Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu, 610064, China.
Asymmetric Synthesis and Chiral Technology Key Laboratory of Sichuan Province, Department of Chemistry, Xihua University, Chengdu, Sichuan 610064, China.
J Mater Chem B. 2024 Apr 17;12(15):3686-3693. doi: 10.1039/d4tb00099d.
Photodynamic therapy (PDT) has emerged as a promising approach for tumor treatment. However, traditional type II PDT faces limitations due to its oxygen-dependent nature. Type-I photosensitizers (PSs) exhibit superiority over conventional type-II PSs owing to their diminished oxygen dependence. Nevertheless, designing effective type-I PSs remains a significant challenge. In this work, we provide a novel strategy to tune the PDT mechanism of an excited photosensitizer through aryl substituent engineering. Using S-rhodamine as the base structure, three PSs were synthesized by incorporating phenyl, furyl, or thienyl groups at the meso position. Interestingly, furyl- or thienyl-substituted S-rhodamine are type-I-dominated PSs that produce O˙, while phenyl S-rhodamine results in O˙ and O through type-I and type-II mechanisms, respectively. Experimental analyses and theoretical calculations showed that the introduction of a five-membered heterocycle at the meso position promoted intersystem crossing (ISC) and electron transfer, facilitating the production of O˙. Furthermore, furyl- or thienyl-substituted S-rhodamine exhibited high phototoxicity at ultralow concentrations. Thienyl-substituted S-rhodamine showed promising PDT efficacy against hypoxic solid tumors. This innovative strategy provides an alternative approach to developing new type-I PSs without the necessity for creating entirely new skeletons.
光动力疗法（PDT）已成为肿瘤治疗的一种有前途的方法。然而，传统的 II 型 PDT 由于其氧依赖性而存在局限性。I 型光敏剂（PSs）由于其对氧的依赖性降低，表现出优于传统的 II 型 PSs 的优势。然而，设计有效的 I 型 PSs 仍然是一个重大挑战。在这项工作中，我们通过芳基取代基工程提供了一种调节激发态光敏剂 PDT 机制的新策略。以 S-罗丹明为基础结构，通过在中位引入苯基、呋喃基或噻吩基，合成了三种 PSs。有趣的是，呋喃基或噻吩基取代的 S-罗丹明是 I 型占主导地位的 PSs，可产生 O˙，而苯基 S-罗丹明则分别通过 I 型和 II 型机制产生 O˙和 O。实验分析和理论计算表明，在中位引入五元杂环促进了系间窜越（ISC）和电子转移，有利于 O˙的产生。此外，呋喃基或噻吩基取代的 S-罗丹明在超低浓度下表现出高光毒性。噻吩基取代的 S-罗丹明对缺氧固体肿瘤表现出有前途的 PDT 疗效。这种创新策略为开发新的 I 型 PSs 提供了一种替代方法，而无需创建全新的骨架。
