Modulated Self-Assembly of Catalytically Active Metal-Organic Nanosheets Containing Zr6 Clusters and Dicarboxylate Ligands.

Two-dimensional metal-organic nanosheets (MONs) have emerged as attractive alternatives to their three-dimensional metal-organic framework (MOF) counterparts for heterogeneous catalysis due to their greater external surface areas and higher accessibility of catalytically active sites. Zr MONs are particularly prized because of their chemical stability and high Lewis and Brønsted acidities of the Zr clusters. Herein, we show that careful control over modulated self-assembly and exfoliation conditions allows the isolation of the first example of a two-dimensional nanosheet wherein Zr6 clusters are linked by dicarboxylate ligands. The hxl topology MOF, termed GUF-14 (GUF = Glasgow University Framework), can be exfoliated into monolayer thickness hns topology MONs, and acid-induced removal of capping modulator units yields MONs with enhanced catalytic activity toward the formation of imines and the hydrolysis of an organophosphate nerve agent mimic. The discovery of GUF-14 serves as a valuable example of the undiscovered MOF/MON structural diversity extant in established metal-ligand systems that can be accessed by harnessing the power of modulated self-assembly protocols.

Pressure-induced postsynthetic cluster anion substitution in a MIL-53 topology scandium metal-organic framework.

Postsynthetic modification of metal-organic frameworks (MOFs) has proven to be a hugely powerful tool to tune physical properties and introduce functionality, by exploiting reactive sites on both the MOF linkers and their inorganic secondary building units (SBUs), and so has facilitated a wide range of applications. Studies into the reactivity of MOF SBUs have focussed solely on removal of neutral coordinating solvents, or direct exchange of linkers such as carboxylates, despite the prevalence of ancillary charge-balancing oxide and hydroxide ligands found in many SBUs. Herein, we show that the µ2-OH ligands in the MIL-53 topology Sc MOF, GUF-1, are labile, and can be substituted for µ2-OCH3 units through reaction with pore-bound methanol molecules in a very rare example of pressure-induced postsynthetic modification. Using comprehensive solid-state NMR spectroscopic analysis, we show an order of magnitude increase in this cluster anion substitution process after exposing bulk samples suspended in methanol to a pressure of 0.8 GPa in a large volume press. Additionally, single crystals compressed in diamond anvil cells with methanol as the pressure-transmitting medium have enabled full structural characterisation of the process across a range of pressures, leading to a quantitative single-crystal to single-crystal conversion at 4.98 GPa. This unexpected SBU reactivity - in this case chemisorption of methanol - has implications across a range of MOF chemistry, from activation of small molecules for heterogeneous catalysis to chemical stability, and we expect cluster anion substitution to be developed into a highly convenient novel method for modifying the internal pore surface and chemistry of a range of porous materials.

Modulated self-assembly of three flexible Cr(III) PCPs for SO2 adsorption and detection.

Modulated self-assembly protocols are used to develop facile, HF-free syntheses of the archetypal flexible PCP, MIL-53(Cr), and novel isoreticular analogues MIL-53(Cr)-Br and MIL-53(Cr)-NO2. All three PCPs show good SO2 uptake (298 K, 1 bar) and high chemical stabilities against dry and wet SO2. Solid-state photoluminescence spectroscopy indicates all three PCPs exhibit turn-off sensing of SO2, in particular MIL-53(Cr)-Br, which shows a 2.7-fold decrease in emission on exposure to SO2 at room temperature, indicating potential sensing applications.

Formation of a meltable purinate metal-organic framework and its glass analogue.

The chemistries that can be incorporated within melt-quenched zeolitic imidazolate framework (ZIF) glasses are currently limited. Here we describe the preparation of a previously unknown purine-containing ZIF which we name ZIF-UC-7. We find that it melts and forms a glass at one of the lowest temperatures reported for 3D hybrid frameworks.

