Chiral Covalent Organic Frameworks Research Articles

Crystalline Olefin-Linked Chiral Covalent Organic Frameworks as a Platform for Asymmetric Catalysis.

The construction of olefin-linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self-healing process. Herein, we successfully synthesized two sets of enantiomeric olefin-linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis. The as-prepared (R)/(S)-CCOF8 exhibits excellent catalytic performance with exceeding 99% enantiomeric excess in the enantioselective electrophilic amination reaction. Moreover, the heterogeneous chiral catalysts are conveniently recycled and could maintain the performance after ten catalytic cycles. Our findings expand the scope to construct stable and crystalline chiral COFs for the asymmetric catalysis.

Crystalline Olefin‐Linked Chiral Covalent Organic Frameworks as a Platform for Asymmetric Catalysis

The construction of olefin‐linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self‐healing process. Herein, we successfully synthesized two sets of enantiomeric olefin‐linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis. The as‐prepared (R)/(S)‐CCOF8 exhibits excellent catalytic performance with exceeding 99% enantiomeric excess in the enantioselective electrophilic amination reaction. Moreover, the heterogeneous chiral catalysts are conveniently recycled and could maintain the performance after ten catalytic cycles. Our findings expand the scope to construct stable and crystalline chiral COFs for the asymmetric catalysis.

Chiral-induced synthesis of chiral covalent organic frameworks core-shell microspheres for HPLC enantioseparation.

Twochiral covalent organic frameworks (CCOFs) core-shell microspheres based on achiral organic precursors by chiral-induced synthesis strategy for HPLC enantioseparationare reported for the first time. Using n-hexane/isopropanol as mobile phase, various kinds of racemates were selected as analytes and separated on the CCOF-TpPa-1@SiO2 and CCOF-TpBD@SiO2-packed columns with a low column backpressure (3 ~ 9bar). The fabricated two CCOFs@SiO2 chiral columns exhibited good separation performance towards various racemates with high column efficiency (e.g., 19,500 plates m-1 for (4-fluorophenyl)ethanol and 18,900 plates m-1 for 1-(4-chlorophenyl)ethanol) and good reproducibility. Some effects have been investigated such as the analyte mass and column temperature on the HPLC enantioseparation. Moreover, the chiral separation results of the CCOF-TpPa-1@SiO2 chiral column and the commercialized Chiralpak AD-H column show a good complementarity. This study demonstrates that the usage of chiral-induced synthesis strategy for preparing CCOFs core-shell microspheres as a novel stationary phase has a good application potential in HPLC.

Homochiral π‐Rich Covalent Organic Frameworks Enabled Chirality Imprinting in Conjugated Polymers: Confined Polymerization and Chiral Memory from Scratch

Optically active π‐conjugated polymers (OACPs) have garnered increasing research interest for their resemblance to biological helices and intriguing chirality‐related functions. Traditional methods for synthesizing involve decorating achiral conjugated polymer architectures with enantiopure side substituents through complex organic synthesis. Here, we report a new approach: the templated synthesis of unsubstituted OACPs via supramolecularly confined polymerizations of achiral monomers within nanopores of 2D or 3D chiral covalent organic frameworks (CCOFs). We show that the chiral π‐rich nanospaces facilitate the in situ enantiospecific polymerization and self‐propagation, akin to nonenzymatic polymerase chain reaction (PCR) system, resulting in chiral imprinting. The stacked polymer chains are kinetically inert enough to memorize the chiral information after liberating from CCOFs, and even after treatment at temperature up to 200 oC. The isolated OACPs demonstrate robust enantiodiscrimination, achieving up to 85% ee in separating racemic amino acids. This underscores the potential of utilizing CCOFs as templates for supramolecularly imprinting optical activity into CPs, paving the way for synthetic evolution and advanced functional exploration of OACPs.

Homochiral π-Rich Covalent Organic Frameworks Enabled Chirality Imprinting in Conjugated Polymers: Confined Polymerization and Chiral Memory from Scratch.

