The key role of coligands in novel ruthenium(II)-cyclopentadienyl bipyridine derivatives: Ranging from non-cytotoxic to highly cytotoxic compounds

J Inorg Biochem. 2015 Sep:150:148-59. doi: 10.1016/j.jinorgbio.2015.06.015. Epub 2015 Jun 20.

Abstract

A new family of eight ruthenium(II)-cyclopentadienyl bipyridine derivatives, bearing nitrogen, sulfur, phosphorous and carbonyl sigma bonded coligands, has been synthesized. Compounds bearing nitrogen bonded coligands were found to be unstable in aqueous solution, while the others presented appropriate stabilities for the biologic assays and pursued for determination of IC50 values in ovarian (A2780) and breast (MCF7 and MDAMB231) human cancer cell lines. These studies were also carried out for the [5: HSA] and [6: HSA] adducts (HSA=human serum albumin) and a better performance was found for the first case. Spectroscopic, electrochemical studies by cyclic voltammetry and density functional theory calculations allowed us to get some understanding on the electronic flow directions within the molecules and to find a possible clue concerning the structural features of coligands that can activate bipyridyl ligands toward an increased cytotoxic effect. X-ray structure analysis of compound [Ru(η(5)-C5H5)(bipy)(PPh3)][PF6] (7; bipy=bipyridine) showed crystallization on C2/c space group with two enantiomers of the [Ru(η(5)-C5H5)(bipy)(PPh3)](+) cation complex in the racemic crystal packing.

Keywords: Cyclic voltammetry; Cyclopentadienyl; Cytotoxicity; Electronic flow; Ruthenium(II).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,2'-Dipyridyl / analogs & derivatives*
  • 2,2'-Dipyridyl / chemical synthesis
  • 2,2'-Dipyridyl / chemistry
  • 2,2'-Dipyridyl / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Electrochemical Techniques
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Chemical
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Ruthenium / chemistry*
  • Serum Albumin / chemistry
  • Spectrometry, Fluorescence
  • Tryptophan / chemistry

Substances

  • Antineoplastic Agents
  • Ligands
  • Organometallic Compounds
  • Serum Albumin
  • 2,2'-Dipyridyl
  • Ruthenium
  • Tryptophan