Intermediate Formation of Macrocycles for Efficient Crystallization of 2D Covalent Organic Frameworks with Enhanced Photocatalytic Hydrogen Evolution

Covalent organic frameworks (COFs) have gained significant attention as key photocatalysts for efficient solar light conversion into hydrogen production. Unfortunately, the harsh synthetic conditions and intricate growth process required to obtain highly crystalline COFs greatly hinder their practical application. Herein, we report a simple strategy for the efficient crystallization of 2D COFs based on the intermediate formation of hexagonal macrocycles. Mechanistic investigation suggests that the use of 2,4,6-triformyl resorcinol (TFR) as the asymmetrical aldehyde build block allows the equilibration between irreversible enol-to-keto tautomerization and dynamic imine bonds to produce the hexagonal β-ketoenamine-linked macrocycles, the formation of which could provide COFs with high crystallinity in half hour. We show that COF-935 with 3 wt % Pt as cocatalyst exhibit a high hydrogen evolution rate of 67.55 mmol g⁻¹ h⁻¹ for water splitting when exposed to visible light. More importantly, COF-935 exhibits an average hydrogen evolution rate of 19.80 mmol g⁻¹ h⁻¹ even at a low loading of only 0.1 wt % Pt, which is a significant breakthrough in this field. This strategy would provide valuable insights into the design of highly crystalline COFs as efficient organic semiconductor photocatalysts.     

Ca2+- and Mg2+-doped covalent organic frameworks exhibiting high hydrogen and acetylene storage

A multiscale theoretical investigation has been performed to study the hydrogen and acetylene storage in Ca²⁺- and Mg²⁺-doped COFs (COF-105 and COF-108). The first-principles calculations show that the Ca²⁺ and Mg²⁺ can be immobilized at the COFs surfaces, and the doped Ca and Mg cations can adsorb five H₂ molecules and three C₂H₂ molecules with ideal binding energies. The Grand Canonical Monte Carlo (GCMC) simulations were carried out to obtain the hydrogen and acetylene uptakes of Ca²⁺- and Mg²⁺-doped COFs at room temperature in the different pressure ranges. Our results demonstrate that, at T = 298 K and p = 100 bar, the total gravimetric uptakes of H₂ in Ca²⁺-doped COF-105 and COF-108 reach 6.78 and 6.54 wt%, respectively, and a higher uptakes of 7.14 and 7.27 wt% have been reached for Mg²⁺-doped COF-105 and COF-108, respectively. At T = 298 K and p = 1 bar, the acetylene uptakes of Ca²⁺-doped COF-105, Ca²⁺-doped COF-108, Mg²⁺-doped COF-105, and Mg²⁺-doped COF-108 are 406.42, 366.24, 308.07, and 319.88 cm³/g (corresponding to the excess uptakes of 358.37, 316.38, 236.7109, and 245.42 cm³/g), respectively. The Ca²⁺-doped COF-105 displays a highest acetylene storage capacity among all materials reported. The Ca²⁺- and Mg²⁺-doped COFs can be very practical hydrogen or acetylene storage medium in the future.     

Isomeric Oligo(Phenylenevinylene)-Based Covalent Organic Frameworks with Different Orientation of Imine Bonds and Distinct Photocatalytic Activities

Imine-linked covalent organic frameworks (COFs) have been extensively studied in photocatalysis because of their easy synthesis and excellent crystallinity. The effect of imine-bond orientation on the photocatalytic properties of COFs, however, is still rarely studied. Herein, we report two novel COFs with different orientations of imine bonds using oligo(phenylenevinylene) moieties. The COFs showed similar structures but great differences in their photoelectric properties. COF-932 demonstrated a superior hydrogen evolution performance compared to COF-923 when triethanolamine was used as the sacrificial agent. Interestingly, the use of ascorbic acid led to the protonation of the COFs, further altering the direction of electron transfer. The photocatalytic performances were increased to 23.4 and 0.73 mmol g⁻¹ h⁻¹ for protonated COF-923 and COF-932, respectively. This study provides a clear strategy for the design of imine-linked COF-based photocatalysts and advances the development of COFs.     

