Theoretical\nInvestigation of Novel Nitrogen-Heterocyclic\nIridium(III) Polypyridyl Complexes as Photosensitizers for Two-Photon\nPhotodynamic Therapy

Two-photon\nphotodynamic therapy (TP-PDT) has become a major cancer\ntreatment due to its larger tissue penetration depth, good spatial\nselectivity, and less damage to normal cells. In this contribution,\na series of novel photosensitizer molecules (<b>Ir-2</b>, <b>Ir-2–1</b>∼<b>Ir-2–4</b>) have been\ndesigned based on the experimentally demonstrated photosensitizer\n[Ir(ppy)<sub>2</sub>(osip)] (PF<sub>6</sub>) by fine tuning the π-conjugated\nstructure and introducing different nitrogen-heterocyclic substituents.\nThe electronic structures, one- and two-photon absorption spectra,\ntriplet excited state lifetime, solvation-free energy, and photosensitizing\nperformance were evaluated by means of density functional theory (DFT)\nand time-dependent density functional theory (TDDFT). The results\nsuggested that the molecule <b>Ir-2</b>, incorporating thiophene\nas the π-connecting group, exhibits a higher probability of\ntriplet state formation, enhanced two-photon absorption cross-section,\nand prolonged triplet state lifetime. Furthermore, the four designed\nnitrogen-heterocyclic complexes <b>Ir-2–1</b>∼<b>Ir-2–4</b> demonstrate favorable photosensitizing properties,\nwith two-photon absorption cross-sections reaching up to 110 GM and\ntriplet excited state lifetimes exceeding 1000 μs for <b>Ir-2–4</b>.