Targeted Drug Delivery in Covalent Organic Nanosheets (CONs) via Sequential Postsynthetic Modification

Covalent organic nanosheets (CONs) have emerged as a new class of functional two-dimensional (2D) porous organic polymeric materials with a high accessible surface, diverse functionality, and chemical stability. They could become versatile candidates for targeted drug delivery. Despite their many advantages, there are limitations to their use for target specific drug delivery. We anticipated that these drawbacks could be overturned by judicious postsynthetic modification steps to use CONs for targeted drug delivery. The postsynthetic modification would not only produce the desired functionality, it would also help to exfoliate to CONs as well. In order to meet this requirement, we have developed a facile, salt-mediated synthesis of covalent organic frameworks (COFs) in the presence of p-toluenesulfonic acid (PTSA). The COFs were subjected to sequential postsynthetic modifications to yield functionalized targeted CONs for targeted delivery of 5-fluorouracil to breast cancer cells. This postsynthetic modification resulted in simultaneous chemical delamination and functionalization to targeted CONs. Targeted CONs showed sustained release of the drug to the cancer cells through receptor mediated endocytosis, which led to cancer cell death via apoptosis. Considering the easy and facile COF synthesis, functionality based postsynthetic modifications, and chemical delamination to CONs for potential advantageous targeted drug delivery, this process can have a significant impact in biomedical applications

Bottom-Up Synthesis of Crystalline Covalent Organic Framework Nanosheets, Nanotubes, and Kippah Vesicles: An Odd-Even Effect Induction

Few-layer organic nanosheets are becoming increasingly attractive as two-dimensional (2D) materials due to their precise atomic connectivity and tailor-made pores. However, most strategies for synthesizing nanosheets rely on surface-assisted methods or top-down exfoliation of stacked materials. A bottom-up approach with well-designed building blocks would be the convenient pathway to achieve the bulk-scale synthesis of 2D nanosheets with uniform size and crystallinity. Herein, we have synthesized crystalline covalent organic framework nanosheets (CONs) by reacting tetratopic thianthrene tetraaldehyde (THT) and aliphatic diamines. The bent geometry of thianthrene in THT retards the out-of-plane stacking, while the flexible diamines introduce dynamic characteristics into the framework, facilitating nanosheet formation. Successful isoreticulation with five diamines with two to six carbon chain lengths generalizes the design strategy. Microscopic imaging reveals that the odd and even diamine-based CONs transmute to different nanostructures, such as nanotubes and hollow spheres. The single-crystal X-ray diffraction structure of repeating units indicates that the odd-even linker units of diamines introduce irregular-regular curvature in the backbone, aiding such dimensionality conversion. Theoretical calculations shed more light on nanosheet stacking and rolling behavior with respect to the odd-even effects.11Nsciescopu

Constructing Ultraporous Covalent Organic Frameworks in Seconds via an Organic Terracotta Process

Research on covalent organic frameworks (COFs) has recently gathered significant momentum by the virtue of their predictive design, controllable porosity, and long-range ordering. However, the lack of solvent-free and easy-to-perform synthesis processes appears to be the bottleneck toward their greener fabrication, thereby limiting their possible potential applications. To alleviate such shortcomings, we demonstrate a simple route toward the rapid synthesis of highly crystalline and ultraporous COFs in seconds using a novel salt-mediated crystallization approach. A high degree of synthetic control in interlayer stacking and layer planarity renders an ordered network with a surface area as high as 3000 m² g^–1. Further, this approach has been extrapolated for the continuous synthesis of COFs by means of a twin screw extruder and <i>in situ</i> processes of COFs into different shapes mimicking the ancient terracotta process. Finally, the regular COF beads are shown to outperform the leading zeolites in water sorption performance, with notably facile regeneration ability and structural integrity

Predesigned Metal-Anchored Building Block for In Situ Generation of Pd Nanoparticles in Porous Covalent Organic Framework: Application in Heterogeneous Tandem Catalysis

The development of nanoparticle–polymer-hybrid-based heterogeneous catalysts with high reactivity and good recyclability is highly desired for their applications in the chemical and pharmaceutical industries. Herein, we have developed a novel synthetic strategy by choosing a predesigned metal-anchored building block for in situ generation of metal (Pd) nanoparticles in the stable, porous, and crystalline covalent organic framework (COF), without using conventional reducing agents. In situ generation of Pd nanoparticles in the COF skeleton is explicitly confirmed from PXRD, XPS, TEM images, and ¹⁵N NMR spectral analysis. This hybrid material is found to be an excellent reusable heterogeneous catalyst for the synthesis of biologically and pharmaceutically important 2-substituted benzofurans from 2-bromophenols and terminal alkynes via a tandem process with the turnover number up to 1101. The heterogeneity of the catalytic process is unambiguously verified by a mercury poisoning experiment and leaching test. This hybrid material shows superior catalytic performance compared to commercially available homogeneous as well as heterogeneous Pd catalysts