Glycopolymer-Functionalized MOF-808 Nanoparticles as a Cancer-Targeted Dual Drug Delivery System for Carboplatin and Floxuridine.

Codelivery of chemotherapeutics via nanomaterials has attracted much attention over the last decades due to improved drug delivery to tumor tissues, decreased systemic effects, and increased therapeutic efficacies. High porosities, large pore volumes and surface areas, and tunable structures have positioned metal-organic frameworks (MOFs) as promising drug delivery systems (DDSs). In particular, nanoscale Zr-linked MOFs such as MOF-808 offer notable advantages for biomedical applications such as high porosity, good stability, and biocompatibility. In this study, we report efficient dual drug delivery of floxuridine (FUDR) and carboplatin (CARB) loaded in MOF-808 nanoparticles to cancer cells. The nanoparticles were further functionalized by a poly(acrylic acid-mannose acrylamide) (PAAMAM) glycopolymer coating to obtain a highly selective DDS in cancer cells and enhance the therapeutic efficacy of chemotherapy. While MOF-808 was found to enhance the individual therapeutic effects of FUDR and CARB toward cancerous cells, combining FUDR and CARB was seen to cause a synergistic effect, further enhancing the cytotoxicity of the free drugs. Enhancement of CARB loading and therefore cytotoxicity of the CARB-loaded MOFs could be induced through a modified activation protocol, while coating of MOF-808 with the PAAMAM glycopolymer increased the uptake of the nanoparticles in cancer cells used in the study and offered a particularly significant selective drug delivery with high cytotoxicity in HepG2 human hepatocellular carcinoma cells. These results show how the enhancement of cytotoxicity is possible through both nanovector delivery and synergistic treatment, and that MOF-808 is a viable candidate for future drug delivery studies.

From Gas Phase Observations to Solid State Reality: The Identification and Isolation of Trinuclear Salicylaldoximato Copper Complexes.

Conditions have been identified in which phenolic aldoximes and ketoximes of the types used in commercial solvent extraction processes can be doubly deprotonated and generate polynuclear Cu complexes with lower extractant:Cu molar ratios than those found in commercial operations. Electrospray mass spectrometry has provided an insight into the solution speciation in extraction experiments and has identified conditions to allow isolation and characterization of polynuclear Cu-complexes. Elevation of pH is effective in enhancing the formation of trinuclear complexes containing planar {Cu3-µ3-O}4+ or {Cu3-µ3-OH}5+ units. DFT calculations suggest that such trinuclear complexes are more stable than other polynuclear species. Solid structures of complexes formed by a salicylaldoxime with a piperidino substituent ortho to the phenolic OH group (L9H2) contain two trinuclear units in a supramolecular assembly, {[Cu3OH(L9H)3(ClO4)](ClO4)} 2, formed by H-bonding between the central {Cu3-µ3-OH}5+ units and oxygen atoms in the ligands of an adjacent complex. Whilst the lower ligand:Cu molar ratios provide more efficient Cu-loading in solvent extraction processes, the requirement to raise the pH of the aqueous phase to achieve this will make it impractical in most commercial operations because extraction will be accompanied by the precipitation (as oxyhydroxides) of Fe(III) which is present in significant quantities in feed solutions generated by acid leaching of most Cu ores.

Controlling the Flexibility of MIL-88A(Sc) Through Synthetic Optimisation and Postsynthetic Halogenation.

Breathing behaviour in metal-organic frameworks (MOFs), the distinctive transformation between a porous phase and a less (or non) porous phase, often controls the uptake of guest molecules, endowing flexible MOFs with highly selective gas adsorptive properties. In highly flexible topologies, breathing can be tuned by linker modification, which is typically achieved pre-synthetically using functionalised linkers. Herein, it was shown that MIL-88A(Sc) exhibits the characteristic flexibility of its topology, which can be tuned by 1) modifying synthetic conditions to yield a formate-buttressed analogue that is rigid and porous; and 2) postsynthetic bromination across the alkene functionality of the fumarate ligand, generating a product that is rigid but non-porous. In addition to providing different methodologies for tuning the flexibility and breathing behaviour of this archetypal MOF, it was shown that bromination of the formate-bridged analogue results in an identical material, representing a rare example of two different MOFs being postsynthetically converted to the same end product.

