Synthesis, single-crystal and solution structure analysis and in vitro cytotoxic activity of two novel complexes of ruthenium(ii) with in situ formed flavanone-based ligands.

Abstract

Synthesis, structure and properties of two new flavanone complexes of Ru(II) are described. The new complexes form during the reaction of ruthenium(III) chloride with 3-aminoflavone (3-af) dissolved in an aliphatic alcohol. The formed products depend on the alcohol used and were found to be: cis-dichloridobis(3-imino-2-methoxyflavanone)ruthenium(II)·3H₂O (1) from a methanolic solution and cis-dichloridobis(3-imino-2-ethoxyflavanone)ruthenium(II)·2H₂O (2) from an ethanolic solution, in which the original ligand 3-af had been converted by dehydrogenative alcoholysis to an entirely new ligand. This paper presents the X-ray structure and detailed ¹H-NMR analysis of both new compounds, as well as the study of their antiproliferative activity. The coordination of Ru(II) is octahedral with [RuCl₂N₂O₂] chromophores, having trans chlorides and common Ru–L distances. Both 1 and 2 are highly cytotoxic towards the cisplatin resistant EJ and L1210 cell lines, and both complexes are as active as cisplatin in the sensitive cell lines. They display the ability to overcome cisplatin resistance in the drug resistant sub-lines EJcisR and L1210R. The present evidence suggests that the mechanism of biological activity may be different for these ruthenium compounds compared to cisplatin.