Nature reviews. Chemistry最新文献

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.

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.

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.

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.