Chiral Covalent Organic Frameworks for Circularly Polarized-light Detection: A Review

Covalent organic frameworks (COFs) are a class of ordered porous organic material formed via the covalent bonding among various organic monomers. Recently, studies of chiral COFs have attracted great attention because chirality plays an important role in medicine, pharmacy and agriculture, and chiral COFs possess many fascinating characteristics like inherent porosity, tunable pore size, structural periodicity, high stability and reusability. Ascribed to the great advantages of chiral COFs, they demonstrate many potential applications in asymmetrical catalysis, asymmetrical separation and so on. One strategy to construct chiral COFs is using multifarious chiral building blocks to directly prepare chiral COFs. Various chiral COFs structures can be designed via choosing different building blocks and adding functional groups to monomers. An alternative strategy to construct chiral COFs is to incorporate metal particles or organic species into COFs via post-synthetic modifications.

Comprehensive SummaryThe preparation and resolution of chiral molecules hold significant importance in scientific and industrial domains, such as drug development and manufacturing. In recent years, chiral porous frameworks have attracted increasing attention in asymmetric catalysis and enantiomer resolution due to their excellent performance. The metal‐organic frameworks (MOFs), covalent organic frameworks (COFs), porous organic cages (POCs), and porous coordination cages (PCCs) are important representative of the porous framework family. Significantly, chirality can be easily introduced into these framework materials through simple bottom‐up or post‐modification methods, thereby promoting their applications related to chirality. In this review, we systematically summarize the synthesis strategies of four classes of chiral framework materials and their applications in asymmetric catalysis and enantiomeric resolution. Finally, we present some perspectives on the future development in chiral porous frameworks. Key ScientistsSignificant progress has been made in the development of chiral porous frameworks, primarily driven by the application of chiral molecules. This area of research has seen contributions from many distinguished scientists. A particularly important milestone was reached in 2000, when Kimoon Kim reported the first catalytic Chiral Metal‐Organic Framework (CMOF). In 2001, Lin et al. reported a new generation of recyclable CMOF capable of chiral separation and heterogeneous catalysis. Simultaneously, researchers such as Cui and Duan have made substantial contributions, advancing the field considerably. Furthermore, notable developments have been made in the area of Chiral Covalent Organic Frameworks (CCOFs), with pioneering work by researchers like Jiang, Wang, and Cui. Meanwhile, some groups such as Su and Li have made significant strides in the chiral cages. These remarkable accomplishments have drawn considerable interest.

The modular construction of covalent organic frameworks (COFs) provides a convenient platform for designing high-performance functional materials, but the synthetic control over their chirality has been relatively barely studied. Here we report a multivariate strategy to prepare chiral COFs (CCOFs) with controlled crystallinity and stability for asymmetric catalysis. By crystallizing mixtures of triamines with and without chiral organocatalysts and with a dialdehyde, a family of two- and three-component 2D porous CCOFs that adopt two different stacking modes is prepared. The organocatalysts are periodically appended on the channel walls, and their contents, which can be synthetically tuned using a three-component condensation system, greatly affect the chemical stability and crystallinity of CCOFs. Specially, the ternary CCOFs displayed relatively high crystallinity and stability compared with the binary CCOFs. Under harsh conditions, the ternary CCOFs can serve as efficient heterogeneous catalysts for an asymmetric aminooxylation reaction, an aldol reaction, and the Diels-Alder reaction, with the stereoselectivity and diastereoselectivity rivaling or surpassing the homogeneous analogues. This work not only opens up a new synthetic route toward CCOFs, but also provides tunable control of COF crystallintity and stability and, in turn, the properties.

Chiral covalent organic frameworks (COFs) hold great promise in heterogeneous asymmetric catalysis due to their designable structures and well-defined chiral microenvironments. However, precise control over the pore size of chiral COFs to optimize asymmetric catalytic performance remains challenging. Herein, we designed a proline-derived dihydrazide chiral monomer (L-DBP-Boc), which was subjected to Schiff-base reactions with two aromatic aldehydes of different lengths, 1,3,5-triformyl phloroglucinol (BTA) and 4,4′,4″-(1,3,5-triazine-2,4,6-triyl)tribenzaldehyde (TZ), to construct two hydrazone-linked chiral COFs with distinct pore sizes (L-DBP-BTA COF and L-DBP-TZ COF). Interestingly, the Boc protecting groups were removed in situ during COF synthesis. We systematically investigated the catalytic performance of these two chiral COFs in asymmetric aldol reactions and found that their pore sizes significantly influenced both catalytic activity and enantioselectivity. The large-pore L-DBP-TZ COF (pore size: 3.5 nm) exhibited superior catalytic performance under aqueous conditions at room temperature, achieving a yield of 98% and an enantiomeric excess (ee) value of 78%. In contrast, the small-pore L-DBP-BTA COF (pore size: 2.0 nm) showed poor catalytic performance. Compared to L-DBP-BTA COF, L-DBP-TZ COF demonstrated a 1.69-fold increase in yield and a 1.56-fold enhancement in enantioselectivity, possibly attributed to the facilitated diffusion and transport of substrates and products within the larger pore, thus improving the accessibility of active sites. This study presents a facile synthesis of pyrrolidine-functionalized chiral COFs and establishes the possible structure–activity relationship in their asymmetric catalysis, offering new insights for the design of efficient chiral COF catalysts.

