Issue 36, 2025

Contrasting effects of ethylene and propylene linkers on the kinetic stability of water-soluble near-infrared-absorbing diradical-PtII complexes

Abstract

Diradical-PtII complexes with o-phenylenediamine ligands exhibit intense near-infrared (NIR) absorption, making them applicable as photothermal agents for cancer imaging and therapy. However, their NIR-absorbing properties can be deactivated by ligand exchange with cellular substances such as glutathione (GSH). To improve the kinetic stability of diradical-PtII complexes, we synthesized two novel tetradentate ligands, 4,4′-(ethane-1,2-diylbis(azanediyl))bis(3-aminobenzenesulfonate) (EABS) and 4,4′-(propane-1,3-diylbis(azanediyl))bis(3-aminobenzenesulfonate) (PABS), in which two 3,4-diaminobenzenesulfonate (DABS) units are connected by an ethylene or propylene linker, respectively. Contrary to the expectation that the resulting chelate ring will enhance stability, [Pt(EABS)]2− readily released its linker to form [Pt(DABS)2]2− owing to its bent and twisted coordination structure. In contrast, [Pt(PABS)]2− was stable owing to its less distorted structure and exhibited an intense absorption peak at 723 nm (8.7 × 104 M−1 cm−1) in aqueous solution. Kinetic analysis of the ligand exchange reaction with GSH showed that the half-life of [Pt(PABS)]2− under intracellular conditions ([GSH] = 1.0 × 10–2 M) is 27 h, approximately 1300 and 16 000 times longer than those of [Pt(DABS)2]2− (72 s) and [Pt(EABS)]2− (5.9 s), respectively. Thus, the linker chain length significantly influences molecular structure and kinetic stability against GSH, with the propylene linker effectively enhancing the stability of diradical-PtII complexes. Additionally, ligand oxidation gradually extinguished the NIR absorption of aqueous [Pt(PABS)]2−, which would prevent unpredictable photothermal damage to healthy tissues after treatment. The ligand design of [Pt(PABS)]2− is expected to enable efficient imaging and therapy for cancer with minimal side effects.

Graphical abstract: Contrasting effects of ethylene and propylene linkers on the kinetic stability of water-soluble near-infrared-absorbing diradical-PtII complexes

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Article information

Article type
Paper
Submitted
29 Jul 2025
Accepted
09 Aug 2025
First published
19 Aug 2025

Dalton Trans., 2025,54, 13598-13608

Contrasting effects of ethylene and propylene linkers on the kinetic stability of water-soluble near-infrared-absorbing diradical-PtII complexes

R. Sawamura, S. Horii, K. Tamura, S. Tsuchiya and N. Iki, Dalton Trans., 2025, 54, 13598 DOI: 10.1039/D5DT01798J

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