New materials capable of separating mixtures of saturated, unsaturated, and aromatic hydrocarbons can enable more efficient industrial processes and cleaner energy. Outstanding challenges in ...hydrocarbon separations stem from the similar structures, properties, and reactivities of the molecules comprising many of these mixtures. With high surface areas, tunable pore geometries, and adjustable surface functionality, metal–organic frameworks hold tremendous promise for effecting previously difficult or impossible separations. In this review, we provide a comprehensive account of the metal–organic frameworks that have been investigated for hydrocarbon separations within the context of their potential relevance for separating various industrial alkane-, alkene-, and aromatic-containing mixtures.
Lung stem cells are instructed to produce lineage-specific progeny through unknown factors in their microenvironment. We used clonal 3D cocultures of endothelial cells and distal lung stem cells, ...bronchioalveolar stem cells (BASCs), to probe the instructive mechanisms. Single BASCs had bronchiolar and alveolar differentiation potential in lung endothelial cell cocultures. Gain- and loss-of-function experiments showed that BMP4-Bmpr1a signaling triggers calcineurin/NFATc1-dependent expression of thrombospondin-1 (Tsp1) in lung endothelial cells to drive alveolar lineage-specific BASC differentiation. Tsp1 null mice exhibited defective alveolar injury repair, confirming a crucial role for the BMP4-NFATc1-TSP1 axis in lung epithelial differentiation and regeneration in vivo. Discovery of this pathway points to methods to direct the derivation of specific lung epithelial lineages from multipotent cells. These findings elucidate a pathway that may be a critical target in lung diseases and provide tools to understand the mechanisms of respiratory diseases at the single-cell level.
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•Lung endothelial cells control lung stem cell differentiation•In vitro expansion and multilineage differentiation of single lung stem cells•Endothelial TSP1 is required for alveolar differentiation and lung regeneration•BMP4 induces lung-specific, calcineurin/NFATc1-dependent TSP1 expression
3D organoid lung cultures reveal a mechanism by which lung endothelial cells instruct lung stem cells to differentiate into a particular lineage, opening up potential avenues for stimulating these stem cells in response to respiratory-disease-associated injury.
Developing novel drug carriers for pulmonary delivery is necessary to achieve higher efficacy and consistency for treating pulmonary diseases while limiting off-target side effects that occur from ...alternative routes of administration. Metal–organic frameworks (MOFs) have recently emerged as a class of materials with characteristics well-suited for pulmonary drug delivery, with chemical tunability, high surface area, and pore size, which will allow for efficient loading of therapeutic cargo and deep lung penetration. UiO-66, a zirconium and terephthalic acid-based MOF, has displayed notable chemical and physical stability and potential biocompatibility; however, its feasibility for use as a pulmonary drug delivery vehicle has yet to be examined. Here, we evaluate the use of UiO-66 nanoparticles (NPs) as novel pulmonary drug delivery vehicles and assess the role of missing linker defects in their utility for this application. We determined that missing linker defects result in differences in NP aerodynamics but have minimal effects on the loading of model and therapeutic cargo, cargo release, biocompatibility, or biodistribution. This is a critical result, as it indicates the robust consistency of UiO-66, a critical feature for pulmonary drug delivery, which is plagued by inconsistent dosage because of variable properties. Not only that, but UiO-66 NPs also demonstrate pH-dependent stability, with resistance to degradation in extracellular conditions and breakdown in intracellular environments. Furthermore, the carriers exhibit high biocompatibility and low cytotoxicity in vitro and are well-tolerated in in vivo murine evaluations of orotracheally administered NPs. Following pulmonary delivery, UiO-66 NPs remain localized to the lungs before clearance over the course of seven days. Our results demonstrate the feasibility of using UiO-66 NPs as a novel platform for pulmonary drug delivery through their tunable NP properties, which allow for controlled aerodynamics and internalization-dependent cargo release while displaying remarkable pulmonary biocompatibility.
The process of carbon capture and sequestration has been proposed as a method of mitigating the build-up of greenhouse gases in the atmosphere. If implemented, the cost of electricity generated by a ...fossil fuel-burning power plant would rise substantially, owing to the expense of removing CO2 from the effluent stream. There is therefore an urgent need for more efficient gas separation technologies, such as those potentially offered by advanced solid adsorbents. Here we show that diamine-appended metal-organic frameworks can behave as 'phase-change' adsorbents, with unusual step-shaped CO2 adsorption isotherms that shift markedly with temperature. Results from spectroscopic, diffraction and computational studies show that the origin of the sharp adsorption step is an unprecedented cooperative process in which, above a metal-dependent threshold pressure, CO2 molecules insert into metal-amine bonds, inducing a reorganization of the amines into well-ordered chains of ammonium carbamate. As a consequence, large CO2 separation capacities can be achieved with small temperature swings, and regeneration energies appreciably lower than achievable with state-of-the-art aqueous amine solutions become feasible. The results provide a mechanistic framework for designing highly efficient adsorbents for removing CO2 from various gas mixtures, and yield insights into the conservation of Mg(2+) within the ribulose-1,5-bisphosphate carboxylase/oxygenase family of enzymes.
