Novel cis-[(NHC)1(NHC)2(L)Cl]platinum(ii) complexes - synthesis, structures, and anticancer activities

Dalton Trans. 2016 Oct 21;45(39):15390-15398. doi: 10.1039/c6dt02350a. Epub 2016 Sep 6.

Abstract

A general synthesis of novel platinum(ii) complexes bearing two different, cis-oriented, N-heterocyclic carbene (NHC) ligands is presented. Easily accessible cis-[PtII(NHC)(DMSO)] precursor complexes were converted to either cis-[PtII(NHC)2Cl2] complexes such as 5a and 5b, or to novel mixed cis-[PtII(NHC)1(NHC)2Cl2] complexes such as 5c-h by successive introduction of the individual carbene ligands. The 'symmetric' complexes 5a and 5b were also converted to cationic cis-[PtII(NHC)2(PPh3)Cl]+Cl- complexes 8a and 8b. The structures of the ten new complexes, comprising benzylated and alkylated imidazol-2-ylidene ligands, were analysed by 1H, 13C and 195Pt NMR spectroscopy and also by X-ray diffraction for 5a, 5d, 5h, and 8a. The neutral complexes 5 were cytotoxic against a panel of seven human cancer cell lines with IC50 values in the low micromolar range, while the cationic complexes 8 reached even nanomolar IC50 values. Complex 5h carrying the substitution pattern of the natural antitumoral agent Combretastatin A-4 showed a conspicuous specificity for cancer cell lines sensitive to this drug. In electrophoretic mobility shift assays, the cis-biscarbene complexes 5b and 8b led to an unwinding or aggregation of plasmid DNA, while the trans-biscarbene complex 1b showed no such effect.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • Heterocyclic Compounds / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Molecular Structure
  • Platinum / chemistry*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Heterocyclic Compounds
  • Ligands
  • carbene
  • Platinum
  • Methane