High Cytotoxicity of Ruthenium(II) and Gold(I) Bimetallic Complexes and Its Precursors

Inorg Chem. 2026 Jan 19;65(2):1463-1476. doi: 10.1021/acs.inorgchem.5c04993. Epub 2026 Jan 6.

Abstract

A series of Ru(II)-PC(n)P-Au(I) (n = 1-5) bimetallic complexes were successfully synthesized and characterized with phosphorus (31P{H}) and proton (1H) nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS), supported by crystallographic data. Correlations between resonance shifts and P-Au(I) bond distances provided insight into the electronic environment of the phosphorus centers, while single-crystal X-ray diffraction confirmed the molecular structures. Hirshfeld surface analysis revealed dominant H···H and F···H/H···F interactions, with contact percentages varying systematically with carbon chain length. Biological evaluation showed that the complexes exhibited higher cytotoxicity than cisplatin and melphalan against HeLa and Caco2 cancer cell lines, with pincer ligand carbon chain-length-dependent activity: shorter chains were more potent in HeLa cells, whereas longer chains were more effective in Caco2 cells. Most complexes displayed cytostatic activity, with compound 2b demonstrating the best overall performance, combining strong cytostatic properties with high selectivity toward cancerous cells. These findings highlight the structural, electronic, and biological relationships of the complexes, underlining their potential as anticancer agents.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Caco-2 Cells
  • 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
  • Gold* / chemistry
  • Gold* / pharmacology
  • HeLa Cells
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Ruthenium* / chemistry
  • Ruthenium* / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Ruthenium
  • Coordination Complexes
  • Gold