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Mitochondrial-DNA-Targeted IrIII -Containing Metallohelices with Tunable Photodynamic Therapy Efficacy in Cancer Cells

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Indexed by:Journal Papers

Date of Publication:2020-01-22

Journal:Angewandte Chemie (International ed. in English)

Included Journals:PubMed

ISSN No.:1521-3773

Key Words:DNA recognition,IrIII complex,cancer,helical structures,photodynamic therapy

Abstract:The development of DNA-targeted photodynamic therapy (PDT) agents for cancer treatment has drawn substantial attention. Herein, the design and synthesis of dinuclear IrIII -containing luminescent metallohelices with tunable PDT efficacy that target mitochondrial DNA in cancer cells are reported. The metallohelices are fabricated using dynamic imine-coupling chemistry between aldehyde end-capped fac-Ir(ppy)3 handles and linear alkanediamine spacers, followed by reduction of the imine linkages. The length and odd-even character of the diamine alkyl linker determined the stereochemistry (helicates vs. mesocates). Compared to the helicates, the mesocates exhibit improved apoptosis-induction upon white-light irradiation. Molecular docking studies indicate that the mesocate with a proper length of diamine spacers shows stronger affinity for the minor groove of DNA. This study highlights the potential of DNA-targeting IrIII -containing metallohelices as PDT agents.© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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