Controlled Encapsulation of Gold Nanoparticles into Zr-Metal-Organic Frameworks with Improved Detection Limitation of Volatile Organic Compounds via Surface-Enhanced Raman Scattering.

Volatile organic compounds (VOCs) have harmful effects on human health and the environment but detecting low levels of VOCs is challenging due to a lack of reliable biomarkers. However, incorporating gold nanoparticles (Au NPs) into metal-organic frameworks (MOFs) shows promise for VOC detection. In this study, we developed nanoscale Au@UiO-66 that exhibited surface-enhanced Raman scattering (SERS) activity even at very low levels of toluene vapors (down to 1.0 ppm) due to the thickness of the shell and strong π-π interactions between benzenyl-type linkers and toluene. The UiO-66 shell also increased the thermal stability of the Au NPs, preventing aggregation up to 550 °C. This development may be useful for sensitive detection of VOCs for environmental protection purposes.

Computer-Aided Design and Synthesis of (Functionalized quinazoline)-(α-substituted coumarin)-arylsulfonate Conjugates against Chikungunya Virus.

Chikungunya virus (CHIKV) has repeatedly spread via the bite of an infected mosquito and affected more than 100 countries. The disease poses threats to public health and the economy in the infected locations. Many efforts have been devoted to identifying compounds that could inhibit CHIKV. Unfortunately, successful clinical candidates have not been found yet. Computations through the simulating recognition process were performed on complexation of the nsP3 protein of CHIKV with the structures of triply conjugated drug lead candidates. The outcomes provided the aid on rational design of functionalized quinazoline-(α-substituted coumarin)-arylsulfonate compounds to inhibit CHIKV in Vero cells. The molecular docking studies showed a void space around the ß carbon atom of coumarin when a substituent was attached at the α position. The formed vacancy offered a good chance for a Michael addition to take place owing to steric and electronic effects. The best conjugate containing a quinazolinone moiety exhibited potency with EC50 = 6.46 µM, low toxicity with CC50 = 59.7 µM, and the selective index (SI) = 9.24. Furthermore, the corresponding 4-anilinoquinazoline derivative improved the anti-CHIKV potency to EC50 = 3.84 µM, CC50 = 72.3 µM, and SI = 18.8. The conjugate with 4-anilinoquinazoline exhibited stronger binding affinity towards the macro domain than that with quinazolinone via hydrophobic and hydrogen bond interactions.

Triboelectric behaviour of selected MOFs in contact with metals.

MOFs have been effectively used to magnify the triboelectric charge of polymers. However, so far the individual triboelectric properties and charge transfer mechanisms of MOFs haven't been reported. Triboelectric property investigation for selected MOFs show that the main mechanism for MOF triboelectrification in contact with metals is electron transfer.

Rapid Fabrication of Biocomposites by Encapsulating Enzymes into Zn-MOF-74 via a Mild Water-Based Approach.

A zinc-based metal organic framework, Zn-MOF-74, which has a unique one-dimensional (1D) channel and nanoscale aperture size, was rapidly obtained in 10 min using a de novo mild water-based system at room temperature, which is an example of green and sustainable chemistry. First, catalase (CAT) enzyme was encapsulated into Zn-MOF-74 (denoted as CAT@Zn-MOF-74), and comparative assays of biocatalysis, size-selective protection, and framework-confined effects were investigated. Electron microscopy and powder X-ray diffraction were used for characterization, while electrophoresis and confocal microscopy confirmed the immobilization of CAT molecules inside the single hexagonal MOF crystals at loading of ∼15 wt %. Furthermore, the CAT@Zn-MOF-74 hybrid was exposed to a denaturing reagent (urea) and proteolytic conditions (proteinase K) to evaluate its efficacy. The encapsulated CAT maintained its catalytic activity in the decomposition of hydrogen peroxide (H2O2), even when exposed to 0.05 M urea and proteinase K, yielding an apparent observed rate constant (kobs) of 6.0 × 10-2 and 6.6 × 10-2 s-1, respectively. In contrast, free CAT exhibited sharply decreased activity under these conditions. Additionally, the bioactivity of CAT@Zn-MOF-74 for H2O2 decomposition was over three times better than that of the biocomposites based on zeolitic imidazolate framework 90 (ZIF-90) owing to the nanometer-scaled apertures, 1D channel, and less confinement effects in Zn-MOF-74 crystallites. To demonstrate the general applicability of this strategy, another enzyme, α-chymotrypsin (CHT), was also encapsulated in Zn-MOF-74 (denoted as CHT@Zn-MOF-74) for action against a substrate larger than H2O2. In particular, CHT@Zn-MOF-74 demonstrated a biological function in the hydrolysis of l-phenylalanine p-nitroanilide (HPNA), the activity of ZIF-90-encapsulated CHT was undetectable due to aperture size limitations. Thus, we not only present a rapid eco-friendly approach for Zn-MOF-74 synthesis but also demonstrate the broader feasibility of enzyme encapsulation in MOFs, which may help to meet the increasing demand for their industrial applications.