Optically active π-conjugated polymers (OACPs) have garnered increasing research interest for their resemblance to biological helices and intriguing chirality-related functions. Traditional methods for synthesizing involve decorating achiral conjugated polymer architectures with enantiopure side substituents through complex organic synthesis. Here, we report a new approach: the templated synthesis of unsubstituted OACPs via supramolecularly confined polymerizations of achiral monomers within nanopores of 2D or 3D chiral covalent organic frameworks (CCOFs). We show that the chiral π-rich nanospaces facilitate the in situ enantiospecific polymerization and self-propagation, akin to nonenzymatic polymerase chain reaction (PCR) system, resulting in chiral imprinting. The stacked polymer chains are kinetically inert enough to memorize the chiral information after liberating from CCOFs, and even after treatment at temperature up to 200 oC. The isolated OACPs demonstrate robust enantiodiscrimination, achieving up to 85% ee in separating racemic amino acids. This underscores the potential of utilizing CCOFs as templates for supramolecularly imprinting optical activity into CPs, paving the way for synthetic evolution and advanced functional exploration of OACPs.

Chiral hydroxyl-controlled covalent organic framework-modified stationary phase for chromatographic enantioseparation.

Chiral covalent organic frameworks (CCOFs) possess asuperior chiral recognition environment, abundant pore configuration, and favorable physicochemical stability. In the post-synthetic chiral modification of COFs, research usually focused on increasing the density of chiral sites as much as possible, and little attention has been paid to the influence of the density of chiral sites on the spatial structure and chiral separation performance of CCOFs. In this article, 1,3,5-tris(4-aminophenyl) benzene (TPB), 2,5-dihydroxyterephthalaldehyde (DHTP), and 2,5-dimethoxyterephthalaldehyde (DMTP) served as the platform molecules to directly establish hydroxyl-controlled COFs through Schiff base condensation reactions. Then the novel chiral selectors 6-deoxy-6-[1-(2-aminoethyl)-3-(4-(4-isocyanatobenzyl)phenyl)urea]-β-cyclodextrin (UB-β-CD) were pended into the micropore structures of COFs via covalent bond for further construction the [UB-β-CD]x-TPB-DMTP COFs (x represents the density of chiral sites). The chiral sites density on [UB-β-CD]x-TPB-DMTP COFs was regulated by changing the construction proportion of DHTP to obtain a satisfactory CCOFs and significantly improve the ability of chiral separation. [UB-β-CD]x-TPB-DMTP COFs were coated on the inner wall of a capillary via a covalently bonding strategy. The prepared open tubular capillary exhibited strong and broad enantioselectivity toward a variety of chiral analytes, including sixteen racemic amino acids and six model chiral drugs. By comparing the outcomes of chromatographic separation, we observed that the density of chiral sites in CCOFs was not positively correlated with their enantiomeric separation performance. The mechanism of chiral recognition [UB-β-CD]x-TPB-DMTP COFs were further demonstrated by molecular docking simulation. This study not only introduces a new high-efficiency member of the COFs-based CSPs family but also demonstrates the enantioseparation potential of CCOFs constructed with traditional post-synthetic modification (PSM) strategy by utilizing the inherent characteristics of porous organic frameworks.

Covalent Organic Frameworks with Tunable Chirality for Chiral-Induced Spin Selectivity.

