Traditional Chemistry Research Articles

Accelerated photo-Fenton degradation of Ciprofloxacin on CoSx@TiO2 amorphous-crystalline interface with S-O bond bridging.

Accelerated photo-Fenton degradation of Ciprofloxacin on CoSx@TiO2 amorphous-crystalline interface with S-O bond bridging.

Multidimensional Roles of Pears in Pear Paste: A Systematic Analysis from Molecular Mechanisms to Clinical Translations

Pear paste is a traditional preparation with both medicinal and nutritional functions. The “pear”, as its core ingredient, plays a crucial role in the efficacy of the preparation. This paper, through the interdisciplinary integration of evidence from traditional Chinese medicine, food chemistry, molecular biology, and clinical medicine, constructs a complete “raw material-component transformation-biological regulation” model for the first time. It is found that in pear paste, pears not only serve as a functional matrix. The polysaccharide-polyphenol-triterpene complex system forms a multi-target cough-relieving and anti-inflammatory network through dual regulation of TRPV1/TRPA1 ion channels, inhibition of the NLRP3 inflammasome, and metabolites of gut microbiota such as SCFAs. The research results provide a theoretical breakthrough for the modern development of pear paste and a scientific basis for the modernization of traditional preparations.

Tumor-specific biochemical nanoconversion of self-assembled peptide-conjugated paclitaxel-docetaxel-based nanoparticles

Docetaxel (DTX, 1) and paclitaxel (PTX, 2) are famous cytotoxic agents widely used in cancer therapy, however, their low specificity for tumor cells often results in severe systemic toxicity. Beyond conventional prodrug strategies, this study introduces a novel nanoconversion technology that chemically modifies DTX to form self-assembled nanoparticles (NPs), which subsequently convert into a paclitaxel-mimicking molecule (PTXm, 3). Hydrophilic acetylated Phe-Arg-Arg-Phe peptide ((Ac)FRRF, 4) and hydrophobic docetaxel were conjugated to prepare self-assembled (Ac)FRRF-DTX NPs. The selective cleavage of the Arg-Phe bond by cathepsin B, which is abundant in cancer cells, facilitated the nanoconversion of PTXm (3) from (Ac)FRRF-DTX NPs, demonstrating effective cytotoxic effects. Utilizing the cleavage site of peptide and specific sequences (ex. Arg-Arg-Phe), this approach does not simply act as a prodrug but allows the nanomaterial to transform into another cytotoxic biomolecule within tumors. (Ac)FRRF-DTX NPs exhibited remarkable physicochemical properties, superior anti-cancer efficacy, and low toxicity, showcasing an innovative conversion in peptide-conjugated nanomedicine. Unlike traditional prodrug chemistry, this tumor-specific nanoconversion process involves the biochemical transformation of DTX (1) into PTXm (3) via enzymatic action. Overall, this study provides an outstanding example of chemical drug molecular modification through the concept of nanoconversion.

Abstract 1570: PermaLink®, a stable and scalable bioconjugation platform as an alternative to maleimide-based conjugation