Creating an Aligned Interface between Nanoparticles and MOFs by Concurrent Replacement of Capping Agents.

Applying metal-organic frameworks (MOFs) on the surface of other materials to form multifunctional materials has recently attracted great attention; however, directing the MOF overgrowth is challenging due to the orders of magnitude differences in structural dimensions. In this work, we developed a universal strategy to mediate MOF growth on the surface of metal nanoparticles (NPs), by taking advantage of the dynamic nature of weakly adsorbed capping agents. During this colloidal process, the capping agents gradually dissociate from the metal surface, replaced in situ by the MOF. The MOF grows to generate a well-defined NP-MOF interface without a trapped capping agent, resulting in a uniform core-shell structure of one NP encapsulated in one single-crystalline MOF nanocrystal with specific facet alignment. The concept was demonstrated by coating ZIF-8 and UiO-66-type MOFs on shaped metal NPs capped by cetyltrimethylammonium surfactants, and the formation of the well-defined NP-MOF interface was monitored by spectroscopies. The defined interface outperforms ill-defined ones generated via conventional methods, displaying a high selectivity to unsaturated alcohols for the hydrogenation of an α,ß-unsaturated aldehyde. This strategy opens a new route to create aligned interfaces between materials with vastly different structural dimensions.

Probing Interactions between Metal-Organic Frameworks and Freestanding Enzymes in a Hollow Structure.

It has been reported that the biological functions of enzymes could be altered when they are encapsulated in metal-organic frameworks (MOFs) due to the interactions between them. Herein, we probed the interactions of catalase in solid and hollow ZIF-8 microcrystals. The solid sample with confined catalase is prepared through a reported method, and the hollow sample is generated by hollowing the MOF crystals, sealing freestanding enzymes in the central cavities of hollow ZIF-8. During the hollowing process, the samples were monitored by small-angle X-ray scattering (SAXS) spectroscopy, electron microscopy, powder X-ray diffraction (PXRD), and nitrogen sorption. The interfacial interactions of the two samples were studied by infrared (IR) and fluorescence spectroscopy. IR study shows that freestanding catalase has less chemical interaction with ZIF-8 than confined catalase, and a fluorescence study indicates that the freestanding catalase has lower structural confinement. We have then carried out the hydrogen peroxide degradation activities of catalase at different stages and revealed that the freestanding catalase in hollow ZIF-8 has higher activity.

Dielectric Spectroscopy of Water Dynamics in Functionalized UiO-66 Metal-Organic Frameworks.

We present a dielectric spectroscopy study of dipolar dynamics in the hydrated UiO-66(Zr) type metal-organic frameworks (MOFs) functionalized with -NH2 and -F groups. Experiments are performed in a broad temperature and frequency ranges allowing us to probe several dipolar relaxations. For both samples at temperature below 220 K, we observe confined supercooled water dynamics, which can be described by the Arrhenius law. At slightly higher temperature, a second less pronounced dipolar relaxation is identified, and its origin is discussed. At even higher temperature, the dielectric permittivity exhibits anomalous increase with increasing temperature due to the proton conductivity. Upon further heating, the permittivity shows a sudden decrease indicating a reversible removal of water molecules. Measurements of the dehydrated samples reveal absence of all three dipolar processes.

