JNII40 is a bis(pyridine-2-carboxamidine) ligand with potent antiparasitic activity that preferentially targets AT-rich DNA. Here, the authors use NMR spectroscopy to elucidate the high-resolution structure of JNII40 bound to AT-rich DNA, revealing direct interactions between amidine protons and DNA phosphate oxygens that explain its affinity and selectivity.

While autoinhibited architectures of talin are known from cryo-electron microscopy, its behaviour in solution has remained underexplored. Here, the authors use size-exclusion chromatography coupled with in-line small-angle X-ray scattering, Monte Carlo modeling and AlphaFold predictions to determine the conformational landscape of full-length talin in solution, showing that this cytoplasmic adapter protein does not adopt a single compact structure but instead populates a broad, flexible conformational ensemble characterized by R3 subdomain repositioning and partial F3-R9 subdomain disengagement.

Overoxidation remains a selectivity challenge in direct benzylic C–H bond hydroxylation. Here, the authors present an electrochemical method using water as the hydroxyl source and N-methyl-2-pyrrolidone as a co-solvent, effectively suppressing overoxidation without external oxidants or metal catalysts.

Artificial intelligence is transforming drug discovery by enabling the generation of novel molecules with tailored properties, however, most generative efforts focus on physicochemical features or target binding, leaving phenotypic discovery largely unexplored. Here, the authors introduce an integrated framework combining high-throughput cytotoxicity screening with bioactivity signature-based machine learning predictors and reinforcement learning-driven generative models to create small molecules with selective cytotoxic activity in pancreatic cancer cells.

Most quantitative RNA detection methods depend on enzymatic reverse transcription to convert RNA into DNA, but this process is subject to inherent biological limitations, and while chemical methods are promising to date none have been competitive alternatives. Here, the authors introduce a non-enzymatic chemical ligation strategy in which DNA oligonucleotides hybridised to a complementary RNA template form an artificial squaramide backbone, enabling highly sensitive RNA detection at sub-attomole levels comparable to enzymatic systems.

The sterile alpha and TIR motif containing 1 (SARM1) is a crucial enzyme in axonal degeneration, making it a potential target for treating nervous system diseases. Here, the authors identify and optimize base-exchange inhibitors (BEXi) targeting SARM1, revealing their limitations and highlighting the complexity of SARM1 as a therapeutic target.

Chemistry programmes worldwide are experiencing declining student enrolment, reflecting shifting career perceptions and competition from emerging fields. This Comment outlines how the discipline is evolving into an integrative field that combines molecular science with data science, automation, and systems thinking, thereby necessitating an evolution of both research practices and educational structures.

Professor Nicola Gaston is the Director of the MacDiarmid Institute for Advanced Materials and Nanotechnology, a New Zealand Centre of Research Excellence, and a Professor in Physics at the University of Auckland, where her research group conducts quantum-mechanical simulations of the electronic and thermodynamic behaviour of nanoscale materials.

Mechanoradicals are known to be sources of damage during polymer processing, and it remains challenging to stabilize, repair or utilize them. Recently, mechanoradicals formed during chain scission were intercepted directly by bis(butyl trithiocarbonate) in the solid state, redirecting the degradation pathways to repolymerization (repair) and complete depolymerization (recovery).

We are pleased to present our Editors’ Highlights Collection, featuring some of our favourite content published in Communications Chemistry in 2025. Here, we highlight why each paper was selected by our Editors and Editorial Board Members.

Mental health should be a priority for all and especially for underrepresented groups, including the women in chemistry. Here, the authors discuss and propose supportive mechanisms within academia for the mental health of undergraduate women in chemistry.

Dr Laura Cattaneo is a group leader at the Max Planck Institute for Nuclear Physics in Heidelberg, Germany. She has an interdisciplinary research background in chemical physics, connecting materials science, liquid crystals, and ultrafast processes in matter.