Photocatalysis offers a promising approach for renewable energy conversion and storage, but short lifetimes of charge-separated states in photocatalysts due to charge recombination limit its utility. Here we report an organic molecule with an acceptor–donor–acceptor configuration that can self assemble into highly crystalline nanoparticles. Transient absorption spectroscopy...
Vinylene-linked two-dimensional (2D) conjugated covalent organic frameworks, or 2D poly(arylene vinylene)s (2D PAVs), are promising polymer semiconductors for (opto-)electronics, photocatalysis and electrochemistry. However, conventional solvothermal synthesis often produces 2D PAVs that are poorly crystalline or difficult to access. Here we introduce a Mannich-elimination...
Metal-mediated chemistries now find increasing application in in vitro biomolecule modification. However, the perceived and potential toxicity of some metals has limited the application of organometallic reagents in more complex biological settings such as inside living cells. Ligands play a crucial role in modulating both the reactivity and availability of transition metals...
Targeted protein degradation modulates protein function beyond the inhibition of enzyme activity or protein–protein interactions. Most degrader drugs function by directly mediating the proximity between a neosubstrate and a hijacked E3 ligase. Here we identify pseudo-natural products derived from (−)-myrtanol, termed iDegs, that inhibit and induce degradation of the...
The catalytic enantioselective [1,2]-Wittig rearrangement of allylic ethers constitutes a recognized synthetic challenge as it is traditionally considered to arise from a non-concerted reaction pathway via formation and recombination of radical pairs. Here we show a catalytic enantioselective solution to this challenge, demonstrating that [1,2]-Wittig products are generated via...
Motifs related to 1,2-diols and 1,2-amino alcohols are found widely in bioactive natural products, drugs and agrochemicals. These highly sought-after substructures would ideally be constructed by the direct addition of alcohols to the C=C bond of alkenes, both common substrate classes in chemical synthesis. However, their direct union is only possible if one of the pair can be...
Metal (hydro)oxides are among the most effective heterogeneous water oxidation catalysts. Elucidating the interactions between oxygen-bridged metal sites at a molecular level is essential for developing high-performing electrocatalysts. Here we demonstrate that adjacent metal-hydroxyl groups function as intramolecular proton–electron transfer relays to enhance water oxidation...
Controlling surface chemistry at the nanoscale is essential for stabilizing structure and tuning function in plasmonic, catalytic and sensing systems, where even trace ligands or ions can reshape surface charge and reactivity. However, probing such dynamic interfaces under operando conditions remains challenging, limiting efforts to engineer nanomaterials with precision. Here...
Designing single molecules that compute general functions of input molecular partners is a major unsolved challenge in molecular design. Here we demonstrate that high-throughput, iterative experimental testing of diverse RNA designs crowdsourced from the online game Eterna yields sensors of increasingly complex functions of input oligonucleotide concentrations. After designing...
Lariat-shaped lipopeptides are important antimicrobial agents; however, their complex structures pose synthetic challenges that hamper efficient structural diversification. Here we report a new chemoenzymatic approach that facilitates access to lariat-shaped macrocycles. Unprotected, branched peptides bearing multiple nucleophiles, including a native amino terminus and a pseudo...
Covalent inhibitors that do not rely on hijacking enzymatic activity have mainly been limited to those targeting cysteine residues. The development of such cysteine-directed covalent inhibitors has greatly profited from the use of competitive residue-specific proteomics to determine their proteome-wide selectivity. Several probes have been developed to monitor other amino acids...
Azetidine, a four-membered aza-cycle, is a crucial structure in many bioactive compounds and drugs. However, their biosynthesis is frequently enigmatic. Here we report the mechanism of azetidine amino acid (polyoximic acid) biosynthesis in the polyoxin antifungal pathway. Genetic, enzymological and structural experiments revealed that PolF is a member of haem-oxygenase-like...
Living cells understand their environment by combining, integrating and interpreting chemical and physical stimuli. Despite considerable advances in the design of enzymatic reaction networks that mimic hallmarks of living systems, these approaches lack the complexity to fully capture biological information processing. Here we introduce a scalable approach to design complex...
RNA condensation is implicated in the formation of neurotoxic RNA foci in cells affected by genomic expansions of trinucleotide or hexanucleotide repeats. However, the biophysical properties of repeat-expansion RNA condensates are poorly understood. Using CAG repeat-expansion RNA as a model system, we show that these RNA condensates cannot be observed with conventional nuclear...
Organic transformations mediated by the transient formation of iminium ions have shown remarkable synthetic potential for the construction of enantioenriched molecules. The possibility to access their first singlet excited state (S1) under light irradiation has led to the development of previously inaccessible transformations. However, the triplet state (T1) reactivity remains...
Photocatalytic proximity labelling has emerged as a powerful tool to resolve a variety of biomolecular and cellular interactions. Although the use of high-resolution probes, such as diazirines, enables cell-surface protein labelling with nanometre precision, intracellular applications are limited by either the intrinsic toxicity of metal-based photocatalysts or by the lower...
Pharmacological activation of STING holds promise in cancer treatment. A recent trend is the development of tumour-specific or conditionally activated STING agonists for enhanced safety and efficacy. Here we explore an unconventional prodrug activation strategy for on-tumour synthesis of a potent agonist. Leveraging the unique mechanism of MSA2, a small-molecule agonist that...
Proton transfer plays an important role in both hydrogen and oxygen evolution reactions during electrocatalytic water splitting to produce green hydrogen. However, directly adapting the conventional proton/deuterium kinetic isotope effect to study proton transfer in heterogeneous electrocatalytic processes is challenging. Here we propose using the shift in the Tafel slope between...
[2,1]-Azaboranaphthalenes represent unique boron–nitrogen (BN) isosteres of naphthalenes, attracting interest for the development of molecules with enhanced therapeutic potency. The existing synthetic strategies are generally two-component reactions with harsh conditions. Here we report an organocatalysed three-component modular synthesis of ring-fused BN isosteres and BN-2,1...