Rapid mechanochemical encapsulation of biocatalysts into robust metal-organic frameworks.

Metal-organic frameworks (MOFs) have recently garnered consideration as an attractive solid substrate because the highly tunable MOF framework can not only serve as an inert host but also enhance the selectivity, stability, and/or activity of the enzymes. Herein, we demonstrate the advantages of using a mechanochemical strategy to encapsulate enzymes into robust MOFs. A range of enzymes, namely ß-glucosidase, invertase, ß-galactosidase, and catalase, are encapsulated in ZIF-8, UiO-66-NH2, or Zn-MOF-74 via a ball milling process. The solid-state mechanochemical strategy is rapid and minimizes the use of organic solvents and strong acids during synthesis, allowing the encapsulation of enzymes into three prototypical robust MOFs while maintaining enzymatic biological activity. The activity of encapsulated enzyme is demonstrated and shows increased resistance to proteases, even under acidic conditions. This work represents a step toward the creation of a suite of biomolecule-in-MOF composites for application in a variety of industrial processes.

Ligand Exchange in the Synthesis of Metal-Organic Frameworks Occurs Through Acid-Catalyzed Associative Substitution.

The syntheses of metal-organic frameworks (MOFs) can be improved through modulated synthesis, synthesis employing precursors, and postsynthetic exchange (PSE) modifications, all of which share ligand exchange as a common and crucial reaction. To date, however, the mechanism of ligand exchange and the underlying principles governing it have remained elusive. Herein, we report energy landscapes for the ligand exchange processes of 1,4-benzenedicarboxylic acid and 2,3,5,6-tetrafluoro-1,4-benzenedicarboxylic acid with Zr6O4(OH)4(OMc)12 (OMc = methacrylate), as calculated using density functional theory (DFT). The rate-limiting step of ligand exchange follows an associative-substitution mechanism catalyzed by protons, consistent with previous kinetic data. Our calculations suggest that the acid catalysis is dependent on the relative basicities of the incoming and outgoing ligands coordinated in the complex, allowing molecular-level rationalization of many seminal MOF syntheses that had previously been interpreted macroscopically. Our results provide new insights for MOF synthesis and new clues for the rational de novo synthesis of MOFs.

Chikungunya virus inhibition by synthetic coumarin-guanosine conjugates.

Since its discovery in Tanganyika, Africa in 1952, chikungunya virus (CHIKV) outbreaks have occurred in Africa, Asia, Europe, and America. Till now chikungunya fever has spread in nearly 40 countries. Because of lack of effective vaccines and antiviral drugs to intervene this disease, 21 new conjugated compounds were designed and synthesized by coupling of 6,8-dithioguanosine at its C-6 position with 3-(chloromethyl)coumarins bearing an F, Cl, Br, Me, or -OMe substituent through the -SCH2- joint. Meanwhile, an organic "dummy" ligand (e.g., methyl, benzyl, and naphthylmethyl) or a coumarinyl moiety was attached at the C-8 position. By high through-put screening, three of these new conjugates were found to inhibit CHIKV in Vero cells with significant potency (EC50 = 9.9-13.9 µM) and showed low toxicity (CC50 = 96.5-212 µM). The selectivity index values were 9.37-21.7. Their structure-activity relationship was deduced, which indicates that the coumarin moiety is essential and the presence of a -OMe group enhances the antiviral activity.

Strategies for Improving the Functionality of Zeolitic Imidazolate Frameworks: Tailoring Nanoarchitectures for Functional Applications.

