Theoretical Investigation of Novel Nitrogen-Heterocyclic Iridium(III) Polypyridyl Complexes as Photosensitizers for Two-Photon Photodynamic Therapy

Two-photon photodynamic therapy (TP-PDT) has become a major cancer treatment due to its larger tissue penetration depth, good spatial selectivity, and less damage to normal cells. In this contribution, a series of novel photosensitizer molecules (<b>Ir-2</b>, <b>Ir-2-1</b>∼<b>Ir-2-4</b>) have been designed based on the experimentally demonstrated photosensitizer [Ir(ppy)₂(osip)] (PF₆) by fine tuning the π-conjugated structure and introducing different nitrogen-heterocyclic substituents. The electronic structures, one- and two-photon absorption spectra, triplet excited state lifetime, solvation-free energy, and photosensitizing performance were evaluated by means of density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results suggested that the molecule <b>Ir-2</b>, incorporating thiophene as the π-connecting group, exhibits a higher probability of triplet state formation, enhanced two-photon absorption cross-section, and prolonged triplet state lifetime. Furthermore, the four designed nitrogen-heterocyclic complexes <b>Ir-2-1</b>∼<b>Ir-2-4</b> demonstrate favorable photosensitizing properties, with two-photon absorption cross-sections reaching up to 110 GM and triplet excited state lifetimes exceeding 1000 μs for <b>Ir-2-4</b>.