Abstract IKSUDA Therapeutics’ proprietary PermaLink® platform comprises simple, stable, and adaptable conjugation chemistry that overcomes the instabilities associated with the retro-Michael exchange of traditional maleimide-based chemistry. This platform enables ADC generation with a range of drug-to-antibody ratios (DAR) and can be applied to multiple payloads and linker chemistries to improve conjugate properties and maximize the therapeutic index of ADC therapeutics. ADCs are generated by reducing the hinge region disulfides and/or decapping engineered cysteines with TCEP, conjugation with PL-payload followed by purification. DAR was measured by HPLC. The stability of PL-based ADCs was compared to traditional maleimide-based ADCs in murine and human plasma. In vitro activity and bystander effect were assessed using mono or co-culture experiments by CellTiter-Glo assay. In vivo efficacy studies were conducted in SCID mice with human cancer xenografts. Toxicology and PK studies were conducted in cynomolgus monkeys. PL-based conjugation followed a simple process of reducing the antibody disulfides with TCEP, conjugation with PL-payload and removal of excess linker toxin by size exclusion chromatography, desalting or filtration. Control of process parameters such as TCEP and linker-payload excesses yielded conjugates with DARs ranging from 4-8 for native wildtype antibodies. Additionally, DAR 10 was achieved for an antibody with two engineered cysteines. The resulting ADCs demonstrated favorable biophysical properties with minimal aggregation by SEC and DAR assessment was consistent by PLRP-HPLC and MS. Typical yields at the research scale ranged from 70-90%. For preclinical proof-of-concept, MMAE conjugates of Isumab01, targeting FRA, were prepared with a protease-cleavable valine-citrulline (vc) and enzymatically cleavable β-glucuronide (glu) linker. Both PL-based conjugates showed excellent stability in murine and human plasma, whereas FDA-approved maleimide-based ADCs brentuximab vedotin and trastuzumab deruxtecan displayed a significant decrease in DAR. PL-MMAE conjugates were highly potent against JEG-3 cancer cells in vitro, with IC50 values in the pM range. Isumab01-PL-glu-MMAE resulted in complete tumor regression in a JEG-3 xenograft model following a single dose of 2.5 mg/kg and was very well tolerated in cynomolgus monkeys at 12 mg/kg single dose and 10 mg/kg Q3W x2 (highest doses tested), showing improved tolerability over MMAE-based ADCs with maleimide-cathepsin B cleavable linkers. The Isumab01-PL-glu-MMAE conjugate demonstrates a favorable PK profile in monkeys with high stability in circulation consistent with improved bioconjugation. PermaLink offers a simple, stable alternative to maleimide-based ADC bioconjugation moieties and confers a favorable preclinical anti-tumor activity and safety profile Citation Format: Adam Lodge, Justyna Mysliwy, Will A. Stanley, James Stephenson, Sarah Robinson, Alexander Sanders, Robert Murawski, Bryony Moss, Patrick Higgs, Jutta Deckert, Jenny Thirlway, Robert J. Lutz. PermaLink®, a stable and scalable bioconjugation platform as an alternative to maleimide-based conjugation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1570.

Heterocycle-based dynamic covalent chemistry for dynamic functional materials

Dynamic covalent chemistry, which renders reusable and degradable thermoset polymers, is a promising tool for solving the global problem of plastic pollution. Although dynamic covalent chemistry can construct dynamic polymer networks, it rarely introduces other functions into polymers, which limits the development of dynamic functional materials. Herein, we develop heterocycle-based dynamic covalent chemistry and demonstrate the reversibility of the aza-Michael addition reaction between functional heterocycle dihydropyrimidin-2(1H)-thione and electron-deficient olefins. Our method produces a degradable linear polymer and recyclable and self-healable crosslinked polymers similar to traditional dynamic covalent chemistry, but the heterocycles endow the polymer with excellent ultraviolet-blocking and high-energy blue light-blocking abilities, and tunable fluorescence and phosphorescence properties. These are difficult to create with ordinary dynamic covalent chemistry. This proof-of-concept study provides insights into heterocycle-based dynamic reactions, and may prompt the development of dynamic chemistry and dynamic functional materials.

Improved Chemical Synthesis of Avenanthramides Family and its Analogs by Mixed Anhydride Method

Amides derived from common hydroxycinnamic acids — including 4‐hydroxycinnamic acid, 3‐methoxy‐4‐hydroxycinnamic acid, 3,4‐dihydroxycinnamic acid, 3,4‐dimethoxycinnamic acid, and 3,4,5‐trimethoxycinnamic acid — along with various free aminobenzoic acids, such as 5‐hydroxy‐2‐aminobenzoic acid, a key component of the avenanthramide family, have been rapidly synthesized using an innovative, environmentally friendly synthetic methodology. This approach, grounded in traditional chemistry, utilizes mixed anhydrides to simultaneously protect and activate hydroxycinnamic acids through the actions of triethylamine and isobutyl chloroformate while employing acetone as a green solvent. The resulting amides, formed from the coupling with free aromatic amino acids, are constructed as O‐carbonate‐protected derivatives with high yields and purity, isolated directly via crystallization, thus eliminating chromatographic or HPLC purifications. Furthermore, free phenols can be conveniently released on demand using morpholine in methanol. Under these conditions, C‐protected aromatic amino acids remain unacylated. This synthetic strategy represents a significant advancement over conventional acyl chloride methodologies, which often rely on toxic reagents and solvents and entail time‐consuming and complex procedures. It enhances the production of important phytochemicals such as Avenanthramides and opens doors to various analogs, paving the way for potential pharmacological applications.