Zeolitic imidazolate frameworks (ZIFs), a subclass of metal-organic frameworks (MOFs) built with tetrahedral metal ions and imidazolates, offer permanent porosity and high thermal and chemical stabilities. While ZIFs possess some attractive physical and chemical properties, it remains important to enhance their functionality for practical application. Here, an overview of the extensive strategies which have been developed to improve the functionality of ZIFs is provided, including linker modifications, functional hybridization of ZIFs via the encapsulation of guest species (such as metal and metal oxide nanoparticles and biomolecules) into ZIFs, and hybridization with polymeric matrices to form mixed matrix membranes for industrial gas and liquid separations. Furthermore, the developed strategies for achieving size and shape control of ZIF nanocrystals are considered, which are important for optimizing the textural characteristics as well as the functional performance of ZIFs and their derived materials/hybrids. Moreover, the recent trends of using ZIFs as templates for the derivation of nanoporous hybrid materials, including carbon/metal, carbon/oxide, carbon/sulfide, and carbon/phosphide hybrids, are discussed. Finally, some perspectives on the potential future research directions and applications for ZIFs and ZIF-derived materials are offered.

Reductive Deamination by Benzyne for Deoxy Sugar Synthesis Through a Domino Reaction.

Benzyne was developed as a reducing agent in the key step of converting amino sugars and ketoses into deoxy sugars, which occur widely in natural products. Many deoxy sugars exhibit antibiotic and anticancer activities, and furthermore, they play essential biological roles. By treatment with CS2 and then Ac2O, amino sugars and ketoses were converted into the corresponding 1,3-thiazolidine-2-thiones. In the key step, these intermediates were treated with 2-trimethylsilylphenyl triflate (2.0 equiv.) and CsF (3.0 equiv.) in MeCN at 25 °C to produce acyclic enol acetates in 60-63 % yields. Saponification of the enol acetates with NaOMe/MeOH followed by intramolecular cyclization afforded the target 2-deoxy sugars. The key step of the reductive deamination involved a domino 1,2-elimination/[3+2]-cycloaddition/retro [3+2]-ring-opening sequence. The generality of this new method was proven by the use of various substrates, including pentoses, hexoses, monosaccharides, disaccharides, aldoses, and ketoses.

Green and rapid synthesis of zirconium metal-organic frameworks via mechanochemistry: UiO-66 analog nanocrystals obtained in one hundred seconds.

A UiO-66 analog was synthesized in 100 s using water-assisted grinding. The linker solubility suggested that tetrafluorobenzene-1,4-dicarboxylic acid was the best linker. Zr-metal-organic framework nanocrystals displayed good topologies and hydrophobicities, and high water/thermal stabilities. The less amorphous complex led to higher porosities and pore volumes with a 60 min grinding time.

Shielding against Unfolding by Embedding Enzymes in Metal-Organic Frameworks via a de Novo Approach.

We show that an enzyme maintains its biological function under a wider range of conditions after being embedded in metal-organic framework (MOF) microcrystals via a de novo approach. This enhanced stability arises from confinement of the enzyme molecules in the mesoporous cavities in the MOFs, which reduces the structural mobility of enzyme molecules. We embedded catalase (CAT) into zeolitic imidazolate frameworks (ZIF-90 and ZIF-8), and then exposed both embedded CAT and free CAT to a denature reagent (i.e., urea) and high temperatures (i.e., 80 °C). The embedded CAT maintains its biological function in the decomposition of hydrogen peroxide even when exposed to 6 M urea and 80 °C, with apparent rate constants kobs (s-1) of 1.30 × 10-3 and 1.05 × 10-3, respectively, while free CAT shows undetectable activity. A fluorescence spectroscopy study shows that the structural conformation of the embedded CAT changes less under these denaturing conditions than free CAT.

Long-Range Olefin Isomerization Catalyzed by Palladium(0) Nanoparticles.

Long-range olefin isomerization of 2-alkenylbenzoic acid derivatives going through two to five sp3-carbon atoms to give (E)-alkenes was achieved with palladium(0) nanoparticles. The substrate scope of this reaction includes carboxylic acid, ester, and primary to tertiary amides and tolerates various substituents on the benzene ring. This isomerization reaction was catalyzed by recyclable Pd(0) nanoparticles, prepared in situ from PdCl2 and characterized by X-ray powder diffraction and scanning electron microscopy analyses. 1H NMR studies and kinetic modeling supported a stepwise process. This new process was applied to synthesize a natural dihydroisocoumarin with good efficiency.

Synthesis and Structure-Activity Relationships of Imidazole-Coumarin Conjugates against Hepatitis C Virus.

