Generation and Stabilization of a Dinickel Catalyst in a Metal-Organic Framework for Selective Hydrogenation Reactions.

Although many monometallic active sites have been installed in metal-organic frameworks (MOFs) for catalytic reactions, there are no effective strategies to generate bimetallic catalysts in MOFs. Here we report the synthesis of a robust, efficient, and reusable MOF catalyst, MOF-NiH, by adaptively generating and stabilizing dinickel active sites using the bipyridine groups in MOF-253 with the formula of Al(OH)(2,2'-bipyridine-5,5'-dicarboxylate) for Z-selective semihydrogenation of alkynes and selective hydrogenation of C=C bonds in α,ß-unsaturated aldehydes and ketones. Spectroscopic studies established the dinickel complex (bpy⋅- )NiII (µ2 -H)2 NiII (bpy⋅- ) as the active catalyst. MOF-NiH efficiently catalyzed selective hydrogenation reactions with turnover numbers of up to 192 and could be used in five cycles of hydrogenation reactions without catalyst leaching or significant decrease of catalytic activities. The present work uncovers a synthetic strategy toward solution-inaccessible Earth-abundant bimetallic MOF catalysts for sustainable catalysis.

Self-adaptive Metal-Organic Framework Assembles Di-iron Active Sites to Mimic Monooxygenases.

Despite significant efforts, it remains a challenge to design artificial enzymes that can mimic both structures and functions of natural enzymes. Here, we report the post-synthetic construction of binuclear iron catalysts in MOF-253 to mimic natural di-iron monooxygenases. The adjacent bipyridyl (bpy) linkers in MOF-253 can freely rotate to form the [(bpy)FeIII(µ2-OH)]2 active site in a self-adaptive fashion. The composition and structure of the [(bpy)FeIII(µ2-OH)]2 active sites in MOF-253 were characterized by a combination of inductively coupled plasma-mass spectrometry, thermogravimetric analysis, X-ray absorption spectrometry, and Fourier-transform infrared spectroscopy. The MOF-based artificial monooxygenase effectively catalyzed oxidative transformations of organic compounds, including C-H oxidation and alkene epoxidation reactions, using O2 as the only oxidant, which indicates the successful recapitulation of the structure and functions of natural monooxygenases using readily accessible MOFs. The di-iron system exhibited at least 27 times higher catalytic activity than the corresponding mononuclear control. DFT calculations showed that the binuclear system had a 14.2 kcal/mol lower energy barrier than the mononuclear system in the rate-determining C-H activation process, suggesting the importance of cooperativity of the iron centers in the [(bpy)FeIII(µ2-OH)]2 active site in the rate-determining step. The stability and recyclability of the MOF-based artificial monooxygenase were also demonstrated.

A Three-in-One Nanoscale Coordination Polymer for Potent Chemo-Immunotherapy.

The addition of immune checkpoint blockade to standard chemotherapy has changed the standards of care for some cancer patients. However, current chemo-immunotherapy strategies do not benefit most colorectal cancer patients and many triple-negative breast cancer patients. Here, the design of a three-in-one nanoscale coordination polymer (NCP), OX/GC/CQ, comprising prodrugs of oxaliplatin (OX), gemcitabine (GC), and 5-carboxy-8-hydroxyquinoline (CQ) for triple-modality chemo-immunotherapy is reported. OX/GC/CQ exhibits optimal pharmacokinetics and enhanced particle accumulation and drug release in acidic tumor tissues, wherein CQ greatly enhances immunogenic cell death induced by OX/GC and downregulates programmed cell death-ligand 1  expression in cancer cells. Consequently, OX/GC/CQ efficiently promotes infiltration and activity of cytotoxic T lymphocytes, while decreasing the proportion of immunosuppressive regulatory T cells. Intravenous injection of OX/GC/CQ reduces the growth of colorectal carcinoma and triple-negative breast cancer, prevents metastasis to lungs, and extends mouse survival by 30-40 days compared to free drugs. This work highlights the potential of NCPs in co-delivering synergistic chemo-immunotherapeutics for the treatment of advanced and aggressive cancers.

A 2D Nanoradiosensitizer Enhances Radiotherapy and Delivers STING Agonists to Potentiate Cancer Immunotherapy.

