Polymorphism and orientation control of copper-dicarboxylate metal-organic framework thin films through vapour- and liquid-phase growth.

Precise control over the crystalline phase and crystallographic orientation within thin films of metal-organic frameworks (MOFs) is highly desirable. Here, we report a comparison of the liquid- and vapour-phase film deposition of two copper-dicarboxylate MOFs starting from an oriented metal hydroxide precursor. X-ray diffraction revealed that the vapour- or liquid-phase reaction of the linker with this precursor results in different crystalline phases, morphologies, and orientations. Pole figure analysis showed that solution-based growth of the MOFs follows the axial texture of the metal hydroxide precursor, resulting in heteroepitaxy. In contrast, the vapour-phase method results in non-epitaxial growth with uniplanar texture only.

Organophosphate Detoxification and Acetylcholinesterase Reactivation Triggered by Zeolitic Imidazolate Framework Structural Degradation.

Organophosphate (OP) toxicity is related to inhibition of acetylcholinesterase (AChE) activity, which plays a key role in the neurotransmission process. In this work, we report the ability of different zinc zeolitic imidazolate frameworks (ZIFs) to behave as potential antidotes against OP poisoning. The Zn-L coordination bond (L = purine, benzimidazole, imidazole, or 2-methylimidazole) is sensitive to the G-type nerve agent model compounds diisopropylfluorophosphate (DIFP) and diisopropylchlorophosphate, leading to P-X (X = F or Cl) bond breakdown into nontoxic diisopropylphosphate. P-X hydrolysis is accompanied by ZIF structural degradation (Zn-imidazolate bond hydrolysis), with the concomitant release of the imidazolate linkers and zinc ions representing up to 95% of ZIF particle dissolution. The delivered imidazolate nucleophilic attack on the OP@AChE adduct gives rise to the recovery of AChE enzymatic function. P-X bond breakdown, ZIF structural degradation, and AChE reactivation are dependent on imidazolate linker nucleophilicity, framework topology, and particle size. The best performance is obtained for 20 nm nanoparticles (NPs) of Zn(2-methylimidazolate)2 (sod ZIF-8) exhibiting a DIFP degradation half-life of 2.6 min and full recovery of AChE activity within 1 h. 20 nm sod ZIF-8 NPs are not neurotoxic, as proven by in vitro neuroblastoma cell culture viability tests.

Fabrication of Oriented Polycrystalline MOF Superstructures.

The field of metal-organic frameworks (MOFs) has progressed beyond the design and exploration of powdery and single-crystalline materials. A current challenge is the fabrication of organized superstructures that can harness the directional properties of the individual constituent MOF crystals. To date, the progress in the fabrication methods of polycrystalline MOF superstructures has led to close-packed structures with defined crystalline orientation. By controlling the crystalline orientation, the MOF pore channels of the constituent crystals can be aligned along specific directions: these systems possess anisotropic properties including enhanced diffusion along specific directions, preferential orientation of guest species, and protection of functional guests. In this perspective, we discuss the current status of MOF research in the fabrication of oriented polycrystalline superstructures focusing on the specific crystalline directions of orientation. Three methods are examined in detail: the assembly from colloidal MOF solutions, the use of external fields for the alignment of MOF particles, and the heteroepitaxial ceramic-to-MOF growth. This perspective aims at promoting the progress of this field of research and inspiring the development of new protocols for the preparation of MOF systems with oriented pore channels, to enable advanced MOF-based devices with anisotropic properties.

Water sensitivity of heteroepitaxial Cu-MOF films: dissolution and re-crystallization of 3D-oriented MOF superstructures.

