Nature has inspired the development of synthetic chemical systems, in which transient supramolecular species emerge with unique properties that can be spatiotemporally controlled at the expense of external energy sources. Herein, we highlight recent advances organized in three sections according to the (de)activation modes that trigger transient assemblies.

The design and synthesis of mechanophores remain a central pursuit in modern polymer mechanochemistry. Nevertheless, the discovery of novel mechanophores frequently relies on empirical trial-and-error approaches. In a recent advance, Kulik and colleagues leveraged machine learning (ML) to establish a universal framework for the high-throughput identification of mechanophores with superior reactivity.

Advanced biofuels in the form of liquid hydrocarbons offer a pathway to decarbonize long-distance heavy transport. Integrating biological acidification with electrocatalytic Kolbe-type decarboxylation provides a promising route for selectively producing linear hydrocarbons from biowaste. However, such cascading systems face challenges including suboptimal carbon utilization, limited product selectivity, and energy-intensive separations. This paper explores microbial chain elongation for generating medium-chain carboxylic acids (MCCAs) from biowaste, alongside CO2 reduction to supply biocompatible electron donors and improve carbon efficiency. Particular attention is placed on waveform-controlled electrosynthesis, which enables selective upgrading of MCCAs into alkanes and alkenes under mild conditions. Framed within a circular bioeconomy, key mechanistic, engineering, and techno-economic gaps are identified to advance bio-electrified hydrocarbons as competitive drop-in fuels.

Boron catalysts are emerging as key players in catalysis, enabling challenging chemical transformations. Boron catalysis can circumvent the issue of metal residues in drug-molecule synthesis, which is particularly beneficial for the pharmaceutical industry. This Forum highlights recent advances in borenium catalysis, focusing on enhanced Lewis acidity and new catalytic modes.

A longstanding goal in supramolecular chemistry has been to enhance the functionality of abiotic catalysts by attaching them to 3D scaffolds, analogous to enzyme active sites. Recent advances in DNA synthesis, DNA sequencing, and DNA-compatible chemical reactions open opportunities to enhance the function and accelerate the discovery of abiotic catalysts by interfacing them with DNA. Here we highlight the ways in which DNA has been merged with abiotic catalysis, including stereoselectivity, regioselectivity, switchability, and scaffolding of multiple reaction components. Furthermore, we describe how the programmable self-assembly and information-encoding properties of DNA enable high-throughput screening of abiotic chemical reactions. We discuss key advances, challenges, and opportunities to harness the potential of synthetic DNA as a scaffold for abiotic catalysis.

Aziridines are versatile functional groups in organic synthesis and medicinal chemistry. Numerous methods for the synthesis of NH-aziridines from alkenes have been reported; however, the direct aziridination of unsubstituted styryl derivatives and electron-deficient alkenes is scarcely reported. To address this topic, an efficient and simple method was developed for the direct synthesis of NH-aziridines from a broad range of alkenes from aqueous ammonia and (diacetoxyiodo)benzene (PIDA).

DNA technology is rapidly expanding, with recent advances pushing functional DNA-based materials toward larger scales. Yet producing chemically modified DNA beyond the milligram-scale remains prohibitively expensive, challenging, and relatively unexplored, limiting industrial and translational use. This review article highlights emerging strategies for sourcing, modifying, and purifying DNA at scales relevant for materials and biotechnology. We compare bio-derived DNA sources (e.g., phage, plasmid, and genomic DNA) to conventional synthetic methods and examine their trade-offs. Critically, we re-examine recent and classic literature to identify chemical and enzymatic reactions practical for modifying bio-derived nucleic acids at relevant scales. Finally, we discuss scalable purification and characterization methods to support high-throughput workflows, enabling broader use of bio-derived dsDNA in next-generation applications.