Extremely strong tubular stacking of aromatic oligoamide macrocycles

As the third-generation rigid macrocycles evolved from progenitor 1, cyclic aromatic oligoamides 3, with a backbone of reduced constraint, exhibit extremely strong stacking with an astoundingly high affinity (estimated lower limit of K _dimer > 10¹³ M^–1 in CHCl₃), which leads to dispersed tubular stacks that undergo further assembly in solution. Computational study reveals a very large binding energy (–49.77 kcal mol^–1) and indicates highly cooperative local dipole interactions that account for the observed strength and directionality for the stacking of 3. In the solid-state, X-ray diffraction (XRD) confirms that the aggregation of 3 results in well-aligned tubular stacks. The persistent tubular assemblies of 3, with their non-deformable sub-nm pore, are expected to possess many interesting functions. One such function, transmembrane ion transport, is observed for 3.     

Biphen[n]arenes

To design and exploit novel macrocyclic synthetic receptors is a permanent and challenging topic in supramolecular chemistry. Here we describe the one-pot synthesis, unique geometries and intriguing host–guest properties of a new class of supramolecular macrocycles – biphen[n]arenes (n = 3, 4), which are made up of 4,4′-biphenol or 4,4′-biphenol ether units linked by methylene bridges at the 3- and 3′- positions. The biphenarene macrocycles are conveniently accessible/modifiable and extremely guest-friendly. Particularly, biphen[4]arene is capable of forming inclusion complexes with not only organic cationic guests but also neutral π-electron deficient molecules. Compared with calixarenes, resorcinarenes, cyclotriveratrylenes and pillararenes with substituted mono-benzene units, the biphen[n]arenes reported here possess significantly different characteristics in both their topologic structures and their recognition properties, and thus can find broad applications in supramolecular chemistry and other areas.     

A macrocycle-assisted nanoparticlization process for bulk Ag2S

We report herein a new nanoparticlization process for the bulk-to-nano transformation of Ag₂S by incorporating both top-down and bottom-up approaches. Bulk Ag₂S was dissolved in solution with the assistance of a macrocyclic ligand, hexamethylazacalix[6]pyridine (Py[6]), to produce polynuclear silver sulfide cluster aggregates. All Ag–S cluster aggregates obtained in three crystalline complexes were protected by Py[6] macrocycles. Removing the protective Py[6] macrocycles by protonation led to the generation of unconventional Ag–S nanoparticles with a large energy gap. Theoretical calculations by a hybrid DFT method demonstrated that the silver sulfide clusters with high Ag/S ratio exhibited more localized HOMO–LUMO orbitals, which consequently enlarged their band gap energies. These experimental and theoretical studies broaden our understanding of the fabrication of nanomaterials by virtue of the advantages of both bottom-up and top-down methods and meanwhile provide a viable means of adjusting the band gap of binary nanomaterials independent of their size.     

Understanding fragility and engineering activation stability in two-dimensional covalent organic frameworks

The sensitivity of covalent organic frameworks (COFs) to pore collapse during activation processes is generally termed activation stability, and activation stability is important for achieving and maintaining COF crystallinity and porosity which are relevant to a variety of applications. However, current understanding of COF stability during activation is insufficient, and prior studies have focused primarily on thermal stability or on the activation stability of other porous materials, such as metal–organic frameworks (MOFs). In this work, we demonstrate and implement a versatile experimental approach to quantify activation stability of COFs and use this to establish a number of relationships between their pore size, the type of pore substituents, pore architecture, and structural robustness. Additionally, density functional theory calculations reveal the impact on both inter-and intra-layer interactions, which govern activation stability, and we demonstrate that activation stability can be systematically tuned using a multivariate synthesis approach involving mixtures of functionalized and unfunctionalized COF building blocks. Our findings provide novel fundamental insights into the activation stability of COFs and offer guidance for the design of more robust COFs.

We establish relationships between COF pore size, the type of pore substituent, pore architecture, and structural robustness and demonstrate that activation stability can be systematically tuned using a multivariate synthesis approach.     