3D-oriented metal-organic framework (MOF) films and patterns have recently emerged as promising platforms for sensing and photonic applications. These oriented polycrystalline materials are typically prepared by heteroepitaxial growth from aligned inorganic nanostructures and display anisotropic functional properties, such as guest molecule alignment and polarized fluorescence. However, to identify suitable conditions for the integration of these 3D-oriented MOF superstructures into functional devices, the effect of water (gaseous and liquid) on different frameworks should be determined. We note that the hydrolytic stability of these heteroepitaxially grown MOF films is currently unexplored. In this work, we present an in-depth analysis of the structural evolution of aligned 2D and 3D Cu-based MOFs grown from Cu(OH)2 coatings. Specifically, 3D-oriented Cu2L2 and Cu2L2DABCO films (L = 1,4-benzenedicarboxylate, BDC; biphenyl-4,4-dicarboxylate, BPDC; DABCO = 1,4-diazabicyclo[2.2.2]octane) were exposed to 50% relative humidity (RH), 80% RH and liquid water. The combined use of X-ray diffraction, infrared spectroscopy, and scanning electron microscopy shows that the sensitivity towards humid environments critically depends on the presence of the DABCO pillar ligand. While oriented films of 2D MOF layers stay intact upon exposure to all levels of humidity, hydrolysis of Cu2L2DABCO is observed. In addition, we report that in environments with high water content, 3D-oriented Cu2(BDC)2DABCO recrystallizes as 3D-oriented Cu2(BDC)2. The heteroepitaxial MOF-to-MOF transformation mechanism was studied with in situ synchrotron experiments, time-resolved AFM measurements, and electron diffraction. These findings provide valuable information on the stability of oriented MOF films for their application in functional devices and highlight the potential for the fabrication of 3D-oriented superstructures via MOF-to-MOF transformations.

Targeting telomerase utilizing zeolitic imidazole frameworks as non-viral gene delivery agents across different cancer cell types.

Telomerase, a ribonucleoprotein coded by the hTERT gene, plays an important role in cellular immortalization and carcinogenesis. hTERT is a suitable target for cancer therapeutics as its activity is highly upregulated in most of cancer cells but absent in normal somatic cells. Here, by employing the two Metal-Organic Frameworks (MOFs), viz. ZIF-C and ZIF-8, based biomineralization we encapsulate Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 plasmid system that targets hTERT gene (CrhTERT) in cancer cells. When comparing the two biocomposites, ZIF-C shows the better loading capacity and cell viability. The loaded plasmid in ZIF-C is highly protected against enzymatic degradation. CrhTERT@ZIF-C is efficiently endocytosed by cancer cells and the subcellular release of CrhTERT leads to telomerase knockdown. The resultant inhibition of hTERT expression decreases cellular proliferation and causing cancer cell death. Furthermore, hTERT knockdown shows a significant reduction in tumour metastasis and alters protein expression. Collectively we show the high potential of ZIF-C-based biocomposites as a promising general tool for gene therapy of different types of cancers.

Fabrication of 3D Oriented MOF Micropatterns with Anisotropic Fluorescent Properties.

Micropatterning crystalline materials with oriented pores is necessary for the fabrication of devices with anisotropic properties. Crystalline and porous metal-organic frameworks (MOFs) are ideal materials as their chemical and structural mutability enables precise tuning of functional properties for applications ranging from microelectronics to photonics. Herein, a patternable oriented MOF film is designed: by using a photomask under X-ray exposure, the MOF film decomposes in the irradiated areas, remaining intact in the unexposed regions. The MOF film acts simultaneously as a resist and as functional porous material. While the heteroepitaxial growth from aligned Cu(OH)2 nanobelts is used to deposit oriented MOF films, the sensitivity to radiation is achieved by integrating a brominated dicarboxylate ligand (Br2 BDC) into a copper-based MOF Cu2 L2 DABCO (DABCO = 1,4-diazabicyclo[2.2.2]octane; L = BDC/Br2 BDC). The lithographed samples act as diffraction gratings upon irradiation with a laser, thus confirming the quality of the extended MOF micropattern. Furthermore, the oriented MOF patterns are functionalized with fluorescent dyes. As a result, by rotating the polarization angle of the laser excitation, the alignment of the dye in the MOF is demonstrated. By controlling the functional response to light, this MOF patterning protocol can be used for the microfabrication of optical components for photonic devices.

