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The ubiquitin E3 ligase substrate adapter cereblon (CRBN) is a target of thalidomide and lenalidomide 1 , therapeutic agents used in the treatment of haematopoietic malignancies 2 – 4 and as ligands for targeted protein degradation 5 – 7 . These agents are proposed to mimic a naturally occurring degron; however, the structural motif recognized by the thalidomide-binding domain of CRBN remains unknown. Here we report that C-terminal cyclic imides, post-translational modifications that arise from intramolecular cyclization of glutamine or asparagine residues, are physiological degrons on substrates for CRBN. Dipeptides bearing the C-terminal cyclic imide degron substitute for thalidomide when embedded within bifunctional chemical degraders. Addition of the degron to the C terminus of proteins induces CRBN-dependent ubiquitination and degradation in vitro and in cells. C-terminal cyclic imides form adventitiously on physiologically relevant timescales throughout the human proteome to afford a degron that is endogenously recognized and removed by CRBN. The discovery of the C-terminal cyclic imide degron defines a regulatory process that may affect the physiological function and therapeutic engagement of CRBN. C-terminal cyclic imides are physiological degrons that enable the ubiquitin E3 ligase adapter protein cereblon to target substrates for degradation.

Pyrroles are structurally important heterocycles. However, the synthesis of polysubstituted pyrroles is often challenging. Here, we report a multicomponent, Ti-catalysed formal [2+2+1] reaction of alkynes and diazenes for the oxidative synthesis of penta- and trisubstituted pyrroles: a nitrenoid analogue to classical Pauson-Khand-type syntheses of cyclopentenones. Given the scarcity of early transition-metal redox catalysis, preliminary mechanistic studies are presented. Initial stoichiometric and kinetic studies indicate that the mechanism of this reaction proceeds through a formally Ti(II)/Ti(IV) redox catalytic cycle, in which an azatitanacyclobutene intermediate, resulting from [2+2] alkyne + Ti imido coupling, undergoes a second alkyne insertion followed by reductive elimination to yield pyrrole and a Ti(II) species. The key component for catalytic turnover is the reoxidation of the Ti(II) species to a Ti(IV) imido via the disproportionation of an η(2)-diazene-Ti(II) complex.

Integration into a soft material of all the molecular components necessary to generate storable fuels is an interesting target in supramolecular chemistry. The concept is inspired by the internal structure of photosynthetic organelles, such as plant chloroplasts, which colocalize molecules involved in light absorption, charge transport and catalysis to create chemical bonds using light energy. We report here on the light-driven production of hydrogen inside a hydrogel scaffold built by the supramolecular self-assembly of a perylene monoimide amphiphile. The charged ribbons formed can electrostatically attract a nickel-based catalyst, and electrolyte screening promotes gelation. We found the emergent phenomenon that screening by the catalyst or the electrolytes led to two-dimensional crystallization of the chromophore assemblies and enhanced the electronic coupling among the molecules. Photocatalytic production of hydrogen is observed in the three-dimensional environment of the hydrogel scaffold and the material is easily placed on surfaces or in the pores of solid supports. Self-assembled ribbons of perylene amphiphiles have been shown to crystallize in the presence of a nickel-based hydrogen production catalyst, allowing efficient electronic coupling between the perylene chromophores. This hydrogel material photocatalyses the production of H 2 , and can be shaped and placed on surfaces for incorporation into devices.

Despite numerous organic semiconducting materials synthesized for organic photovoltaics in the past decade, fullerenes are widely used as electron acceptors in highly efficient bulk-heterojunction solar cells. None of the non-fullerene bulk heterojunction solar cells have achieved efficiencies as high as fullerene-based solar cells. Design principles for fullerene-free acceptors remain unclear in the field. Here we report examples of helical molecular semiconductors as electron acceptors that are on par with fullerene derivatives in efficient solar cells. We achieved an 8.3% power conversion efficiency in a solar cell, which is a record high for non-fullerene bulk heterojunctions. Femtosecond transient absorption spectroscopy revealed both electron and hole transfer processes at the donor−acceptor interfaces. Atomic force microscopy reveals a mesh-like network of acceptors with pores that are tens of nanometres in diameter for efficient exciton separation and charge transport. This study describes a new motif for designing highly efficient acceptors for organic solar cells. In organic photovoltaics, the best-performing devices are often based on fullerene derivatives as the electron acceptor counterpart. Here, the authors present new molecular electron acceptors with a helical structure and achieve 8.3% power conversion efficiency.

The functions of complex crystalline systems derived from supramolecular biological and non-biological assemblies typically emerge from homochiral programmed primary structures via first principles involving secondary, tertiary and quaternary structures. In contrast, heterochiral and racemic compounds yield disordered crystals, amorphous solids or liquids. Here, we report the self-assembly of perylene bisimide derivatives in a supramolecular helix that in turn self-organizes in columnar hexagonal crystalline domains regardless of the enantiomeric purity of the perylene bisimide. We show that both homochiral and racemic perylene bisimide compounds, including a mixture of 21 diastereomers that cannot be deracemized at the molecular level, self-organize to form single-handed helical assemblies with identical single-crystal-like order. We propose that this high crystalline order is generated via a cogwheel mechanism that disregards the chirality of the self-assembling building blocks. We anticipate that this mechanism will facilitate access to previously inaccessible complex crystalline systems from racemic and homochiral building blocks. The structural order of supramolecular assemblies typically depends on the enantiomeric purity of their building blocks. Now, a perylene bisimide (PBI) derivative has been described that assembles into a single-handed supramolecular helix, which in turn packs into domains with an identical crystalline order irrespective of the PBI's chirality. A cogwheel mechanism is proposed.

