Department of Chemistry and International Institute of Nanotechnology , Northwestern University , 2145 Sheridan Road , Evanston , Illinois 60208 , United States.
Department of Chemical and Biological Engineering , Northwestern University , 2145 Sheridan Road , Evanston , Illinois 60208 , United States.
J Am Chem Soc. 2019 Feb 13;141(6):2568-2576. doi: 10.1021/jacs.8b12525. Epub 2019 Feb 1.
Uremic toxins often accumulate in patients with compromised kidney function, like those with chronic kidney disease (CKD), leading to major clinical complications including serious illness and death. Sufficient removal of these toxins from the blood increases the efficacy of hemodialysis, as well as the survival rate, in CKD patients. Understanding the interactions between an adsorbent and the uremic toxins is critical for designing effective materials to remove these toxic compounds. Herein, we study the adsorption behavior of the uremic toxins, p-cresyl sulfate, indoxyl sulfate, and hippuric acid, in a series of zirconium-based metal-organic frameworks (MOFs). The pyrene-based MOF, NU-1000, offers the highest toxin removal efficiency of all the MOFs in this study. Other Zr-based MOFs possessing comparable surface areas and pore sizes to NU-1000 while lacking an extended aromatic system have much lower toxin removal efficiency. From single-crystal X-ray diffraction analyses assisted by density functional theory calculations, we determined that the high adsorption capacity of NU-1000 can be attributed to the highly hydrophobic adsorption sites sandwiched by two pyrene linkers and the hydroxyls and water molecules on the Zr nodes, which are capable of hydrogen bonding with polar functional groups of guest molecules. Further, NU-1000 almost completely removes p-cresyl sulfate from human serum albumin, a protein that these uremic toxins bind to in the body. These results offer design principles for potential MOFs candidates for uremic toxin removal.
尿毒症毒素通常在肾功能受损的患者中积累，如患有慢性肾病 (CKD) 的患者，导致严重的临床并发症，包括重病和死亡。从血液中充分清除这些毒素可以提高 CKD 患者血液透析的疗效和生存率。了解吸附剂与尿毒症毒素之间的相互作用对于设计有效去除这些有毒化合物的材料至关重要。在此，我们研究了一系列基于锆的金属有机骨架 (MOF) 中尿毒症毒素对甲酚硫酸盐、吲哚硫酸盐和马尿酸的吸附行为。基于芘的 MOF NU-1000 对所有研究 MOF 中具有最高的毒素去除效率。其他具有可比表面积和孔尺寸但缺乏扩展芳构体系的基于 Zr 的 MOF 的毒素去除效率要低得多。通过密度泛函理论计算辅助的单晶 X 射线衍射分析，我们确定 NU-1000 具有高吸附容量，这归因于由两个芘连接体和 Zr 节点上的羟基和水分子夹在中间的高度疏水吸附位点，这些吸附位点能够与客体分子的极性官能团形成氢键。此外，NU-1000 几乎可以完全从人血清白蛋白中去除对甲酚硫酸盐，这些尿毒症毒素在体内与人血清白蛋白结合。这些结果为潜在的用于尿毒症毒素去除的 MOF 候选物提供了设计原则。
