A multifunctional protein pre-coated metal-organic framework for targeted delivery with deep tissue penetration.

Targeted drug delivery using metal-organic frameworks (MOFs) has shown significant progress. However, the tumor microenvironment (TME) impedes efficient MOF particle transfer into tumor cells. To tackle this issue, we pre-coated nano-sized MOF-808 particles with multifunctional proteins: glutathione S-transferase (GST)-affibody (Afb) and collagenase, aiming to navigate the TME more effectively. The surface of MOF-808 particles is coated with GST-Afb-a fusion protein of GST and human epidermal growth factor receptor 2 (HER2) Afb or epidermal growth factor receptor (EGFR) Afb which has target affinity. We also added collagenase enzymes capable of breaking down collagen in the extracellular matrix (ECM) through supramolecular conjugation, all without chemical modification. By stabilizing these proteins on the surface, GST-Afb mitigate biomolecule absorption, facilitating specific tumor cell targeting. Simultaneously, collagenase degrades the ECM in the TME, enabling deep tissue penetration of MOF particles. Our resulting system, termed collagenase-GST-Afb-MOF-808 (Col-Afb-M808), minimizes undesired interactions between MOF particles and external biological proteins. It not only induces cell death through Afb-mediated cell-specific targeting, but also showcases advanced cellular internalization in 3D multicellular spheroid cancer models, with effective deep tissue penetration. The therapeutic efficacy of Col-Afb-M808 was further assessed via in vivo imaging and evaluation of tumor inhibition following injection of IR-780 loaded Col-Afb-M808 in 4T1tumor-bearing nude mice. This study offers key insights into the regulation of the multifunctional protein-adhesive surface of MOF particles, paving the way for the designing even more effective targeted drug delivery systems with nano-sized MOF particles.

Unveiling the Power of Cloaking Metal-Organic Framework Platforms via Supramolecular Antibody Conjugation.

Targeted drug delivery systems based on metal-organic frameworks (MOFs) have progressed tremendously since inception and are now widely applicable in diverse scientific fields. However, translating MOF agents directly to targeted drug delivery systems remains a challenge due to the biomolecular corona phenomenon. Here, we observed that supramolecular conjugation of antibodies to the surface of MOF particles (MOF-808) via electrostatic interactions and coordination bonding can reduce protein adhesion in biological environments and show stealth shields. Once antibodies are stably conjugated to particles, they were neither easily exchanged with nor covered by biomolecule proteins, which is indicative of the stealth effect. Moreover, upon conjugation of the MOF particle with specific targeted antibodies, namely, anti-CD44, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR), the resulting hybrid exhibits an augmented targeting efficacy toward cancer cells overexpressing these receptors, such as HeLa, SK-BR-3, and 4T1, as evidenced by flow cytometry. The therapeutic effectiveness of the antibody-conjugated MOF (anti-M808) was further evaluated through in vivo imaging and the assessment of tumor inhibition effects using IR-780-loaded EGFR-M808 in a 4T1 tumor xenograft model employing nude mice. This study therefore provides insight into the use of supramolecular antibody conjugation as a promising method for developing MOF-based drug delivery systems.

Deciphering Reaction Products in Formamidine-Based Perovskites with Methylammonium Chloride Additive.

The fabrication of formamidinium lead iodide (FAPbI3) perovskite solar cells (PSCs) involves the addition of methylammonium chloride (MACl) to promote low-temperature α-phase formation and grain growth. However, as the added MACl deprotonates and volatilizes into methylamine (MA0) and HCl for removal, MA0 can chemically interact with formamidinium (FA+), forming methyl formamidinium (MFA+) as a byproduct. Despite its significance, the chemical interactions among FAPbI3 perovskites, MACl additives, and their byproducts remain poorly understood. Our findings reveal that the FA+ and MA0 reaction primarily yields a mixture of cis/trans-N-methyl formamidinium iodide (MFAI) isomers, with cis-MFAI prevailing as the dominant species. Moreover, MFAI subsequently reacts with PbI2 to yield fully formed cis-MFAPbI3 2H-phase perovskite. We elucidated the effects of MFAI on the crystal growth, phase stability, and band gap of formamidine-based perovskites through the growth of single crystals. This research offers valuable insights into the role of these byproducts in influencing the efficiency and long-term stability of future PSCs.