Despite potent preclinical antitumor activity, activation of stimulator of interferon genes (STING) has shown modest therapeutic effects in clinical studies. Many STING agonists, including 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), show poor pharmacokinetic properties for sustaining STING activation in tumors and achieving optimal antitumor efficacy. Improved delivery of STING agonists and their effective combination with other treatments are needed to enhance their therapeutic effects. Herein, a 2D nanoplatform, cGAMP/MOL, is reported via conjugating cGAMP to a nanoscale metal-organic layer (MOL) for simultaneous STING activation and radiosensitization. The MOL not only exhibits strong radiosensitization effects for enhanced cancer killing and induction of immunogenic cell death, but also retains cGAMP in tumors for sustained STING activation. Compared to free cGAMP, cGAMP/MOL elicits stronger STING activation and regresses local tumors upon X-ray irradiation. Further combination with an immune checkpoint inhibitor bridges innate and adaptive immune systems by activating the tumor microenvironment to elicit systemic antitumor responses.

Dimensional Reduction of Lewis Acidic Metal-Organic Frameworks for Multicomponent Reactions.

Owing to hindered diffusions, the application of porous catalytic materials has been limited to relatively simple organic transformations with small substrates. Herein we report a dimensional reduction strategy to construct a two-dimensional metal-organic framework (MOF), Zr6OTf-BTB, with 96% accessible Lewis acidic sites as probed by the bulky Lewis base pivalonitrile. With nearly free substrate accessibility, Zr6OTf-BTB outperformed two three-dimensional MOF counterparts of similar Lewis acidity (Zr6OTf-BPDC and Zr6OTf-BTC) in catalyzing sterically hindered multicomponent reactions (MCRs) for the construction of tetrahydroquinoline and aziridine carboxylate derivatives with high turnover numbers (TONs). Zr6OTf-BTB was also superior to the homogeneous benchmark Sc(OTf)3 with nearly 14 times higher TON and 9 times longer catalyst lifetime. Furthermore, the topology-activity relationships in these Zr-based Lewis acidic MOFs were rationalized by comparing their Lewis acidity, numbers of Lewis acidic sites, and sterically accessible Lewis acidic sites. Zr6OTf-BTB was successfully used to construct several bioactive molecules via MCRs with excellent efficiency. This dimensional reduction strategy should allow the development of other MOF catalysts for synthetically useful and complicated organic transformations.

Rational Construction of an Artificial Binuclear Copper Monooxygenase in a Metal-Organic Framework.

Artificial enzymatic systems are extensively studied to mimic the structures and functions of their natural counterparts. However, there remains a significant gap between structural modeling and catalytic activity in these artificial systems. Herein we report a novel strategy for the construction of an artificial binuclear copper monooxygenase starting from a Ti metal-organic framework (MOF). The deprotonation of the hydroxide groups on the secondary building units (SBUs) of MIL-125(Ti) (MIL = Matériaux de l'Institut Lavoisier) allows for the metalation of the SBUs with closely spaced CuI pairs, which are oxidized by molecular O2 to afford the CuII2(µ2-OH)2 cofactor in the MOF-based artificial binuclear monooxygenase Ti8-Cu2. An artificial mononuclear Cu monooxygenase Ti8-Cu1 was also prepared for comparison. The MOF-based monooxygenases were characterized by a combination of thermogravimetric analysis, inductively coupled plasma-mass spectrometry, X-ray absorption spectroscopy, Fourier-transform infrared spectroscopy, and UV-vis spectroscopy. In the presence of coreductants, Ti8-Cu2 exhibited outstanding catalytic activity toward a wide range of monooxygenation processes, including epoxidation, hydroxylation, Baeyer-Villiger oxidation, and sulfoxidation, with turnover numbers of up to 3450. Ti8-Cu2 showed a turnover frequency at least 17 times higher than that of Ti8-Cu1. Density functional theory calculations revealed O2 activation as the rate-limiting step in the monooxygenation processes. Computational studies further showed that the Cu2 sites in Ti8-Cu2 cooperatively stabilized the Cu-O2 adduct for O-O bond cleavage with 6.6 kcal/mol smaller free energy increase than that of the mononuclear Cu sites in Ti8-Cu1, accounting for the significantly higher catalytic activity of Ti8-Cu2 over Ti8-Cu1.

Metal-Organic Frameworks Integrate Cu Photosensitizers and Secondary Building Unit-Supported Fe Catalysts for Photocatalytic Hydrogen Evolution.

We report here the synthesis of a series of metal-organic frameworks (MOFs), FeX@Zr6-Cu, comprising cuprous photosensitizing linkers (Cu-PSs) and catalytically active FeII centers supported on secondary building units (SBUs) for photocatalytic H2 evolution. Close proximity (∼1 nm) between Cu-PS and SBU-supported Fe sites and stabilization of Fe sites by periodically ordered SBUs led to exceptionally high H2 evolution activity for FeX@Zr6-Cu, with turnover numbers of up to 33 700 and turnover frequencies of up to 880 h-1. Photocatalytic H2 evolution activities of FeX@Zr6-Cu correlate with the lability of X counteranions, suggesting that open coordination environments of Fe sites generated by labile X groups facilitate the formation of Fe-hydride intermediates before hydrogen evolution. This work highlights the potential of using MOFs to integrate Earth-abundant components for solar energy utilization.

