Cyclometalated Palladium(II) N-Heterocyclic Carbene Complexes: Anticancer Agents for Potent In Vitro Cytotoxicity and In Vivo Tumor Growth Suppression

Angew Chem Int Ed Engl. 2016 Sep 19;55(39):11935-9. doi: 10.1002/anie.201602814. Epub 2016 Aug 29.


Palladium(II) complexes are generally reactive toward substitution/reduction, and their biological applications are seldom explored. A new series of palladium(II) N-heterocyclic carbene (NHC) complexes that are stable in the presence of biological thiols are reported. A representative complex, [Pd(C^N^N)(N,N'-nBu2 NHC)](CF3 SO3 ) (Pd1 d, HC^N^N=6-phenyl-2,2'-bipyridine, N,N'-nBu2 NHC=N,N'-di-n-butylimidazolylidene), displays potent killing activity toward cancer cell lines (IC50 =0.09-0.5 μm) but is less cytotoxic toward a normal human fibroblast cell line (CCD-19Lu, IC50 =11.8 μm). In vivo anticancer studies revealed that Pd1 d significantly inhibited tumor growth in a nude mice model. Proteomics data and in vitro biochemical assays reveal that Pd1 d exerts anticancer effects, including inhibition of an epidermal growth factor receptor pathway, induction of mitochondrial dysfunction, and antiangiogenic activity to endothelial cells.

Keywords: N-heterocyclic carbenes; anticancer agents; palladium; proteomics; thiol reactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Coordination Complexes / therapeutic use*
  • Humans
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Methane / pharmacology
  • Methane / therapeutic use
  • Mice, Nude
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Palladium / chemistry
  • Palladium / pharmacology
  • Palladium / therapeutic use*


  • Antineoplastic Agents
  • Coordination Complexes
  • carbene
  • Palladium
  • Methane