Rhodium(III) Dihalido Complexes: The Effect of Ligand Substitution and Halido Coordination on Increasing Cancer Cell Potency

Inorg Chem. 2021 Feb 1;60(3):2076-2086. doi: 10.1021/acs.inorgchem.0c03704. Epub 2021 Jan 19.

Abstract

This work presents the synthesis of eight new rhodium(III) dihalido complexes, [RhX2(L)(LH)] (where X = Cl or I), which incorporate two bidentate N-(3-halidophenyl)picolinamide ligands. The ligands have different binding modes in the complexes, whereby one is neutral and bound via N,N (LH) coordination, while the other is anionic and bound via N,O (L) coordination. The solid state and solution studies confirm multiple isomers are present when X = Cl; however, after a halide exchange with potassium iodide (X = I) the complexes exist exclusively as single stable trans isomers. NMR studies reveal the Rh(III) trans diiodido complexes remain stable in aqueous solution with no ligand exchange reported over 96 h. Chemosensitivity data against a range of cancer cell lines show two cytotoxic complexes, where L = N-(3-bromophenyl)picolinamide ligand. The results have been compared to the analogous Ru(III) complexes and overall highlight the Rh(III) trans diiodido complex to be ∼78× more cytotoxic than the analogous Rh(III) dichlorido complex, unlike the Ru(III) complexes which are equitoxic against all cell lines. Additionally, the Rh(III) trans diiodido complex is more selective toward cancerous cells, with selectivity index (SI) values >25-fold higher than cisplatin against colorectal carcinoma.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chlorides / chemistry
  • Chlorides / pharmacology*
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Iodine / chemistry
  • Iodine / pharmacology*
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Ruthenium / chemistry
  • Ruthenium / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Chlorides
  • Coordination Complexes
  • Ligands
  • Ruthenium
  • Iodine