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.

Exploring new strategies for construction of chiral covalent organic frameworks (COFs) is of paramount importance yet remains a challenge. Herein, we report the rational design and construction of chiral COFs through a linker decomposition chiral induction (LDCI) strategy. Three pairs of azine‐linked chiral COFs are successfully synthesized by the condensation reactions of C3‐symmetric 4,4′,4′′‐(1,3,5‐triazine‐2,4,6‐triyl)tribenzaldehyde (Tz) with flexible chiral dihydrazide linkers derived from malic acid, aspartic acid and tartaric acid, respectively. Remarkably, upon complete or partial decomposition from flexible chiral dihydrazides to hydrazine during COF synthesis, the homochirality of these COFs, originating from the single‐handedness conformation of propeller‐like Tz cores, is well preserved. Such a stereoselective chiral memory realized via the LDCI strategy is confirmed by time‐dependent powder X‐ray diffraction (PXRD), Fourier transform infrared (FT‐IR) and diffuse reflectance circular dichroism (DRCD). Moreover, the resultant azine‐linked chiral COFs are used as the active materials to fabricate photodetectors to directly distinguish circularly polarized light (CPL), showing impressive recognition performances on the identification of left‐handed circularly (LHC) and right‐handed circularly (RHC) polarized lights. Notably, the residual undecomposed flexible chiral linkers within the COFs are found to be conducive to improving the polarization discrimination ratio. This work highlights LDCI as a new and effective strategy for constructing homochiral COFs with promising future in chiral optical application.

Exploring new strategies for construction of chiral covalent organic frameworks (COFs) is of paramount importance yet remains a challenge. Herein, we report the rational design and construction of chiral COFs through a linker decomposition chiral induction (LDCI) strategy. Three pairs of azine‐linked chiral COFs are successfully synthesized by the condensation reactions of C3‐symmetric 4,4′,4′′‐(1,3,5‐triazine‐2,4,6‐triyl)tribenzaldehyde (Tz) with flexible chiral dihydrazide linkers derived from malic acid, aspartic acid and tartaric acid, respectively. Remarkably, upon complete or partial decomposition from flexible chiral dihydrazides to hydrazine during COF synthesis, the homochirality of these COFs, originating from the single‐handedness conformation of propeller‐like Tz cores, is well preserved. Such a stereoselective chiral memory realized via the LDCI strategy is confirmed by time‐dependent powder X‐ray diffraction (PXRD), Fourier transform infrared (FT‐IR) and diffuse reflectance circular dichroism (DRCD). Moreover, the resultant azine‐linked chiral COFs are used as the active materials to fabricate photodetectors to directly distinguish circularly polarized light (CPL), showing impressive recognition performances on the identification of left‐handed circularly (LHC) and right‐handed circularly (RHC) polarized lights. Notably, the residual undecomposed flexible chiral linkers within the COFs are found to be conducive to improving the polarization discrimination ratio. This work highlights LDCI as a new and effective strategy for constructing homochiral COFs with promising future in chiral optical application.

Chiral covalent organic frameworks (CCOFs) are promising candidates for chiral optoelectronics and sensing, but their weak solid-state fluorescence and chiroptical responses often limit practical utility. Here, we introduce a novel CCOF synthesized from achiral monomers, 2-hydroxy-1,3,5-benzenetricarbaldehyde and hydrazine, via imine condensation with a chiral induction strategy, yielding salicylaldehyde azine units with aggregation-induced emission. Optimized catalyst and chiral inducer stoichiometry endow the framework with exceptional chiroptical properties (|gabs| = 2.2×10-2, ellipticity≈1000 mdeg). In the solid state, the CCOF exhibits intense red fluorescence (λem≈645 nm) with a large stoke shift and favorable circularly polarized luminescence (CPL, |glum| = 5.2×10-2), marking the first CCOF derived solely from achiral building blocks with robust solid-state CPL. When integrated into polydimethylsiloxane, it forms flexible and semitransparent composite films suitable for CPL-based applications. The CCOF also functions as a highly enantioselective fluorescent sensor for chiral analytes, including 2-aminocyclohenanol and dimethyl-1,2-cyclohexanediamine. Furthermore, it demonstrates reversible hydrochromism, transitioning from yellow to orange (ΔE≈42.7), and water-induced chiroptical enhancement (ellipticity up to 2100 medg, |gabs| = 5.5×10-2), achieving the highest ground-state chirality reported for CCOFs through enol-to-keto tautomerism upon water adsorption. This stimuli-responsive CCOF overcomes persistent limitations in solid-state CPL and paves the way for chiral sensing, optical displays, and responsive materials.

