(150h) Capitalizing on the Cooperative Action of Multiple Modifiers to Control the Crystallization of Calcium Oxalate

The role of (macro)molecular additives as crystal growth modifiers plays a significant role in the regulation of pathological diseases, such as kidney stones, where the most common inorganic constituent is calcium oxalate monohydrate (COM) crystals.¹ COM crystals grow classically by the birth and spread of layers through monomer addition. Introducing modifiers can alter crystal growth by complexing with solution (locally reducing the supersaturation) and/or blocking solute attachment.^2-3 Research on COM crystallization over the past two decades has revealed unique mechanisms by which modifiers either inhibit or promote crystal nucleation and growth.^4-6 Here, we examine the impact that two or more modifiers have on COM growth modification. Cooperativity can result in either synergism or antagonism. Our studies probe events at both macroscopic and microscopic length scales using a microfluidic platform and atomic force microscopy (AFM), respectively. Our findings identified highly efficient combinations of modifiers capable of inhibiting COM growth as well as enhancing dissolution under different environments. These collective results have the potential to aid the design of new therapies for the pathological crystallization of kidney stones.

References:

1. Wesson, J. A.; Ward, M. D., Pathological Biomineralization of Kidney Stones. Elements 2007,3 (6), 415-421.
2. Alamani, B. G., Rimer, J. D., Molecular modifiers of kidney stones. Curr Opin Nephrol Hy 2017.
3. Olafson, K. N.; Li, R.; Alamani, B. G.; Rirner, J. D., Engineering Crystal Modifiers: Bridging Classical and Nonclassical Crystallization. Chemistry of Materials 2016,28 (23), 8453-8465.
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.
5. 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.
6. 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.