Nucleic acid therapeutics such as small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) have become powerful tools to modulate gene expression, but their clinical potential is limited by delivery challenges. We explore how chemistry-driven bioconjugates, especially covalent conjugates of oligonucleotides with targeting ligands, are among the most promising strategies to overcome systemic delivery barriers. Rational bioconjugation can address issues of renal clearance, endosomal entrapment, and off-target toxicity by enabling cell-specific uptake and controlled intracellular release. Recent advances in organ-targeted conjugates for the liver, kidney, brain, and lung highlight the versatility of this approach. Machine learning (ML) techniques applied to ligand and linker design and identification of new tissue target sites are crucial for advancing the precise delivery of nucleic acid therapeutics.

G-quadruplexes (G4s) and i-motifs (iMs) are noncanonical DNA structures that regulate transcription. Recent structural analysis of an iM within the MYD88 promoter reveals its stability and interaction with CTCF, suggesting secondary-structure-mediated transcriptional control. Understanding G4/iM dynamics may enable selective therapeutic targeting of DNA folding in immune regulation.

The rapid evolution of nucleic acid-guided proteins (e.g., CRISPR/Cas12a, Argonaute) has positioned them as transformative tools for aquatic contaminant sensing. Their programmability, compatibility with diverse signal transducers, and field-deployable designs enable unprecedented on-site environmental monitoring. This review outlines the fundamental mechanisms of nucleic acid (NA)-guided proteins, critically analyzes implementation strategies (including field-deployable platforms), and systematically highlights their applications in the sensing of aquatic pollutants. We further discuss current challenges and future research directions to further advance multiplexing, sensitivity enhancement, artificial intelligence (AI)-assisted engineering, and integrated on-site detection areas. By providing comprehensive insights into this emerging field, we hope that this review will serve as an important resource for researchers developing next-generation NA-guided proteins-based environmental surveillance tools to address ‘One Health’ challenges at aquatic interfaces.

Therapeutic RNA molecules have undergone a profound transformation, evolving from limited application of small RNAs to a diverse array of RNA types that target multiple levels of cellular regulation in treating various diseases previously untreatable. This review introduces a general design framework that integrates chemical synthesis, structural biology, and computational approaches to overcome key challenges in RNA therapeutics. We explore how this framework enhances RNA stability, minimizes undesired immunogenicity, improves therapeutic potency, and enables targeted delivery. We also highlight a prime example of this synergy: the rapid development and success of mRNA vaccines during the recent pandemic. This framework serves as a guide for researchers, enabling the creation of more effective, safer, and highly specific RNA-based medicines for a wide spectrum of diseases.

Steroids are ubiquitous natural compounds that play essential physiological roles in both plants and animals. Owing to their diverse biological activities, including anti-inflammatory, antitumor, antiviral, and antimicrobial effects, steroidal compounds have found widespread therapeutic uses in the treatment of numerous clinical conditions. Unsurprisingly, the global steroid market is valued at approximately US$4 billion. Despite their broad impact in chemical research and the pharmaceutical industry, the synthesis of steroids remains challenging due to the structural complexity and limited availability of efficient synthetic methodologies. This review highlights recent advances in electrochemically enabled approaches for steroid activation and functionalization, aiming to inspire innovative and sustainable strategies for steroid manipulation and production.

Detection of nucleic acids is essential for modern diagnostics, but standard polymerase chain reaction (PCR) and fluorescence assays are costly and infrastructure-dependent. Paper-based electrochemical devices (ePADs) offer low-cost, portable alternatives but face electrode architecture limitations. A new platform, FiberSens, eliminates complex functionalization, providing a scalable, clinically-relevant solution for decentralized healthcare, veterinary, and environmental applications.

Modified peptide natural products are renowned for their exceptional structural diversity, which translates into a broad spectrum of bioactivities and therapeutic potential. For their biosynthesis, nature has evolved two fundamentally different strategies – through a ribosomal and a nonribosomal route. Pivotal to the peptides’ structural diversity are their underlining amino acid building blocks, often transformed by specialized biosynthetic enzymes into noncanonical residues, frequently crucial for their bioactivities. In this review, we highlight recent advances in deciphering the biosynthesis of unusual and highly modified amino acids across peptide natural product biosynthetic pathways. We introduce different tailoring routes that may lead to similar or even the same products and outline unexpected combinations of pathway types discovered to produce complex chemistry.