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.

Post-Synthetic Modification of a Metal-Organic Framework Glass.

Melt-quenched metal-organic framework (MOF) glasses have gained significant interest as the first new category of glass reported in 50 years. In this work, an amine-functionalized zeolitic imidazolate framework (ZIF), denoted ZIF-UC-6, was prepared and demonstrated to undergo both melting and glass formation. The presence of an amine group resulted in a lower melting temperature compared to other ZIFs, while also allowing material properties to be tuned by post-synthetic modification (PSM). As a prototypical example, the ZIF glass surface was functionalized with octyl isocyanate, changing its behavior from hydrophilic to hydrophobic. PSM therefore provides a promising strategy for tuning the surface properties of MOF glasses.

MOF nanoparticles as heterogeneous catalysts for direct amide bond formations.

The influence of composition and textural characteristics of a family of ultra-small isoreticular UiO-type metal-organic frameworks (MOFs) with different functionalized and extended linkers on their catalytic performance is evaluated. Two direct amide bond formations across four different substrates (benzylamine + phenylacetic acid and aniline + formic acid) are employed as proof-of-concept reactions to test the activity of the Zr-MOF nanoparticles. The reaction rates of amide bond formation are evaluated against physico-chemical properties such as crystallinity, porosity, particle size or linker functionality, alongside the Lewis acid and hydrophobic properties of the MOFs, in order to gain insights into the catalytic mechanism and optimal properties for its enhancement.

Exploring and expanding the Fe-terephthalate metal-organic framework phase space by coordination and oxidation modulation.

The synthesis of phase pure metal-organic frameworks (MOFs) - network solids of metal clusters connected by organic linkers - is often complicated by the possibility of forming multiple diverse phases from one metal-ligand combination. For example, there are at least six Fe-terephthalate MOFs reported to date, with many examples in the literature of erroneous assignment of phase based on diffraction data alone. Herein, we show that modulated self-assembly can be used to influence the kinetics of self-assembly of Fe-terephthalate MOFs. We comprehensively assess the effect of addition of both coordinating modulators and pH modulators on the outcome of syntheses, as well as probing the influence of the oxidation state of the Fe precursor (oxidation modulation) and the role of the counteranion on the phase(s) formed. In doing so, we shed light on the thermodynamic landscape of this phase system, uncover mechanistics of modulation, provide robust routes to phase pure materials, often as single crystals, and introduce two new Fe-terephthalate MOFs to an already complex system. The results highlight the potential of modulated self-assembly to bring precision control and new structural diversity to systems that have already received significant study.

Photophysics of Azobenzene Constrained in a UiO Metal-Organic Framework: Effects of Pressure, Solvation and Dynamic Disorder.

Photophysical studies of chromophoric linkers in metal-organic frameworks (MOFs) are undertaken commonly in the context of sensing applications, in search of readily observable changes of optical properties in response to external stimuli. The advantages of the MOF construct as a platform for investigating fundamental photophysical behaviour have been somewhat overlooked. The linker framework offers a unique environment in which the chromophore is geometrically constrained and its structure can be determined crystallographically, but it exists in spatial isolation, unperturbed by inter-chromophore interactions. Furthermore, high-pressure studies enable the photophysical consequences of controlled, incremental changes in local environment or conformation to be observed and correlated with structural data. This approach is demonstrated in the present study of the trans-azobenzene chromophore, constrained in the form of the 4,4'-azobenzenedicarboxylate (abdc) linker, in a UiO topology framework. Previously unobserved effects of pressure-induced solvation and conformational distortion on the lowest energy, nπ* transition are reported, and interpreted the light of crystallographic data. It was found that trans-azobenzene remains non-fluorescent (with a quantum yield less than 10-4 ) despite the prevention of trans-cis isomerization by the constraining MOF structure. We propose that efficient non-radiative decay is mediated by the local, pedal-like twisting of the azo group that is evident as dynamic disorder in the crystal structure.