Metal-Organic Framework-Supported Catalase Delivery for Enhanced Photodynamic Therapy via Hypoxia Mitigation.

Tumor hypoxia poses a significant challenge in photodynamic therapy (PDT), which uses molecular oxygen to produce reactive oxygen species upon light excitation of a photosensitizer. For hypoxia mitigation, an enzyme catalase (CAT) can be beneficially used to convert intracellular hydrogen peroxide to molecular oxygen, but its utility is significantly limited due to the intrinsic membrane impermeability. Herein, we present direct integration of CAT into the outer surface of unmodified metal-organic framework (MOF) nanoparticles (NPs) via supramolecular interactions for effective cellular entry of CAT and consequent enhancement of PDT. The results demonstrated that CAT-loaded MOF NPs could successfully enter hypoxic cancer cells, after which the intracellularly delivered CAT molecules became dissociated from the MOF surface to efficiently initiate the oxygen generation and PDT process along with a co-delivered photosensitizer IR780. This achievement suggests that our protein-MOF integration strategy holds great potential in biomedical studies to overcome tumor hypoxia as well as to efficiently deliver biomolecular cargos.

Symmetry-Mismatched SBU Transformation in MOFs: Postsynthetic Metal Exchange from Zn to Fe and Its Effects on Gas Adsorption and Dye Selectivity.

This research explores the alteration of metal-organic frameworks (MOFs) using a method called postsynthetic metal exchange. We focus on the shift from a Zn-based MOF containing a [Zn4O(COO)6] secondary building unit (SBU) of octahedral site symmetry (ANT-1(Zn)) to a Fe-based one with a [Fe3IIIO(COO)6]+ SBU of trigonal prismatic site symmetry (ANT-1(Fe)). The symmetry-mismatched SBU transformation cleverly maintains the MOF's overall structure by adjusting the conformation of the flexible 1,3,5-benzenetribenzoate linker to alleviate the framework strain. The process triggers a decrease in the framework volume and pore size alongside a change in the framework's charge. These alterations influence the MOF's ability to adsorb gas and dye. During the transformation, core-shell MOFs (ANT-1(Zn@Fe)) are formed as intermediate products, demonstrating unique gas sorption traits and adjusted dye adsorption preferences due to the structural modifications at the core-shell interface. Heteronuclear clusters, located at the framework interfaces, enhance the heat of CO2 adsorption. Furthermore, they also influence the selectivity of the dye size. This research provides valuable insights into fabricating novel MOFs with unique properties by modifying the SBU of a MOF with flexible organic linkers from one site symmetry to another.

Ligand functionalization of defect-engineered Ni-MOF-74.

Incorporating functionality into the framework of metal-organic frameworks (MOFs) has attracted substantial interest because the physical and chemical properties of MOFs can be tuned by functionalizing pores. The ligand functionalization of MOF-74 is challenging because of its pristine organic ligand and framework structure. Herein, we report a series of ligand-functionalized Ni-MOF-74 derivatives synthesized by defect engineering using a mixed-ligand approach. Defect generation and ligand functionalization of Ni-MOF-74 were simultaneously achieved by incorporation of fragmented organic ligands such as 5-formylsalicylic acid, 3-hydroxysalicylic acid, 2-hydroxynicotinic acid and 5-hydroxy-1H-benzimidazole-4-carboxylic acid. The resulting defect-engineered Ni-MOF-74 derivatives maintained relatively good crystallinity up to fragment incorporation levels of ∼20% and exhibited modified permanent porosity and CO2 adsorption properties depending on the functional groups and defect concentrations in the framework.

Spatial distribution modulation of mixed building blocks in metal-organic frameworks.

The placement of mixed building blocks at precise locations in metal-organic frameworks is critical to creating pore environments suitable for advanced applications. Here we show that the spatial distribution of mixed building blocks in metal-organic frameworks can be modulated by exploiting the different temperature sensitivities of the diffusion coefficients and exchange rate constants of the building blocks. By tuning the reaction temperature of the forward linker exchange from one metal-organic framework to another isoreticular metal-organic framework, core-shell microstructural and uniform microstructural metal-organic frameworks are obtained. The strategy can be extended to the fabrication of inverted core-shell microstructures and multi-shell microstructures and applied for the modulation of the spatial distribution of framework metal ions during the post-synthetic metal exchange process of a Zn-based metal-organic framework to an isostructural Ni-based metal-organic framework.