Enhancing Generalizability in Molecular Conformation Generation with METRIZATION-Informed Geometric Diffusion Pretraining

Diffusion-based generative models have recently excelled in generating molecular conformations but struggled with the generalization issue -- models trained on one dataset may produce meaningless conformations on out-of-distribution molecules. On the other hand, distance geometry serves as a generalizable tool for the traditional computational chemistry methods of molecular conformation, which is predicated on the assumption that it is possible to adequately define the set of all potential conformations of any non-rigid molecular system using purely geometric constraints. In this work, we for the first time explicitly incorporate distance geometry constraints into pretraining phase of diffusion-based molecular generation models to improve the generalizability. Inspired by the classical distance geometry solution designed for solving the molecular distance geometry problem, we propose MiGDiff, a Metrization-Informed Geometric Diffusion framework. MiGDiff injects distance geometry constraints by pretraining the deep geometric diffusion backbone within the Metrization sampling approach, yielding a "Metrization-driven pretraining + Data-driven finetuning" paradigm. Experimental results demonstrate that MiGDiff outperforms state-of-the-art methods and possesses strong generalization capabilities, particularly on generating previously unseen molecules, revealing the vast untapped potential of combining traditional computational methods with deep generative models for 3D molecular generation.

Strategies to Improve the Sustainability of Silicone Polymers.

Silicones underpin an enormous range of simple and advanced technologies. Often, only small quantities of silicone are used to enable a technology such that, on a "per use" basis, one might suppose the environmental impact is low. However, silicone preparation processes have a very high carbon footprint, and billions of kg are produced each year. To provide context to the consideration of new strategies to improve silicone sustainability, we first outline traditional silicone chemistry and then describe strategies to improve the degree to which silicones are green, sustainable and circular. One strategy involves dilution of the silicone oil or elastomer by tethering organic entities, particularly natural products, that may provide new properties including facilitated degradation in nature at end-of-life. A greater focus is given to strategies that permit extensive reuse and repurposing of oils and elastomers (e.g., with thermoplastic elastomers), before the silicone undergoes recycling. Each reuse, repurposing or recycling step reduces the net carbon footprint. These mostly involve straightforward, high-yielding organic chemical processes that work efficiently in a silicone milieu. Silicones will eventually end up in the environment, where linear oils are known to rapidly degrade, particularly when compared to organic polymers. Alternative strategies that permit triggered or biological degradation of oils and, more importantly elastomers, are described, including enzymatic degradation and composting.

Catalysis in Chemical Modification of Proteins

Advancement of catalytic transformations in traditional synthetic organic chemistry have made significant impacts on development of novel bioconjugation technologies. While a wide range of applications have become possible through catalytic protein bioconjugation approaches, there has been a lack of literature collectively reviewing advances of chemical modification of proteins through the lens of catalysis. This review article is focused on design principles and chemical strategies of nonenzymatic catalysis for targeting natural protein substrates by identifying seven catalysis patterns as organizing topics: Electrocatalysis, photocatalysis, metal catalysis, acid catalysis, organocatalysis, supramolecular catalysis, and heterogeneous catalysis. Many literature examples demonstrated possibility of simple translation of small molecule‐based catalysis into protein bioconjugation methodologies whereas others demonstrated unique approaches such as dual catalytic systems and polypeptide structure‐specific catalysis design. With a series of successful examples, the survey of catalytic approaches for protein bioconjugation also highlighted the remaining challenges and potential future directions of the area of catalytic bioconjugation.

Multigram Scale Synthesis of Mechanically-Interlocked Derivatives of SWNT using Mechanochemical Methods.

The grinding of chemical reagents enables mixing, promotes molecular collisions, and provides the thermal energy required for chemical reactions, while reducing the need for solvent (often to none) and significantly speeding up reactions. This has made mechanochemistry a powerful alternative to traditional solution chemistry. Here, we show that mechanically interlocked derivatives of single-walled carbon nanotubes (MINTs) can be made via mechanochemistry in a multigram scale. Compared to the previously reported method in suspension, mechanochemistry allows us to reduce the amount of solvent by two orders of magnitude and the reaction time from 72 h to 5 min. The mechanochemical synthesis of MINTs is proven to work both with purified (6,5)-SWNTs and affordable TuballTM SWNTs, enabling the cheap, fast, and environmentally friendly multigram scale synthesis of MINTs. With this new synthetic methodology, we open the door to the real-world applications of MINTs in fields such as polymer composites.

