The industrial synthesis of ammonia has traditionally relied on the energy-intensive Haber–Bosch process, which accounts for a significant share of global CO2 emissions. Recent innovations are reshaping this landscape by integrating low-carbon hydrogen sources, next-generation catalysts, plasma-assisted techniques, and electrified modular reactors capable of operating under milder conditions. This article provides a comprehensive overview of these technological breakthroughs and offers a quantitative assessment of their technology readiness levels to enable fair benchmarking and informed decision-making by stakeholders. We also discuss key techno-economic considerations, scale-up challenges, and opportunities to align ammonia synthesis with renewable energy and carbon management strategies. Collectively, these developments mark a pivotal shift toward a cleaner and more resilient ammonia production ecosystem.

Synthesis of multilayered carbon nanobelts constitutes a long-standing challenge. A recent breakthrough by Anderson et al. reports the precise synthesis of a family of triple-stranded porphyrin nanobelts with highly delocalized nonalternant topologies that embody an ideal quantum ring. This work represents a pivotal achievement in molecular nanocarbon science.

Switchable transformations, which enable the selective formation of two or more structurally distinct products from identical starting materials, represent an attractive synthetic tool by varying the catalyst or reaction conditions. Recently, a palladium/phosphine-catalyzed system was developed for the chemo- and regiodivergent cross-couplings of propargyl carbonates with allyl boronates. The phosphine ligand precisely controls the reductive elimination pathway to afford either 1,4-enallenes or 1,5-enynes, depending on the ligand choice.

Polymer and polyelectrolyte (PE) chains adopt brush-like conformations when densely grafted on solid surfaces or backbones of other polymer chains. In this forum article, we highlight recent advancements and explore emerging directions in applying machine learning (ML) techniques to uncover new applications and fundamental insights in polymer and PE brush-grafted systems.

Nanoparticles constructed from polymers already find widespread use in catalysis, drug delivery, and sensing contexts. However, almost all current applications do not consider how nanoparticles could behave when connected together. Herein I explore emerging approaches to use polymer nanoparticles as building blocks for developing both physically connected and chemically communicating systems.

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.