Electrosynthesis is reshaping natural product total synthesis by replacing stoichiometric oxidants and reductants, reducing waste, and enabling orthogonal reactivity. We highlight recent advances that demonstrate mediator and catalyst platforms alongside sustainability metrics, including anodic functionalization, reductive couplings, and electrochemical oxidative dearomatization-induced (ODI)-[5+2] cascades. These strategies deliver safer, scalable, and low-carbon synthetic routes, extending access to targets previously unattainable by conventional methods.

Nucleoside analogues (NAs) continue to be a rich source of antiviral and anticancer drug leads and critical components of oligonucleotide therapeutics (ONTs). To support drug development, significant effort has been directed towards their synthesis. For several decades, these processes relied heavily on carbohydrates as key chiral building blocks. While carbohydrates possess structural and stereochemical features common to nucleosides, significant protecting group and redox manipulations are required to produce many modern NA drugs and ONTs. This can limit comprehensive structure–activity relationship studies and challenge process chemistry efforts. Recent advances now enable production of NAs from non-carbohydrate materials and create opportunities for accelerating NA and ONT discovery. This review will summarize and showcase these methods and their application in NA synthesis.

Production of high-purity biomacromolecules with high yield is a core issue for the biopharmaceutical sector. Membrane technology, a non-thermal process based on size exclusion, is a primary technique for bioseparation. Despite its broad application, membrane technology still faces many challenges in the accurate isolation of biomolecules. The flexibility of biomolecular conformations causes dynamic size changes and irregular transmembrane transport. Meanwhile, the inhomogeneous distribution of membrane pore size and suboptimal operational conditions substantially compromise size-exclusion performance, especially for species with similar molecular weight. This article aims to identify the causes of low separation precision in biomolecule purification and reviews recent technological advances in fine separation methods by analyzing bio-solution characteristics, membrane physicochemical properties, and industrial process design.

DNA-encoded libraries (DELs) have emerged as a critical technology for rapid hit identification in drug discovery. The effectiveness of DEL selection fundamentally depends on the chemical diversity present within the library. As DNA-compatible chemistry plays a central role in expanding both the chemical space and molecular diversity of DELs, this area has seen significant advancements in recent years. Additionally, research in DNA-compatible chemistry and bioconjugation chemistry demonstrates a synergistic relationship. This review focuses on the most recent developments in DNA-compatible chemistry and highlights its expanding applications beyond traditional library construction. Current synthetic challenges are examined, and potential directions for future research and development are explored.

Recently, lipid nanoparticles (LNPs) have transformed drug delivery, particularly for nucleic acid vaccines and gene therapy. LNPs provide biocompatibility, enhanced bioavailability, and controlled release. However, nonspecific distribution remains a limitation for conventional LNPs. This review highlights the evolution of targeted LNPs (tLNPs) as precision drug delivery systems, with emphasis on recent innovations in surface functionalization, lipid composition tuning, and organ-specific delivery. Unlike prior reviews focused on general LNP formulations, we explore active targeting strategies, including ligand conjugation and structure-driven targeting, that redefine therapeutic precision and reduce off-target effects. This review presents a comprehensive overview of how tLNPs are advancing towards clinical applications across immunotherapy, gene editing, and personalized medicine.

Given the rise in prominence of nucleic acid therapeutics and technologies (e.g., gene editing, antisense, siRNA), the development of efficient, sustainable routes towards the discovery and manufacture of requisite nucleoside analogue building blocks is pressing. Adenosine deaminase (ADA) is a ubiquitous enzyme that catalyses an irreversible hydrolytic deamination of adenosine to inosine within purine metabolism. It has been exploited for biotechnological purposes, affording synthetic access to modified nucleoside analogues, through to applications in gene editing and therapeutic intervention. This review outlines structural modifications in purine substrates and their impact upon ADA activity. We also offer a perspective on future directions, highlighting a need for increased data towards enzyme engineering and promiscuous ADA activity for biotechnological applications.

This review describes three general approaches for the mild (