Chiral liquid membrane separation is crucial in pharmaceuticals and chemical synthesis for its simplicity and stability, yet designing membrane carriers that enable efficient enantioseparation remains a challenge. Here, we demonstrated for the first time that chiral porous materials can act as mobile carriers of bulk liquid membranes (BLMs) to enhance enantioselective transport and separation. We design and prepare three 2D chiral covalent organic frameworks (CCOFs) by imine condensations of a chiral dialdehyde with triamines containing ethyl, fluorine and/or isopropyl groups. These isostructural CCOFs feature ABC stacking, excellent water, acid and base tolerance, and chiral amine groups in 1D porous channels, promoting efficient enantioselective transportation of amino acid enantiomers. Among them, the CCOF with both -F and -iPr groups showing superior transport performance. Exfoliating the CCOF into chiral nanosheets creates flexible layers with accessible active sites, enabling nanosheet-mediated liquid membranes to separate chiral drug enantiomers, a feat unattainable with the pristine CCOF. This work establishes CCOFs as a promising platform for chiral BLM separations and will guide the design of high-performance BLMs using porous materials for enantioselective separation.

Chiral liquid membrane separation is crucial in pharmaceuticals and chemical synthesis for its simplicity and stability, yet designing membrane carriers that enable efficient enantioseparation remains a challenge. Here, we demonstrated for the first time that chiral porous materials can act as mobile carriers of bulk liquid membranes (BLMs) to enhance enantioselective transport and separation. We design and prepare three 2D chiral covalent organic frameworks (CCOFs) by imine condensations of a chiral dialdehyde with triamines containing ethyl, fluorine and/or isopropyl groups. These isostructural CCOFs feature ABC stacking, excellent water, acid and base tolerance, and chiral amine groups in 1D porous channels, promoting efficient enantioselective transportation of amino acid enantiomers. Among them, the CCOF with both ‐F and ‐iPr groups showing superior transport performance. Exfoliating the CCOF into chiral nanosheets creates flexible layers with accessible active sites, enabling nanosheet‐mediated liquid membranes to separate chiral drug enantiomers, a feat unattainable with the pristine CCOF. This work establishes CCOFs as a promising platform for chiral BLM separations and will guide the design of high‐performance BLMs using porous materials for enantioselective separation.

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.

Covalent organic frameworks (COFs) featuring chirality, stability, and function are of both fundamental and practical interest, but are yet challenging to achieve. Here we reported the metal-directed synthesis of two chiral COFs (CCOFs) by imine-condensations of enantiopure 1,2-diaminocyclohexane with C3-symmetric trisalicylaldehydes having one or zero 3-tert-butyl group. Powder X-ray diffraction and modeling studies, together with pore size distribution analysis demonstrate that the Zn(salen)-based CCOFs possess a two-dimensional hexagonal grid network with AA stacking. Dramatic enhancement in the chemical stability toward acidic (1 M HCl) and basic (9 M NaOH) conditions was observed for the COF incorporated with tert-butyl groups on the pore walls compared to the nonalkylated analog. The Zn(salen) modules in the CCOFs allow for installing multivariate metals into the frameworks by postsynthetic metal exchange. The exchanged CCOFs maintain high crystallinity and porosity and can serve as efficient and recyclable heterogeneous catalysts for asymmetric cyanation of aldehydes, Diels-Alder reaction, alkene epoxidation, epoxide ring-opening, and related sequential reactions with up to 97% ee.

Chiral drugs, characterized by their enantioselective biological activities and pharmacological effects, necessitate precise separation techniques to ensure therapeutic efficacy and safety. This review systematically summarizes the advancements in chiral separation technologies, with a focus on the application of chiral covalent organic frameworks (CCOFs) in chromatographic enantioseparation. Traditional methods such as crystallization, asymmetric synthesis, and chromatography-based approaches are discussed, highlighting their limitations in scalability, cost, and solvent compatibility. In contrast, CCOFs, emerging as a novel class of chiral stationary phases (CSPs), exhibit exceptional structural tunability, high porosity, and robust stability, enabling efficient enantiomer resolution across gas chromatography (GC), high-performance liquid chromatography (HPLC), and capillary electrochromatography (CEC). Key synthesis strategies for CCOFs—post-synthesis modification, chiral induction, and bottom-up assembly—are critically evaluated, alongside their performance in separating pharmaceuticals, amino acids, and agrochemicals. Recent breakthroughs, including β-cyclodextrin-functionalized COFs and camphorsulfonyl chloride-modified CCOFs, demonstrate superior separation efficiency and reproducibility. This review underscores the potential of CCOFs to address longstanding challenges in chiral separation while identifying future directions for optimizing their design and scalability in industrial applications.

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.

Stable hydrazone-linked chiral covalent organic frameworks: Synthesis, modification, and chiral signal inversion from monomers