A Red-Emitting Benzothiazole-Based Tridentate Iridium(III) Complex for Mitochondria-Targeting Anticancer Therapy

Fei Luo,Qin Zhou,Ruixia Liu,Anli Liu,Zhigang Niu,Fabiao Yu,Gaonan Li

First published: 09 July 2026

https://doi.org/10.1002/aoc.70621Digital Object Identifier (DOI)

ABSTRACT

Given the limitations of platinum-based drugs in terms of toxicity and drug resistance, the development of highly efficient and low-toxicity iridium complexes has become a focal point in anticancer research. In this study, a new tridentate iridium complex, Ir-BTQCl, was rationally designed and synthesized, displaying red emission at 616 nm in solution with a photoluminescence quantum yield of 5.7%. The complex exhibited potent inhibitory effects across multiple tumor cell lines and demonstrated a remarkably lower IC50 value (2.97 μM) against A549 cells than cisplatin (20.01 μM). Mechanistic studies revealed that Ir-BTQCl primarily localizes in mitochondria, leading to a decrease in mitochondrial membrane potential (MMP), elevated reactive oxygen species (ROS) levels, G0/G1 cell-cycle arrest, and apoptosis via the mitochondrial pathway. In an A549 tumor-bearing mouse model, the complex achieved a tumor inhibition rate of 76.85%, significantly outperforming cisplatin (53.62%) while showing lower systemic toxicity. This study provides new insights into the development of highly efficient and low-toxicity mitochondria-targeted iridium-based antitumor agents.

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