Synthesis, structural characterization, DNA/protein binding and in vitro cytotoxicity of three structurally different organoruthenium metallates from single pot

Abstract

One pot synthesis of three structurally different ruthenium(II) carbonyl complexes [Ru(N,S-H-Nap-mtsc)(CO)Cl(PPh3)2](1a), [Ru(N,N,S-H-Nap-mtsc)(CO)Cl(PPh3)2](1b) and [Ru(Nap-mtsc)(CO)(PPh3)2] (1c) were prepared from a reaction of 2-hydroxy-1-naphthaldehyde-4(N)-methylthiosemicarbazone and [RuHCl(CO)(PPh3)3] in benzene. However, the same reaction in ethanol, methanol and DMF afforded only 1a and 1c. The new complexes were characterized by various spectro analytical techniques. The structure of the complexes 1a and 1c were solved by X-ray crystallography. In 1a the ligand behaved as bidentate monobasic by forming an unusual four member chelate ring. However, in 1c the ligand behaved as tridentate bibasic (ONS) donor by forming five and six member chelate rings. Attempts to crystallize 1b were unsuccessful due to the structural conversion of 1b to 1c. DFT studies were carried out to know more on the structural aspects of these new complexes. From the results, it is inferred that ONS chelate (1c) has comparatively lesser energy than NS five (1b) and four (1a) member chelates. The structural conversion of 1b to 1c in polar solvents at room temperature prevents 1b to introduce for biological investigation. From the DNA binding studies, it is found that the complexes 1a and 1c bind through intercalative mode. In addition, they had a strong binding affinity with bovine serum albumin (BSA) through static quenching. The complexes 1a and 1c were subjected to in vitro cytotoxicity studies against human lung cancer cells (A549) and liver cancer cells (HepG2). The IC50 values of the complexes 1a and 1c were found to be lower than cisplatin in A549 cell line. However, in HepG2 cell line; IC50 values were found in the following order 1c < cisplatin < 1a. Among the two metallates, 1c found to possess higher cytotoxicity and this may be due to the increase in electron delocalization within five and six member rings, which facilitates the reduction of electron density on ruthenium ion and subsequent increase in the cell permeability.