Cerium-Based Metal-Organic Layers Catalyze Hydrogen Evolution Reaction through Dual Photoexcitation.

Cerium-based materials such as ceria are increasingly used in catalytic reactions. We report here the synthesis of the first Ce-based metal-organic layer (MOL), Ce6-BTB, comprising Ce6 secondary building units (SBUs) and 1,3,5-benzenetribenzoate (BTB) linkers, and its functionalization for photocatalytic hydrogen evolution reaction (HER). Ce6-BTB was postsynthetically modified with photosensitizing [(MBA)Ir(ppy)2]Cl or [(MBA)Ru(bpy)2]Cl2 (MBA = 2-(5'-methyl-[2,2'-bipyridin]-5-yl)acetate, ppy = 2-phenylpyridine, bpy = 2,2'-bipyridine) to afford Ce6-BTB-Ir or Ce6-BTB-Ru MOLs, respectively. The proximity of photosensitizing ligands and Ce6 SBUs in the MOLs facilitates electron transfer to drive photocatalytic HER under visible light with turnover numbers of 1357 and 484 for Ce6-BTB-Ir and Ce6-BTB-Ru, respectively. Photophysical and electrochemical studies revealed a novel dual photoexcitation pathway whereby the excited photosensitizers in the MOL are reductively quenched and then transfer electrons to Ce6 SBUs to generate CeIII centers, which are further photoexcited to CeIII* species for HER.

Multistep Engineering of Synergistic Catalysts in a Metal-Organic Framework for Tandem C-O Bond Cleavage.

Cleavage of strong C-O bonds without breaking C-C/C-H bonds is a key step for catalytic conversion of renewable biomass to hydrocarbon feedstocks. Herein we report multistep sequential engineering of orthogonal Lewis acid and palladium nanoparticle (NP) catalysts in a metal-organic framework (MOF) built from (Al-OH)n secondary building units and a mixture of 2,2'-bipyridine-5,5'-dicarboxylate (dcbpy) and 1,4-benzenediacrylate (pdac) ligands (1) for tandem C-O bond cleavage. Ozonolysis of 1 selectively removed pdac ligands to generate Al2(OH)(OH2) sites, which were subsequently triflated with trimethylsilyl triflate to afford strongly Lewis acidic sites for dehydroalkoxylation. Coordination of Pd(MeCN)2Cl2 to dcbpy ligands followed by in situ reduction produced orthogonal Pd NP sites in 1-OTf-PdNP as the hydrogenation catalyst. The selective and precise transformation of 1 into 1-OTf-PdNP was characterized step by step using powder X-ray diffraction, transmission electron microscopy, thermogravimetric analysis, inductively coupled plasma mass spectrometry, infrared spectroscopy, and X-ray absorption spectroscopy. The hierarchical incorporation of orthogonal Lewis acid and Pd NP active sites endowed 1-OTf-PdNP with outstanding catalytic performance in apparent hydrogenolysis of etheric, alcoholic, and esteric C-O bonds to generate saturated alkanes via a tandem dehydroalkoxylation-hydrogenation process under relatively mild conditions. The reactivity of C-O bonds followed the trend of tertiary carbon > secondary carbon > primary carbon. Control experiments demonstrated the heterogeneous nature and recyclability of 1-OTf-PdNP and its superior catalytic activity over the homogeneous counterparts. Sequential engineering of multiple catalytic sites in MOFs thus presents a unique opportunity to address outstanding challenges in sustainable catalysis.

Metal-Organic Frameworks Significantly Enhance Photocatalytic Hydrogen Evolution and CO2 Reduction with Earth-Abundant Copper Photosensitizers.

We report here the design of two multifunctional metal-organic frameworks (MOFs), mPT-Cu/Co and mPT-Cu/Re, comprising cuprous photosensitizers (Cu-PSs) and molecular Co or Re catalysts for photocatalytic hydrogen evolution (HER) and CO2 reduction (CO2RR), respectively. Hierarchical organization of Cu-PSs and Co/Re catalysts in these MOFs facilitates multielectron transfer to drive HER and CO2RR under visible light with an HER turnover number (TON) of 18 700 for mPT-Cu/Co and a CO2RR TON of 1328 for mPT-Cu/Re, which represent a 95-fold enhancement over their homogeneous controls. Photophysical and electrochemical investigations revealed the reductive quenching pathway in HER and CO2RR catalytic cycles and attributed the significantly improved performances of MOFs over their homogeneous counterparts to enhanced electron transfer due to close proximity between Cu-PSs and active catalysts and stabilization of Cu-PSs and molecular catalysts by the MOF framework.