Unraveling the timescale of the structural photo-response within oriented metal-organic framework films.

Fundamental knowledge on the intrinsic timescale of structural transformations in photo-switchable metal-organic framework films is crucial to tune their switching performance and to facilitate their applicability as stimuli-responsive materials. In this work, for the first time, an integrated approach to study and quantify the temporal evolution of structural transformations is demonstrated on an epitaxially oriented DMOF-1-on-MOF film system comprising azobenzene in the DMOF-1 pores (DMOF-1/AB). We employed time-resolved Grazing Incidence Wide-Angle X-Ray Scattering measurements to track the structural response of the DMOF-1/AB film upon altering the length of the azobenzene molecule by photo-isomerization (trans-to-cis, 343 nm; cis-to-trans, 450 nm). Within seconds, the DMOF-1/AB response occurred fully reversible and over several switching cycles by cooperative photo-switching of the oriented DMOF-1/AB crystallites as confirmed further by infrared measurements. Our work thereby suggests a new avenue to elucidate the timescales and photo-switching characteristics in structurally responsive MOF film systems.

Multi-layered ZIF-coated cells for the release of bioactive molecules in hostile environments.

Metal-organic framework (MOF) coatings on cells enhance viability in cytotoxic environments. Here, we show how protective multi-layered MOF bio-composite shells on a model cell system (yeast) enhance the proliferation of living cells exposed to hostile protease-rich environments via the dissolution of the shells and release of a protease inhibitor (antitrypsin).

How Reproducible are Surface Areas Calculated from the BET Equation?

Porosity and surface area analysis play a prominent role in modern materials science. At the heart of this sits the Brunauer-Emmett-Teller (BET) theory, which has been a remarkably successful contribution to the field of materials science. The BET method was developed in the 1930s for open surfaces but is now the most widely used metric for the estimation of surface areas of micro- and mesoporous materials. Despite its widespread use, the calculation of BET surface areas causes a spread in reported areas, resulting in reproducibility problems in both academia and industry. To prove this, for this analysis, 18 already-measured raw adsorption isotherms were provided to sixty-one labs, who were asked to calculate the corresponding BET areas. This round-robin exercise resulted in a wide range of values. Here, the reproducibility of BET area determination from identical isotherms is demonstrated to be a largely ignored issue, raising critical concerns over the reliability of reported BET areas. To solve this major issue, a new computational approach to accurately and systematically determine the BET area of nanoporous materials is developed. The software, called "BET surface identification" (BETSI), expands on the well-known Rouquerol criteria and makes an unambiguous BET area assignment possible.

Combining a Genetically Engineered Oxidase with Hydrogen-Bonded Organic Frameworks (HOFs) for Highly Efficient Biocomposites.

Enzymes incorporated into hydrogen-bonded organic frameworks (HOFs) via bottom-up synthesis are promising biocomposites for applications in catalysis and sensing. Here, we explored synthetic incorporation of d-amino acid oxidase (DAAO) with the metal-free tetraamidine/tetracarboxylate-based BioHOF-1 in water. N-terminal enzyme fusion with the positively charged module Zbasic2 strongly boosted the loading (2.5-fold; ≈500 mg enzyme gmaterial-1 ) and the specific activity (6.5-fold; 23 U mg-1 ). The DAAO@BioHOF-1 composites showed superior activity with respect to every reported carrier for the same enzyme and excellent stability during catalyst recycling. Further, extension to other enzymes, including cytochrome P450 BM3 (used in the production of high-value oxyfunctionalized compounds), points to the versatility of genetic engineering as a strategy for the preparation of biohybrid systems with unprecedented properties.

Self-Assembly of Oriented Antibody-Decorated Metal-Organic Framework Nanocrystals for Active-Targeting Applications.

