No abstract

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 6 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.

Metal–organic frameworks (MOFs) with coordinatively unsaturated metal sites are appealing as adsorbent materials due to their tunable functionality and ability to selectively bind small molecules. Through the use of computational screening methods based on periodic density functional theory, we investigate O2 and N2 adsorption at the coordinatively unsaturated metal sites of several MOF families. A variety of design handles are identified that can be used to modify the redox activity of the metal centers, including changing the functionalization of the linkers (replacing oxido donors with sulfido donors), anion exchange of bridging ligands (considering μ-Br–, μ-Cl–, μ-F–, μ-SH–, or μ-OH– groups), and altering the formal oxidation state of the metal. As a result, we show that it is possible to tune the O2 affinity at the open metal sites of MOFs for applications involving the strong and/or selective binding of O2. In contrast with O2 adsorption, N2 adsorption at open metal sites is predicted to be relatively weak across the MOF dataset, with the exception of MOFs containing synthetically elusive V2+ open metal sites. As one example from the screening study, we predicted that exchanging the μ-Cl– ligands of M2Cl2(BBTA) (H2BBTA = 1H,5H-benzo­(1,2-d:4,5-d′)­bistriazole) with μ-OH– groups would significantly enhance the strength of O2 adsorption at the open metal sites without a corresponding increase in the N2 affinity. Experimental investigation of Co2Cl2(BBTA) and Co2(OH)2(BBTA) confirms that the former exhibits weak physisorption of both N2 and O2, whereas the latter is capable of chemisorbing O2 at room temperature in a highly selective manner. The O2 chemisorption behavior is attributed to the greater electron-donating character of the μ-OH– ligands and the presence of H-bonding interactions between the μ-OH– bridging ligands and the reduced O2 adsorbate.

We introduce a new hybrid molecular orbital/density-functional modified divide-and-conquer (mDC) approach that allows the linear-scaling calculation of very large quantum systems. The method provides a powerful framework from which linear-scaling force fields for molecular simulations can be developed. The method is variational in the energy, and has simple, analytic gradients and essentially no break-even point with respect to the corresponding full electronic structure calculation. Furthermore, the new approach allows intermolecular forces to be properly balanced such that non-bonded interactions can be treated, in some cases, to much higher accuracy than the full calculation. The approach is illustrated using the second-order self-consistent charge density-functional tight-binding model (DFTB2). Using this model as a base Hamiltonian, the new mDC approach is applied to a series of water systems, where results show that geometries and interaction energies between water molecules are greatly improved relative to full DFTB2. In order to achieve substantial improvement in the accuracy of intermolecular binding energies and hydrogen bonded cluster geometries, it was necessary to extend the DFTB2 model to higher-order atom-centered multipoles for the second-order self-consistent intermolecular electrostatic term. Using generalized, linear-scaling electrostatic methods, timings demonstrate that the method is able to calculate a water system of 3000 atoms in less than half of a second, and systems of up to one million atoms in only a few minutes using a conventional desktop workstation.

Metal–organic frameworks (MOFs) have been reported to be versatile catalysts because of their amenability to modular design and tunability. Recently, a series of zirconium-based MOFs have been used to catalyze the hydrolytic destruction of chemical warfare agents (CWAs) that contain phosphate ester bonds. Here, we adopt density functional theory calculations to study the hydrolysis of the CWA simulant methylparaoxon on the Zr-based MOF NU-1000. Our calculated energy barriers are in quantitative agreement with previous experimental kinetics data. Comparison between uncatalyzed aqueous hydrolysis and the MOF-catalyzed reaction reveals the origin of the catalytic effects of NU-1000 and shows a resemblance to enzymatic catalysis of similar reactions. The effect of node distortion on the catalytic mechanism is also examined, and the results are consistent with experimental findings, where the distorted node of NU-1000 shows an increase in the rate of methylparaoxon hydrolysis compared to the completely hydrated regular form of NU-1000.