Reimagining Dearomatization: Arenophile-Mediated Single-Atom Insertions and π-Extensions.

ConspectusDearomatization of simple aromatics serves as one of the most direct strategies for converting abundant chemical feedstocks into three-dimensional value-added products. Among such transformations, cycloadditions between arenes and alkenes have historically offered effective means to construct complex polycyclic architectures. However, traditionally harsh conditions, such as high-energy UV light irradiation, have greatly limited the scope of this transformation. Nevertheless, recent progress has led to the development of visible-light-promoted dearomative photocycloadditions with expanded scope capable of preparing complex bicyclic structures.A fundamentally distinct approach to dearomative photocycloadditions involves the visible-light activation of arenophiles, which undergo para-photocycloaddition with various aromatic compounds to produce arene-arenophile cycloadducts. While only transiently stable and subject to retro-cycloaddition, further functionalization of the photocycloadducts has allowed for the development of a wide collection of dearomatization methodologies that access products orthogonal to existing chemical and biological processes. Central to this strategy was the observation that arene-arenophile photocycloaddition reveals a π-system that can be functionalized through traditional olefin chemistry. Coupled with subsequent [4 + 2]-cycloreversion of the arenophile, this process acts to effectively isolate a single π-system from an aromatic ring. We have developed several transformations that bias this methodology to perform dearomative single-atom insertion and π-extension reactions to prepare unique products that cannot be prepared easily through traditional means.Through the application of a dearomative epoxidation, we were able to develop a method for the epoxidation of arenes and pyridines to arene-oxides and pyridine-oxides, respectively. Notably, when this arenophile chemistry is applied to polycyclic arenes, photocycloaddition reveals a π-system transposed from the site of native olefinic reactivity, enabling unique site-selectivity for dearomative functionalization. As a result, we were able to perform a single-atom insertion of oxygen into polycyclic (aza)arenes to prepare 3-benzoxepines. When applying this strategy in the context of cyclopropanations, we were able to accomplish a dearomative cyclopropanation of polycyclic (aza)arenes which yield benzocycloheptatrienes upon cycloreversion. Notably, while the Buchner ring expansion is a powerful method for the direct single-atom insertion of carbon into arenes, the corresponding cyclopropanation of polycyclic arenes does not yield ring-expanded products. Furthermore, this strategy could be utilized for the synthesis of novel nanographenes through the development of an M-region annulative π-extension (M-APEX) reaction. Traditionally, methods for π-extension rely on the native reactivity of polycyclic aromatics at the K- and bay-region. However, photocycloaddition of polycyclic aromatics with arenophiles acts as a strategy to activate the M-region for further reactivity. As a result, arenophile-mediated dearomative diarylation, followed by cycloreversion, could deliver π-extended nanographenes with exclusive M-region site selectivity.

BB-SAR: An Application for Data-driven Analysis and Rational Design of Medicinal Chemistry Series.

In drug discovery, medicinal chemists face the challenge of generating and analyzing large data sets, often exceeding a thousand molecules and numerous physicochemical and biological properties. To address this, we introduced BB-SAR, an interpolative methodology that tackles both data complexity and interpretability, by breaking down molecules into their constituent building blocks (BBs). Establishing a direct correlation between molecules and their constituent BBs enables the association of these BBs with their respective biological and physicochemical properties. This facilitates more intuitive data analysis and enables the identification of critical trends between molecular features and their associated properties. While individual BBs rarely dictate property behavior, their combinations do. BB-SAR identifies impactful combinations for designing new, improved compounds. Additionally, it simplifies traditional medicinal chemistry analysis strategies and enhances the efficiency of drug discovery by providing a more inherent understanding of complex data sets within a concise framework.

