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Copper compounds with artificial metallo-nuclease (AMN) activity are mechanistically unique compared to established metallodrugs. Here, we describe the development of a new dinuclear copper AMN, Cu2-BPL-C6 (BPL-C6 = bis-1,10-phenanthroline-carbon-6), prepared using click chemistry that demonstrates site-specific DNA recognition with low micromolar cleavage activity. The BPL-C6 ligand was designed to force two redox-active copper centres-central for enhancing AMN activity-to bind DNA, via two phenanthroline ligands separated by an aliphatic linker.

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Dinuclear Dicationic Iridium Complexes for Highly Synergistic Photodynamic and Photothermal Therapy to Chemoresistant Cancer.

Inorg Chem

January 2025

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Provincial Center for Research and Development of Natural Products; School of Pharmacy, Yunnan University, Kunming 650500, P. R. China.

A series of dinuclear Ir(III) complexes have been constructed for enhanced photodynamic and photothermal therapy (PDT and PTT) for cisplatin-resistant non-small-cell lung cancer. They enter cells via caveolar endocytosis, target mitochondria but not nuclear, generate both singlet oxygen and superoxide anion, and release heat when exposed to infrared (IR) irradiation, thus inducing reactive oxygen species (ROS)-associated cell disruption and thermal ablation. The IR-generated ROS can further activate caspases, triggering apoptosis.

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This study focuses on the use of three isostructural NO donor ligands, specifically known to form complexes with copper ions, to chelate Cu(II) from aqueous solutions. The corresponding Cu(II) complexes feature a dinuclear copper core mimicking the active site of natural superoxide dismutase (SOD) enzymes while also creating a coordination environment favorable for catalase (CAT) activity, being thus appealing as catalytic antioxidant systems. Given the critical role of copper dysregulation in the pathophysiology of Alzheimer's disease (AD), these complexes may help mitigate the harmful effects of free Cu(II) ions: the goal is to transform copper's reactive oxygen species (ROS)-generating properties into beneficial ROS-scavenging action.

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The ability of photosensitizers (PSs) to generate reactive oxygen species (ROS) is crucial for photodynamic therapy (PDT). However, many traditional PSs face the drawbacks that aggregation-caused quenching (ACQ) and highly expressed glutathione (GSH) in the tumor microenvironment seriously limit their ROS generation ability. Herein, we report two cationic dinuclear iridium complexes, and , which possess aggregation-induced emission (AIE).

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Cancer is a prominent global cause of mortality. Palladium complexes have the potential to serve as effective anticancer and pharmacological agents, offering a viable alternative to platinum medications. This work focused on the development of a new thiolato-bridged dinuclear [Pd(M3MPyThU)Cl]2 and mononuclear palladium [Pd(M3MPyThU)2] complexes containing 1-methyl-3-(3-methylpyridin-2-yl) thiourea (HM3MPyThU) ligand.

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