Browse Articles

The biomolecular principles underlying the formation of multiphasic condensates have been difficult to elucidate owing to a paucity of tools, especially within living cells. In this work synthetic orthogonal protein scaffolds alongside molecular simulations are used to highlight how the oligomerization of disordered proteins can asymmetrically drive miscibility–immiscibility transitions.

A method for carbon isotope exchange involving a metal-catalysed metathesis reaction of in situ formed acyl chlorides is demonstrated. The platform provides access to ¹³C- or ¹⁴C-enriched carboxylic acids, including natural products and pharmaceuticals, without the need for radioactive gases, using a single carboxylic acid carbon donor.

Actinide–metal multiple bonds are relatively rare, with isolable examples under normal experimental conditions typically restricted to complexes containing a polar covalent σ bond supplemented by up to two dative π bonds. Now complexes featuring polar covalent double and triple bonds between thorium and antimony have been synthesized.

New drug leads can be developed through modification of a natural product’s framework, but this is possible only if the compound is abundant and contains modifiable moieties. Now a strategy is introduced for accessing a scarce indole alkaloid and several expanded, contracted and distorted analogues, one of which shows anti-cancer activity.

The design of open-shell nanographenes is commonly limited to systems featuring a single magnetic origin. Now a strategy that combines topological frustration and electron–electron interactions has been developed to generate a butterfly-shaped nanographene that hosts four highly entangled π-spins and exhibits both ferromagnetic and anti-ferromagnetic coupling.

Valence tautomerism in lanthanide-based materials is rare. Now a one-dimensional samarium–pyrazine polymer has been shown to exhibit a temperature-induced hysteretic Sm(III)-to-Sm(II) reversible switch. The transition temperature is modulated in a 150 K window by alloying with Yb(II), presenting a strategy for developing new materials with chemically tunable magnetic switchability.

The preparation of ¹⁴C-labelled compounds is a crucial step in pharmaceutical development but typically requires using toxic, radioactive gases. Now a broadly applicable functional group metathesis reaction has been developed that forms ¹⁴C-labelled carboxylic acids in one pot, without added gases, via dynamic exchange with an easily handled carboxylic acid ¹⁴C source.

Replicating the ability of enzymes and transport proteins to effectively bind anions is a considerable challenge for supramolecular chemists. A neutral organic cage has now been developed that selectively binds sulfate anions in water.

Lipidomics aims to uncover lipid functions in biological systems and disease. Quantifying lipids is challenging due to highly diverse chemical structures. Here a diazobutanone-assisted isobaric labelling method is developed that relies on diazobutanone and isobaric mass tags to target phosphate- and sulfate-containing lipids, enabling multiplexed lipidomic quantification in complex mixtures.

Design strategies that possess both biological relevance and structural diversity may lead to compound collections that are enriched in diverse bioactivities. Now a diverse pseudo-natural product design principle has been established to efficiently explore biologically relevant chemical space. Through dearomatization reactions, a compound collection enriched in both structural and biological diversity was rapidly generated.

Covalent protein conjugation facilitates the study of biological processes and the synthesis of therapeutic biomacromolecules. A method that uses vinyl thianthrenium reagents for the site-selective formation of highly reactive episulfonium species on proteins is demonstrated. These in situ-formed intermediates react with diverse nucleophiles, providing access to protein conjugates in one step without purification.

Molecules containing a chiral S(VI) moiety have found extensive applications in drug design and organic synthesis, despite a lack of diverse asymmetric methods for their creation. Now, a ligand-mediated process has enabled the production of enantioenriched S(VI)–F motifs, providing a foundation for further stereospecific elaborations.

Although surface-bound molecular catalysts offer well-defined active sites on heterogeneous supports, it is challenging to identify key radical intermediates in the reaction mechanism. Now, a characterization method has been developed that combines film electrochemistry and EPR spectroscopy to track radical intermediates in real time, exemplified by alcohol oxidation with a surface-immobilized nitroxide.

The mechanism for the oxidative addition of aryl halides to nickel(0)–phosphine complexes was proposed over four decades ago. Now, this elementary reaction, which occurs during common cross-coupling reactions, has been re-examined. Both one- and two-electron pathways occur, and their relative contribution depends on the electronic properties of the reaction partners.

Chirality is an intrinsic property in unsymmetric three-dimensional molecular assembly, contributing to the utility of the corresponding process and the resulting scaffolds. Now, on the sulfur(VI) hub, a three-step sequential ligand-exchange method has been established with precise stereocontrol, enabling the enantioselective synthesis of optically active S(VI) functional molecules.

The use of biocatalysis to support early-stage drug discovery campaigns remains largely untapped. Here, engineered biocatalysts enable the synthesis of sp³-rich polycyclic compounds through an intramolecular cyclopropanation of benzothiophenes, affording a class of complex scaffolds potentially useful for fragment-based drug discovery campaigns.

Very few charge-neutral synthetic anion receptors can function in water, and those known typically select weakly hydrated anions such as iodide. Now a neutral molecular cage capable of donating 12 hydrogen bonds has been synthesized and found to bind highly hydrated sulfate in water with a strong selectivity over weakly hydrated anions.

A protein-templated selection approach has been developed for the discovery of full ligands from dual-pharmacophore DNA-encoded libraries by incorporating fragment linking into the selection process. The performance of this method was demonstrated with selections against protein–protein interaction and protein–DNA interaction targets, through which potent and selective inhibitors were identified.

Achieving selectivity control in allylic arylations is a long-standing challenge in catalysis. Now a rhodium-catalysed system demonstrates chemo-, regio- and enantioselectivity, enabling Suzuki–Miyaura-type arylation with racemic, non-symmetrical, acyclic allylic systems; chelation is speculated to facilitate oxidative addition and enable both enantiomers of the starting material to converge onto a single product.