Chiral covalent organic frameworks (CCOFs) have attracted extensive interest for their potential applications in various enantioselective processes. However, the exploitation of chirality-induced spin selectivity (CISS) that enables a new technology for the injection of spin polarized current without the need for a permanent magnetic layer within CCOFs remains a largely untapped area of research. Here, we demonstrate that, for the first time, COFs can be an attractive platform to develop spin filter materials with efficient CISS. This facilitates the design and synthesis of a new family of Zn(salen)-based 2D CCOFs, namely, CCOFs-9-12, by imine condensation of chiral 1,2-diaminocyclohexane and tri- or tetra(salicylaldehyde) derivatives. CCOF-9, distinguished by its unique C2 symmetric "armchair" tetrasubstituted pyrene conformation, exhibits the most pronounced chirality among these materials and serves as a solid-state host, enabling the enantioselective adsorption of racemic drugs with an enantiomeric excess (ee) of up to 97%. After substituting diamagnetic zinc(II) ions for paramagnetic cobalt(II), the resulting CCOF-9-Co not only retains its high crystallinity, porosity, and exceptional chirality but also exhibits enhanced conductivity, a crucial factor for the effective observation of CISS. Magnetic conductive atomic force microscopy showed that CCOF-9-Co exhibited a remarkable CISS effect with up to an 88-94% spin polarization ratio. This phenomenon is further confirmed by the increased intensity in the magnetic circular dichroism (MCD) when CCOF-9-Co is under an external magnetic field. This work therefore shows the tremendous potential of CCOFs for controlling spin selectivity and will stimulate the creation of new types of crystalline polymers with strong CISS effects for spin filters.

Chiral Ru-Based Covalent Organic Frameworks as An Electrochemiluminescence-Active Platform for the Enantioselective Sensing of Amino Acids.

Although several studies related with the electrochemiluminescence (ECL) technique have been reported for chiral discrimination, it still has to face some limitations, namely, complex synthetic pathways and a relatively low recognition efficiency. Herein, this study introduces a facile strategy for the synthesis of ECL-active chiral covalent organic frameworks (COFs) employed as a chiral recognition platform. In this artificial structure, ruthenium(II) coordinated with the dipyridyl unit of the COF and enantiopure cyclohexane-1,2-diamine was harnessed as the ECL-active unit, which gave strong ECL emission in the presence of the coreactant reagent (K2S2O8). When the as-prepared COF was used as a chiral ECL-active platform, clear discrimination was observed in the response of the ECL intensity toward l- and d-enantiomers of amino acids, including tryptophan, leucine, methionine, threonine, and histidine. The biggest ratio of the ECL intensity between different configurations was up to 1.75. More importantly, a good linear relationship between the enantiomeric composition and the ECL intensity was established, which was successfully employed to determine the unknown enantiomeric compositions of the real samples. In brief, we believe that the proposed ECL-based chiral platform provides an important reference for the determination of the configuration and enantiomeric compositions.

Postsynthetic Modification Strategy for Constructing Electrochemiluminescence-Active Chiral Covalent Organic Frameworks Performing Efficient Enantioselective Sensing.

Electrochemiluminescence (ECL), integrating the characteristics of electrochemistry and fluorescence, has the advantages of high sensitivity and low background. However, only a few studies have been reported for enantioselective sensing based on the ECL-active platform because of the huge challenges in constructing tunable chiral ECL luminophores. Here, we developed a facile strategy to design and prepare ECL-active chiral covalent organic frameworks (COFs) Ph-triPy+-(R)-Ru(II) for enantioselective sensing. In such an artificial structure, the ionic skeleton of COFs was beneficial to the electron transfer on the working electrode surface and the chiral Ru-ligand was used as the chiral ECL-active luminophore. It was found that Ph-triPy+-(R)-Ru(II) coupled with sodium persulfate (Na2S2O8) as the coreactant exhibited obvious ECL signals. More importantly, a clear difference toward l- and d-enantiomers was observed in the response of the ECL intensity, resulting in a uniform recognition law. That is, for amino alcohols, d-enantiomers (1 mM) measured by Ph-triPy+-(R)-Ru(II) showed a higher ECL intensity compared with l-enantiomers. Differently, amino acids (1 mM) gave an inverse recognition phenomenon. The ECL intensity ratios between l- and d-enantiomers (1 mM) are in the range of 1.25-1.94 for serine, aspartic acid, glutamic acid, valine, leucine, leucinol, and valinol. What is more interesting is that the ECL intensity was closely related to the concentration of l-amino alcohols and d-amino acids, whereas their inverse configurations remained unchanged. In a word, the present concept demonstrates a feasible direction toward chiral ECL-active COFs and their potential for efficient enantioselective sensing.

