Abstract
AbstractThe 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.
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