Antibody (Ab)-targeted nanoparticles are becoming increasingly important for precision medicine. By controlling the Ab orientation, targeting properties can be enhanced; however, to afford such an ordered configuration, cumbersome chemical functionalization protocols are usually required. This aspect limits the progress of Abs-nanoparticles toward nanomedicine translation. Herein, a novel one-step synthesis of oriented monoclonal Ab-decorated metal-organic framework (MOF) nanocrystals is presented. The crystallization of a zinc-based MOF, Zn2 (mIM)2 (CO3 ), from a solution of Zn2+ and 2-methylimidazole (mIM), is triggered by the fragment crystallizable (Fc) region of the Ab. This selective growth yields biocomposites with oriented Abs on the MOF nanocrystals (MOF*Ab): the Fc regions are partially inserted within the MOF surface and the antibody-binding regions protrude from the MOF surface toward the target. This ordered configuration imparts antibody-antigen recognition properties to the biocomposite and shows preserved target binding when compared to the parental antibodies. Next, the biosensing performance of the system is tested by loading MOF*Ab with luminescent quantum dots (QD). The targeting efficiency of the QD-containing MOF*Ab is again, fully preserved. The present work represents a simple self-assembly approach for the fabrication of antibody-decorated MOF nanocrystals with broad potential for sensing, diagnostic imaging, and targeted drug delivery.

Crystallizing Sub 10 nm Covalent Organic Framework Thin Films via Interfacial-Residual Concomitance.

Synthesis of covalent organic framework (COF) thin films on different supports with high crystallinity and porosity is crucial for their potential applications. We have designed a new synchronized methodology, residual crystallization (RC), to synthesize sub 10 nm COF thin films. These residual crystallized COF thin films showcase high surface area, crystallinity, and conductivity at room temperature. We have used interfacial crystallization (IC) as a rate-controlling tool for simultaneous residual crystallization. We have also diversified the methodology of residual crystallization by utilizing two different crystallization pathways: fiber-to-film (F-F) and sphere-to-film (S-F). In both cases, we could obtain continuous COF thin films with high crystallinity and porosity grown on various substrates (the highest surface area of a TpAzo COF thin film being 2093 m2 g-1). Precise control over the crystallization allows the synthesis of macroscopic defect-free sub 10 nm COF thin films with a minimum thickness of ∼1.8 nm. We have synthesized two COF thin films (TpAzo and TpDPP) using F-F and S-F pathways on different supports such as borosilicate glass, FTO, silicon, Cu, metal, and ITO. Also, we have investigated the mechanism of the growth of these thin films on various substrates with different wettability. Further, a hydrophilic support (glass) was used to grow the thin films in situ for four-probe system device fabrication. All residual crystallized COF thin films exhibit outstanding conductivity values. We could obtain a conductivity of 3.7 × 10-2 mS cm-1 for the TpAzo film synthesized by S-F residual crystallization.

On the completeness of three-dimensional electron diffraction data for structural analysis of metal-organic frameworks.

Three-dimensional electron diffraction (3DED) has been proven as an effective and accurate method for structure determination of nano-sized crystals. In the past decade, the crystal structures of various new complex metal-organic frameworks (MOFs) have been revealed by 3DED, which has been the key to understand their properties. However, due to the design of transmission electron microscopes (TEMs), one drawback of 3DED experiments is the limited tilt range of goniometers, which often leads to incomplete 3DED data, particularly when the crystal symmetry is low. This drawback can be overcome by high throughput data collection using continuous rotation electron diffraction (cRED), where data from a large number of crystals can be collected and merged. Here, we investigate the effects of improving completeness on structural analysis of MOFs. We use ZIF-EC1, a zeolitic imidazolate framework (ZIF), as an example. ZIF-EC1 crystallizes in a monoclinic system with a plate-like morphology. cRED data of ZIF-EC1 with different completeness and resolution were analyzed. The data completeness increased to 92.0% by merging ten datasets. Although the structures could be solved from individual datasets with a completeness as low as 44.5% and refined to a high precision (better than 0.04 Å), we demonstrate that a high data completeness could improve the structural model, especially on the electrostatic potential map. We further discuss the strategy adopted during data merging. We also show that ZIF-EC1 doped with cobalt can act as an efficient electrocatalyst for oxygen reduction reactions.