Creating Tunable Mesoporosity by Temperature-Driven Localized Crystallite Agglomeration.

A new synthetic approach for tunable mesoporous metal-organic frameworks (MeMs) is developed. In this approach, mesopores are created in the process of heat conversion of highly mosaic metal-organic framework (MOF) crystals with non-interpenetrated low-density nanocrystallites into MOF crystals with two-fold interpenetrated high-density nanocrystallites. The two-fold interpenetration reduces the volume of the nanocrystallites in the mosaic crystal, and the accompanying localized agglomeration of the nanocrystallites results in the formation of mesopores among the localized crystallite agglomerates. The pore size can be easily modulated from 7 to 90 nm by controlling the heat treatment conditions, that is, the aging temperature and aging time. Various proteins can be encapsulated in the MeM, and immobilized enzymes show catalyst activity comparable to that of the free native enzymes. Immobilized ß-galactosidase is recyclable and the enzyme activity of the immobilized catalase is maintained after exposure to high temperatures and various organic solvents.

Superprotonic Conductivity of MOF-808 Achieved by Controlling the Binding Mode of Grafted Sulfamate.

A metal-organic framework (MOF) having superprotonic conductivity, MOF-808, is prepared by modulating the binding mode of the sulfamate (SA) moieties grafted onto the metal clusters. The activation of the SA-grafted MOF-808 at 150 °C changes the binding mode of the grafted SA from monodentate to bridging bidentate, thus converting the neutral amido (-S-NH2 ) moiety of the grafted SA to the more acidic cationic sulfiliminium (-S=NH2+ ) moiety. Further, the acidic sulfiliminium moiety of MOF-808-4SA-150 results in more efficient proton conduction than the amido moiety of MOF-808-4SA-60. At 60 °C and 95 % relative humidity, MOF-808-4SA-150 is found to have a proton conductivity of 7.89×10-2  S cm-1 , which is more than 30-times higher than that of MOF-808-4SA-60. Moreover, this superprotonic conductivity is well maintained over 1000 cycles of conductivity measurements and for similar cyclic measurements each day for seven days.

Amine-Tagged Fragmented Ligand Installation for Covalent Modification of MOF-74.

MOF-74 is one of the most explored metal-organic frameworks (MOFs), but its functionalization is limited to the dative post-synthetic modification (PSM) of the monodentate solvent site. Owing to the nature of the organic ligand and framework structure of MOF-74, the covalent PSM of MOF-74 is very demanding. Herein, we report, for the first time, the covalent PSM of amine-tagged defective Ni-MOF-74, which is prepared by de novo solvothermal synthesis by using aminosalicylic acid as a functionalized fragmented organic ligand. The covalent PSM of the amino group generates metal binding sites, and subsequent post-synthetic metalation with PdII ions affords the PdII -incorporated Ni-MOF-74 catalyst. This catalyst exhibits highly efficient, size-selective, and recyclable catalytic activity for the Suzuki-Miyaura cross-coupling reaction. This strategy is also useful for the covalent modification of amine-tagged defective Ni2 (DOBPDC), an expanded analogue of MOF-74.

Selective photocatalytic production of CH4 using Zn-based polyoxometalate as a nonconventional CO2 reduction catalyst.

Efficient and selective production of CH4 through the CO2 reduction reaction (CO2RR) is a challenging task due to the high amount of energy consumption and various reaction pathways. Here, we report the synthesis of Zn-based polyoxometalate (ZnPOM) and its application in the photocatalytic CO2RR. Unlike conventional Zn-based catalysts that produce CO, ZnPOM can selectively catalyze the production of CH4 in the presence of an Ir-based photosensitizer (TIr3) through the photocatalytic CO2RR. Photophysical and computation analyses suggest that selective photocatalytic production of CH4 using ZnPOM and TIr3 can be attributed to (1) the exceptionally fast transfer of photogenerated electrons from TIr3 to ZnPOM through the strong molecular interactions between them and (2) effective transfer of electrons from ZnPOM to *CO intermediates due to significant hybridization of their molecular orbitals. This study provides insights into the design of novel CO2RR catalysts for CH4 production beyond the limitations in conventional studies that focus on Cu-based materials.

