Aggregation can profoundly alter the excited-state properties of organic chromophores; however, crystalline supramolecular polymers are often targeted for photocatalytic conversion of solar energy due to favourable charge delocalization or exciton transport. Here we exploit aggregation as a strategy for organic chromophore rigidification to activate photocatalysis by stabilizing...
Reconstructing cellular complexity is a central challenge in synthetic biology, with profound implications for understanding life and advancing bio-inspired nanotechnologies. A critical step towards this goal is replicating the dynamic interplay among membrane components and their functions. Here we demonstrate a double-necked synthetic cell microreactor (DCM) that incorporates...
The development of single-molecule magnets for high-density data storage has advanced from poly(metallic) cages to lanthanide complexes. Since 2017, highly axial dysprosium bis(cyclopentadienide) complexes have demonstrated exceptional energy barriers to magnetic reversal (Ueff) and high hysteresis temperatures (TH), with further enhancement achieved in 2025 using bulky amide...
Amino acids are one of nature’s most privileged building blocks for generating molecular diversity on length scales ranging from small molecules to proteins. While amino acid products arising from certain class-defined biosynthetic pathways can be found with established bioinformatic strategies, those that fall outside of these types remain difficult to identify. Here, to address...
Hydrophobicity controls many aspects of protein and enzyme function. Although hydrophobic tuning can be somewhat achieved with canonical amino acids, the incorporation of non-canonical amino acids further extends this ability to enable new and improved functionality. Here we engineer an aminoacyl-tRNA synthetase/tRNA pair for the site-specific genetic encoding of a set of bulky...
Histone modifications, including Nε-lysine acetylation and methylation, play critical roles in the regulation of eukaryotic transcription. The addition of acetyl and methyl groups and removal of acetyl groups to histones involve redox-neutral reactions. Demethylation is O2-dependent, as reported for reactions catalysed by the 2-oxoglutarate-dependent hypoxia-inducible factor (HIF...
Photocatalytic overall water splitting holds great promise for sustainable hydrogen production. For overall water splitting performed by one-step excitation, both the hydrogen evolution and oxygen evolution reactions are hindered kinetically; hence, it is necessary to employ site-selective modification of photocatalysts with hydrogen-evolving and oxygen-evolving cocatalysts...
Cyclic peroxides are highly reactive oxygen-containing species that play important roles in chemical synthesis, yet, aside from dioxiranes (R2CO2), well-defined cyclic peroxides of main-group elements remain rare. In particular, cyclic peroxides featuring boron–oxygen frameworks have not been explored. Here we show that boron peroxides can be prepared directly from accessible...
For chemical probe and drug discovery campaigns, the pairing of mass spectrometry-based chemoproteomics with photoaffinity labelling has emerged as a favoured approach for target discovery and mode of action assignment. However, photocrosslinked peptide-compound adducts raise analytic challenges for quantitative binding site discovery. Here, to address these challenges, we...
Modifying glass compositions is key to creating silicate-based glasses for technologies including optical fibres, catalytic supports, protective coatings and separation membranes. Here we extend this concept to metal–organic framework (MOF) glasses by modifying the MOF glass former ZIF-62 with Li(bim) and Na(bim) as compatible glass modifiers (benzimidazolate, bim−). Melt...
Although naphthalene motifs are frequently encountered in drugs and lead compounds, their flat, sp2-rich nature and susceptibility to cytochrome P450-mediated metabolism often limit their developability. Here we report the study of derivatizable aryl-fused bicyclo[3.1.1]heptanes (BCHeps) as sp3-rich bioisosteric replacements for naphthalene and other fused bicyclic (hetero...
Cell-free enzymatic reaction networks (ERNs) enable the production of value-added compounds in a single reaction. However, allosteric interactions, product inhibition, reversibility and competition for shared cofactors only become apparent once the ERN is assembled. These emergent dynamics create kinetic barriers that limit the overall yield. Here we introduce a model-guided...
In biomacromolecules, many amino acids or nucleotides are needed to obtain defined secondary structures and concomitant advanced functionalities. However, when researchers generate synthetic model analogues composed of dyes to predict the (photo-)functional properties of the respective solid-state aggregates they often use dimer models. Here we introduce a foldamer series of...
Peptide aggregation is a long-standing challenge in chemical peptide synthesis, limiting its efficiency and reliability. Although data-driven methods have enhanced our understanding of many sequence-based phenomena, no comprehensive approach addresses so-called non-random difficult couplings (generally linked to aggregation) during solid-phase peptide synthesis. Here we leverage...
Targeted protein degradation can intervene with the function of disease-related proteins, but most current approaches rely on direct ligand engagement of a protein target, limiting their applicability to proteins that are difficult to bind selectively. Here we present a conceptually unique approach to degrade proteins associated with DNA G-quadruplex (G4) secondary structures in...
Fluorochemicals improve our quality of life; however, there is increasing concern over how they are produced and their negative effects on health and the environment. Here we report an approach to the recycling of fluorochemicals. Treatment of hydrofluorocarbons with a potassium base (KHMDS or KOtBu) results in rapid defluorination to produce anhydrous potassium fluoride. This...
[n.1.1]Propellanes are key precursors to bicyclo[n.1.1]alkanes, rigid small-ring hydrocarbons that have emerged as important building blocks in contemporary drug design as bioisosteres for disubstituted benzene rings. [n.1.1]Propellanes featuring heterocyclic rings could enable the direct synthesis of a wide diversity of bridged bicyclic heterocycles, which should exhibit...
Constructing ubiquitous bridged bicyclic scaffolds from simple aliphatic feedstocks via multiple C(sp3)–H functionalizations is a significant challenge in organic synthesis, demanding powerful catalysts capable of precise selectivity control. Here we demonstrate a catalytic system that enables abundant cyclic carboxylic acids to couple with dienophiles in a formal Diels–Alder...
Long-chain nitrogen ions and radicals ([Nn]x+/[Nn]x−, n > 3) are naturally occurring under the intense radiative conditions of the Earth’s ionosphere and those of other planetary bodies. However, the strong thermodynamic driving force to lose N2 renders these types of molecule extremely reactive under ambient conditions such that they can typically be studied only under extreme...
Electron transfer through molecular wires underpins numerous research fields, ranging from single-molecule electronics to fundamental biological processes and their application in (bio)electrocatalysis. Here we report a series of 1–3-nm-long ferrocene-terminated conjugated molecular wires, anchored to indium tin oxide electrodes, that exhibit an electron transfer mechanism...
Understanding the electric double layer (EDL) of stepped Pt electrodes is crucial for comprehending the reaction environment for electrocatalytically relevant Pt electrodes, which typically comprise a complex mixture of facet orientations, steps and defects. Here we systematically investigate the EDL structure of these surfaces by periodically perturbing (111) terraces by either...
Electrochemical gradients are essential to the functioning of cells and form across membranes using active transporters. Here we show in contrast that condensed biomolecular systems—often termed condensates—sustain pH gradients without any external energy input. By studying individual condensates on the micrometre scale using a microdroplet platform, we reveal dense-phase pH...
Alkenes typically have trigonal planar geometries at each terminus, with favourable σ- and π-bonding leading to a bond order of ~2. Here we consider unusual alkenes that possess an extreme form of geometric distortion, termed hyperpyramidalization. In a hyperpyramidalized alkene, geometries deviate remarkably from the typical trigonal planar alkene geometry, leading to weak π...