Applications of nanoscale metal-organic frameworks as imaging agents in biology and medicine.

Nanoscale metal-organic frameworks (NMOFs) are an interesting and unique class of hybrid porous materials constructed by the self-assembly of metal ions/clusters with organic linkers. The high storage capacities, facile synthesis, easy surface functionalization, diverse compositions and excellent biocompatibilities of NMOFs have made them promising agents for theranostic applications. By combination of a large variety of metal ions and organic ligands, and incorporation of desired molecular functionalities including imaging modalities and therapeutic molecules, diverse MOF structures with versatile functionalities can be obtained and utilized in biomedical imaging and drug delivery. In recent years, NMOFs have attracted great interest as imaging agents in optical imaging (OI), magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET) and photoacoustic imaging (PAI). Furthermore, the significant porosity of MOFs allows them to be loaded with multiple imaging agents and therapeutics simultaneously and applied for multimodal imaging and therapy as a single entity. In this review, which is intended as an introduction to the use of MOFs in biomedical imaging for a reader entering the subject, we summarize the up-to-date progress of NMOFs as bioimaging agents, giving (i) a broad perspective of the varying imaging techniques that MOFs can enable, (ii) the different routes to manufacturing functionalised MOF nanoparticles and hybrids, and (iii) the integration of imaging with differing therapeutic techniques. The current challenges and perspectives of NMOFs for their further clinical translation are also highlighted and discussed.

Immobilising giant unilamellar vesicles with zirconium metal-organic framework anchors.

Lipid bilayer vesicles have provided a window into the function and fundamental properties of cells. However, as is the case for most living and soft matter, vesicles do not remain still. This necessitates some microscopy experiments to include a preparatory immobilisation step. Here, we describe a straightforward method to immobilise giant unilamellar vesicles (GUVs) using zirconium-based metal-organic frameworks (MOFs) and demonstrate that GUVs bound in this way will stay in position on a timescale of minutes to hours.

Identifying Differing Intracellular Cargo Release Mechanisms by Monitoring In Vitro Drug Delivery from MOFs in Real Time.

Metal-organic frameworks (MOFs) have been proposed as biocompatible candidates for the targeted intracellular delivery of chemotherapeutic payloads, but the site of drug loading and subsequent effect on intracellular release is often overlooked. Here, we analyze doxorubicin delivery to cancer cells by MIL-101(Cr) and UiO-66 in real time. Having experimentally and computationally verified that doxorubicin is pore loaded in MIL-101(Cr) and surface loaded on UiO-66, different time-dependent cytotoxicity profiles are observed by real-time cell analysis and confocal microscopy. The attenuated release of aggregated doxorubicin from the surface of Dox@UiO-66 results in a 12 to 16 h induction of cytotoxicity, while rapid release of pore-dispersed doxorubicin from Dox@MIL-101(Cr) leads to significantly higher intranuclear localization and rapid cell death. In verifying real-time cell analysis as a versatile tool to assess biocompatibility and drug delivery, we show that the localization of drugs in (or on) MOF nanoparticles controls delivery profiles and is key to understanding in vitro modes of action.

Controlled Transdermal Release of Antioxidant Ferulate by a Porous Sc(III) MOF.

The Sc(III) MOF-type MFM-300(Sc) is demonstrated in this study to be stable under physiological conditions (PBS), biocompatible (to human skin cells), and an efficient drug carrier for the long-term controlled release (through human skin) of antioxidant ferulate. MFM-300(Sc) also preserves the antioxidant pharmacological effects of ferulate while enhancing the bio-preservation of dermal skin fibroblasts, during the delivery process. These discoveries pave the way toward the extended use of Sc(III)-based MOFs as drug delivery systems (DDSs).

