Electron beam and thermal stabilities of MFM-300(M) metal-organic frameworks.

This work reports the thermal and electron beam stabilities of a series of isostructural metal-organic frameworks (MOFs) of type MFM-300(M) (M = Al, Ga, In, Cr). MFM-300(Cr) was most stable under the electron beam, having an unusually high critical electron fluence of 1111 e- Å-2 while the Group 13 element MOFs were found to be less stable. Within Group 13, MFM-300(Al) had the highest critical electron fluence of 330 e- Å-2, compared to 189 e- Å-2 and 147 e- Å-2 for the Ga and In MOFs, respectively. For all four MOFs, electron beam-induced structural degradation was independent of crystal size and was highly anisotropic, although both the length and width of the channels decreased during electron beam irradiation. Notably, MFM-300(Cr) was found to retain crystallinity while shrinking up to 10%. Thermal stability was studied using in situ synchrotron X-ray diffraction at elevated temperature, which revealed critical temperatures for crystal degradation to be 605, 570, 490 and 480 °C for Al, Cr, Ga, and In, respectively. The pore channel diameters contracted by ≈0.5% on desorption of solvent species, but thermal degradation at higher temperatures was isotropic. The observed electron stabilities were found to scale with the relative inertness of the cations and correlate well to the measured lifetime of the materials when used as photocatalysts.

Light and Guest Responsive Behavior in a Porous Coordination Network Enabled by Reversible [2+2] Photocycloaddition.

Stimuli-responsive physisorbents that undergo reversible structural transformations induced by external stimuli (e.g. light, guests, or heat) offer the promise of utility in gas storage and separation. Whereas reports on guest or light-responsive sorbents have increased in recent years, we are unaware of reports on sorbents that exhibit both light and guest-induced structural transformations. Herein, we report that the square lattice, sql, topology coordination network Zn(fba)(bis) ⋅ 2DMF (sql-5,6-Zn-α, 5=trans-4,4'-bis(1-imidazolyl)stilbene=bis, 6=2,2-bis(4-carboxyphenyl)hexafluoropropane=H2fba) underwent single-crystal-to-single-crystal transformation (SCSC) upon activation, affording nonporous sql-5,6-Zn-ß. Parallel alignment at 3.23 Šof olefinic moieties on adjacent bis ligands in sql-5,6-Zn-α enabled SCSC [2+2] photocycloaddition upon exposure to UV light (365 nm) or sunlight. sql-5,6-Zn-α thereby transformed to mot-5,6-Zn-α, which was subsequently activated to the narrow pore phase mot-5,6-Zn-ß. sql-5,6-Zn-ß and mot-5,6-Zn-ß both exhibited S-shaped adsorption isotherms characteristic of guest-induced structural changes when exposed to CO2 at 195 K (type-F-IV and type F-I, respectively). Cycling experiments conducted upon sql-5,6-Zn-ß reduced particle size after cycle 1 and induced transformation into a rare example of a shape memory coordination network, sql-5,6-Zn-γ. Insight into this smorgasbord of SCSC phase changes was gained from in situ PXRD, single crystal XRD and 1H NMR spectroscopy experiments.

Nanosheets of a Layered Metal-Organic Framework for Separation of CO2/CH4 using Mixed Matrix Membranes.

Mixed matrix membranes represent an important technology for gas separations. Nanosheets of metal-organic framework (MOF) materials of high aspect ratio and size-selective gas transport properties have the potential to promote the efficient mixing of components to form membranes for gas separation. Herein, we report a bottom-up synthesis of extended sheets of kagomé (kgm) topology, kgmt-Bu, via the linkage of [Cu2(O2CR)4] paddlewheels with 5-tert-butylisophthalic acid. The growth of the layered structure can be controlled by the choice of solvent and modulator. Nanosheets of kgmt-Bu of average thickness of 20 nm and aspect ratio of 40 to 50 can be obtained, and the sieving effect of the channels in kgmt-Bu boost the efficient separation of CO2 over CH4. A mixed matrix membrane comprising kgmt-Bu nanosheets with Matrimid shows a 32% enhancement in CO2/CH4 selectivity compared with the membrane incorporating the MOF in the particulate form.

Formation of extended polyiodides at large cation templates.

