N-Heterocyclic Carbene Platinum(IV) as Metallodrug Candidates: Synthesis and 195Pt NMR Chemical Shift Trend

Molecules. 2020 Jul 9;25(14):3148. doi: 10.3390/molecules25143148.

Abstract

A series of octahedral platinum(IV) complexes functionalized with both N-heterocyclic carbene (NHC) ligands were synthesized according to a straightforward procedure and characterized. The coordination sphere around the metal was varied, investigating the influence of the substituted NHC and the amine ligand in trans position to the NHC. The influence of those structural variations on the chemical shift of the platinum center were evaluated by 195Pt NMR. This spectroscopy provided more insights on the impact of the structural changes on the electronic density at the platinum center. Investigation of the in vitro cytotoxicities of representative complexes were carried on three cancer cell lines and showed IC50 values down to the low micromolar range that compare favorably with the benchmark cisplatin or their platinum(II) counterparts bearing NHC ligands.

Keywords: 195Pt NMR; N-heterocyclic carbene; metal complexes; platinum.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Drug Screening Assays, Antitumor
  • HCT116 Cells
  • Humans
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Neoplasms / drug therapy*
  • Nuclear Magnetic Resonance, Biomolecular
  • Organoplatinum Compounds* / chemical synthesis
  • Organoplatinum Compounds* / chemistry
  • Organoplatinum Compounds* / pharmacology
  • PC-3 Cells

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • carbene
  • Methane