UiO-66, a zirconium(IV) metal–organic framework composed of six-metal clusters and terephthalic acid ligands, displays excellent thermal and chemical stability and has functions in gas storage, ...catalysis, selective adsorption, and drug delivery. Though the stability of UiO-66 is highly advantageous, simultaneous synthetic control over particle size and defectiveness of UiO-66 remains difficult to attain. Using an acid-free solvothermal synthesis, we demonstrate that particle size, defectiveness, and inherent fluorescence of UiO-66 can be precisely tuned using the molar ligand-to-metal ratio, quantified water content, and reaction time during synthesis. These three synthetic handles allow for reproducible modulation of UiO-66 defectiveness between 0 and 12% and particle size between 20 and 120 nm, while maintaining high crystallinity in the nanoparticles that were formed. We also find that particle defectiveness is linked to common overestimation of particle size measurements obtained via dynamic light scattering and propose a model to correct elevated hydrodynamic diameter measurements. Finally, we report inherent fluorescence of nonfunctionalized UiO-66, which exhibits peak fluorescence at a wavelength of 390 nm following excitation at 280 nm and is maximized in large, defect-free particles. Overall, this synthetic approach and characterization of defect, size, and fluorescence represent new opportunities to tune the physiochemical properties of UiO-66.
Purification of the C8 alkylaromatics o-xylene, m-xylene, p-xylene, and ethylbenzene remains among the most challenging industrial separations, due to the similar shapes, boiling points, and ...polarities of these molecules. Herein, we report the evaluation of the metal–organic frameworks Co2(dobdc) (dobdc4– = 2,5-dioxido-1,4-benzenedicarboxylate) and Co2(m-dobdc) (m-dobdc4– = 4,6-dioxido-1,3-benzenedicarboxylate) for the separation of xylene isomers using single-component adsorption isotherms and multicomponent breakthrough measurements. Remarkably, Co2(dobdc) distinguishes among all four molecules, with binding affinities that follow the trend o-xylene > ethylbenzene > m-xylene > p-xylene. Multicomponent liquid-phase adsorption measurements further demonstrate that Co2(dobdc) maintains this selectivity over a wide range of concentrations. Structural characterization by single-crystal X-ray diffraction reveals that both frameworks facilitate the separation through the extent of interaction between each C8 guest molecule with two adjacent cobalt(II) centers, as well as the ability of each isomer to pack within the framework pores. Moreover, counter to the presumed rigidity of the M2(dobdc) structure, Co2(dobdc) exhibits an unexpected structural distortion in the presence of either o-xylene or ethylbenzene that enables the accommodation of additional guest molecules.
Background: The relation between knee meniscal structural damage and cartilage degradation is plausible but not yet clearly proven. Objectives: To quantitate the cartilage volume changes in knee ...osteoarthritis using magnetic resonance imaging (MRI), and determine whether meniscal alteration predicts cartilage volume loss over time. Methods: 32 patients meeting ACR criteria for symptomatic knee osteoarthritis were studied. MRI knee acquisitions were done every six months for two years. The cartilage volumes of different knee regions were measured. Three indices of structural change in the medial and lateral menisci were evaluated—degeneration, tear, and extrusion—using a semiquantitative scale. Results: 24 patients (75%) had mild to moderate or severe meniscal damage (tear or extrusion) at baseline. A highly significant difference in global cartilage volume loss was observed between severe medial meniscal tear and absence of tear (mean (SD), −10.1 (2.1)% v −5.1 (2.4)%, p = 0.002). An even greater difference was found between the medial meniscal changes and medial compartment cartilage volume loss (−14.3 (3.0)% in the presence of severe tear v −6.3 (2.7)% in the absence of tear; p<0.0001). Similarly, a major difference was found between the presence of a medial meniscal extrusion and loss of medial compartment cartilage volume (−15.4 (4.1)% in the presence of extrusion v −4.5 (1.7)% with no extrusion; p<0.001). Conclusions: Meniscal tear and extrusion appear to be associated with progression of symptomatic knee osteoarthritis.
Metal–organic frameworks featuring ligands with open chelating groups are versatile platforms for the preparation of a diverse set of heterogeneous catalysts through postsynthetic metalation. The ...crystalline nature of these materials allows them to be characterized via X-ray diffraction, which provides valuable insight into the structure of the metal sites that facilitate catalysis. A highly porous and thermally robust zirconium-based metal–organic framework, Zr6O4(OH)4(bpydc)6 (bpydc2– = 2,2′-bipyridne-5,5′-dicarboxylate), bears open bipyridine sites that readily react with a variety of solution- and gas-phase metal sources to form the corresponding metalated frameworks. Remarkably, Zr6O4(OH)4(bpydc)6 undergoes a single-crystal-to-single-crystal transformation upon metalation that involves a change in space group from Fm3̅m to Pa3̅. This structural transformation leads to an ordering of the metalated linkers within the framework, allowing structural characterization of the resulting metal complexes. Furthermore, Zr6O4(OH)4(bpydc)6 yields an active heterogeneous catalyst for arene C–H borylation when metalated with Ir(COD)2BF4 (COD = 1,5-cyclooctadiene). These results highlight the unique potential of metal–organic frameworks as a class of heterogeneous catalysts that allow unparalleled structural characterization and control over their active sites.
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