By studying the structures of (µ-1,4,10,13-tetrathia-7,16-diazacyclooctadecane)bis[iodidopalladium(II)] diiodide penta(diiodine), [Pd2I2(C12H26N2S4)](I)2·5I2 or [Pd2I2([18]aneN2S4)](I)2·(I2)5, and 4,7,13,16,21,24-hexaoxa-1,10-diazoniabicyclo[8.8.8]hexacosane triiodide iodide hemipenta(diiodine) dichloromethane monosolvate, C18H38N2O62+·I3-·I-·2.5I2·CH2Cl2 or [H2([2.2.2]cryptand)](I3)(I)(I2)2.5·CH2Cl2, we confirm the structural variety of extended polyiodides achievable upon changing the shape, charge and dimensions of the cation template, by altering the synthetic strategy adopted and/or the experimental conditions. Although it is still often difficult to characterize discrete [I2m+n]n- polyiodides higher than I3- on the basis of structural parameters, such as I-I bond distances, FT-Raman spectroscopy appears to identify them as aggregates of I2, I- and (symmetric or slightly asymmetric) I3- building blocks linked by I...I interactions of varying strengths. However, because FT-Raman spectroscopy carries no information about the topological features of extended polyiodides, the two techniques should therefore be applied in combination to enhance the analysis of this kind of compounds.

Binding of carbon dioxide and acetylene to free carboxylic acid sites in a metal-organic framework.

The functionalisation of organic linkers in metal-organic frameworks (MOFs) to improve gas uptake is well-documented. Although the positive role of free carboxylic acid sites in MOFs for binding gas molecules has been proposed in computational studies, relatively little experimental evidence has been reported in support of this. Primarily this is because of the inherent synthetic difficulty to prepare MOF materials bearing free, accessible -COOH moieties which would normally bind to metal ions within the framework structure. Here, we describe the direct binding of CO2 and C2H2 molecules to the free -COOH sites within the pores of MFM-303(Al). MFM-303(Al) exhibits highly selective adsorption of CO2 and C2H2 with a high selectivity for C2H2 over C2H4. In situ synchrotron X-ray diffraction and inelastic neutron scattering, coupled with modelling, highlight the cooperative interactions of adsorbed CO2 and C2H2 molecules with free -COOH and -OH sites within MFM-303(Al), thus rationalising the observed high selectivity for gas separation.

Direct Observation of Enhanced Iodine Binding within a Series of Functionalized Metal-Organic Frameworks with Exceptional Irradiation Stability.

Optimization of active sites and stability under irradiation are important targets for sorbent materials that might be used for iodine (I2) storage. Herein, we report the direct observation of I2 binding in a series of Cu(II)-based isostructural metal-organic frameworks, MFM-170, MFM-172, MFM-174, NJU-Bai20, and NJU-Bai21, incorporating various functional groups (-H, -CH3, - NH2, -C≡C-, and -CONH-, respectively). MFM-170 shows a reversible uptake of 3.37 g g-1 and a high packing density of 4.41 g cm-3 for physiosorbed I2. The incorporation of -NH2 and -C≡C- moieties in MFM-174 and NJU-Bai20, respectively, enhances the binding of I2, affording uptakes of up to 3.91 g g-1. In addition, an exceptional I2 packing density of 4.83 g cm-3 is achieved in MFM-174, comparable to that of solid iodine (4.93 g cm-3). In situ crystallographic studies show the formation of a range of supramolecular and chemical interactions [I···N, I···H2N] and [I···C≡C, I-C═C-I] between -NH2, -C≡C- sites, respectively, and adsorbed I2 molecules. These observations have been confirmed via a combination of solid-state nuclear magnetic resonance, X-ray photoelectron, and Raman spectroscopies. Importantly, γ-irradiation confirmed the ultraresistance of MFM-170, MFM-174, and NJU-Bai20 suggesting their potential as efficient sorbents for cleanup of radioactive waste.

High adsorption of ammonia in a titanium-based metal-organic framework.

We report the high adsorption of NH3 in a titanium-based metal-organic framework, MFM-300(Ti), comprising extended [TiO6]∞ chains linked by biphenyl-3,3',5,5'-tetracarboxylate ligands. At 273 K and 1 bar, MFM-300(Ti) shows an exceptional NH3 uptake of 23.4 mmol g-1 with a record-high packing density of 0.84 g cm-3. Dynamic breakthrough experiments confirm the excellent uptake and separation of NH3 at low concentration (1000 ppm). The combination of in situ neutron powder diffraction and spectroscopic studies reveal strong, yet reversible binding interactions of NH3 to the framework oxygen sites.

DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance.

Targeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug discovery. So far only a few ligases have been utilized for TPD. Interestingly, the workhorse ligase CRBN has been observed to be downregulated in settings of resistance to immunomodulatory inhibitory drugs (IMiDs). Here we show that the essential E3 ligase receptor DCAF1 can be harnessed for TPD utilizing a selective, non-covalent DCAF1 binder. We confirm that this binder can be functionalized into an efficient DCAF1-BRD9 PROTAC. Chemical and genetic rescue experiments validate specific degradation via the CRL4DCAF1 E3 ligase. Additionally, a dasatinib-based DCAF1 PROTAC successfully degrades cytosolic and membrane-bound tyrosine kinases. A potent and selective DCAF1-BTK-PROTAC (DBt-10) degrades BTK in cells with acquired resistance to CRBN-BTK-PROTACs while the DCAF1-BRD9 PROTAC (DBr-1) provides an alternative strategy to tackle intrinsic resistance to VHL-degrader, highlighting DCAF1-PROTACS as a promising strategy to overcome ligase mediated resistance in clinical settings.

Direct Synthesis of N-formamides by Integrating Reductive Amination of Ketones and Aldehydes with CO2 Fixation in a Metal-Organic Framework.

Formamides are important feedstocks for the manufacture of many fine chemicals. State-of-the-art synthesis of formamides relies on the use of an excess amount of reagents, giving copious waste and thus poor atom-economy. Here, we report the first example of direct synthesis of N-formamides by coupling two challenging reactions, namely reductive amination of carbonyl compounds, particularly biomass-derived aldehydes and ketones, and fixation of CO2 in the presence of H2 over a metal-organic framework supported ruthenium catalyst, Ru/MFM-300(Cr). Highly selective production of N-formamides has been observed for a wide range of carbonyl compounds. Synchrotron X-ray powder diffraction reveals the presence of strong host-guest binding interactions via hydrogen bonding and parallel-displaced π⋅⋅⋅π interactions between the catalyst and adsorbed substrates facilitating the activation of substrates and promoting selectivity to formamides. The use of multifunctional porous catalysts to integrate CO2 utilisation in the synthesis of formamide products will have a significant impact in the sustainable synthesis of feedstock chemicals.

Analysis of a Cu-Doped Metal-Organic Framework, MFM-520(Zn1-x Cux ), for NO2 Adsorption.

MFM-520(Zn) confines dimers of NO2 with a high adsorption of 4.52 mmol g-1 at 1 bar at 298 K. The synthesis and the incommensurate structure of Cu-doped MFM-520(Zn) are reported. The introduction of paramagnetic Cu2+ sites allows investigation of the electronic and geometric structure of metal site by in situ electron paramagnetic resonance (EPR) spectroscopy upon adsorption of NO2 . By combining continuous wave and electron-nuclear double resonance spectroscopy, an unusual reverse Berry distorted coordination geometry of the Cu2+ centers is observed. Interestingly, Cu-doped MFM-520(Zn0.95 Cu0.05 ) shows enhanced adsorption of NO2 of 5.02 mmol g-1 at 1 bar at 298 K. Whereas MFM-520(Zn) confines adsorbed NO2 as N2 O4 , the presence of monomeric NO2 at low temperature suggests that doping with Cu2+ centers into the framework plays an important role in tuning the dimerization of NO2 molecules in the pore via the formation of specific host-guest interactions.

Exceptional capture of methane at low pressure by an iron-based metal-organic framework.

The selective capture of methane (CH4) at low concentrations and its separation from N2 are extremely challenging owing to the weak host-guest interactions between CH4 molecules and any sorbent material. Here, we report the exceptional adsorption of CH4 at low pressure and the efficient separation of CH4/N2 by MFM-300(Fe). MFM-300(Fe) shows a very high uptake for CH4 of 0.85 mmol g-1 at 1 mbar and 298 K and a record CH4/N2 selectivity of 45 for porous solids, representing a new benchmark for CH4 capture and CH4/N2 separation. The excellent separation of CH4/N2 by MFM-300(Fe) has been confirmed by dynamic breakthrough experiments. In situ neutron powder diffraction, and solid-state nuclear magnetic resonance and diffuse reflectance infrared Fourier transform spectroscopies, coupled with modelling, reveal a unique and strong binding of CH4 molecules involving Fe-OH⋯CH4 and C⋯phenyl ring interactions within the pores of MFM-300(Fe), thus promoting the exceptional adsorption of CH4 at low pressure.

Discovery of Ligands for TRIM58, a Novel Tissue-Selective E3 Ligase.