Raising the Asymmetric Catalytic Efficiency of Chiral Covalent Organic Frameworks by Tuning the Pore Environment.

Chiral covalent organic frameworks (COFs) hold considerable promise in the realm of heterogeneous asymmetric catalysis. However, fine-tuning the pore environment to enhance both the activity and stereoselectivity of chiral COFs in such applications remains a formidable challenge. In this study, we have successfully designed and synthesized a series of clover-shaped, hydrazone-linked chiral COFs, each with a varying number of accessible chiral pyrrolidine catalytic sites. Remarkably, the catalytic efficiencies of these COFs in the asymmetric aldol reaction between cyclohexanone and 4-nitrobenzaldehyde correlate well with the number of accessible pyrrolidine sites within the frameworks. The COF featuring nearly one pyrrolidine moiety at each nodal point demonstrated excellent reaction yields and enantiomeric excess (ee) values, reaching up to 97 and 83%, respectively. The findings not only underscore the profound impact of a deliberately controlled chiral pore environment on the catalytic efficiencies of COFs but also offer a new perspective for the design and synthesis of advanced chiral COFs for efficient asymmetric catalysis.

Mercapto-β-cyclodextrin covalent organic frameworks for enantioselective liquid-liquid extraction

β-Cyclodextrin (β-CD) exhibits exceptional chiral recognition ability, and covalent organic frameworks (COFs) have been reported as highly promising chiral carriers. Therefore, incorporating cyclodextrin into COFs may result in chiral covalent organic frameworks (CCOFs) suitable for chiral applications. In this work, a solvothermal method was employed to synthesize a classical porous covalent organic framework (COF-V), while β-CD underwent a two-step modification process, resulting in the synthesis of mercapto-β-cyclodextrin (β-CD-SH). Subsequently, a β-CD-based covalent organic framework (COF-S-CD) was synthesized through a Thiol-Ene “click” reaction. The synthesized COF-S-CD was successfully applied in enantioselective liquid-liquid extraction for five racemic arylcarboxylic acids, including 2-phenylpropionic acid, 2-(4-methylphenyl) propionic acid, 2-(3-chlorophenyl) propionic acid, 2-(4-nitrophenyl) propionic acid and α-cyclohexylmandelic acid. Under optimized conditions, enantioseparation factors for the five racemates reached 1.78, 2.20, 1.84, 1.76 and 1.96, respectively, which indicated a significant enhancement in chiral recognition ability upon the incorporation of cyclodextrin into the COF material. This new application suggested that the synthesis of covalent organic framework materials incorporating β-CD, with the ability to uniformly disperse in the aqueous phase, holds promising potential for highly effective enantioselective liquid-liquid extraction.

A Liquid–Liquid Interfacial Strategy for Construction of Electroactive Chiral Covalent–Organic Frameworks with the Aim to Enlarge the Testing Scope of Chiral Electroanalysis

A Liquid–Liquid Interfacial Strategy for Construction of Electroactive Chiral Covalent–Organic Frameworks with the Aim to Enlarge the Testing Scope of Chiral Electroanalysis

Mixed-Linker Chiral 2D Covalent Organic Frameworks with Controlled Layer Stacking for Electrochemical Asymmetric Catalysis.

Covalent organic frameworks (COFs) have undergone extensive research as heterogeneous catalysts for a wide range of significant reactions, but they have not yet been investigated in the realm of electrochemical asymmetric catalysis, despite their recognition as an economical and sustainable strategy for producing enantiopure compounds. Here, we report a mixed-linker strategy to design multicomponent two-dimensional (2D) chiral COFs with tunable layer stacking for highly enantioselective electrocatalysis. By crystallizing mixtures of triamines with and without the MacMillan imidazolidinone catalyst or aryl substituent (ethyl and isopropyl) and a dialdehyde derivative of thieno-[3,2-b]thiophene, we synthesized and structurally characterized a series of three-component homochiral 2D COFs featuring either AA or ABC stacking. The stacking modes that can be synthetically controlled through steric tuning using different aryl substituents affect their chemical stability and electrochemical performance. With the MacMillan catalyst periodically appended on their channels, all three COFs with conductive thiophene moieties can be highly enantioselective and recyclable electrocatalysts for the asymmetric α-arylation of aldehydes, affording alkylated anilines with up to 97% enantiomeric excess by an anodic oxidation/organocatalytic protocol. Presumably due to their higher charge transfer ability, the ABC stacking COFs exhibit improved reactivity compared to the AA stacking analogue. This work therefore advances COFs as electrocatalysts for asymmetric catalysis and may facilitate the design of more redox-active crystalline organic polymers for electrochemical enantioselective processes.

