Research articles

Formation of biomolecular condensates composed of proteins and RNA facilitates the regulation of gene expression by modulating translation or facilitating RNA processing. Now, synthetic ribonucleoprotein granules created with engineered intrinsically disordered proteins selectively sequester mRNA and enhance protein translation in cells. These highly liquid-like condensates exchange biomolecules across the cell and facilitate target mRNA and ribosome partitioning.

Preliminary clinical trials suggest that ibogaine and its active metabolite noribogaine have powerful anti-addictive properties, Now, a strategy for the scalable, asymmetric total synthesis of ibogaine has been developed that also provides access to iboga analogues. Biological testing identified a psychoplastogenic iboga analogue that is a potent modulator of the serotonin transporter.

CO₂ electroreduction to higher-value carbons can occur through adsorbed hydrogen or through proton-coupled electron transfer from water. Understanding the impact of each route on product selectivity is challenging. Now H/D isotopic labelling reveals the contribution of each mechanism towards product formation and shows that adsorbed hydrogen dominates the reaction.

Perovskite solar cells often rely on ordered molecular contacts for favourable charge-carrier transport, and any organizational disruption reduces device efficiency. Now a contact featuring an orthogonal π-skeleton has been shown to afford a high resilience to external stimuli plus long-term durability in accelerated-ageing tests.

Substituted bicyclo[1.1.1]pentanes (BCPs) are widely used as bioisosteres for para-substituted phenyl rings, providing improved pharmacological profiles for drug candidates, but strategies for the preparation of chiral BCPs remain limited. Now a route to chiral bridge-substituted BCPs has been developed via a nitrogen-atom insertion-and-deletion strategy, enabling a practical avenue towards chiral BCP bioisosteres of lomitapide.

Molecular approaches in quantum information science are highly promising, but the synthesis and scale-up of suitable covalently linked moieties represent major challenges. Here it is demonstrated that efficient spin mixing between photogenerated spin centres is possible through hydrogen bonds, advancing supramolecular chemistry as a valuable tool to address these challenges.

Solvent-mediated interaction networks control a wide range of protein functions, but their design has been neglected owing to a lack of accurate computational tools. Now it is shown that allosteric signalling membrane proteins can be engineered through such networks, revealing a broader space of designable protein interactions and functions.

Understanding ligated metal clusters’ reactivities is challenging. Now, a methodology has been developed to explore dynamic mixtures of metal clusters. Interrelated cluster populations are constructed through organometallic precursor chemistry. Structural information on mixed-metal systems is obtained with a bias-free computational framework, and reactivities towards CO₂ and alkynes are investigated in situ.

Due to the inert C_Ar–NO₂ bond, direct denitrative substitution reactions with unactivated nitroarenes are challenging. Now, using visible-light irradiation, a strategy has been developed to enable direct aromatic denitrative chlorination. Chlorine radicals can replace the NO₂ moiety in a wide range of unactivated nitroarenes as well as nitroalkenes.

The tailoring of reticular materials is key for enhancing the complexity and diversity of their structure and function. Now, a series of isomeric pillar-layered metal–organic frameworks with tunable topologies have been prepared through altering the layer stacking, which enables variability on the backbone structure, pillar spatial arrangements and pore structure.

The chemistry of precious-metal-based open-shell mononuclear complexes remains underdeveloped. Now it has been shown that iridium metalloradicals enable Ir(II)/Ir(IV) redox cycles and catalyse olefin isomerization more efficiently than their more commonly used closed-shell analogues, which typically operate through Ir(I)/Ir(III) or Ir(III)/Ir(V) cycles.

All-metal aromatic monocycles are still rare, in contrast to their ubiquitous organic counterparts, because metal atoms tend to form clusters with multiply bonded atoms instead. Now a planar aromatic Bi₅^− ring has been synthesized as part of a mixed-valence Co⁰/Co^I inverse-sandwich-type complex.

Vibrational weak and strong light–matter coupling in infrared nanocavities modifies chemical processes. Now it has been shown that this coupling can control thermally driven reactions through enhanced radiative energy transport.

Amyloid fibrils grow through the recruitment of soluble monomer to the fibril end that propagates the fibril structure. Here the transition state, the rate-limiting conformation, of such a reaction has been characterized by Φ-value analysis. An energy landscape model has been developed and fibril growth rates predicted from first principles.

The demand for large, position-specific modified RNA molecules is high across diverse fields. Now a DNA polymerase has been engineered to enable the efficient and flexible synthesis of such molecules using a pause–restart strategy. This methodology can be implemented in both liquid and hybrid solid–liquid phases.

Natural vesicles typically consist of a lipid membrane enclosing substances. Now a coacervate vesicle formed by liquid–liquid phase separation of cholesterol-modified DNA and histones has been developed. Unlike traditional vesicles, these lack a membrane and feature a high-density liquid layer around a water-filled cavity, offering enhanced kinetic stability and potential as a biopharmaceutical delivery system.

G protein-coupled receptors and their effectors can now be released directly from a lipid bilayer using infrared irradiation for proteoform-level characterization by native top-down mass spectrometry. This represents a critical development for drug discovery, as the direct role of post-translational modifications in protein–protein and protein–drug interactions can be characterized.

The co-crystallization of nanoclusters with functional organic molecules can provide access to superlattices with unique properties, but this process remains synthetically challenging. Now it has been shown that silver nanoclusters and organic macrocycles can be assembled through a supramolecular approach into ionic co-crystals with tunable structures and large chiroptical effects.

Synthetic nanocages that can adapt the size and shape of their cavity in response to a given guest have potential applications in various areas, including chemical purification. Now a flexible, pseudo-cubic metal–organic cage has been developed that is able to dynamically expand its cavity from 46% to 154% of its initial volume by flipping its cage faces.

Three-dimensional covalent organic frameworks hold great potential for diverse applications, but their structural diversity is constrained by the synthetic approaches available. Now it is shown that ‘eight-connected’ building blocks with reduced symmetry enable the synthesis of such frameworks with rare topologies and enhanced gas adsorption performance.