Redirecting E3 ligases to neo-substrates, leading to their proteasomal disassembly, known as targeted protein degradation (TPD), has emerged as a promising alternative to traditional, occupancy-driven pharmacology. Although the field has expanded tremendously over the past years, the choice of E3 ligases remains limited, with an almost exclusive focus on CRBN and VHL. Here, we report the discovery of novel ligands to the PRY-SPRY domain of TRIM58, a RING ligase that is specifically expressed in erythroid precursor cells. A DSF screen, followed by validation using additional biophysical methods, led to the identification of TRIM58 ligand TRIM-473. A basic SAR around the chemotype was established by utilizing a competitive binding assay employing a short FP peptide probe derived from an endogenous TRIM58 substrate. The X-ray co-crystal structure of TRIM58 in complex with TRIM-473 gave insights into the binding mode and potential exit vectors for bifunctional degrader design.

SGC-CLK-1: A chemical probe for the Cdc2-like kinases CLK1, CLK2, and CLK4.

Small molecule modulators are important tools to study both basic biology and the complex signaling of protein kinases. The cdc2-like kinases (CLK) are a family of four kinases that have garnered recent interest for their involvement in a diverse set of diseases such as neurodegeneration, autoimmunity, and many cancers. Targeted medicinal chemistry around a CLK inhibitor hit identified through screening of a kinase inhibitor set against a large panel of kinases allowed us to identify a potent and selective inhibitor of CLK1, 2, and 4. Here, we present the synthesis, selectivity, and preliminary biological characterization of this compound - SGC-CLK-1 (CAF-170). We further show CLK2 has the highest binding affinity, and high CLK2 expression correlates with a lower IC50 in a screen of multiple cancer cell lines. Finally, we show that SGC-CLK-1 not only reduces serine arginine-rich (SR) protein phosphorylation but also alters SR protein and CLK2 subcellular localization in a reversible way. Therefore, we anticipate that this compound will be a valuable tool for increasing our understanding of CLKs and their targets, SR proteins, at the level of phosphorylation and subcellular localization.

Photocatalytic Dehalogenative Deuteration of Halides over a Robust Metal-Organic Framework.

Deuterium labelling of organic compounds is an important process in chemistry. We report the first example of photocatalytic dehalogenative deuteration of both arylhalides and alkylhalides (40 substrates) over a metal-organic framework, MFM-300(Cr), using CD3 CN as the deuterium source at room temperature. MFM-300(Cr) catalyses high deuterium incorporation and shows excellent tolerance to various functional groups. Synchrotron X-ray powder diffraction reveals the activation of halogenated substrates via confined binding within MFM-300(Cr). In situ electron paramagnetic resonance spectroscopy confirms the formation of carbon-based radicals as intermediates and reveals the reaction pathway. This protocol removes the use of precious-metal catalysts from state-of-the-art processes based upon direct hydrogen isotope exchange and shows high photocatalytic stability, thus enabling multiple catalytic cycles.

Impact of Host-Guest Interactions on the Dielectric Properties of MFM-300 Materials.

Metal-organic framework (MOF) materials are attracting increasing interest in the field of electronics due to their structural diversity, intrinsic porosity, and designable host-guest interactions. Here, we report the dielectric properties of a series of robust materials, MFM-300(M) (M = Al, Sc, Cr, Fe, Ga, In), when exposed to different guest molecules. MFM-300(Fe) exhibits the most notable increase in dielectric constant to 35.3 ± 0.3 at 10 kHz upon adsorption of NH3. Structural analysis suggests that the electron delocalization induced by host-guest interactions between NH3 and the MOF host, as confirmed by neutron powder diffraction studies, leads to structural polarization, resulting in a high dielectric constant for NH3@MFM-300(Fe). This is further supported by ligand-to-metal charge-transfer transitions observed by solid-state UV/vis spectroscopy. The high detection sensitivity and stability to NH3 suggest that MFM-300(Fe) may act as a powerful dielectric-based sensor for NH3.

Direct Conversion of Methane to Ethylene and Acetylene over an Iron-Based Metal-Organic Framework.

