Volume 17 Issue 4, April 2025

Although molecular qubits offer precise, controllable design for quantum information science, their scalability remains a challenge. Now, it has been shown that photoinduced spin polarization can be transferred via hydrogen bonding pathways, enabling the fabrication of 2D arrays of molecular qubits through alternative noncovalent design strategies.

Recyclable alternatives to polyethylene plastics — that do not sacrifice its valuable properties — are highly desirable. Now, an earth-abundant manganese catalyst has transformed plant-based alcohols into polyethylene mimics that combine versatile performances with complete recyclability.

Proton pump inhibitors, commonly prescribed for excessive gastric acid secretion, may lead to unexpected side effects. Now a chemoproteomic method enables a comprehensive profiling of their off-target interactions, offering valuable insights into their mechanism of action in living cells.

Understanding the layer stacking in two-dimensional covalent organic frameworks remains a significant challenge. A study now reports the on-surface synthesis of bilayer covalent organic frameworks where the interlayer orientation — the twist angle — can be modulated through tuning the monomer structure.

Metal clusters are highly dynamic under catalytic conditions, which presents a challenge when it comes to recognizing active species. Now, the identification and categorization of metastable cluster states into ‘living libraries’ has been shown to clarify their crucial role in catalysis, pointing towards new design strategies for more efficient catalysts.

N-monofluoromethyl amides (N-CH₂F) have been challenging to prepare. Now, a general method for the synthesis of N-CH₂F amides is developed. The strategy can be applied for the N-CH₂F modification of peptides and drug derivatives. Moreover, the N-CH₂F amides are relatively stable in various media, which could be beneficial for drug development.

Mastering the synthesis of hierarchical molecular assemblies at the mesoscale—mimicking the precision of biomolecular assembly—has been challenging due to the lack of well-defined methodologies for controlling non-covalent interactions at multiple levels. In this Review, secondary nucleation is presented as a promising strategy for constructing mesoscale hierarchical structures.

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.

Bio-based polyethylene-like materials with tunable thermal and mechanical properties have been synthesized from plant-derived diols using an acceptorless dehydrogenative polymerization strategy. Now it has been shown that this atom-economical and mass-economical approach employing non-precious metal catalysts enables closed-loop recycling and advances sustainable solutions for the circular plastic economy.

Proton pump inhibitors (PPIs) are prodrugs that are activated by protonation in the highly acidic environment of the stomach lining. Now, coordination of PPIs to protein-bound zinc ions is revealed as another pathway to PPI activation. Acting as a Lewis acid, the zinc ion facilitates conjugation of the drug to zinc-coordinating cysteine residues.

On-surface synthesis of two-dimensional polymers is a useful strategy for designing the lattice, orbital and spin symmetries of materials, but controlling their layer stacking remains challenging. Now, a method to synthesize bilayer two-dimensional covalent organic frameworks at a liquid–substrate interface through monomer condensation has been developed; large-area moiré superlattices emerge from the twisted bilayer stacking.

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.

The monofluoromethyl (CH₂F) motif is valuable as it can mimic CH₃ and CH₂OH motifs frequently found in bioactive molecules, but the synthesis of N-CH₂F amides is challenging. Now the synthesis of numerous N-CH₂F amides has been achieved via successive acylation and fluorination of imines, enriching pathways for N-methylation of biomolecules.

The mutual neutralization of hydronium and hydroxide ions is a reaction of fundamental interest that has recently been implicated in the generation of high concentrations of hydroxyl radicals at the surface of water microdroplets. Using three-dimensional imaging of the coincident neutral products of the reaction of D₃O⁺ and OD⁻, two competing pathways for OH radical formation have now been experimentally observed.

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.

Although several inorganic analogues of cyclopentadiene have been reported with group-15 elements, examples featuring the heavier elements Sb and Bi remain scarce. Now, a Bi₅ ring has been stabilized between two Nb(cyclopentadienyl) units, forming a triple-decker sandwich structure; the bonding analysis indicates that a Nb–Nb bond goes through the centre of the Bi₅ plane.

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.

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.

Antibiotic resistance can be addressed by reinventing classes of antibiotics through chemical synthesis. Here BT-33—a fully synthetic antibiotic—affords broad-spectrum activity against the bacterial ribosome. X-ray crystallography, theoretical calculations and structure–activity relationship studies reveal the structural features that contribute to the enhanced antibacterial activity and metabolic stability of BT-33.

Origins-of-life research has focused on specific chemical reactions that might lead to biological molecules. Now an experimental model of chemical evolution based on oscillating water activity has been established. This system undergoes continuous chemical change, and demonstrates combinatorial compression, stringent chemical selection and synchronicity of molecular populations.

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 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.

Lithium–sulfur batteries are a promising electrochemical energy storage technology; however, they are limited by the dissolution of polysulfide intermediates. Now, it has been shown that sparingly solvating electrolytes containing a phase mediator can avoid polysulfide dissolution and accelerate surface-localized solution-phase sulfur reaction to improve battery performances.

Zoe Hoffpauir and Audrey Lamb outline the history and prospects of riboflavin, also known as vitamin B₂, a molecule found in food that is required for the formation of coenzymes involved in metabolic processes.