Modification of C^N cyclometalated ligands: theoretical design of structurally diverse Ir( <scp>iii</scp> ) complexes for two-photon photodynamic therapy

To develop novel photodynamic therapy (PDT) photosensitizers with high two-photon absorption cross-sections (<i>δ</i>_TPA) and long triplet-state lifetimes, and to provide clues for future practical PDT agents, we have designed a series of novel Ir(III) complexes by means of modification to the C^N ligand based on the experimentally synthesized high-performance photosensitizer [Ir(ppy)₂(osip)](PF₆). Subsequently, a comprehensive theoretical assessment was then conducted to systematically explore the impacts of C^N ligand modifications on the key characteristics of these photosensitizers. The results indicate that, compared to electron-donating substituents, introducing electron-withdrawing groups can effectively modulate the charge transfer types and significantly reduce the contribution of metal d-orbitals to the first excited singlet state S₁, while effectively enhancing electron-hole overlap. Thus, with such modifications complexes 3-5 exhibit not only larger <i>δ</i>_TPA and stronger fluorescence emission intensities but also longer triplet excited-state lifetimes. Overall, molecule 4 demonstrates the most outstanding photosensitizing properties among them, with the highest <i>δ</i>_TPA (78 GM), a high intersystem crossing efficiency (90.8%), and a long triplet-state lifetime (151.8 μs).