Conversion of methane (CH4) to ethylene (C2H4) and/or acetylene (C2H2) enables routes to a wide range of products directly from natural gas. However, high reaction temperatures and pressures are often required to activate and convert CH4 controllably, and separating C2+ products from unreacted CH4 can be challenging. Here, we report the direct conversion of CH4 to C2H4 and C2H2 driven by non-thermal plasma under ambient (25 °C and 1 atm) and flow conditions over a metal-organic framework material, MFM-300(Fe). The selectivity for the formation of C2H4 and C2H2 reaches 96% with a high time yield of 334 µmol gcat-1 h-1. At a conversion of 10%, the selectivity to C2+ hydrocarbons and time yield exceed 98% and 2056 µmol gcat-1 h-1, respectively, representing a new benchmark for conversion of CH4. In situ neutron powder diffraction, inelastic neutron scattering and solid-state nuclear magnetic resonance, electron paramagnetic resonance (EPR), and diffuse reflectance infrared Fourier transform spectroscopies, coupled with modeling studies, reveal the crucial role of Fe-O(H)-Fe sites in activating CH4 and stabilizing reaction intermediates via the formation of an Fe-O(CH3)-Fe adduct. In addition, a cascade fixed-bed system has been developed to achieve online separation of C2H4 and C2H2 from unreacted CH4 for direct use. Integrating the processes of CH4 activation, conversion, and product separation within one system opens a new avenue for natural gas utility, bridging the gap between fundamental studies and practical applications in this area.

Analysis and Refinement of Host-Guest Interactions in Metal-Organic Frameworks.

ConspectusMetal-organic frameworks (MOFs) are a class of hybrid porous materials characterized by their periodic assembly using metal ions and organic ligands through coordination bonds. Their high crystallinity, extensive surface area, and adjustable pore sizes make them promising candidates for a wide array of applications. These include gas adsorption and separation, substrate binding, and catalysis, of relevance to tackling pressing global issues such as climate change, energy challenges, and pollution. In comparison to traditional porous materials such as zeolites and activated carbons, the design flexibility of organic ligands in MOFs, coupled with their orderly arrangement with associated metal centers, allows for the precise engineering of uniform pore environments. This unique feature enables a rich variety of interactions between the MOF host and adsorbed gas molecules, which are fundamental to understanding the observed uptake capacity and selectivity for target gas molecules and thus the overall performance of the material.In this Account, a data set for three-dimensional MOFs has been constructed based upon the structural analysis of host-guest interactions using the largest experimental database, the Cambridge Structural Database (CSD). A full screening was performed on structures with guest molecules of H2, C2H2, CO2, and SO2, and the relationship between the primary binding site, the isosteric heats of adsorption (Qst), and the adsorption uptake was extracted and established. We review the methodologies to refine host-guest interactions based primarily on our studies on the host-guest chemistry of MOFs. The methods include ligand functionalization, variation of metal centers, formation of defects, addition of single atom sites, and control of pore size and structure. In situ structural and dynamic investigations using diffraction and spectroscopic techniques are powerful tools to visualize the details of host-guest interactions upon the above modifications, affording key insights into functional performance at a molecular level. Finally, we give an outlook of future research priorities in the study of host-guest chemistry in MOF materials. We hope this Account will encourage the rational development and improvement of future MOF-based sorbents for applications in challenging gas adsorption, separations, and catalysis.

Ultra-fast Proton Conduction and Photocatalytic Water Splitting in a Pillared Metal-Organic Framework.

Proton-exchange membrane fuel cells enable the portable utilization of hydrogen (H2) as an energy resource. Current electrolytic materials have limitation, and there is an urgent need to develop new materials showing especially high proton conductivity. Here, we report the ultra-fast proton conduction in a novel metal-organic framework, MFM-808, which adopts an unprecedented topology and a unique structure consisting of two-dimensional layers of {Zr6}-clusters. By replacing the bridging formate with sulfate ligands within {Zr6}-layers, the modified MFM-808-SO4 exhibits an exceptional proton conductivity of 0.21 S·cm-1 at 85 °C and 99% relative humidity. Modeling by molecular dynamics confirms that proton transfer is promoted by an efficient two-dimensional conducting network assembled by sulfate-{Zr6}-layers. MFM-808-SO4 also possesses excellent photocatalytic activity for water splitting to produce H2, paving a new pathway to achieve a renewable hydrogen-energy cycle.

Discovery of New Binders for DCAF1, an Emerging Ligase Target in the Targeted Protein Degradation Field.

In this study, we describe the rapid identification of potent binders for the WD40 repeat domain (WDR) of DCAF1. This was achieved by two rounds of iterative focused screening of a small set of compounds selected on the basis of internal WDR domain knowledge followed by hit expansion. Subsequent structure-based design led to nanomolar potency binders with a clear exit vector enabling DCAF1-based bifunctional degrader exploration.