Furan oxidation by Mn(iii)/Co(ii) catalysts - application to benzofuran synthesis.

Furans containing a ß-ketoester group at 2-position undergo oxidative ring-opening by Mn(iii)/Co(ii) catalysts under an O2 atmosphere to produce 1,4-dicarbonyl moieties through an endoperoxide intermediate, which consecutively cyclized with the ß-ketoester unit to afford 4-hydroxy-2-cyclohexen-1-ones. This oxidation/cyclization products were efficiently transformed into versatile benzofuran derivatives after consecutive aromatization and Paal-Knorr reaction.

The rise of metal-organic polyhedra.

Metal-organic polyhedra are a member of metal-organic materials, and are together with metal-organic frameworks utilized as emerging porous platforms for numerous applications in energy- and bio-related sciences. However, metal-organic polyhedra have been significantly underexplored, unlike their metal-organic framework counterparts. In this review, we will cover the topologies and the classification of metal-organic polyhedra and share several suggestions, which might be useful to synthetic chemists regarding the future directions in this rapid-growing field.

Pore space partition of a fragile Ag(i)-carboxylate framework via post-synthetic linker insertion.

The pore space partition approach via post-synthetic linker insertion was used to modulate the porosity of a fragile Ag(i)-carboxylate framework with potentially large pore space. The resulting Ag(i)-MOFs with partitioned pores showed enhanced permanent porosity compared with a nonpartitioned Ag(i)-carboxylate framework.

Symmetry-guided syntheses of mixed-linker Zr metal-organic frameworks with precise linker locations.

While the one-pot reaction of zirconium metal ions with a mixture of two dicarboxylate heterolinkers yielded a 12-c fcu Zr MOF with randomly distributed linkers, the symmetry-guided stepwise reaction produced the same MOF with both linkers precisely located in the framework. In the latter method, linear terephthalic acid (H2BDC) derivatives with mmm symmetry were inserted into the mmm-symmetry sites of the flexible Zr MOF with 8-c bcu topology (ZRN-bcu), which is composed of zigzag 2,6-naphthalenedicarboxylic acid with 2/m symmetry. Although the length of the symmetry-matching BDC2- derivatives was much shorter than the distance between the unlinked nearest-neighbor Zr clusters in ZRN-bcu, induced fitting of the derivatives into the framework was possible, resulting in well-defined locations for the two different dicarboxylate linkers. Thus, controlled synthesis of MOFs with the desired topology and functionality can be achieved using a symmetry-guided approach.

Hydrophobic Shielding of Outer Surface: Enhancing the Chemical Stability of Metal-Organic Polyhedra.

Metal-organic polyhedra (MOP) are a promising class of crystalline porous materials with multifarious potential applications. Although MOPs and metal-organic frameworks (MOFs) have similar potential in terms of their intrinsic porosities and physicochemical properties, the exploitation of carboxylate MOPs is still rudimentary because of the lack of systematic development addressing their chemical stability. Herein we describe the fabrication of chemically robust carboxylate MOPs via outer-surface functionalization as an a priori methodology, to stabilize those MOPs system where metal-ligand bond is not so strong. Fine-tuning of hydrophobic shielding is key to attaining chemical inertness with retention of the framework integrity over a wide range of pH values, in strong acidic conditions, and in oxidizing and reducing media. These results are further corroborated by molecular modelling studies. Owing to the unprecedented transition from instability to a chemically ultra-stable regime using a rapid ambient-temperature gram-scale synthesis (within seconds), a prototype strategy towards chemically stable MOPs is reported.

Zirconium-Formate Macrocycles and Supercage: Molecular Packing versus MOF-like Network for Water Vapor Sorption.