Assessing Crystallisation Kinetics of Zr Metal-Organic Frameworks through Turbidity Measurements to Inform Rapid Microwave-Assisted Synthesis.

Controlling the crystallisation of metal-organic frameworks (MOFs), network solids of metal ions or clusters connected by organic ligands, is often hindered by the significant number of synthetic variables inherent to their synthesis. Coordination modulation, the addition of monotopic competing ligands to solvothermal syntheses, can allow tuning of physical properties (particle size, porosity, surface chemistry), enhance crystallinity, and select desired phases, by modifying the kinetics of self-assembly, but its mechanism(s) are poorly understood. Herein, turbidity measurements were used to assess the effects of modulation on the solvothermal synthesis of the prototypical Zr terephthalate MOF UiO-66 and the knowledge gained was applied to its rapid microwave synthesis. The studied experimental parameters-temperature, reagent concentration, reagent aging, metal precursor, water content, and modulator addition-all influence the time taken for onset of nucleation, and subsequently allow microwave synthesis of UiO-66 in as little as one minute. The simple, low cost turbidity measurements align closely with previously reported in situ synchrotron X-ray diffraction studies, proving their simplicity and utility for probing the nucleation of complex materials while offering significant insights to the synthetic chemist.

Design of a Functionalized Metal-Organic Framework System for Enhanced Targeted Delivery to Mitochondria.

Mitochondria play a key role in oncogenesis and constitute one of the most important targets for cancer treatments. Although the most effective way to deliver drugs to mitochondria is by covalently linking them to a lipophilic cation, the in vivo delivery of free drugs still constitutes a critical bottleneck. Herein, we report the design of a mitochondria-targeted metal-organic framework (MOF) that greatly increases the efficacy of a model cancer drug, reducing the required dose to less than 1% compared to the free drug and ca. 10% compared to the nontargeted MOF. The performance of the system is evaluated using a holistic approach ranging from microscopy to transcriptomics. Super-resolution microscopy of MCF-7 cells treated with the targeted MOF system reveals important mitochondrial morphology changes that are clearly associated with cell death as soon as 30 min after incubation. Whole transcriptome analysis of cells indicates widespread changes in gene expression when treated with the MOF system, specifically in biological processes that have a profound effect on cell physiology and that are related to cell death. We show how targeting MOFs toward mitochondria represents a valuable strategy for the development of new drug delivery systems.

Correlating Pressure-Induced Emission Modulation with Linker Rotation in a Photoluminescent MOF.

Conformational changes of linker units in metal-organic frameworks (MOFs) are often responsible for gate-opening phenomena in selective gas adsorption and stimuli-responsive optical and electrical sensing behaviour. Herein, we show that pressure-induced bathochromic shifts in both fluorescence emission and UV/Vis absorption spectra of a two-fold interpenetrated Hf MOF, linked by 1,4-phenylene-bis(4-ethynylbenzoate) ligands (Hf-peb), are induced by rotation of the central phenyl ring of the linker, from a coplanar arrangement to a twisted, previously unseen conformer. Single-crystal X-ray diffraction, alongside in situ fluorescence and UV/Vis absorption spectroscopies, measured up to 2.1 GPa in a diamond anvil cell on single crystals, are in excellent agreement, correlating linker rotation with modulation of emission. Topologically isolating the 1,4-phenylene-bis(4-ethynylbenzoate) units within a MOF facilitates concurrent structural and spectroscopic studies in the absence of intermolecular perturbation, allowing characterisation of the luminescence properties of a high-energy, twisted conformation of the previously well-studied chromophore. We expect the unique environment provided by network solids, and the capability of combining crystallographic and spectroscopic analysis, will greatly enhance understanding of luminescent molecules and lead to the development of novel sensors and adsorbents.