Theoretical Study of Iridium-Based PDT Photosensitizers for Improving Two-Photon Absorption, Triplet Lifetime, and Lipophilicity through Ligand Tuning
Year: 2026
Type: article
Abstract: Iridium-based photosensitizers have attracted significant attention in photodynamic therapy (PDT) due to their exceptional photophysical properties and chemical stability, as well as tunable phosphorescence emission spectrum and high triplet state production yields. Photosensitizers with large two-photon absorption (TPA) and mitochondrial targeting capabilities are particularly promising for clinical PDT, as they enable deeper tissue penetration and reduced damage to normal cells. In this study, we theoretically studied photophysical and photodynamic properties and the photosensitization reaction mechanism of a series of iridium-based photosensitizers with modified C^N and N^N ligands (a2–a6, b1/b1-r, and b2/b2-r) by TDDFT/DFT methods. The photophysical properties, including one- and two-photon absorption spectra, frontier molecular orbitals, and singlet and triplet excitation energies, were calculated. Additionally, rate constants for intersystem crossing, fluorescence, and phosphorescence, along with water solubility and lipophilicity metrics (logP), were determined to assess both efficacy and biocompatibility. The results elucidate the modulation roles of the chelated ligands and ancillary ligands in TP-PDT efficiency, indicating that the asymmetric iso-fused-benzene ring modification of the N^N ligand is a robust design strategy for comprehensively enhancing photosensitization performance. Complexes a2, b2, and b1-r show greater promise as candidates for two-photon PDT photosensitizers owing to their large TPA cross sections, extended triplet state lifetimes, and balanced water solubility and lipophilicity. Notably, the b1-r complex can undergo both Type I and Type II PDT photosensitization mechanisms, which will help address the issue of drug resistance arising from the hypoxic environment in deep-seated tumors.
Institution: Northeast Normal University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7160597657
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