Enhanced hydrolytic stability of self-assembling alkylated two-dimensional covalent organic frameworks

The stability and bulk properties of two-dimensional boronate ester-linked covalent organic frameworks (COFs) were investigated upon exposure to aqueous environments. Enhanced stability was observed for frameworks with alkylation in the pores of the COF compared to nonalkylated, bare-pore frameworks. COF-18? and COF-5 were analyzed as "bare-pore" COFs, while COF-16? (methyl), COF-14? (ethyl), and COF-11? (propyl) were evaluated as "alkylated-pore" materials. Upon submersion in aqueous media, the porosity of alkylated COFs decreased ～25%, while the nonalkylated COFs were almost completely hydrolyzed, virtually losing all porosity. Similar trends were observed for the degree of crystallinity for these materials, with ～40% decrease for alkylated COFs and 95% decrease for nonalkylated COFs. SEM was used to probe the particle size and morphology for these hydrolyzed materials. Stability tests, using absorbance spectroscopy and (1)H NMR, monitored the release of monomers as the COF degraded. While nonalkylated COFs were stable in organic solvent, hydrolysis was rapid in aqueous environments, more so in basic compared to neutral or acidic aqueous media (minutes to hours, respectively). Notably, alkylation in the pores of COFs slows hydrolysis, exhibiting up to a 50-fold enhancement in stability for COF-11? over COF-18?.     

Porphyrin-based donor–acceptor COFs as efficient and reusable photocatalysts for PET-RAFT polymerization under broad spectrum excitation

Covalent organic frameworks (COFs) are crystalline and porous organic materials attractive for photocatalysis applications due to their structural versatility and tunable optical and electronic properties. The use of photocatalysts (PCs) for polymerizations enables the preparation of well-defined polymeric materials under mild reaction conditions. Herein, we report two porphyrin-based donor–acceptor COFs that are effective heterogeneous PCs for photoinduced electron transfer-reversible addition–fragmentation chain transfer (PET-RAFT). Using density functional theory (DFT) calculations, we designed porphyrin COFs with strong donor–acceptor characteristics and delocalized conduction bands. The COFs were effective PCs for PET-RAFT, successfully polymerizing a variety of monomers in both organic and aqueous media using visible light (λ_max from 460 to 635 nm) to produce polymers with tunable molecular weights (MWs), low molecular weight dispersity, and good chain-end fidelity. The heterogeneous COF PCs could also be reused for PET-RAFT polymerization at least 5 times without losing photocatalytic performance. This work demonstrates porphyrin-based COFs that are effective catalysts for photo-RDRP and establishes design principles for the development of highly active COF PCs for a variety of applications.

Porphyrin-based donor–acceptor COFs are effective heterogeneous photocatalysts for photoinduced electron transfer-reversible addition–fragmentation chain transfer (PET-RAFT), including for aqueous polymerizations and under red-light excitation.     

Solar-microbial hybrid device based on oxygen-deficient niobium pentoxide anodes for sustainable hydrogen production

Hydrogen gas is emerging as an attractive fuel with high energy density for the direction of energy resources in the future. Designing integrated devices based on a photoelectrochemical (PEC) cell and a microbial fuel cell (MFC) represents a promising strategy to produce hydrogen fuel at a low price. In this work, we demonstrate a new solar-microbial (PEC–MFC) hybrid device based on the oxygen-deficient Nb₂O₅ nanoporous (Nb₂O_5–x NPs) anodes for sustainable hydrogen generation without external bias for the first time. Owing to the improved conductivity and porous structure, the as-prepared Nb₂O_5–x NPs film yields a remarkable photocurrent density of 0.9 mA cm^–2 at 0.6 V (vs. SCE) in 1 M KOH aqueous solution under light irradiation, and can achieve a maximum power density of 1196 mW m^–2 when used as an anode in a MFC device. More importantly, a solar-microbial hybrid system by combining a PEC cell with a MFC is designed, in which the Nb₂O_5–x NPs electrodes function as both anodes. The as-fabricated PEC–MFC hybrid device can simultaneously realize electricity and hydrogen using organic matter and solar light at zero external bias. This novel design and attempt might provide guidance for other materials to convert and store energy.     

