Role of Polyprotic Acids as Inhibitors of Calcium Oxalate Crystallization
| dc.contributor.advisor | Rimer, Jeffrey D. | |
| dc.contributor.committeeMember | Vekilov, Peter G. | |
| dc.contributor.committeeMember | Robertson, Megan L. | |
| dc.contributor.committeeMember | Miljanić, Ognjen Š. | |
| dc.contributor.committeeMember | Reynolds, Michael A. | |
| dc.creator | Chung, Jihae | |
| dc.date.accessioned | 2019-09-14T19:41:06Z | |
| dc.date.available | 2019-09-14T19:41:06Z | |
| dc.date.created | May 2017 | |
| dc.date.issued | 2017-05 | |
| dc.date.submitted | May 2017 | |
| dc.date.updated | 2019-09-14T19:41:08Z | |
| dc.description.abstract | Crystallization is a ubiquitous phenomenon in many synthetic, natural, and biological systems that is often mediated by the action of foreign molecules (or modifiers) to tune the physicochemical properties of crystalline materials. Pathological biomineralization is an example of an undesirable crystallization process where modifiers act as inhibitors to reduce the rate of crystal growth. Here, we focus on the effects of modifiers and parametric studies of the growth medium on the crystallization of calcium oxalate monohydrate (COM), which is the most prevalent constituent of human kidney stones. We performed a systematic study to observe the specificity and efficacy of polyprotic organic acids, including the current drug citrate and its structural analogues, on COM crystallization. Interestingly, we identified modifiers that exhibit different modes of inhibitory action. A notable example is that of hydroxycitrate, which induces dissolution of the crystal surface in highly supersaturated growth solutions. Combined results from in situ atomic force microscopy studies and density functional theory calculations support our hypothesis that modifier-crystal interactions induce localized strain on the crystal lattice, which, in turn, leads to surface dissolution. We also studied the effects of solute and modifier speciation on COM crystallization under varying solution alkalinity that encompasses physiological conditions. We observe a pronounced disparity in the efficacy of modifiers with solution alkalinity owing to changes in local supersaturation near the crystal surface. Collectively, the improved fundamental understanding of modifier-crystal interactions coupled with high-resolution characterization techniques serve as a platform to developing new therapeutics for kidney stone disease as well as elucidating the role of natural biomolecules in the pathological biomineralization of calcium oxalate stones. | |
| dc.description.department | Chemical and Biomolecular Engineering, Department of | |
| dc.format.digitalOrigin | born digital | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.citation | Portions of this document appear in: Chung, Jihae, Ignacio Granja, Michael G. Taylor, Giannis Mpourmpakis, John R. Asplin, and Jeffrey D. Rimer. "Molecular modifiers reveal a mechanism of pathological crystal growth inhibition." Nature 536, no. 7617 (2016): 446. | |
| dc.identifier.uri | https://hdl.handle.net/10657/4616 | |
| dc.language.iso | eng | |
| dc.rights | The author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s). | |
| dc.subject | Crystallization | |
| dc.subject | Growth modifier | |
| dc.subject | Calcium oxalate | |
| dc.subject | Kidney stone | |
| dc.subject | Renal health | |
| dc.subject | Kidney health | |
| dc.title | Role of Polyprotic Acids as Inhibitors of Calcium Oxalate Crystallization | |
| dc.type.dcmi | Text | |
| dc.type.genre | Thesis | |
| thesis.degree.college | Cullen College of Engineering | |
| thesis.degree.department | Chemical and Biomolecular Engineering, Department of | |
| thesis.degree.discipline | Chemical Engineering | |
| thesis.degree.grantor | University of Houston | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy |