Triphenylamine-appended cyclometallated iridium(III) complexes: Preparation, photophysical properties and application in biology/luminescence imaging

J Inorg Biochem. 2019 Oct:199:110757. doi: 10.1016/j.jinorgbio.2019.110757. Epub 2019 Jun 27.

Abstract

Four triphenylamine (TPA)-appended cyclometallated iridium(III) complexes were designed and synthesized. Photophysical properties of these complexes were studied, and density functional theory (DFT) was utilized to analyze the influence of the ancillary ligands (TPA-modified bipyridine) to these complexes. The introduction of TPA units could effectively adjust the lipid solubility of complexes (logP), and endowed complexes with potential bioactivity (anticancer, antibacterial and bactericidal activity), especially in the field of anticancer (the best value of IC50 is 4.34±0.01μM). Interestingly, complexe 4 show some selectivity for cancer cells versus normal cells. Meanwhile, complexes could effectively prevent the metastasis of cancer cells. Complexes can be transported by serum albumin and followed by the static quenching mechanism (Kq: 1013M-1s-1), disturb cell cycle at G0/G1 phase, and induce apoptosis. The favorable fluorescence property confirmed these complexes followed by an energy-dependent cellular uptake mechanism, effectively accumulated in lysosomes (PCC: >0.95) and induced lysosomal damage, and eventually leaded to cell death. Our study demonstrates that these complexes are potential anticancer agents with dual functions, including metastasis inhibition and lysosomal damage.

Keywords: Bioactivity; Cyclometallated iridium complex; Luminescence imaging; Photophysical property; Triphenylamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Aniline Compounds / chemistry*
  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cattle
  • Cell Cycle / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Proliferation / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology*
  • Drug Screening Assays, Antitumor
  • Escherichia coli / drug effects
  • Humans
  • Iridium / chemistry*
  • Luminescence
  • Lysosomes / drug effects
  • Membrane Potential, Mitochondrial
  • Microbial Sensitivity Tests
  • Serum Albumin, Bovine / chemistry
  • Structure-Activity Relationship

Substances

  • Aniline Compounds
  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Coordination Complexes
  • Serum Albumin, Bovine
  • Iridium