Strongly Lewis Acidic Metal-Organic Frameworks for Continuous Flow Catalysis.

The synthesis of highly acidic metal-organic frameworks (MOFs) has attracted significant research interest in recent years. We report here the design of a strongly Lewis acidic MOF, ZrOTf-BTC, through two-step transformation of MOF-808 (Zr-BTC) secondary building units (SBUs). Zr-BTC was first treated with 1 M hydrochloric acid solution to afford ZrOH-BTC by replacing each bridging formate group with a pair of hydroxide and water groups. The resultant ZrOH-BTC was further treated with trimethylsilyl triflate (Me3SiOTf) to afford ZrOTf-BTC by taking advantage of the oxophilicity of the Me3Si group. Electron paramagnetic resonance spectra of Zr-bound superoxide and fluorescence spectra of Zr-bound N-methylacridone provided a quantitative measurement of Lewis acidity of ZrOTf-BTC with an energy splitting (ΔE) of 0.99 eV between the πx* and πy* orbitals, which is competitive to the homogeneous benchmark Sc(OTf)3. ZrOTf-BTC was shown to be a highly active solid Lewis acid catalyst for a broad range of important organic transformations under mild conditions, including Diels-Alder reaction, epoxide ring-opening reaction, Friedel-Crafts acylation, and alkene hydroalkoxylation reaction. The MOF catalyst outperformed Sc(OTf)3 in terms of both catalytic activity and catalyst lifetime. Moreover, we developed a ZrOTf-BTC@SiO2 composite as an efficient solid Lewis acid catalyst for continuous flow catalysis. The Zr centers in ZrOTf-BTC@SiO2 feature identical coordination environment to ZrOTf-BTC based on spectroscopic evidence. ZrOTf-BTC@SiO2 displayed exceptionally high turnover numbers (TONs) of 1700 for Diels-Alder reaction, 2700 for epoxide ring-opening reaction, and 326 for Friedel-Crafts acylation under flow conditions. We have thus created strongly Lewis acidic sites in MOFs via triflation and constructed the MOF@SiO2 composite for continuous flow catalysis of important organic transformations.

Titanium Hydroxide Secondary Building Units in Metal-Organic Frameworks Catalyze Hydrogen Evolution under Visible Light.

Herein we report the design of two new titanium metal-organic frameworks (MOFs), Ti3-BPDC-Ir and Ti3-BPDC-Ru, by doping [Ir(ppy)2(dcbpy)]Cl or [Ru(bpy)2(dcbpy)]Cl2 (bpy = 2,2'-bipyridine, ppy = 2-phenylpyridine, dcbpy = 2,2'-bipyridine-5,5'-dicarboxylate) into the Ti3-BPDC framework (BPDC = biphenyl-4,4'-dicarboxylate). Hierarchical assembly of photosensitizing ligands and Ti3(OH)2 secondary building units (SBUs) facilitates multielectron transfer to drive photocatalytic hydrogen evolution (HER) under visible light with turnover numbers of 6632 and 786 for Ti3-BPDC-Ir and Ti3-BPDC-Ru, respectively. Photophysical and electrochemical studies establish the photocatalytic HER via reductive quenching of the excited photosensitizers followed by electron transfer from the reduced photosensitizers to Ti3(OH)2 SBUs and explain the catalytic difference between the two MOFs. Density functional theory calculations reveal key steps of HER via protonation of TiIII-OH to generate the TiIII species with a vacant coordination site followed by proton-coupled electron transfer to afford the key TiIV-H intermediate.

Metal-Organic Framework Stabilizes a Low-Coordinate Iridium Complex for Catalytic Methane Borylation.

Catalytic borylation has recently been suggested as a potential strategy to convert abundant methane to fine chemicals. However, synthetic utility of methane borylation necessitates significant improvement of catalytic activities over original phenanthroline- and diphosphine-Ir complexes. Herein, we report the use of metal-organic frameworks (MOFs) to stabilize low-coordinate Ir complexes for highly active methane borylation to afford the monoborylated product. The mono(phosphine)-Ir based MOF, Zr-P1-Ir, significantly outperformed other Ir catalysts in methane borylation to afford CH3Bpin with a turnover number of 127 at 110 °C. Density functional theory calculations indicated a significant reduction of activation barrier for the rate limiting oxidative addition of methane to the four-coordinate (P1)IrIII(Bpin)3 catalyst to form the six-coordinate (P1)IrV(Bpin)3(CH3)(H) intermediate, thus avoiding the formation of sterically encumbered seven-coordinate IrV intermediates as found in other Ir catalysts based on chelating phenanthroline, bipyridine, and diphosphine ligands. MOF thus stabilizes the homogeneously inaccessible, low-coordinate (P1)Ir(boryl)3 catalyst to provide a unique strategy to significantly lower the activation barrier for methane borylation. This MOF-based catalyst design holds promise in addressing challenging catalytic reactions involving highly inert substrates.

