Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK.
IRR Chemistry Hub, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK.
Nat Commun. 2024 Sep 3;15(1):7689. doi: 10.1038/s41467-024-51872-y.
Controlling the succession of chemical processes with high specificity in complex systems is advantageous for widespread applications, from biomedical research to drug manufacturing. Despite synthetic advances in bioorthogonal and photochemical methodologies, there is a need for generic chemical approaches that can universally modulate photodynamic reactivity in organic photosensitizers. Herein we present a strategy to fine-tune the production of singlet oxygen in multiple photosensitive scaffolds under the activation of bioresponsive and bioorthogonal stimuli. We demonstrate that the photocatalytic activity of nitrobenzoselenadiazoles can be fully blocked by site-selective incorporation of electron-withdrawing carbamate moieties and restored on demand upon uncaging with a wide range of molecular triggers, including abiotic transition-metal catalysts. We also prove that this strategy can be expanded to most photosensitizers, including diverse structures and spectral properties. Finally, we show that such advanced control of singlet oxygen generation can be broadly applied to the photodynamic ablation of human cells as well as to regulate the release of singlet oxygen in the semi-synthesis of natural product drugs.
在复杂体系中，通过高特异性控制化学过程的继替对于从生物医学研究到药物制造的广泛应用是有利的。尽管在生物正交和光化学方法学方面取得了合成进展，但仍需要通用的化学方法，以便能够普遍调节有机光敏剂中的光动力反应性。在此，我们提出了一种策略，可在生物响应性和生物正交刺激物的激活下，对多种光敏支架中 singlet oxygen 的生成进行精细调控。我们证明，通过选择性地引入吸电子氨基甲酸酯基团，可以完全阻断硝基苯并硒二唑的光催化活性，并且通过使用广泛的分子触发剂（包括非生物过渡金属催化剂）进行解笼，可以按需恢复其活性。我们还证明，该策略可以扩展到大多数光敏剂，包括各种结构和光谱特性的光敏剂。最后，我们表明，这种对 singlet oxygen 生成的高级控制可以广泛应用于人类细胞的光动力消融，以及调节天然产物药物半合成中 singlet oxygen 的释放。