In systematic efforts toward a new type of molecule-based porous materials, facile and efficient synthetic methods have been established to obtain macrocyclic [Zr6]6 and supercage-like {[Zr6]6}8, where [Zr6] represents [Zr6O4(OH)4(CO2) n] building unit commonly found in Zr-based metal-organic frameworks. The reactions involve in situ hydrolysis of DMF solvent to produce formate linkers and thus do not require any organic ligand. A minor variation in the composition of two cyclic hexamers thus obtained results in dramatic differences in crystal packing which in turn lead to distinctive and selective sorption behavior for water vapor. It is shown that the high heat of water adsorption and unrestricted uptake under high humidity are consequences of the highly polar surface and flexible crystal packing. The reversibility of water adsorption is demonstrated by cyclic measurements of uptake and regeneration under dynamic flow conditions.

Efficient separation of C2 hydrocarbons in a permanently porous hydrogen-bonded organic framework.

A highly robust porous hydrogen-bonded organic framework (HOF) constructed by 4,4',4''-benzene-1,3,5-triyl-tris(benzoic acid) not only achieves the highest uptakes of ethylene and ethane among the HOF materials, but also exhibits unusual adsorption selectivity of C2H6 over other C2 gases. Besides, it exhibits the second highest acetylene uptake among all the reported HOF materials.

Synthesis and characterization of heteroleptic titanium MOCVD precursors for TiO2 thin films.

Heteroleptic titanium alkoxides with three different ligands, i.e., [Ti(OiPr)(X)(Y)] (X = tridentate, Y = bidentate ligands), were synthesized to find efficient metal organic chemical vapor deposition (MOCVD) precursors for TiO2 thin films. Acetylacetone (acacH) or 2,2,6,6-tetramethyl-3,5-heptanedione (thdH) was employed as a bidentate ligand, while N-methyldiethanolamine (MDEA) was employed as a tridentate ligand. It was expected that the oxygen and moisture susceptibility of titanium alkoxides, as well as their tendency to form oligomers, would be greatly reduced by placing multidentate and bulky ligands around the center Ti atom. The synthesized heteroleptic titanium alkoxides were characterized both physicochemically and crystallographically, and their thermal behaviors were also investigated. [Ti(OiPr)(MDEA)(thd)] was found to be monomeric and stable against moisture; it also showed good volatility in the temperature window between volatilization and decomposition. This material was used as a single-source precursor during MOCVD to generate TiO2 thin films on silicon wafers. The high thermal stability of [Ti(OiPr)(MDEA)(thd)] enabled the fabrication of TiO2 films over a wide temperature range, with steady growth rates between 500 and 800 °C.

Coordination-Driven Self-Assembly of Heterotrimetallic Barrel and Bimetallic Cages Using a Cobalt Sandwich-Based Tetratopic Donor.

Three-dimensional molecular architectures self-assembled with tripodal and tetratopic donors are valuable because of their encapsulation properties. Here, we present Co(I)-Fe(II)-Pd(II) heterotrimetallic trifacial barrel 1, which was self-assembled using a newly synthesized tetratopic donor [CpCo(CbR4)] [L; Cp = cyclopentadienyl, Cb = cyclobudiene, and R = 4-(4-pyridylphenyl)] and a 90° acceptor [ cis-(dppf)Pd(OTf)2] (A1; dppf = (diphenylphosphino)ferrocene and OTf = CF3SO3-). The heterotrimetallic barrel 1 exhibited selective 1:1 interaction with a N, N'-dimethyl-1,4,5,8-naphthalenetetracarboxylic diimide guest, as revealed by 1H NMR analysis. The self-assembly of donor L with two other Ru(II)-based 180° acceptors [( p-cymene)2Ru2(OO∩OO)(OTf)2] [OO∩OO = 6,11-dioxido-5,12-naphthacenedione (A2) and oxalate (A3)] resulted in tetragonal-prismatic cages. Self-assembly using the longer acceptor A2 provided rare isomers of a tetragonal-prismatic cage by varying the orientation of the cyclopentadienyl moiety out-out (2a) or out-in (2b) of the cavity, whereas self-assembly using the shorter acceptor A3 selectively resulted in the tetragonal-prismatic cage 3. The three-dimensional molecular architectures 1-3 were characterized by combined spectroscopic and elemental analyses. The structures of molecular barrel 1 and prismatic cage 3 were elucidated by single-crystal X-ray analysis.