Many subcellular compartments are biomolecular condensates made of multiple components, often including several distinct proteins and nucleic acids. However, current tools to measure condensate composition are limited and cannot capture this complexity quantitatively because they either require fluorescent labels, which can perturb composition, or can distinguish only one or two...
The sluggish kinetics of the oxygen evolution reaction are an energetic bottleneck for green hydrogen production via water electrolysis. The reaction proceeds over a surface that undergoes (frustrated) phase transitions to accommodate bias-dependent excess charge. Here we perform Arrhenius analysis of common catalysts and correlate the activation energy and pre-exponential factor...
The flexible and modular design of synthetic cells, comprising lipid vesicles capable of imitating the structure and function of living cells, facilitates their application as drug delivery devices. The ability to control the synthesis of biomolecules within synthetic cells using a tissue-penetrating stimulus opens up additional levels of functionality that has the potential to...
The ability to selectively edit organic molecules at the atomic level has the potential to streamline lead discovery and optimization in the pharmaceutical and agrochemical industry. While numerous atom insertion and deletion reactions have recently been reported, examples of single atom swaps remain scarce due to the challenge of orchestrating the selective cleavage and...
Controlling quantum spins using electric rather than magnetic fields promises substantial architectural advantages for developing quantum technologies. In this context, spins in molecular magnets offer tunability of spin–electric couplings (SECs) by rational chemical design. Here we demonstrate systematic control of SECs in a family of Mn(II)-containing molecules by varying the...
Non-covalent interactions are central to the organization of matter and molecular recognition processes, yet they are difficult to characterize. Here we devise a platform strategy to systematically build non-covalent interactions with selective chemical groups into precisely designed configurations by using metal–organic frameworks (MOFs) as the molecular scaffold. Using the...
Photochemistry involves elementary steps in which single electrons are transferred, but artificial photosynthesis requires multi-electron reactions. This discrepancy necessitates light-driven charge accumulation, which has so far proved very difficult to achieve without sacrificial redox reagents. Here we report a molecular donor–photosensitizer–acceptor compound in which light...
Among all enzymatic metallocofactors, those found in nitrogenases, the P and L or M clusters, stand out for their intricate structures. They are assembled by proteins of the Nif gene cluster from Fe2S2 rhombs—the smallest building blocks in FeS cluster chemistry—through a sequence of reactions constructing a Fe8S8 precursor. To advance our understanding of how enzymes selectively...
Natural, covalently modified cytosine bases within genomic DNA function as important epigenetic markers. Approaches for single-base-resolution sequencing of cytosine modifications typically deploy chemistry for modification-selective C-to-T code conversion and can require error-prone subtractive analysis of complex data. Here we report the sequencing of an epigenetic base by...
Protein phosphorylation is a central signalling mechanism in eukaryotic cells. The scope of this post-translational modification includes protein pyro- and polyphosphorylation. Here we report the discovery of another mode of phosphorylation: protein oligophosphorylation. Using site-specifically phosphorylated and pyrophosphorylated nucleoside diphosphate kinase A (NME1), the...
Quadrupolar dyes, such as acceptor–donor–acceptor molecules, are highly relevant for applications in nonlinear optics and photovoltaics. They are also versatile models for exploring photoinduced charge-transfer dynamics. The interplay between electronic and vibronic couplings in these molecules may break excited-state symmetry, resulting in intramolecular charge separation and...
Since the early days of space exploration, the efficient production of oxygen and hydrogen via water electrolysis has been a central task for regenerative life-support systems. Water electrolysers are, however, challenged by the near-absence of buoyancy in microgravity, resulting in hindered gas bubble detachment from electrodes and diminished electrolysis efficiencies. Here we...
Aggregation of microtubule-associated protein tau into conformationally distinct fibrils underpins neurodegenerative tauopathies. Fluorescent probes (fluoroprobes) such as thioflavin T have been essential tools for studying tau aggregation; however, most of them do not discriminate between amyloid fibril conformations (polymorphs). This gap is due, in part, to a lack of high...
Quantum-mechanical simulations can offer atomic-level insights into chemical processes on surfaces that are crucial to advancing applications in heterogeneous catalysis, energy storage and greenhouse gas sequestration. Unfortunately, achieving the accuracy needed for reliable predictions has proven challenging. Density functional theory, widely used for its efficiency, can be...
The existence and intermediacy of halogen-substituted silylium ions have been the subject of speculation for decades. These elusive reactive intermediates are synthetically attractive because of their computationally predicted super Lewis acidity and their relevance in several synthetic transformations such as recycling of waste from the Müller–Rochow process and...
Optical control of electron spin states is important for quantum sensing and computing applications, as developed with the diamond nitrogen vacancy centre. This requires electronic excitations, excitons, with net spin. Here we report a molecular diradical where two trityl radical groups are coupled via a meta-linked fluorene bridge. The singlet exciton is at lower energy than the...
The most popular and universally predictive protein simulation models employ all-atom molecular dynamics, but they come at extreme computational cost. The development of a universal, computationally efficient coarse-grained (CG) model with similar prediction performance has been a long-standing challenge. By combining recent deep-learning methods with a large and diverse training...
Chiral catalysts that can engage multiple substrates, via distinct ground-state activation modes, to deliver enantioenriched products with high levels of fidelity are often described as ‘privileged’. Achieving generality in excited-state processes remains challenging, and efforts to identify privileged chiral photocatalysts are being intensively pursued. Aluminium–salen complexes...
The well-defined catalytic conversion of dinitrogen (N2) to ammonia (NH3) by molecular complexes is of fundamental interest and important for providing an atomic-level understanding of reactivity that can be related to industrial and biological nitrogen-fixation processes. Molecular catalytic N2 to NH3 conversion currently involves the reduction and protonation of terminal or...
Efficient sunlight-to-energy conversion requires materials that can generate long-lived charge carriers upon illumination. However, the targeted design of semiconductors possessing intrinsically long lifetimes remains a key challenge. Here using a series of transition metal oxides, we establish a link between carrier lifetime and electronic configuration in transition metal-based...
DNA-encoded libraries (DELs) are useful for hit discovery in the pharmaceutical industry. Although a large number of individually coded molecules are accessible through DELs, their structural diversity is limited because few transformations are benign and chemoselective enough to be applied in the presence of DNA in aqueous environments. In particular, C–H functionalization...
Information propagation by sequence-specific, template-catalysed molecular assembly is a key process facilitating life’s biochemical complexity, yielding thousands of sequence-defined proteins from only 20 distinct building blocks. However, exploitation of catalytic templating is rare in non-biological contexts, particularly in enzyme-free environments, where even the template...
Post-translational modifications such as phosphorylation and acetylation are often minor structural modifications that can have profound effects on protein structure and thus broaden protein functions. Nevertheless, studying these effects directly is often out of reach because no general chemistry exists to introduce small modifications selectively; either a large, stable linker...
RNA replication is considered a key process in the origins of life. However, both enzymatic and non-enzymatic RNA replication cycles are impeded by the ‘strand separation problem’, a form of product inhibition arising from the extraordinary stability of RNA duplexes and their rapid reannealing kinetics. Here we show that RNA trinucleotide triphosphates can overcome this problem...