The dynamic translocation of a metal catalyst along an alkyl side chain - often coined as 'chain-walking' - has opened new retrosynthetic possibilities that enable functionalization at unactivated C(sp)-H sites. The use of nickel complexes in chain-walking strategies has recently gained considerable momentum owing to their versatility for forging sp architectures and their redox promiscuity that facilitates both one-electron or two-electron reaction manifolds. This Review discusses the relevance and impact that these processes might have in synthetic endeavours, including mechanistic considerations when appropriate. Particular emphasis is given to the latest discoveries that leverage the potential of Ni-catalysed chain-walking scenarios for tackling transformations that would otherwise be difficult to accomplish, including the merger of chain-walking with other new approaches such as photoredox catalysis or electrochemical activation.

The many synthetic possibilities that arise when using radical intermediates, in place of their polar counterparts, make contemporary radical chemistry research an exhilarating field. The introduction of photocatalysis has helped tame aryl radicals, leading to a resurgence of interest in their chemistry, and an expansion of viable coupling partners and attainable transformations. These methods are more selective and safer than classical approaches, and they utilize new radical precursors. Given the importance of sustainability in current organic synthesis and our interest in light-assisted metal-free transformations, this Review focuses on recent advances in the use of aryl radicals in photoinduced cross-couplings that do not rely on metals for the crucial bond-forming event, and it is structured according to the key step that the aryl radicals engage in.

Photodynamic therapy (PDT) - which combines light, oxygen and photosensitizers (PS) to generate reactive oxygen species - has emerged as an effective approach for targeted ablation of pathogenic cells with reduced risk of inducing resistance. Some organic PS are now being applied for PDT in the clinic or undergoing evaluation in clinical trials. A limitation of the first-generation organic PS was their potential off-target toxicity. This shortcoming prompted the design of constructs that can be activated by the presence of specific biomolecules - from small biomolecules to large enzymes - in the target cells. Here, we review advances in the design and synthesis of activatable organic PS and their contribution to PDT in the past decade. Important areas of research include novel synthetic methodologies to engineer smart PS with tuneable singlet oxygen generation, their integration into larger constructs such as bioconjugates, and finally, representative examples of their translational potential as antimicrobial and anticancer therapies.

With the advent of photoredox catalysis, new synthetic paradigms have been established with many novel transformations being achieved. Nevertheless, modern photoredox chemistry has several drawbacks, namely, deficiencies in reaction efficiency and scalability. Furthermore, wavelengths of light in excess of the energy required for a chemical reaction are often used. In this Review, we document recent developments of low-energy light-absorbing catalysts and their cognate photochemical methods, advantageously mitigating off-cycle photochemical reactivity of excited-state species in the reaction mixture and improving batch scalability of photochemical reactions. Finally, developments in red-light photoredox catalysis are leading the next-generation applications to polymer science and biochemistry-chemical biology, enabling catalytic reactions within media composites - including mammalian tissue - that are historically recalcitrant with blue-light photoredox catalysis.

Lignin, the heterogeneous aromatic macromolecule found in the cell walls of vascular plants, is an abundant feedstock for the production of biochemicals and biofuels. Many valorization schemes rely on lignin depolymerization, with decades of research focused on accessing monomers through C-O bond cleavage, given the abundance of β-O-4 bonds in lignin and the large number of available C-O bond cleavage strategies. Monomer yields are, however, invariably lower than desired, owing to the presence of recalcitrant C-C bonds whose selective cleavage remains a major challenge in catalysis. In this Review, we highlight lignin C-C cleavage reactions, including those of linkages arising from biosynthesis (β-1, β-5, β-β and 5-5) and industrial processing (5-CH-5 and α-5). We examine multiple approaches to C-C cleavage, including homogeneous and heterogeneous catalysis, photocatalysis and biocatalysis, to identify promising strategies for further research and provide guidelines for definitive measurements of lignin C-C bond cleavage.

Over the past three decades, chiral phase-transfer catalysts (PTCs) have emerged as highly successful organocatalysts in a diverse range of asymmetric reactions. A substantial number of chiral PTCs have now already been discovered and utilized in dependable routes to enantioenriched products. These extend beyond the classical cationic PTCs with the emergence of anionic phase-transfer catalysis and hydrogen-bonding phase-transfer catalysis providing new asymmetric synthetic approaches. Nevertheless, the application level of chiral PTCs in both academic and industrial processes is below our expectation. This Review highlights the notable advances in chiral PTCs, including challenges, limitations and efforts to overcome them. Following this, the potential for sustainable chiral PTCs is described with a focus on using photocatalysed, flow and electrochemical synthesis.

In the canonical genetic code, the 61 sense codons are assigned to the 20 proteinogenic amino acids. Advancements in genetic code manipulation techniques have enabled the ribosomal incorporation of nonproteinogenic amino acids (npAAs). The critical molecule for translating messenger RNA (mRNA) into peptide sequences is aminoacyl-transfer RNA (tRNA), which recognizes the mRNA codon through its anticodon. Because aminoacyl-tRNA synthetases (ARSs) are highly specific for their respective amino acid-tRNA pairs, it is not feasible to use natural ARSs to prepare npAA-tRNAs. However, flexizymes are adaptable aminoacylation ribozymes that can be used to prepare diverse aminoacyl-tRNAs at will using amino acids activated with suitable leaving groups. Regarding recognition elements, flexizymes require only an aromatic ring in either the leaving group or side chain of the activated amino acid, and the conserved 3'-end CCA of the tRNA. Therefore, flexizymes allow virtually any amino acid to be charged onto any tRNA. The flexizyme system can handle not only L-α-amino acids with side chain modifications but also various backbone-modified npAAs. This Review describes the development of flexizyme variants and discusses their structure and mechanism and their applications in genetic code reprogramming for the synthesis of unique peptides and proteins.

Porous nanoreactors mimic the structures and functions of cells, providing an adaptable material with multiple functions and effects. These reactors can be nanoscale containers and shuttles or catalytic centres, drawing in reactants for cascading reactions with multishelled designs. The detailed construction of multi-level reactors at the nanometre scale remains a great challenge, but to regulate the reaction pathways within a reactor, designs of great intricacy are required. In this Review, we define the basic structural characteristics of porous nanoreactors, while also discussing the design principles and synthetic chemistry of these structures with respect to their emerging applications in energy storage and heterogeneous catalysis. Finally, we describe the difficulties of the structural optimization of these reactors and propose possible ways to improve porous nanoreactor design for future applications.

Supramolecular chemistry has been used to tackle some of the major challenges in modern science, including cancer therapy and diagnosis. Supramolecular platforms provide synthetic flexibility, rapid generation through self-assembly, facile labelling, unique topologies, tunable reversibility of the enabling noncovalent interactions, and opportunities for host-guest chemistry and mechanical bonding. In this Review, we summarize recent advances in the design and radiopharmaceutical application of discrete self-assembled coordination complexes and mechanically interlocked molecules - namely, metallacages and rotaxanes, respectively - as well as in situ-forming supramolecular aggregates, specifically pinpointing their potential as next-generation radiotheranostic agents. The outlook of such supramolecular constructs for potential applications in the clinic is discussed.