growth modifier. These results have the potential to guide future design of therapeutics targeting pathological crystallization of kidney stones and other related diseases.

References:

1. Wesson, J. A.; Ward, M. D., Pathological biomineralization of kidney stones. Elements 2007,3 (6), 415-421.
2. Chung, J.; Granja, I.; Taylor, M. G.; Mpourmpakis, G.; Asplin, J. R.; Rimer, J. D., Molecular modifiers reveal a mechanism of pathological crystal growth inhibition. Nature 2016,536 (7617), 446-450.
3. Farmanesh, S.; Ramamoorthy, S.; Chung, J. H.; Asplin, J. R.; Karande, P.; Rimer, J. D., Specificity of growth inhibitors and their cooperative effects in calcium oxalate monohydrate crystallization. Journal of the American Chemical Society 2014,136 (1), 367-376.
4. Farmanesh, S.; Alamani, B. G.; Rimer, J. D., Identifying alkali metal inhibitors of crystal growth: a selection criterion based on ion pair hydration energy. Chemical Communications 2015,51 (73), 13964-13967.