Cytotoxic activity and protein binding through an unusual oxidative mechanism by an iridium(I)-NHC complex

Chem Commun (Camb). 2015 Feb 21;51(15):3151-3. doi: 10.1039/c4cc10014j.

Abstract

A new NHC iridium(I) complex (1) showing significant antiproliferative properties in vitro is described here. Its crystal structure, solution behaviour and interactions with the model proteins cytochrome c (cyt c) and lysozyme were investigated. High resolution ESI-MS measurements suggest that this iridium(i) complex acts as a prodrug and binds cyt c tightly through an unusual "oxidative" mechanism. Eventually, an iridium(III)-NHC fragment is found associated to the protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology
  • Cytochromes c / chemistry
  • HEK293 Cells
  • HT29 Cells
  • Heterocyclic Compounds / chemistry*
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Iridium / chemistry*
  • Iridium / pharmacology
  • MCF-7 Cells
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Methane / pharmacology
  • Muramidase / chemistry
  • Oxidation-Reduction

Substances

  • Coordination Complexes
  • Heterocyclic Compounds
  • carbene
  • Iridium
  • Cytochromes c
  • Muramidase
  • Methane