State Key Laboratory of Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China.
Department of Nephrology, Zhongshan Hospital of Fudan University, Shanghai 200032, China.
J Phys Chem B. 2024 Sep 19;128(37):8886-8895. doi: 10.1021/acs.jpcb.4c02830. Epub 2024 Sep 3.
With the increasing incidence of chronic kidney disease, the effective control of protein-bound uremic toxins (PBUTs), which are difficult to remove through dialysis, has become a priority. In this study, the adsorption and diffusion behaviors of several metal-organic frameworks (MOFs) for PBUTs (indoxyl sulfate and -cresyl sulfate) were studied by molecular dynamics (MD) simulations and umbrella sampling. For the NU series of MOFs, good correlations between the Gibbs free energy (Δ) and the experimental clearance rates of PBUTs are found. For the adsorption behaviors, in terms of Δ, DAJWET exhibits the best adsorption effect for indoxyl sulfate (IS), whereas NU-1000 shows the best effect for -cresyl sulfate (pCS). Similar trends observed in the radial distribution function and mean square displacement results suggest that the π-π stacking interactions play a crucial role in the adsorption and diffusion of PBUTs by MOFs. Furthermore, it can be concluded that MOFs with highly conjugated groups (porphyrin rings and pyrene groups) tend to generate more PBUT attraction, and provide design principles for potential MOF candidates in the removal of PBUTs.
随着慢性肾脏病发病率的不断上升，有效控制透析难以清除的蛋白结合性尿毒症毒素（PBUTs）已成为当务之急。本研究通过分子动力学（MD）模拟和伞状采样研究了几种金属-有机骨架（MOFs）对 PBUTs（吲哚硫酸酯和 - 甲苯硫酸酯）的吸附和扩散行为。对于 NU 系列 MOFs，发现 Gibbs 自由能（Δ）与 PBUTs 的实验清除率之间存在良好的相关性。就吸附行为而言，就 Δ 而言，DAJWET 对吲哚硫酸酯（IS）表现出最佳的吸附效果，而 NU-1000 对 - 甲苯硫酸酯（pCS）表现出最佳的效果。径向分布函数和均方位移结果中观察到的相似趋势表明，π-π 堆积相互作用在 MOFs 对 PBUTs 的吸附和扩散中起着至关重要的作用。此外，可以得出结论，具有高共轭基团（卟啉环和芘基团）的 MOFs 往往会产生更多的 PBUT 吸引力，为去除 PBUTs 的潜在 MOF 候选物提供了设计原则。