Cobalt-bridged secondary building units in a titanium metal-organic framework catalyze cascade reduction of N-heteroarenes.

We report here a novel Ti3-BPDC metal-organic framework (MOF) constructed from biphenyl-4,4'-dicarboxylate (BPDC) linkers and Ti3(OH)2 secondary building units (SBUs) with permanent porosity and large 1D channels. Ti-OH groups from neighboring SBUs point toward each other with an O-O distance of 2 Å, and upon deprotonation, act as the first bidentate SBU-based ligands to support CoII-hydride species for effective cascade reduction of N-heteroarenes (such as pyridines and quinolines) via sequential dearomative hydroboration and hydrogenation, affording piperidine and 1,2,3,4-tetrahydroquinoline derivatives with excellent activity (turnover number ∼ 1980) and chemoselectivity.

Titanium-Based Nanoscale Metal-Organic Framework for Type I Photodynamic Therapy.

Nanoscale metal-organic frameworks (nMOFs) have shown great potential as nanophotosensitizers for photodynamic therapy (PDT) owing to their high photosensitizer loadings, facile diffusion of reactive oxygen species (ROSs) through their porous structures, and intrinsic biodegradability. The exploration of nMOFs in PDT, however, remains limited to an oxygen-dependent type II mechanism. Here we report the design of a new nMOF, Ti-TBP, composed of Ti-oxo chain secondary building units (SBUs) and photosensitizing 5,10,15,20-tetra( p-benzoato)porphyrin (TBP) ligands, for hypoxia-tolerant type I PDT. Upon light irradiation, Ti-TBP not only sensitizes singlet oxygen production, but also transfers electrons from excited TBP* species to Ti4+-based SBUs to afford TBP•+ ligands and Ti3+ centers, thus propagating the generation of superoxide, hydrogen peroxide, and hydroxyl radicals. By generating four distinct ROSs, Ti-TBP-mediated PDT elicits superb anticancer efficacy with >98% tumor regression and 60% cure rate.

Trivalent Zirconium and Hafnium Metal-Organic Frameworks for Catalytic 1,4-Dearomative Additions of Pyridines and Quinolines.

We report the quantitative conversion of [MIV6(µ3-O)4(µ3-OH)4Cl12]6- nodes in the MCl2-BTC metal-organic framework into the [MIII6(µ3-O)4(µ3-ONa)4H6]6- nodes in MIIIH-BTC (M = Zr, Hf; BTC is 1,3,5-benzenetricarboxylate) via bimetallic reductive elimination of H2 from putative [MIV6(µ3-O)4(µ3-OH)4H12]6- nodes. The coordinatively unsaturated MIIIH centers in MIIIH-BTC are highly active and selective for 1,4-dearomative hydroboration and hydrosilylation of pyridines and quinolines. This work demonstrated the potential of secondary building unit transformation in generating electronically unique and homogeneously inaccessible single-site solid catalysts for organic synthesis.

Single-Site Cobalt Catalysts at New Zr12(µ3-O)8(µ3-OH)8(µ2-OH)6 Metal-Organic Framework Nodes for Highly Active Hydrogenation of Nitroarenes, Nitriles, and Isocyanides.

We report here the synthesis of a robust and porous metal-organic framework (MOF), Zr12-TPDC, constructed from triphenyldicarboxylic acid (H2TPDC) and an unprecedented Zr12 secondary building unit (SBU): Zr12(µ3-O)8(µ3-OH)8(µ2-OH)6. The Zr12-SBU can be viewed as an inorganic node dimerized from two commonly observed Zr6 clusters via six µ2-OH groups. The metalation of Zr12-TPDC SBUs with CoCl2 followed by treatment with NaBEt3H afforded a highly active and reusable solid Zr12-TPDC-Co catalyst for the hydrogenation of nitroarenes, nitriles, and isocyanides to corresponding amines with excellent activity and selectivity. This work highlights the opportunity in designing novel MOF-supported single-site solid catalysts by tuning the electronic and steric properties of the SBUs.