Precision Synthesis Strategies and Emerging Applications of Bioorthogonal Click Chemistry in Tissue Engineering and Regenerative Medicine

Bioorthogonal click chemistry is a reaction that covalently connect two components via clickable groups at room or body temperature, without side reactions or by-products. It solves the common problems of traditional organic chemistry, such as harsh reaction conditions, slow reaction rate and extremely low yield. Importantly, the specificity between clickable groups does not affect other biochemical reactions in the life system during the reaction. Therefore, it not only makes the organic synthesis reaction more simple, accurate and efficient, but also successfully introduces it into organisms, enabling people to intervene and study a series of biological processes in the life system. Due to its unique advantages in the construction of biomaterials and the transformation of cells, bioorthogonal click chemistry plays an increasingly important role in the field of tissue engineering and regenerative medicine, and has made considerable progress. Herein, we present the latest progress of bioorthogonal click chemistry in the synthesis and functionalization of biomaterials, the interaction between biomaterials and cells. In addition, we also introduced examples of the application of these strategies in the repair of bone, skin, nerve and other tissue or organ damage, and discussed the future development direction of these strategies as cross-linking tools in the field of tissue engineering and regenerative medicine.

From Traditional Use to Modern Evidence: The Medicinal Chemistry of Antimalarials from Genus Artemisia.

While the use of plants in traditional medicine dates back to 1500 B.C., modern advancements led to the development of innovative therapeutic techniques. On the other hand, in the field of anti-infective agents, lack of efficacy and the onset of resistance stimulate the search for novel agents. Genus Artemisia is one of the most diverse among perennial plants with a variety of species, properties, and chemical components. The genus is known for its therapeutic values and, in particular, for its role in the origin of antimalarial agents derived from artemisinin. In this review, we aim to provide an updated overview of the evolution of natural and nature-inspired compounds related to the genus Artemisia that have been proven, in vitro and in vivo, to possess antimalarial properties. An overview of the chemical composition and a description of the ethnopharmacological aspects will be presented, as well as an updated report on in vitro and in vivo evidence that allowed the translation of artemisinin and its derivatives from traditional chemistry into modern medicinal chemistry. The biological and structural properties will be discussed, also dedicating attention to the challenging tasks that still are open, such as the identification of optimal combination strategies, the routes of administration, and the full assessment of the mechanism of action.

Wood Species Differentiation: A Comparative Study of Direct Analysis in Real-Time and Chromatography Mass Spectrometry

This study reports for the first time the fingerprinting extractives analysis of the indigenous wood species of Podocarpus totara from New Zealand, Eucalyptus saligna from Australia and Pinus radiata imported from California, USA and grown in New Zealand. We evaluated the use of analytical techniques for wood species discrimination. We compared the chemical fingerprinting of extractive compounds obtained using traditional chromatographic techniques with direct analysis in real-time–time of flight-mass spectrometry (DART-TOF-MS) with the auxiliary of chemometrics and principal component analysis. The traditional wet chemistry analysis of wood extracts provided a comprehensive characterisation of all extractive components. However, the more eco-friendly, sustainable and faster DART-TOF-MS technique effectively distinguished between wood species when heartwood and sapwood samples were combined. Notably, neither wet chemistry nor DART-TOF-MS could clearly differentiate between heartwood and sapwood within the same wood species. DART-TOF-MS analysis demonstrates potential as a reliable quality control tool for identifying wood species necessary in commercial and timber trading markets as well as for detecting the illicit trade of counterfeit wood products.

An Introduction to the Complete Blood Count for Clinical Chemists: White Blood Cells.

The most frequently ordered laboratory test worldwide is the complete blood count (CBC). As clinical chemists are increasingly assigned to assist or direct laboratories outside of the traditional clinical chemistry sections, such as the automated hematology section, expertise must be established. This review article is a dedication to that ongoing effort. In this primer, the white blood cell (WBC) test components of the CBC are introduced, followed by a discussion of the laboratory evaluation of leukopenia and leukocytosis. The laboratorian's approach to consult cases should be guided by the patient's clinical history and presentation while being able to provide key laboratory-based insights to assist in resolving result discrepancies that may otherwise go unnoticed.

A multiscale molecular structural neural network for molecular property prediction.

