The synthesis of 3D covalent organic frameworks (COFs) adopting novel topologies is challenging, and so far 3D COFs have only been reported for nets based on building blocks with tetrahedral geometry. We demonstrate the targeted synthesis of an anionic 3D COF crystallizing in a three-coordinated srs net by exploiting a recently developed linkage for the formation of anionic silicate COFs based on hypercoordinate silicon nodes. The framework, named SiCOF-5, was synthesized by reticulating dianionic hexacoordinate [SiO] nodes with triangular triphenylene building blocks and adopts a two-fold interpenetrated srs-c net with an overall composition of Na[Si(CHO)] (where CHO is triphenylene-2,3,6,7,10,11-hexakis(olate)). A key requirement for the crystallization of SiCOF-5 was the careful control over the nucleation and growth rate by gradual generation of the silicon source during the course of the reaction.

Herein we detail a practical synthesis of bullvalene and a variety of mono- and disubstituted analogues through cobalt-catalysed [6+2] cycloaddition of cyclooctatetraene to alkynes, followed by photochemical di-π-methane rearrangement. The application of isomer-network analysis, coupled with quantum-chemical calculations, provides a powerful automated tool for predicting the properties of bullvalene isomer networks.

Substituted bullvalenes are dynamic shape-shifting molecules that exist within complex reaction networks. Herein, we report the synthesis of di-and trisubstituted bullvalenes and investigate their dynamic properties. Trisubstituted bullvalenes share a common major isomer which shows kinetic metastability. A survey of the thermodynamic and kinetic landscapes through computational analysis together with kinetic simulation provides a map of the internal dynamics of these systems.

The alarming rise in superbugs that are resistant to drugs of last resort, including vancomycin-resistant enterococci and staphylococci, has become a significant global health hazard. Here we report the click chemistry synthesis of an unprecedented class of shapeshifting vancomycin dimers (SVDs) that display potent activity against bacteria that are resistant to the parent drug, including the ESKAPE pathogens, vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA) as well as vancomycin-resistant S. aureus (VRSA). The shapeshifting modality of the dimers is powered by a click-linked bullvalene core, hence exploiting the dynamic covalent rearrangements of the fluxional carbon cage and creating ligands with the capacity to inhibit bacterial cell wall biosynthesis. The new shapeshifting antibiotics are not disadvantaged by the common mechanism of vancomycin resistance resulting from the alteration of the C-terminal dipeptide with the corresponding D-Ala-D-Lac depsipeptide. Further, evidence suggests that the shapeshifting ligands destabilize the complex formed between the flippase MurJ and lipid II, inferring the potential for a new mode of action for polyvalent glycopeptides. The SVDs show little propensity for acquired resistance by enterococci, suggesting that this new class of shapeshifting antibiotic will display durable antimicrobial activity not prone to rapidly acquired clinical resistance.