Constructing Chiral Covalent-Organic Frameworks for Circularly Polarized Light Detection.

The use of chiral covalent organic frameworks (COFs) as active elements in photodetectors to directly identify circularly polarized light (CPL) can meet the requirement of integration and miniaturization of the as-fabricated devices. Herein, the design and synthesis of two isoreticular chiral two-dimensional (2D) COFs (CityU-7 and CityU-8) by introducing photosensitive porphyrin-based amines (5,10,15,20-tetrakis(4-aminophenyl)porphyrin) to enhance the optical absorption and chiral aldehyde linkage (2,5-bis((S/R))-2-methylbutoxy)terephthalaldehyde) to engender chirality for direct CPL detection are reported. Their crystalline structures were confirmed by powder X-ray diffraction, Fourier-transform infrared spectroscopy, and low-dose transition electron microscopy. Employing both chiral COFs as the active layers in photodetectors, left-handed circularly (LHC) and right-handed circularly (RHC) polarized light at 405nm can be well distinguishable with short response time, high responsivity, and satisfying detectivity. The study provides the first example on the design and synthesis of chiral COFs for direct detection of CPL.

Chirality-Controlled Mercapto-β-cyclodextrin Covalent Organic Frameworks for Selective Adsorption and Chromatographic Enantioseparation.

Chiral covalent organic frameworks (CCOFs) benefit from superior stability, abundant chiral environment, and homogeneous pore configuration. In its constructive tactics, only the post-modification method allows for the integration of supramolecular chiral selectors into achiral COFs. Here, the finding utilizes 6-deoxy-6-mercapto-β-cyclodextrin (SH-β-CD) as chiral subunits and 2,5-dihydroxy-1,4-benzenedicarboxaldehyde (DVA) as the platform molecule to synthesize chiral functional monomers through thiol-ene click reactions and directly establish ternary "pendant-type" SH-β-CD COFs. The chiral site density on SH-β-CD COFs was regulated by changing the proportion of chiral monomers to obtain an optimal construction strategy and remarkably improve the ability of chiral separation. SH-β-CD COFs were coated on the inner wall of the capillary in a covalently bound manner. The prepared open tubular capillary was achieved for the separation of six chiral drugs. By combining the outcomes of selective adsorption and chromatographic separation, we observed the higher density of chiral sites in the CCOFs, and poorer results were achieved. From the perspective of spatial conformational distribution, we interpret the variation in the performance of these chirality-controlled CCOFs for selective adsorption and chiral separation.

Postmodification of an Amine-Functionalized Covalent Organic Framework for Enantioselective Adsorption of Tyrosine.

