Research articles

Although hydrogels with complex, heterogeneous and reconfigurable structures are promising materials for use in intelligent systems, fabricating such hydrogels is challenging. Now it has been shown that they can be fabricated by reversibly gluing different hydrogel units using a photocontrolled metallopolymer adhesive. This method can be used to design hydrogels with customized functions.

Atomistic simulations have a broad range of applications from drug design to materials discovery. Machine learning interatomic potentials (MLIPs) have become an efficient alternative to computationally expensive ab initio simulations. Now a general reactive MLIP (called ANI-1xnr) has been developed and validated against a broad range of condensed-phase reactive systems.

A previous investigation of the anti-aromatic dianion of [18]annulene concluded that it consists of a mixture of two isomers. Now it has been shown that this dianion exists as a single isomer, with a different geometry from neutral [18]annulene, and that it can be reduced further to an aromatic tetraanion.

The rapid generation of molecular complexity from a given molecular scaffold is crucial to drug discovery and development. Now the chemodivergent molecular editing of indoles using fluoroalkyl carbenes has been developed to modularly access four different types of fluorine-containing N-heterocyclic compound with high molecular complexity.

Electrolysers can upgrade CO₂ into high-value chemicals, but there are few tools capable of tracking the reactions that occur within these devices during operation. Now an electrolysis optical coherence tomography platform has been developed to visualize the electrochemical conversion of CO₂ to CO, plus the movement of components, within the device.

Developing a generalizable method for blocking and rescuing tryptophan (Trp) interactions would enable the gain-of-function manipulation of various Trp-containing proteins but has so far been challenging. Now a genetically encoded N¹-vinyl-caged Trp capable of rapid and bioorthogonal decaging enables site-specific activation of Trp on a protein of interest within living cells.

Although photoinduced concerted multiple-bond-rotation processes are known in photoactive biological systems, the synthesis of compounds exhibiting similar behaviour has proven challenging. Now a thioamide-based system featuring chalcogen substituents has been shown to exhibit photoinduced C–N/C–C rotation; the rotation mode can be switched depending on external stimuli such as temperature and light irradiation.

While chlorinated compounds are ubiquitous in chemical synthesis, they have a negative impact on human health and the environment. Now, a sustainable tandem catalytic process has been developed that uses chlorine-containing waste as chlorination reagents. This approach represents a promising way for the viable management of chlorinated compounds.

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.

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.

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.

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.