A series of new conjugated compounds with a -SCH2- linkage were synthesized by chemical methods from imidazole and coumarin derivatives. The experimental results indicate that of the twenty newly synthesized imidazole-coumarin conjugates, three of them exhibited appealing EC50 values (5.1-8.4 µM) and selective indices >20 against hepatitis C virus. Their potency and selectivity were increased substantially by modification of their structure with two factors: imidazole nucleus with a hydrogen atom at the N(1) position and coumarin nucleus with a substituent, such as Cl, F, Br, Me, and OMe. These guidelines provide valuable information for further development of conjugated compounds as anti-viral agents.

Cytotoxicity of Postmodified Zeolitic Imidazolate Framework-90 (ZIF-90) Nanocrystals: Correlation between Functionality and Toxicity.

Using a simple method, the aldehyde groups of zeolitic imidazolate framework-90 (ZIF-90) nanocrystals were converted into carboxyl, amino, and thiol groups, without affecting the integrity of the framework. Notably, for the first time, correlations between functionality and cytotoxicity are also demonstrated via in vitro cytotoxicity assays. The positive charged aminated-ZIF-90 presumably results in either perturbation of cell membrane, more efficient cell uptake, or both. Therefore, the half-maximal effective (EC50 ) concentration of aminated-ZIF-90 has a higher cytotoxicity of about 30 µg mL(-1) .

Formation of hollow and mesoporous structures in single-crystalline microcrystals of metal-organic frameworks via double-solvent mediated overgrowth.

The creation of hierarchical porosity in metal-organic frameworks (MOFs) could benefit various applications of MOFs such as gas storage and separation. Having single-crystalline microcrystals instead of poly-crystalline composites is critical for these potential applications of MOFs with hierarchical porosity. We developed a room temperature synthetic method to generate uniform hollow and mesoporous zeolitic imidazolate framework-8 (ZIF-8) microcrystals with a single-crystalline structure via overgrowing a ZIF-8 shell in methanol solution on a ZIF-8 core with water adsorbed in the pores. The cavities formed as a result of the different solvent micro-environment. This double-solvent mediated overgrowth method could be applied to prepare other MOFs with hierarchical porosity.

Benzouracil-coumarin-arene conjugates as inhibiting agents for chikungunya virus.

Chikungunya virus (CHIKV) is an arbovirus that was first recognized in an epidemic form in East Africa in 1952-1953. The virus is primarily transmitted through mosquitoes and the resulting disease, chikungunya fever, is found in nearly 40 countries. Neither an effective vaccine nor a specific antiviral drug exists for treatments of chikungunya fever. Thus 22 new conjugated compounds of uracil-coumarin-arene were designed and synthesized as potential inhibiting agents. Their chemical structures were determined unambiguously by spectroscopic methods, including single-crystal X-ray diffraction crystallography. The three units in these conjugates were connected by specially designed -SCH2- and -OSO2- joints. Five of these new conjugates were found to inhibit CHIKV in Vero cells with significant potency (EC50 = 10.2-19.1 µM) and showed low toxicity (CC50 = 75.2-178 µM). The selective index values were 8.8-11.5 for three conjugates. By analysis of the data from the anti-viral assays, the structure-activity relationship is derived on the basis of the nature of the uracil, the functional groups attached to the arene, and the joints between the ring units.

Imparting functionality to biocatalysts via embedding enzymes into nanoporous materials by a de novo approach: size-selective sheltering of catalase in metal-organic framework microcrystals.

We develop a new concept to impart new functions to biocatalysts by combining enzymes and metal-organic frameworks (MOFs). The proof-of-concept design is demonstrated by embedding catalase molecules into uniformly sized ZIF-90 crystals via a de novo approach. We have carried out electron microscopy, X-ray diffraction, nitrogen sorption, electrophoresis, thermogravimetric analysis, and confocal microscopy to confirm that the ~10 nm catalase molecules are embedded in 2 µm single-crystalline ZIF-90 crystals with ~5 wt % loading. Because catalase is immobilized and sheltered by the ZIF-90 crystals, the composites show activity in hydrogen peroxide degradation even in the presence of protease proteinase K.