Large ring-forming alkylations provide facile access to composite macrocycles

Macrocyclic compounds have potential to enable drug discovery for protein targets with extended, solvent-exposed binding sites. Crystallographic structures of peptides bound at such sites show strong surface complementarity and frequent aromatic side-chain contacts. In an effort to capture these features in stabilized small molecules, we describe a method to convert linear peptides into constrained macrocycles based upon their aromatic content. Designed templates initiate the venerable Friedel–Crafts alkylation to form large rings efficiently at room temperature – routinely within minutes – and unimpeded by polar functional groups. No protecting groups, metals, or air-free techniques are required. Regiochemistry can be tuned electronically to explore diverse macrocycle connectivities. Templates with additional reaction capabilities can further manipulate macrocycle structure. The chemistry lays a foundation to extend studies of how the size, shape and constitution of peptidyl macrocycles correlate with their pharmacological properties.     

Chemical sensing in two dimensional porous covalent organic nanosheets

Two new imide-based crystalline, porous, and chemically stable covalent organic frameworks (COFs) (TpBDH and TfpBDH) have been successfully synthesized employing solvothermal crystallization route. Furthermore, thin layered covalent organic nanosheets (CONs) were derived from these bulk COFs by the simple liquid phase exfoliation method. These 2D CONs showcase increased luminescence intensity compared to their bulk counterparts (COFs). Notably, TfpBDH-CONs showcase good selectivity and prominent, direct visual detection towards different nitroaromatic analytes over TpBDH-CONs. Quite interestingly, TfpBDH-CONs exhibit a superior “turn-on” detection capability for 2,4,6-trinitrophenol (TNP) in the solid state, but conversely, they also show a “turn-off” detection in the dispersion state. These findings describe a new approach towards developing an efficient, promising fluorescence chemosensor material for both visual and spectroscopic detection of nitroaromatic compounds with very low [10^–5 (M)] analyte concentrations.     

First-principles study of hydrogen adsorption in metal-doped COF-10

Covalent organic frameworks (COFs), due to their low-density, high-porosity, and high-stability, have promising applications in gas storage. In this study we have explored the potential of COFs doped with Li and Ca metal atoms for storing hydrogen under ambient thermodynamic conditions. Using density functional theory we have performed detailed calculations of the sites Li and Ca atoms occupy in COF-10 and their interaction with hydrogen molecules. The binding energy of Li atom on COF-10 substrate is found to be about 1.0 eV and each Li atom can adsorb up to three H(2) molecules. However, at high concentration, Li atoms cluster and, consequently, their hydrogen storage capacity is reduced due to steric hindrance between H(2) molecules. On the other hand, due to charge transfer from Li to the substrate, O sites provide additional enhancement for hydrogen adsorption. With increasing concentration of doped metal atoms, the COF-10 substrate provides an additional platform for storing hydrogen. Similar conclusions are reached for Ca doped COF-10.     

Stereoselective synthesis of macrocyclic peptides via a dual olefin metathesis and ethenolysis approach

Macrocyclic compounds occupy an important chemical space between small molecules and biologics and are prevalent in many natural products and pharmaceuticals. The growing interest in macrocycles has been fueled, in part, by the design of novel synthetic methods to these compounds. One appealing strategy is ring-closing metathesis (RCM) that seeks to construct macrocycles from acyclic diene precursors using defined transition-metal alkylidene catalysts. Despite its broad utility, RCM generally gives rise to a mixture of E- and Z-olefin isomers that can hinder efforts for the large-scale production and isolation of such complex molecules. To address this issue, we aimed to develop methods that can selectively enrich macrocycles in E- or Z-olefin isomers using an RCM/ethenolysis strategy. The utility of this methodology was demonstrated in the stereoselective formation of macrocyclic peptides, a class of compounds that have gained prominence as therapeutics in drug discovery. Herein, we report an assessment of various factors that promote catalyst-directed RCM and ethenolysis on a variety of peptide substrates by varying the olefin type, peptide sequence, and placement of the olefin in macrocycle formation. These methods allow for control over olefin geometry in peptides, facilitating their isolation and characterization. The studies outlined in this report seek to expand the scope of stereoselective olefin metathesis in general RCM.     

