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      In Search of Effective UiO-66 Metal–Organic Frameworks for Artificial Kidney Application

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          Abstract

          The removal of uremic toxins from patients with acute kidney injury is a key issue in improving the quality of life for people requiring peritoneal dialysis. The currently utilized method for the removal of uremic toxins from the human organism is hemodialysis, performed on semipermeable membranes where the uremic toxins, along with small molecules, are separated from proteins and blood cells. In this study, we describe a mixed-linker modulated synthesis of zirconium-based metal–organic frameworks for efficient removal of uremic toxins. We determined that the efficient adsorption of uremic toxins is achieved by optimizing the ratio between −amino functionalization of the UiO-66 structure with 75% of −NH 2 groups within organic linker structure. The maximum adsorption of hippuric acid and 3-indoloacetic acid was achieved by UiO-66-NH 2 (75%) and by UiO-66-NH 2 (75%) 12.5% HCl prepared by modulated synthesis. Furthermore, UiO-66-NH 2 (75%) almost completely adsorbs 3-indoloacetic acid bound to bovine serum albumin, which was used as a model protein to which uremic toxins bind in the human body. The high adsorption capacity was confirmed in recyclability test, which showed almost 80% removal of 3-indoloacetic acid after the third adsorption cycle. Furthermore, in vitro cytotoxicity tests as well as hemolytic activity assay have proven that the UiO-66-based materials can be considered as potentially safe for hemodialytic purposes in living organisms.

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          Modulated synthesis of Zr-based metal-organic frameworks: from nano to single crystals.

          We present an investigation on the influence of benzoic acid, acetic acid, and water on the syntheses of the Zr-based metal-organic frameworks Zr-bdc (UiO-66), Zr-bdc-NH(2) (UiO-66-NH(2)), Zr-bpdc (UiO-67), and Zr-tpdc-NH(2) (UiO-68-NH(2)) (H(2) bdc: terephthalic acid, H(2) bpdc: biphenyl-4,4'-dicarboxylic acid, H(2) tpdc: terphenyl-4,4''-dicarboxylic acid). By varying the amount of benzoic or acetic acid, the synthesis of Zr-bdc can be modulated. With increasing concentration of the modulator, the products change from intergrown to individual crystals, the size of which can be tuned. Addition of benzoic acid also affects the size and morphology of Zr-bpdc and, additionally, makes the synthesis of Zr-bpdc highly reproducible. The control of crystal and particle size is proven by powder XRD, SEM and dynamic light scattering (DLS) measurements. Thermogravimetric analysis (TGA) and Ar sorption experiments show that the materials from modulated syntheses can be activated and that they exhibit high specific surface areas. Water proved to be essential for the formation of well-ordered Zr-bdc-NH(2) . Zr-tpdc-NH(2), a material with a structure analogous to that of Zr-bdc and Zr-bpdc, but with the longer, functionalized linker 2'-amino-1,1':4',1''-terphenyl-4,4''-dicarboxylic acid, was obtained as single crystals. This allowed the first single-crystal structural analysis of a Zr-based metal-organic framework.
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            Defect Engineering: Tuning the Porosity and Composition of the Metal–Organic Framework UiO-66 via Modulated Synthesis

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              Review on uremic toxins: classification, concentration, and interindividual variability.

              The choice of the correct concentration of potential uremic toxins for in vitro, ex vivo, and in vivo experiments remains a major area of concern; errors at this level might result in incorrect decisions regarding therpeutic correction of uremia and related clinical complications. An encyclopedic list of uremic retention solutes was composed, containing their mean normal concentration (CN), their highest mean/median uremic concentration (CU), their highest concentration ever reported in uremia (CMAX), and their molecular weight. A literature search of 857 publications on uremic toxicity resulted in the selection of data reported in 55 publications on 90 compounds, published between 1968 and 2002. For all compounds, CU and/or CMAX exceeded CN. Molecular weight was lower than 500 D for 68 compounds; of the remaining 22 middle molecules, 12 exceeded 12,000 D. CU ranged from 32.0 ng/L (methionine-enkephalin) up to 2.3 g/L (urea). CU in the ng/L range was found especially for the middle molecules (10/22; 45.5%), compared with 2/68 (2.9%) for a molecular weight <500 D (P < 0.002). Twenty-five solutes (27.8%) were protein bound. Most of them had a molecular weight <500 D except for leptin and retinol-binding protein. The ratio CU/CN, an index of the concentration range over which toxicity is exerted, exceeded 15 in the case of 20 compounds. The highest values were registered for several guanidines, protein-bound compounds, and middle molecules, to a large extent compounds with known toxicity. A ratio of CMAX/CU <4, pointing to a Gaussian distribution, was found for the majority of the compounds (74/90; 82%). For some compounds, however, this ratio largely exceeded 4 [e.g., for leptin (6.81) or indole-3-acetic acid (10.37)], pointing to other influencing factors than renal function, such as gender, genetic predisposition, proteolytic breakdown, posttranslation modification, general condition, or nutritional status. Concentrations of retention solutes in uremia vary over a broad range, from nanograms per liter to grams per liter. Low concentrations are found especially for the middle molecules. A substantial number of molecules are protein bound and/or middle molecules, and many of these exert toxicity and are characterized by a high range of toxic over normal concentration (CU/CN ratio). Hence, uremic retention is a complex problem that concerns many more solutes than the current markers of urea and creatinine alone. This list provides a basis for systematic analytic approaches to map the relative importance of the enlisted families of toxins.
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                Author and article information

                Journal
                ACS Appl Mater Interfaces
                ACS Appl Mater Interfaces
                am
                aamick
                ACS Applied Materials & Interfaces
                American Chemical Society
                1944-8244
                1944-8252
                14 September 2021
                29 September 2021
                : 13
                : 38
                : 45149-45160
                Affiliations
                []Faculty of Chemical Engineering and Technology, Cracow University of Technology , Warszawska 24, 30-155 Kraków, Poland
                []Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences , Niezapominajek 8, 30-239 Kraków, Poland
                [§ ]Małopolska Centre of Biotechnology, Jagiellonian University , ul. Gronostajowa 7A, 30-387 Kraków, Poland
                []Faculty of Materials Science and Ceramics, AGH University of Science and Technology , Mickiewicza 30, 30-059 Kraków, Poland
                []Strata Mechanics Research Institute, Polish Academy of Sciences , Reymonta 27, 30-059 Kraków, Poland
                [# ]Independent Laboratory of Behavioral Studies, Medical University of Lublin , 4A Chodzki Str., 20-093 Lublin, Poland
                []Department of Medical Chemistry, Medical University of Lublin , 4A Chodzki Str., 20-093 Lublin, Poland
                Author notes
                Author information
                https://orcid.org/0000-0002-8339-2710
                https://orcid.org/0000-0002-1005-8068
                https://orcid.org/0000-0003-2554-6539
                Article
                10.1021/acsami.1c05972
                8485328
                34520182
                d789c9ef-53cd-4e97-ab52-cee8a90f79b9
                © 2021 The Authors. Published by American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 02 April 2021
                Funding
                Funded by: Faculty of Materials Science and Ceramics, AGH University of Science and Technology, doi NA;
                Award ID: 16.16.160.557
                Funded by: Faculty of Chemical Engineering and Technology, Cracow University of Technology, doi NA;
                Award ID: NA
                Categories
                Research Article
                Custom metadata
                am1c05972
                am1c05972

                Materials technology
                metal−organic frameworks,uio-66,uio-66-nh2,uremic toxins,adsorption
                Materials technology
                metal−organic frameworks, uio-66, uio-66-nh2, uremic toxins, adsorption

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