Junyao Li

To date, the application of chiral covalent organic frameworks (CCOFs) as membranes has encountered considerable challenges in attaining high enantioselectivity. In this study, a pair of charged CCOFs, constructed from pyridinium units serving as the framework linkages, was synthesized via a bottom-up synthetic strategy. The incorporation of these irreversible bonds confers substantial stability, particularly under aqueous conditions. These porous chiral materials were subsequently incorporated into a polytetrafluoroethylene membrane, which functioned as the supporting substrate for membrane separation. The resulting membrane exhibited pronounced enantioselectivity toward mandelic acid, tryptophan, and phenylalanine. Enantioseparation analyses revealed that the (S)-CCOF possessed a strong affinity for l-enantiomers, facilitated by multiple intermolecular interactions. Notably, the ionic-pairing effect enhanced the retention of l-enantiomers within the membrane's cavity channels, thereby allowing d-enantiomers to permeate more readily through the porous structure. This separation strategy achieved a maximum enantiomeric excess of 96.2 ± 0.5%. Furthermore, the membrane demonstrated satisfactory reproducibility. In brief, these findings underscore the considerable potential of charged CCOFs to enhance functional performance in membrane-based enantioseparation processes.

To enhance the therapeutic efficacy of breast cancer, multimodal therapy with the aid of a pH-responsive controlled release platform is proposed in this work. Indocyanine green (ICG) is loaded in honeycomb MnO₂ (hMnO₂) synthesized by a template method, which is coencapsulated with 5-fluorouracil (5-FU) in the hydrogels cross-linked between carboxymethyl chitosan (CMCS) and oxidized hyaluronic acid (OHA). The imine linkage (-HC═N-) between CMCS and OHA is hydrolyzed under weakly acidic conditions, leading to the release of 5-FU for chemotherapy and ICG/hMnO₂. The hMnO₂ can convert the optical energy of near-infrared (NIR) light into heat for photothermal therapy (PTT). Additionally, the hMnO₂ can be reduced to Mn²⁺ at low pH and high glutathione (GSH) level, and the produced Mn²⁺ can further react with H₂O₂ to generate hydroxyl radicals (·OH) through a Fenton-like reaction for chemodynamic therapy (CDT). ICG can be simultaneously released during the reduction of hMnO₂, which can catalyze the conversion of oxygen to singlet oxygen (¹O₂) upon exposure to NIR light for photodynamic therapy (PDT). Due to the synergistic effects of chemotherapy, PTT, CDT, and PDT, the developed ICG/hMnO₂/5-FU/CMCS/OHA hydrogels can significantly inhibit the growth of the 4T1 mouse breast cancer cell line.

A vitamin K3 (VK3)-loaded metal-organic framework (Cu/ZIF-8/VK3) was synthesized by a one-pot method. After the coencapsulation of Cu/ZIF-8/VK3 and 5-fluorouracil (5-FU) in the hyaluronate acid (HA)/carboxymethyl chitosan (CMCS) hydrogels formed via an amidation reaction, a drug-controlled release system (Cu/ZIF-8/VK3/5-FU/HA/CMCS) was obtained. In the weakly acidic media, the amide bonds in the HA/CMCS hydrogels are prone to be hydrolyzed, resulting in the release of 5-FU and Cu/ZIF-8/VK3; and the Cu/ZIF-8/VK3 is further degraded in the acidic environment, leading to the release of VK3 and Cu²⁺. The released Cu²⁺ can be reduced by glutathione (GSH) to Cu⁺, which can react with intracellular H₂O₂ to produce cytotoxic hydroxyl radicals (·OH) for chemodynamic therapy (CDT). On the other hand, H₂O₂ can be replenished through the redox cycling of VK3 in the presence of NAD(P)H: quinone oxidoreductase-1 (NQO1), generating stable ·OH for enhanced CDT. Cytotoxicity assay demonstrates that the developed drug-controlled release system has excellent biocompatibility, which can effectively inhibit the growth of mouse breast tumor cells 4T1 due to the synergistic chemotherapy and enhanced CDT.

A surface molecularly imprinted chiral sensor is designed for colorimetric resolution of cysteine (Cys) enantiomers by utilizing oxidase mimicking of Mn₂O₃ and reducing capacity of Cys. As the templates, l-Cys is anchored to the Mn₂O₃ nanozymes through Mn-S bonds, and the resultant Mn₂O₃-l-Cys is coated by the rigid silicon dioxide (SiO₂) imprinting layer. After the l-Cys templates are removed by calcination, molecularly imprinted SiO₂@Mn₂O₃ (MI-SiO₂@Mn₂O₃) is obtained. Owing to the oxidase mimicking of Mn₂O₃, colorless 3,3',5,5'-tetramethylbenzidine (TMB) can be converted into blue oxidized TMB (oxTMB) by the MI-SiO₂@Mn₂O₃; while the blue colored oxTMB can be reduced to colorless TMB by the reductive Cys. Due to the higher affinity of MI-SiO₂@Mn₂O₃ for l-Cys, more d-Cys is left in the solution after the Cys enantiomers are respectively incubated with the MI-SiO₂@Mn₂O₃, which can make the fading of oxTMB easier. Therefore, colorimetric resolution of the Cys enantiomers can be achieved by the developed molecularly imprinted chiral sensor.

