Synthesis and cytotoxic activities of organometallic Ru(II) diamine complexes.

ABSTRACT

A series of mono and bimetallic ruthenium(II) arene complexes bearing diamine (Ru1-6) were prepared and fully characterized by 1H, 13C, 19F, and 31P NMR spectroscopy and elemental analysis. The crystal structure of the bimetallic complex (Ru5) was determined by X-ray crystallography. Monometallic analogues (Ru1-3) were synthesized to investigate the contributions of ruthenium and the other organic groups (aren, ethylenediamine, butyl) to the activity. The electrochemical behaviors of mono and bimetallic complexes were obtained from the relationship between cyclic voltammetry (CV) and the biological activities of the compounds. The cytotoxic activities of the complexes (Ru1-6) were tested against wide-scale cancer cell lines, namely HeLa, MDA-MB-231, DU-145, LNCaP, Hep-G2, Saos-2, PC-3, and MCF-7, and normal cell lines 3T3-L1 and Vero. Diamine Ru(II) arene complexes have unique biological characteristics and they are promising models for new anticancer drug development. MTT analysis reveals that each synthesized Ru complex showed cytotoxic activity towards the different cancer cells. In particular, three Ru complexes (Ru3, Ru5 and Ru6) showed less toxic effects on the cancer cells than the others. These novel Ru complexes affected both cancer and normal cell lines. As they had a toxic effect on the cells, the dosage applied should be tested before being used for in vivo applications. Cytotoxicity tests have shown that the bimetallic complex Ru6 was effective on all cancer cells. The effect of bimetallic enhancement on cancer cell lines, the systematic variation of the intermetallic distance and the ligand donor properties of the mono and bimetallic complexes were explored based on the cytotoxic activity. The interaction with FS-DNA and the stability/aquation of the complexes (Ru3 and Ru6) were investigated with 1H NMR spectroscopy. The binding modes between the complexes (Ru3 and Ru6) and DNA were investigated via UV-Vis spectroscopy.