环金属化铱 (III) 配合物已成为癌症治疗诊断学的多功能候选者，为光动力疗法 (PDT) 提供集成诊断成像和有效的单线态氧 (1O2) 生成。然而，它们的应用受到光致发光减弱的限制，这主要是由于分子内运动引起的激发能量耗散。在本研究中，我们通过设计和合成五种新型铱 (III) 配合物来解决这些局限性：IrC2、IrC4、IrC6、IrC8 和 IrC12。我们的方法采用细致的侧链延伸策略来调节侧链长度，从而减少分子内运动并显着增强聚集状态下的一光子和三光子发射以及 1O2 产量。详细的光物理研究，在晶体学见解的支持下，表明侧链伸长大大增强了这些特性。在合成的复合物中，IrC8 脱颖而出，成为细胞和 3D 肿瘤球体模型中图像引导光动力治疗的优异候选者。这项研究开创了通过铱 (III) 复合物中新型侧链延伸策略同时增强双光子发射和 PDT 功效的先河，为其在临床治疗诊断中的转化应用铺平了道路。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Cyclometalated iridium(III) complexes have emerged as versatile candidates for cancer theranostics, offering integrated diagnostic imaging and potent singlet oxygen (1O2) generation for photodynamic therapy (PDT). However, their application has been limited by subdued photoluminescence, primarily due to intramolecular motion-induced excited energy dissipation. In this study, we address these limitations through the design and synthesis of five novel iridium(III) complexes: IrC2, IrC4, IrC6, IrC8, and IrC12. Our approach employs meticulous side-chain extending strategy to modulate side-chain length, thereby reducing intramolecular motion and significantly enhancing both one- and three-photon emissions and 1O2 production in the aggregated state. Detailed photophysical investigations, supported by crystallographic insights, reveal that side-chain elongation substantially amplifies these properties. Among the synthesized complexes, IrC8 stands out as a superior candidate for image-guided photodynamic therapy in cellular and 3D tumor spheroid models. This investigation pioneers the simultaneous enhancement of dual-photon emissions and PDT efficacy through a novel side-chain extension strategy in iridium(III) complexes, paving the way for their translational application in clinical theranostics.Copyright © 2024 Elsevier Inc. All rights reserved.