Chelate-free metal ion binding and heat-induced radiolabeling of iron oxide nanoparticles

A novel reaction for chelate-free, heat-induced metal ion binding and radiolabeling of ultra-small paramagnetic iron oxide nanoparticles (USPIOs) has been established. Radiochemical and non-radioactive labeling studies demonstrated that the reaction has a wide chemical scope and is applicable to p-, d- and f-block metal ions with varying ionic sizes and formal oxidation states from 2+ to 4+. Radiolabeling studies found that ⁸⁹Zr–Feraheme (⁸⁹Zr–FH or ⁸⁹Zr–ferumoxytol) can be isolated in 93 ± 3% radiochemical yield (RCY) and >98% radiochemical purity using size-exclusion chromatography. ⁸⁹Zr–FH was found to be thermodynamically and kinetically stable in vitro using a series of ligand challenge and plasma stability tests, and in vivo using PET/CT imaging and biodistribution studies in mice. Remarkably, ICP-MS and radiochemistry experiments showed that the same reaction conditions used to produce ⁸⁹Zr–FH can be employed with different radionuclides to yield ⁶⁴Cu–FH (66 ± 6% RCY) and ¹¹¹In–FH (91 ± 2% RCY). Electron magnetic resonance studies support a mechanism of binding involving metal ion association with the surface of the magnetite crystal core. Collectively, these data suggest that chelate-free labeling methods can be employed to facilitate clinical translation of a new class of multimodality PET/MRI radiotracers derived from metal-based nanoparticles. Further, this discovery is likely to have broader implications in drug delivery, metal separation science, ecotoxicology of nanoparticles and beyond.     

Efficacious and sustained release of an anticancer drug mitoxantrone from new covalent organic frameworks using protein corona

Solid porous and crystalline covalent organic frameworks (COFs) are characterized by their higher specific BET surface areas and functional pore walls, which allow the adsorption of various bioactive molecules inside the porous lattices. We have introduced a perylene-based COF, PER@PDA-COF-1, which acts as an effective porous volumetric reservoir for an anticancer drug, mitoxantrone (MXT). The drug-loaded COF (MXT–PER@PDA-COF-1) exhibited zero cellular release of MXT towards cancer cells, which can be attributed to the strong intercalation between the anthracene-dione motif of the drug and the perylene-based COF backbone. Here, we have introduced a strategy involving the serum-albumin-triggered intracellular release of mitoxantrone from MXT–PER@PDA-COF-1. The serum albumin acts as an exfoliating agent and as a colloidal stabilizer in PBS medium (pH = 7.4), rapidly forming a protein corona around the exfoliated COF crystallites and inducing the sustained release of MXT from the COF into tumorigenic cells.

Solid porous and crystalline covalent organic frameworks (COFs) are characterized by their higher specific BET surface areas and functional pore walls, which allow the adsorption of various bioactive molecules inside the porous lattices.     

Reaction-based Indicator displacement Assay (RIA) for the selective colorimetric and fluorometric detection of peroxynitrite

Using the self-assembly of aromatic boronic acids with Alizarin Red S (ARS), we developed a new chemosensor for the selective detection of peroxynitrite. Phenylboronic acid (PBA), benzoboroxole (BBA) and 2-(N,N-dimethylaminomethyl)phenylboronic acid (NBA) were employed to bind with ARS to form the complex probes. In particular, the ARS–NBA system with a high binding affinity can preferably react with peroxynitrite over hydrogen peroxide and other ROS/RNS due to the protection of the boron via the solvent-insertion B–N interaction. Our simple system produces a visible colorimetric change and on–off fluorescence response towards peroxynitrite. By coupling a chemical reaction that leads to an indicator displacement, we have developed a new sensing strategy, referred to herein as RIA (Reaction-based Indicator displacement Assay).     