Designing single-template molecularly imprinted chiral sensors for the enantioselective recognition of various chiral amino acids (AAs) is of great importance for chiral analysis. Here, a dummy template-based chiral sensor is developed by using l-alanine (l-Ala) as the dummy template and poly(o-phenylenediamine) as the imprinting layer, which can be used for the enantioselective recognition of various chiral AAs such as Ala, tryptophan (Trp), tyrosine (Tyr), cysteine (Cys), and arginine (Arg). Compared with conventional single-template molecularly imprinted chiral sensors, the designed single-template chiral sensor shows great universality for the recognition of chiral AAs since all chiral AAs possess an Ala-analogous segment. Also, in this work, it is found that the enantioselective recognition of different chiral AAs is greatly influenced by the sizes and isoelectric points of the AAs.

Designing alloys with intrinsic chirality for chiral analysis is an interesting subject, since most alloys are achiral. Here, a starfish-shaped AuCu alloy is facilely prepared through simultaneous reduction of chloroauric acid (HAuCl₄) and copper chloride (CuCl₂) by l-ascorbic acid (l-AA). The resultant AuCu alloy exhibits fascinating chirality due to the chiral lattice distortion generated in the alloy. More interestingly, the chirality of the AuCu alloy is exactly opposite to that of Au nanoparticles (AuNPs) and Cu nanoparticles (CuNPs) prepared through the reduction of HAuCl₄ and CuCl₂ by l-AA. Additionally, the AuCu alloy also has good electrical conductivity, and thus, it is used in the construction of the electrochemical chiral sensing platform for chiral analysis. The tryptophan (Trp) enantiomers can be discriminated with the AuCu alloy-based chiral sensing platform. Moreover, this chiral sensing platform can also be used for the detection of l-Trp in the concentration ranging from 10 nM to 10 mM with a limit of detection (LOD) of 3.12 nM.

Porous chiral materials accompanied by electrochemiluminescence (ECL) activity are rarely reported for enantioselective discrimination because of the big challenges to integrate the stereogenic center and ECL-active unit in the backbone. In the present study, ionic chiral covalent organic frameworks (iCCOFs) consisting of the pyridinium unit as the ECL-active species were prepared by a facile strategy. We were amazed that such iCCOFs could display strong cathodic ECL responses. Meanwhile, the as-prepared ECL-active iCCOFs performed enantioselective ECL quenching toward amino acid enantiomers, attributed to the enhanced photoinduced electron transfer process derived from the formed complex between the iCCOFs and amino acids via an electrostatic attraction effect. The iCCOF with an (S)-configuration was prone to interact with l-amino acids, producing a lower ECL intensity. The maximum intensity ratio between the d- and l-enantiomers was 33.0. Finally, the enantiomeric compositions of the measured amino acids presented a good linear relation with the obtained ECL intensity, which was fit for the determination of samples with unknown enantiomeric purity. In brief, the obtained results convince us that this study advances a new generation of ECL-active iCCOFs and displays great potential in enantioselective sensing.

Although covalent organic frameworks (COFs) accompanied by electrochemiluminescence (ECL) behavior have been introduced in recent years, they are still rarely applied for ECL-based enantioselective sensing, especially giving high recognition efficiency. In the current study, an achiral ionic COF comprised of the pyridinium unit is synthesized in the linkage of the carbon-nitrogen cation bond through the Zincke reaction. Interestingly, the synthesized ionic COF can generate clear ECL owing to the presence of electroactive species. Then, the ECL-active achiral COF is employed to absorb the chiral Co(III) complex for enantioselective sensing. As a result, the developed ECL sensor displays discriminative responses toward amino alcohol enantiomers. When the chiral Co(III) complex with (R)-configuration is used, the examined (S)-amino alcohols result in ECL enhancement, whereas (R)-amino alcohols lead to ECL quenching. The maximum ECL intensity ratio between (S)- and (R)-amino alcohols is up to 47.7. In addition, the recognition mechanism is investigated in detail. Finally, a good linear relation between enantiomeric composition and ECL intensity is developed and appropriate for the accurate analysis of the enantiomeric purities of unknown samples. In short, we believe that this study constructs an effective strategy to combine the respective advantages of COFs and ECL for high-efficiency enantioselective sensing.