Influence of the Synthesis and Storage Conditions on the Activity of Candida antarctica Lipase B ZIF-8 Biocomposites.

The biomimetic mineralization of zeolitic imidazolate framework-8 (ZIF-8) has been reported as a strategy for enzyme immobilization, enabling the heterogenization and protection of biomacromolecules. Here, we report the preparation of different Candida antarctica lipase B biocomposites (CALB@ZIF-8) formed by altering the concentrations of Zn2+ and 2-methylimidazole (2-mIM). The influence of synthetic conditions on the catalytic activity of the lipase CALB was examined by hydrolysis and transesterification assays in aqueous and organic media, respectively. We demonstrated that for both reactions, activity was retained for the biocomposites formed at low Zn2+/2-mIM ratios but notably almost entirely lost when the ligand concentration used to form the biocomposites was increased. Additionally, phosphate buffer could regenerate the activity of larger particles by degrading the crystal surfaces and releasing encapsulated CALB into solution. Transesterification reactions using CALB@ZIF-8 biocomposites were undertaken in 100% hexane, giving rise to enhanced CALB activity relative to the free enzyme. These observations highlight the fundamental importance of synthetic protocols and operating parameters for developing enzyme@MOF biocomposites with improved activity in challenging conditions.

Stabilization of supramolecular membrane protein-lipid bilayer assemblies through immobilization in a crystalline exoskeleton.

Artificial native-like lipid bilayer systems constructed from phospholipids assembling into unilamellar liposomes allow the reconstitution of detergent-solubilized transmembrane proteins into supramolecular lipid-protein assemblies called proteoliposomes, which mimic cellular membranes. Stabilization of these complexes remains challenging because of their chemical composition, the hydrophobicity and structural instability of membrane proteins, and the lability of interactions between protein, detergent, and lipids within micelles and lipid bilayers. In this work we demonstrate that metastable lipid, protein-detergent, and protein-lipid supramolecular complexes can be successfully generated and immobilized within zeolitic-imidazole framework (ZIF) to enhance their stability against chemical and physical stressors. Upon immobilization in ZIF bio-composites, blank liposomes, and model transmembrane metal transporters in detergent micelles or embedded in proteoliposomes resist elevated temperatures, exposure to chemical denaturants, aging, and mechanical stresses. Extensive morphological and functional characterization of the assemblies upon exfoliation reveal that all these complexes encapsulated within the framework maintain their native morphology, structure, and activity, which is otherwise lost rapidly without immobilization.

High-Throughput Electron Diffraction Reveals a Hidden Novel Metal-Organic Framework for Electrocatalysis.

Metal-organic frameworks (MOFs) are known for their versatile combination of inorganic building units and organic linkers, which offers immense opportunities in a wide range of applications. However, many MOFs are typically synthesized as multiphasic polycrystalline powders, which are challenging for studies by X-ray diffraction. Therefore, developing new structural characterization techniques is highly desired in order to accelerate discoveries of new materials. Here, we report a high-throughput approach for structural analysis of MOF nano- and sub-microcrystals by three-dimensional electron diffraction (3DED). A new zeolitic-imidazolate framework (ZIF), denoted ZIF-EC1, was first discovered in a trace amount during the study of a known ZIF-CO3 -1 material by 3DED. The structures of both ZIFs were solved and refined using 3DED data. ZIF-EC1 has a dense 3D framework structure, which is built by linking mono- and bi-nuclear Zn clusters and 2-methylimidazolates (mIm- ). With a composition of Zn3 (mIm)5 (OH), ZIF-EC1 exhibits high N and Zn densities. We show that the N-doped carbon material derived from ZIF-EC1 is a promising electrocatalyst for oxygen reduction reaction (ORR). The discovery of this new MOF and its conversion to an efficient electrocatalyst highlights the power of 3DED in developing new materials and their applications.

