In the reported mechanisms of reversible photoacidity, protons were dissociated from compounds which contained hydroxyl, indazole or formed hydroxyl via intramolecular hydrogen abstraction under irradiation. Herein, a water-dependent reversible photoacidity (W-RPA) mechanism mediated by a thiadiazoloquinoxaline compound (TQs-Th-PEG5) has been found, in which the proton is not dissociated from TQs-Th-PEG5 itself but from a water locked by TQs-Th-PEG5 under the irradiation of a 660 nm laser. After turning off the laser, the produced acid will disappear quickly. This process is repeatable with no consumption of TQs-Th-PEG5. More importantly, water is indispensable. Furthermore, it is confirmed that there is no other element involved in the process except TQs-Th-PEG5, light and water. Excitingly, W-RPA therapy mediated by TQs-Th-PEG5 nanoparticle exhibits remarkable antitumor effect both in vitro and in vivo, especially in hypoxic tumors with diameter larger than 10 mm owing to its oxygen-independent feature. This study not only discovers a W-RPA mechanism but also provides a novel phototherapy strategy for cancer treatment.

在报道的可逆光酸性机制中，质子从含有羟基、吲唑的化合物中解离出来，或在照射下通过分子内夺氢而形成羟基。在此，已发现由噻二唑并喹喔啉化合物 (TQs-Th-PEG5) 介导的水依赖性可逆光酸 (W-RPA) 机制，其中质子不是从 TQs-Th-PEG5 本身解离，而是从由TQs-Th-PEG5 在 660 nm 激光照射下。关闭激光后，产生的酸会很快消失。这个过程是可重复的，不消耗 TQs-Th-PEG5。更重要的是，水是不可或缺的。此外，证实该过程中除了TQs-Th-PEG5、光和水之外没有其他元素参与。令人兴奋的是，在体外和体内，尤其是在直径大于 10 mm 的缺氧肿瘤中，由于其不依赖氧的特性。该研究不仅发现了W-RPA机制，而且为癌症治疗提供了一种新的光疗策略。