Articles

Photoinduced electron transfer (PET) occurs in many chemical processes and has various applications. Here ionizing radiation was used to trigger PET for controlled drug release from an antibody–drug conjugate using a picolinium cage. The radiotherapy-activated prodrug system demonstrated high antitumour efficacy and minimal side effects.

Key molecular features that drive protein liquid–liquid phase separation (LLPS) for biomolecular condensate have been reported. A spectrum of additional interactions that influence protein LLPS and material properties have now been characterized. These interactions extend beyond a limited set of residue types and can be modulated by environmental factors such as temperature and salt concentration.

Negatively charged lysine acylations—malonylation, succinylation and glutarylation—impact protein structure and function, which can affect cellular processes. Now temporarily masked thioester derivatives of succinylation and glutarylation can be used for site-specific modification of diverse bacterial and mammalian proteins, which can facilitate the study of how these lysine modifications impact enzymatic activity and control protein–protein and protein–DNA interactions.

Accessing longer-wavelength emitting organic fluorophores is critical for diagnostic imaging. Here a series of silicon-RosIndolizine fluorophores with emission maxima at 1,300 nm, 1,550 nm and 1,700 nm were synthesized. The fluorophores generate high-resolution in vivo fluorescence images in mice and establish design principles for future shortwave-infrared fluorophore designs.

Although the light-driven generation of hydrogen from water is a promising approach to renewable fuels, the H–H bond formation step represents a persistent mechanistic question. Now light-harvesting molecular catalysts have been shown to self-assemble into nanoscale aggregates that feature improved efficiency for photoelectrochemical H₂ evolution.

Time-resolved femtosecond crystallography (TR-SFX) is a powerful technique to monitor structural transitions in protein crystals at the atomic level, but its use in non-protein synthetic materials remains limited. Now TR-SFX has been used to visualize the structural dynamics of metal–organic frameworks, showing the potential of this tool to study the dynamic motion of crystalline porous materials.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) can have vast structural diversity and biological functions enabled by disparate post-translational modifications (PTMs). However, unconventional PTMs derived from non-RiPP biosynthesis are rarely reported. Now a class of lipopeptides featuring a distinct fatty-acyl-modified N terminus and the responsible RiPP/fatty-acid hybrid biosynthetic machinery have been characterized.

Enantioenriched α-disubstituted α-ethynylamines are valuable synthons to chiral α-tertiary amines and azacycles, but their facile access remains challenging. Now, sterically confined pyridinebisoxazoline ligands have been developed to facilitate highly enantioselective Cu(I)-catalysed propargylic amination of both aliphatic and aryl ketone-derived propargylic carbonates to give α-tertiary ethynylamines. Related tandem sequences are reported to synthesize quaternary azacycles.

The spontaneous recombination of photogenerated radicals surrounded by solvent molecules is an important energy-wasting elementary step in photoredox reactions. Now the decisive role that cage escape plays in these reactions is shown in three benchmark photocatalytic reactions, with quantitative correlations observed between photoredox product formation rates and cage escape quantum yields.

High-throughput proteome-wide methods for identifying endogenous proteins that phase separate or partition into condensates during certain physiological events are needed but remain a challenge. Now, a high-throughput, unbiased and quantitative strategy can identify endogenous biomolecular condensates and screen proteins involved in phase separation on a proteome-wide scale.

The underlying mechanism for how heterotypic protein–RNA interactions modulate the liquid to amyloid transition of hnRNPA1A, a protein involved in amyotrophic lateral sclerosis, has so far remained elusive. Now characterization of hnRNPA1A condensate formation and aggregation in vitro reveals that the RNA/protein stoichiometry affects the molecular pathways leading to amyloid formation.

The insertion of metal atoms and heteroaromatic units provides a way to tune the optical, electronic and magnetic properties of graphene nanoribbons. Now the synthesis of a porphyrin-fused graphene nanoribbon with a narrow bandgap and high charge mobility has been achieved, and this material used to fabricate field-effect and single-electron transistors.

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.