A pillar[5]arene-based covalent organic framework with pre-encoded selective host–guest recognition

It is highly desirable to maintain both permanent accessible pores and selective molecular recognition capability of macrocyclic cavitands in the solid state. Integration of well-defined discrete macrocyclic hosts into ordered porous polymeric frameworks (e.g., covalent organic frameworks, COFs) represents a promising strategy to transform many supramolecular chemistry concepts and principles well established in the solution phase into the solid state, which can enable a broad range of practical applications, such as high-efficiency molecular separation, heterogeneous catalysis, and pollution remediation. However, it is still a challenging task to construct macrocycle-embedded COFs. In this work, a novel pillar[5]arene-derived (P5) hetero-porous COF, denoted as P5-COF, was rationally designed and synthesized. Featuring the unique backbone structure, P5-COF exhibited selective adsorption of C₂H₂ over C₂H₄ and C₂H₆, as well as significantly enhanced host–guest binding interaction with paraquat, in comparison with the pillar[5]arene-free COF analog, Model-COF. The present work established a new strategy for developing COFs with customizable molecular recognition/separation properties through the bottom-up “pre-porous macrocycle to porous framework” design.

A novel pillar[5]arene-derived (P5) COF was rationally designed and synthesized, which exhibited superior performance in selective gas adsorption and paraquat binding.     

Design of well-defined shell–core covalent organic frameworks/metal sulfide as an efficient Z-scheme heterojunction for photocatalytic water splitting

Development of a covalent–organic framework (COF)-based Z-scheme heterostructure is a promising strategy for solar energy driven water splitting, but the construction of a COF-based Z-scheme heterostructure with well-defined architecture, large contact area and intimate contact interfaces is scarce. Herein, we fabricated a direct Z-scheme heterostructure COF–metal sulfide hybrid (T-COF@CdS) with shell–core architecture by self-polymerization of 1,3,5-benzenetricarboxaldehyde and 2,4,6-tris(4-aminophenyl)-1,3,5-triazine in situ on CdS. The formed C–S chemical bonding between T-COF and CdS could provide a very tight and stable interface. Owing to the properly staggered band alignment, strong interfacial interaction and large interfacial contact area between T-COF and CdS, a Z-scheme route for charge separation and transfer is realized, resulting in electron accumulation in CdS for H₂O reduction. The obtained Z-scheme heterostructure T-COF@CdS-3 exhibits a high apparent quantum efficiency of 37.8% under 365 nm monochromatic light irradiation, and long-term stability arising from shell–core structures in which the T-COF shell protects the catalytic centers of CdS against deactivation, as well as acts as oxidation sites to avoid the photocorrosion of CdS. This work provides a strategy for the construction of a shell–core direct Z-scheme heterostructure photocatalyst for water splitting with high performance.

A stable Z-scheme with well-defined architecture by in situ growth of COFs on CdS for photocatalytic water splitting is constructed. The T-COF shell can protect the catalytic center of CdS from deactivation and photocorrosion.     

Nanoparticle Size‐Fractionation through Self‐Standing Porous Covalent Organic Framework Films

Covalent organic frameworks (COFs) have attracted attention due to their ordered pores leading to important industrial applications like storage and separation. Combined with their modular synthesis and pore engineering, COFs could become ideal candidates for nanoseparations. However, the fabrication of these microcrystalline powders as continuous, crack‐free, robust films remains a challenge. Herein, we report a simple, slow annealing strategy to construct centimeter‐scale COF films ( Tp‐Azo and Tp‐TTA ) with micrometer thickness. The as‐synthesized films are porous (SA_BET=2033 m² g^?1 for Tp‐Azo ) and chemically stable. These COFs have distinct size cut‐offs (ca. 2.7 and ca. 1.6 nm for Tp‐Azo and Tp‐TTA , respectively), which allow the size‐selective separation of gold nanoparticles. Unlike, other conventional membranes, the durable structure of the COF films allow for excellent recyclability (up to 4 consecutive cycles) and easy recovery of the gold nanoparticles from the solution.