Articles in 2025

This Review explores how ionizing radiation triggers drug release via water radiolysis, detailing reactive species, drug activation mechanisms and strategies for designing radiation-sensitive prodrugs and nanocarriers to enhance chemoradiation therapy with reduced systemic toxicity.

Proteolysis targeting chimeras (PROTACs) are an emerging platform in drug discovery with the potential to unlock novel pharmacology and tackle undruggable targets. This Review highlights learnings from the first cohort of clinical-stage PROTACs, which use short, ring-rich linkers, often complemented with one basic centre, to achieve good bioavailability and metabolic stability.

Ahead of his 80th birthday, Steven V. Ley, Professor of Chemistry at the University of Cambridge, discussed his career from drawing chemicals by hand to his work generating complex natural product architectures using machines.

In 2025, peptide research saw the convergence of chemical synthesis and computational modelling. Advances in artificial intelligence-guided design and new macrocyclic and covalent frameworks expanded structural creativity, transforming peptides into programmable molecules with functions beyond traditional design.

Epoxides, which readily undergo C–O bond cleavage, also undergo skeletal rearrangements via C–C bond activation. This Review discusses modes of epoxide C–C bond cleavage and their applications, highlighting the mechanistic features which lead to selective bond scission.

The roles of organic A-cations in halide perovskite photovoltaics are discussed from a molecular point of view by considering their chemical, lattice and electronic interactions. Prospects for future research directions, opportunities and challenges are also presented.

Unsymmetric coordination environments are prevalent in metalloenzymes. By contrast, most synthetic homogeneous catalysts rely on symmetric ligand frameworks. This Review highlights biological unsymmetric bimetallic centres along with their roles in catalysis and illustrates how intentionally incorporated unsymmetry in synthetic systems mimics nature’s strategies for achieving cooperative and complementary reactivity.

Light-responsive molecular systems, capable of interconverting between isomers using light, can be integrated into biological membranes to mimic and control their dynamic behaviour. This Review discusses the key design principles and experimental challenges while discussing and highlighting recent advances.

Molten salts have promising applications in clean energy technologies, but the hazards and dynamics of these systems complicate their chemical analysis. This year, exciting developments in equipment design and simulation accuracy and efficiency have brought these materials closer than ever to application.

Genomic therapy offers a promising strategy for addressing central nervous system disorders. This Review highlights recent advances in chemical strategies and delivery platforms, such as lipid nanoparticles, polymers and oligonucleotide conjugates, and it discusses future directions to improve the application of genomic therapy in brain disorders.

Integrative catalytic pairs are poised to redefine the boundaries of heterogeneous catalysis through programmable synergy and spatial precision. This Review outlines current advances and identifies key challenges towards realizing next-generation catalysts with molecular-level control.

As scientists, our instinct is often to view physical systems within a Euclidean geometric space, defined by distances and angles measurable through techniques like X-ray scattering and imaging. Yet, history shows that our disciplines have repeatedly adapted their mathematical languages to better process data, interpret observations and build new theories.

Targeted alpha therapy (TAT) is a growing field in medicinal chemistry owing to the ability of alpha particles to selectively deliver radiation to tumour cells. In the past year, these research efforts have resulted in clinical trials in TAT using ²²⁵Ac, ²¹²Pb, ²²³Ra, and ²¹¹At as alpha emitters.

Photochemical labelling of proteins mediated by a small organic molecule has enabled researchers to track the progress of peptides through a cell — from entry and trafficking to endocytosis.

Developing universal machine learning potentials for heterogeneous catalysis still presents challenges. Recently, an element-based potential using random exploration via imaginary chemicals was developed and predicts reactions accurately across various scenarios related to catalytic systems and materials science.

Ahead of her 73rd birthday, Lidia Morawska, Distinguished Professor at Queensland University of Technology, discusses her life as a researcher and advocate of clean air.

Fifty years ago, researchers from Beecham Pharmaceuticals reported on the structure of clavulanic acid. Itself only a weak antibiotic, clavulanic acid inhibits serine β-lactamases and thus this work pioneered combination therapy to protect antibiotics against the development of resistance.

Chimeric antigen receptor (CAR) T cells are a promising and effective cancer therapy but are difficult to regulate once implanted. This Review covers an emerging wave of small-molecule-based systems developed to control, augment and direct CAR T cell therapeutics.

Catalytic methods for converting bio-derived feedstocks into lactones are reviewed, emphasizing scalable, energy-efficient processes. Free energy analysis guides process design and pathway selection, whereas literature highlights accessible lactone precursors from various metabolic and chemo-catalytic pathways.