(C^Npz^C)AuIII complexes of acyclic carbene ligands: synthesis and anticancer properties

Dalton Trans. 2017 Oct 10;46(39):13397-13408. doi: 10.1039/c7dt02804k.

Abstract

A series of cyclometallated gold(iii) complexes supported by pyrazine-based (C^Npz^C)-type pincer ligands were synthesized via two different pathways. Nucleophilic attack on the isocyanide complex [(C^Npz^C)Au(C[triple bond, length as m-dash]NC6H3Me2-2,6)]SbF6 (2) gave [(C^Npz^C)Au(ACC)]SbF6 complexes with aniline (4·SbF6), adamantylamine (5), glycine ethyl ester (6), alanine methyl ester (7), valine methyl ester (8), phenylglycine methyl ester (9) and methionine methyl ester (10) substituents (ACC = acyclic carbene). The pathway via isocyanide insertion into gold-amide bonds was also investigated; e.g. the reaction of xylyl isocyanide with (C^Npz^C)AuNHPh followed by protonation with HBF4·OEt2 gave the acyclic carbene complex 4·BF4. To the best of our knowledge compounds 6-10 represent the first examples of gold(iii) acyclic carbene complexes bearing amino acid functions. The compounds provide a versatile platform for the study of the anti-proliferative properties of gold(iii) complexes. Tests against human adenoma-type lung cancer cells identified 5, 6, 7 and 10 as particularly promising and demonstrate the synthetic flexibility of acyclic carbene complexes and the potential of that class of compounds for anticancer applications. Compared to cisplatin, amino ester-containing ACC complexes showed improved selectivity for MCF-7 breast cancer cells over that for healthy fibroblasts.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Carbon / chemistry
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Glutathione / chemistry
  • Glutathione / metabolism
  • Gold / chemistry*
  • Humans
  • Ligands
  • MCF-7 Cells
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Molecular Conformation
  • Nitrogen / chemistry
  • Pyrazines / chemistry*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Ligands
  • Pyrazines
  • Reactive Oxygen Species
  • carbene
  • Carbon
  • Gold
  • Glutathione
  • Nitrogen
  • Methane