The development of chiral covalent organic frameworks (COFs) by postsynthetic modification is challenging due to the common occurrences of racemization and crystallinity decrement under harsh modification conditions. Herein, we employ an effective site-selective synthetic strategy for the fabrication of an amine-functionalized hydrazone-linked COF, NH2-Th-Tz COF, by the Schiff-base condensation between aminoterephthalohydrazide (NH2-Th) and 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tribenzaldehyde (Tz). The resulting NH2-Th-Tz COF with free amine groups on the pore walls provides an appealing platform to install desired chiral moieties through postsynthetic modification. Three chiral moieties including tartaric acid, camphor-10-sulfonyl chloride, and diacetyl-tartaric anhydride were postsynthetically integrated into NH2-Th-Tz COF by reacting amine groups with acid, acyl chloride, and anhydride, giving rise to a series of chiral COFs with distinctive chiral pore surfaces. Moreover, the crystallinity, porosity, and chirality of chiral COFs were retained after modification. Remarkably, the chiral COFs exhibited an exceptional enantioselective adsorption capability toward tyrosine with a maximum enantiomeric excess (ee) value of up to 25.20%. Molecular docking simulations along with experimental results underscored the pivotal role of hydrogen bonds between chiral COFs and tyrosine in enantioselective adsorption. This work highlights the potential of site-selective synthesis as an effective tool for the preparation of highly crystalline and robust amine-decorated COFs, which offer an auspicious platform for the facile synthesis of tailor-made chiral COFs for enantioselective adsorption and beyond.

Self‐Assembly of Helical Nanofibrous Chiral Covalent Organic Frameworks

AbstractDespite significant progress on the design and synthesis of covalent organic frameworks (COFs), precise control over microstructures of such materials remains challenging. Herein, two chiral COFs with well‐defined one‐handed double‐helical nanofibrous morphologies were constructed via an unprecedented template‐free method, capitalizing on the diastereoselective formation of aminal linkages. Detailed time‐dependent experiments reveal the spontaneous transformation of initial rod‐like aggregates into the double‐helical microstructures. We have further demonstrated that the helical chirality and circular dichroism signal can be facilely inversed by simply adjusting the amount of acetic acid during synthesis. Moreover, by transferring chirality to achiral fluorescent molecular adsorbents, the helical COF nanostructures can effectively induce circularly polarized luminescence with the highest luminescent asymmetric factor (glum) up to ≈0.01.

Self-Assembly of Helical Nanofibrous Chiral Covalent Organic Frameworks.

Despite significant progress on the design and synthesis of covalent organic frameworks (COFs), precise control over microstructures of such materials remains challenging. Herein, two chiral COFs with well-defined one-handed double-helical nanofibrous morphologies were constructed via an unprecedented template-free method, capitalizing on the diastereoselective formation of aminal linkages. Detailed time-dependent experiments reveal the spontaneous transformation of initial rod-like aggregates into the double-helical microstructures. We have further demonstrated that the helical chirality and circular dichroism signal can be facilely inversed by simply adjusting the amount of acetic acid during synthesis. Moreover, by transferring chirality to achiral fluorescent molecular adsorbents, the helical COF nanostructures can effectively induce circularly polarized luminescence with the highest luminescent asymmetric factor (glum ) up to ≈0.01.

The effect of enantioselective chiral covalent organic frameworks and cysteine sacrificial donors on photocatalytic hydrogen evolution

Covalent organic frameworks (COFs) have constituted an emerging class of organic photocatalysts showing enormous potential for visible photocatalytic H2 evolution from water. However, suffering from sluggish reaction kinetics, COFs often cooperate with precious metal co-catalysts for essential proton-reducing capability. Here, we synthesize a chiral β-ketoenamine-linked COF coordinated with 10.51 wt% of atomically dispersed Cu(II) as an electron transfer mediator. The enantioselective combination of the chiral COF-Cu(II) skeleton with L-/D-cysteine sacrificial donors remarkably strengthens the hole extraction kinetics, and in turn, the photoinduced electrons accumulate and rapidly transfer via the coordinated Cu ions. Also, the parallelly stacking sequence of chiral COFs provides the energetically favorable arrangement for the H-adsorbed sites. Thus, without precious metal, the visible photocatalytic H2 evolution rate reaches as high as 14.72 mmol h−1 g−1 for the enantiomeric mixtures. This study opens up a strategy for optimizing the reaction kinetics and promises the exciting potential of chiral COFs for photocatalysis.

Asymmetric A3-Coupling Reaction Promoted by Chiral Covalent Organic Frameworks

Key words A3-coupling reaction - covalent organic framework - one-pot reaction - propargylamines - asymmetric catalysis