Silicone-rubber baby teats used to bottle-feed infants are frequently disinfected by moist heating. However, infant exposure to small microplastics (<10 μm) potentially released from the heated teats by hydrothermal decomposition has not been studied, owing to the limitations of conventional spectroscopy in visualizing microplastic formation and in characterizing the particles at the submicrometre scale. Here both the surfaces of silicone teats subjected to steam disinfection and the wash waters of the steamed teats were analysed using optical-photothermal infrared microspectroscopy. This new technique revealed submicrometre-resolved steam etching on and chemical modification of the teat surface. Numerous flake- or oil-film-shaped micro(nano)plastics (MNPs) (in the size range of 0.6–332 μm) presented in the wash waters, including cyclic and branched polysiloxanes or imides, which were generated by the steam-induced degradation of the base polydimethylsiloxane elastomer and the polyamide resin additive. The results indicated that by the age of one year, a baby could ingest >0.66 million elastomer-derived micro-sized plastics (MPs) (roughly 81% in 1.5–10 μm). Global MP emission from teat disinfection may be as high as 5.2 × 1013 particles per year. Our findings highlight an entry route for surface-active silicone-rubber-derived MNPs into both the human body and the environment. The health and environmental risks of the particles are as yet unknown.Steam disinfection of silicone-rubber baby teats can lead to steam etching and chemical modification of the teat surface. This can release micro- and nanoplastics and result in ingestion. The results suggested that by the age of one year, a baby could ingest more than 600,000 microplastics.

Electroreduction of carbon dioxide (CO₂)—a key component of artificial photosynthesis—has largely been stymied by the impractically high overpotentials necessary to drive the process. We report an electrocatalytic system that reduces CO₂ to carbon monoxide (CO) at overpotentials below 0.2 volt. The system relies on an ionic liquid electrolyte to lower the energy of the (CO₂)⁻ intermediate, most likely by complexation, and thereby lower the initial reduction barrier. The silver cathode then catalyzes formation of the final products. Formation of gaseous CO is first observed at an applied voltage of 1.5 volts, just slightly above the minimum (i.e., equilibrium) voltage of 1.33 volts. The system continued producing CO for at least 7 hours at Faradaic efficiencies greater than 96%.

Water-soluble, self-assembled nanocapsules composed of a functional bilayer membrane and enclosed guest molecules can provide smart (that is, condition responsive) sensors for a variety of purposes. Owing to their outstanding optical and redox properties, perylene bisimide chromophores are interesting building blocks for a functional bilayer membrane in a water environment. Here, we report water-soluble perylene bisimide vesicles loaded with bispyrene-based energy donors in their aqueous interior. These loaded vesicles are stabilized by in situ photopolymerization to give nanocapsules that are stable over the entire aqueous pH range. On the basis of pH-tunable spectral overlap of donors and acceptors, the donor-loaded polymerized vesicles display pH-dependent fluorescence resonance energy transfer from the encapsulated donors to the bilayer dye membrane, providing ultrasensitive pH information on their aqueous environment with fluorescence colour changes covering the whole visible light range. At pH 9.0, quite exceptional white fluorescence could be observed for such water-soluble donor-loaded perylene vesicles. Artificial vesicles consisting of encapsulated fluorescence resonance energy transfer (FRET)-donor molecules and a FRET-acceptor bilayer dye-membrane provide ultrasensitive pH information in aqueous media by displaying pH-dependent fluorescence colour covering the entire visible light range. An exceptional white fluorescence was observed at pH 9.

Attractive in theory and confirmed to exist, anion– π interactions have never really been seen at work. To catch them in action, we prepared a collection of monomeric, cyclic and rod-shaped naphthalenediimide transporters. Their ability to exert anion– π interactions was demonstrated by electrospray tandem mass spectrometry in combination with theoretical calculations. To relate this structural evidence to transport activity in bilayer membranes, affinity and selectivity sequences were recorded. π -acidification and active-site decrowding increased binding, transport and chloride > bromide > iodide selectivity, and supramolecular organization inverted acetate > nitrate to nitrate > acetate selectivity. We conclude that anion– π interactions on monomeric surfaces are ideal for chloride recognition, whereas their supramolecular enhancement by π , π -interactions appears perfect to target nitrate. Chloride transporters are relevant to treat channelopathies, and nitrate sensors to monitor cellular signaling and cardiovascular diseases. A big impact on organocatalysis can be expected from the stabilization of anionic transition states on chiral π -acidic surfaces. For quadrupole moments up to +39 Buckinghams, increasing π -acidity of aromatic surfaces is shown to cause tighter anion binding in tandem mass spectrometry experiments, higher binding energies in molecular models, stronger charge-transfer absorption bands, and increasingly effective and selective anion transport across lipid-bilayer membranes.

Hard and soft structural composites found in biology provide inspiration for the design of advanced synthetic materials. Many examples of bio-inspired hard materials can be found in the literature; far less attention has been devoted to soft systems. Here we introduce deterministic routes to low-modulus thin film materials with stress/strain responses that can be tailored precisely to match the non-linear properties of biological tissues, with application opportunities that range from soft biomedical devices to constructs for tissue engineering. The approach combines a low-modulus matrix with an open, stretchable network as a structural reinforcement that can yield classes of composites with a wide range of desired mechanical responses, including anisotropic, spatially heterogeneous, hierarchical and self-similar designs. Demonstrative application examples in thin, skin-mounted electrophysiological sensors with mechanics precisely matched to the human epidermis and in soft, hydrogel-based vehicles for triggered drug release suggest their broad potential uses in biomedical devices. Soft biological composites have great potential in areas such as artificial tissue constructs and bio-integrated devices, but receive little attention. Here, the authors design soft biomimetic materials that can precisely reproduce the non-linear mechanics of relevant biological materials.