Metal-Organic Framework-Based Enzyme Biocomposites.

Because of their efficiency, selectivity, and environmental sustainability, there are significant opportunities for enzymes in chemical synthesis and biotechnology. However, as the three-dimensional active structure of enzymes is predominantly maintained by weaker noncovalent interactions, thermal, pH, and chemical stressors can modify or eliminate activity. Metal-organic frameworks (MOFs), which are extended porous network materials assembled by a bottom-up building block approach from metal-based nodes and organic linkers, can be used to afford protection to enzymes. The self-assembled structures of MOFs can be used to encase an enzyme in a process called encapsulation when the MOF is synthesized in the presence of the biomolecule. Alternatively, enzymes can be infiltrated into mesoporous MOF structures or surface bound via covalent or noncovalent processes. Integration of MOF materials and enzymes in this way affords protection and allows the enzyme to maintain activity in challenge conditions (e.g., denaturing agents, elevated temperature, non-native pH, and organic solvents). In addition to forming simple enzyme/MOF biocomposites, other materials can be introduced to the composites to improve recovery or facilitate advanced applications in sensing and fuel cell technology. This review canvasses enzyme protection via encapsulation, pore infiltration, and surface adsorption and summarizes strategies to form multicomponent composites. Also, given that enzyme/MOF biocomposites straddle materials chemistry and enzymology, this review provides an assessment of the characterization methodologies used for MOF-immobilized enzymes and identifies some key parameters to facilitate development of the field.

Can 3D electron diffraction provide accurate atomic structures of metal-organic frameworks?

Many framework materials such as metal-organic frameworks (MOFs) or porous coordination polymers (PCPs) are synthesized as polycrystalline powders, which are too small for structure determination by single crystal X-ray diffraction (SCXRD). Here, we show that a three-dimensional (3D) electron diffraction method, namely continuous rotation electron diffraction (cRED), can be used for ab initio structure determination of such materials. As an example, we present the complete structural analysis of a biocomposite, denoted BSA@ZIF-CO3-1, in which Bovine Serum Albumin (BSA) was encapsulated in a zeolitic imidazolate framework (ZIF). Low electron dose was combined with ultrafast cRED data collection to minimize electron beam damage to the sample. We demonstrate that the atomic structure obtained by cRED is as reliable and accurate as that obtained by single crystal X-ray diffraction. The high accuracy and fast data collection open new opportunities for investigation of cooperative phenomena in framework structures at the atomic level.

Direct X-ray and electron-beam lithography of halogenated zeolitic imidazolate frameworks.

Metal-organic frameworks (MOFs) offer disruptive potential in micro- and optoelectronics because of the unique properties of these microporous materials. Nanoscale patterning is a fundamental step in the implementation of MOFs in miniaturized solid-state devices. Conventional MOF patterning methods suffer from low resolution and poorly defined pattern edges. Here, we demonstrate the resist-free, direct X-ray and electron-beam lithography of MOFs. This process avoids etching damage and contamination and leaves the porosity and crystallinity of the patterned MOFs intact. The resulting high-quality patterns have excellent sub-50-nm resolution, and approach the mesopore regime. The compatibility of X-ray and electron-beam lithography with existing micro- and nanofabrication processes will facilitate the integration of MOFs in miniaturized devices.

Hierarchical Metal-Organic Framework Films with Controllable Meso/Macroporosity.

The structuring of the metal-organic framework material ZIF-8 as films and membranes through the vapor-phase conversion of ZnO fractal nanoparticle networks is reported. The extrinsic porosity of the resulting materials can be tuned from 4% to 66%, and the film thickness can be controlled from 80 nm to 0.23 mm, for areas >100 cm2. Freestanding and pure metal-organic frameworks (MOF) membranes prepared this way are showcased as separators that minimize capacity fading in model Li-S batteries.