Molecular Property Prediction (MPP) is a fundamental task in important research fields such as chemistry, materials, biology, and medicine, where traditional computational chemistry methods based on quantum mechanics often consume substantial time and computing power. In recent years, machine learning has been increasingly used in computational chemistry, in which graph neural networks have shown good performance in molecular property prediction tasks, but they have some limitations in terms of generalizability, interpretability, and certainty. In order to address the above challenges, a Multiscale Molecular Structural Neural Network (MMSNet) is proposed in this paper, which obtains rich multiscale molecular representations through the information fusion between bonded and non-bonded "message passing" structures at the atomic scale and spatial feature information "encoder-decoder" structures at the molecular scale; a multi-level attention mechanism is introduced on the basis of theoretical analysis of molecular mechanics in order to enhance the model's interpretability; the prediction results of MMSNet are used as label values and clustered in the molecular library by the K-NN (K-Nearest Neighbors) algorithm to reverse match the spatial structure of the molecules, and the certainty of the model is quantified by comparing virtual screening results across different K-values. Experimental results in the authoritative small molecule dataset QM9 and the macromolecular protein database PDBbind demonstrate that MMSNet has optimal prediction accuracy, model complexity, and generalizability compared with more than ten existing state-of-the-art (SOTA) models in a variety of different types of prediction tasks; it has a great potential for downstream tasks such as chemical research, drug discovery, and material design.

Sustainable and solvent-free synthesis of molecules of pharmaceutical importance by ball milling.

The solvent-free mechanochemical reactions under ball milling have emerged as a promising alternative to traditional solution-based chemistry. This approach not only eliminates the necessity for large quantities of solvents and minimizes waste production, but it also facilitates a unique reaction environment that enables strategies, reactions, and compound syntheses that are typically unattainable in solution. This solvent-less synthetic strategy under ball-milling has been well employed in synthetic organic chemistry in accessing various potential organic molecules including pharmaceutically important molecules and pharmaceuticals or drug-molecules. This review highlights the potential of ball milling in the synthesis of pharmaceutically important classes of molecules without using any solvent (solvent-free conditions).

Concluding remarks: Atmospheric chemistry in cold environments.

Atmospheric chemistry in cold environments refers to key chemical processes occurring in Earth's atmosphere in locations relevant for society including the polar areas, the free and upper troposphere, and the stratosphere. Atmospheric chemistry in these areas is relevant for local air quality, ecosystem health, regional and global climate. This Faraday Discussion comprised excellent coverage of these areas in terms of longitude and latitude, altitude and temperature. It also featured a broad coverage of disciplines between physical, analytical and theoretical chemistry and also the related fields covering aspects of biology, health, meteorology, social sciences and even including policy and economic aspects. A core aspect of the discussions was rooted in interfacing the related diverse competences. Because traditional atmospheric chemistry has evolved around knowledge of mechanisms and kinetics of chemical reactions first in the gas phase and later including condensed phases of aerosol particles and ground surfaces centering around room temperature, the speciality of relevance in this Faraday Discussion was the recent progress in better understanding the evolution of multiphase chemistry at low temperatures, where many relevant properties such as solubility and volatility change dramatically. This was embedded in discussions of the results and challenges of the most recent measurements from a range of campaigns and long-term observations at research stations. The discussion evolved around the chemical cycles of important trace constituents, the formation and evolution of particulate matter under cold conditions, the link between cloud glaciation and air-mass characteristics, air-quality in cold urban environments, biosphere-atmosphere interactions in a warming Arctic, but also the role of interfacial chemistry and reactivity as they are involved in multiphase chemistry processes. Future threats for the cold part of our atmosphere come from increasing human activities in both polar regions with their impacts on ecosystems, air quality and broader scale atmospheric composition as well as from discussions of geoengineering via solar radiation modification by stratospheric aerosol injection.

Exploring frustrated radical pairs through the persistent radical effect: methods of generation and recent applications.

Radicals have long fascinated chemists owing to their structure, reactivity, and other features. The recent discovery of frustrated radical pairs (FRPs) has added a new dimension to this field. These unique radicals, which do not conform to traditional radical behavior, have opened a world of intriguing possibilities. FRPs have been categorized into neutral and ionic frustrated radical pairs and both are addressed as FRPs in this review. These pairs consist of two different (transient and persistent) radicals or radical ion pairs that do not react with each other. Such orthogonal reactivities and the resultant "persistent radical effect" enable chemical transformations that are difficult to achieve using traditional radical chemistry. This highlight uses recent examples to explore the different ways of generating these radical pairs and their working principle, highlighting the novelty and potential of this emerging field.