Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage.

In vivo Realization of Dual Photodynamic and Photothermal Therapy for Melanoma by Mitochondria Targeting Dinuclear Ruthenium Complexes under Civil Infrared Low-power Laser.

A series of dinuclear Ru complexes with extremely high TPA cross sections in the range of 800-900 nm have been designed. The amphiphilic complex Ru3 containing tert-butyl groups has balanced performance in singlet oxygen generation and photothermal conversion and becomes the ideal drug candidate of the series. Ru3 targets mitochondria without penetrating the nucleus, which substantially increases its photodynamic therapy activity and reduces its dark cytotoxicity.

Cyclometalated Iridium(III) Complexes as High-Sensitivity Two-Photon Excited Mitochondria Dyes and Near-Infrared Photodynamic Therapy Agents.

Photodynamic therapy (PDT) using two-photon near-infrared light excitation is a very effective way to avoid the use of short-wavelength ultraviolet or visible light which cannot efficiently penetrate into the biological tissues and is harmful to the healthy cells. Herein, a series of cyclometalated Ir(III) complexes with a structurally simple diimine ligand were designed and the synthetic route and preparation procedure were optimized, so that the complexes could be obtained in apparently higher yield, productivity, and efficiency in comparison to the traditional methods. Their ground state and excited singlet and triplet state properties were studied by spectroscopy and quantum chemistry theoretical calculations to investigate the effect of substituent groups on the photophysical properties of the complexes.