Dipicolinate‐Ruthenium‐NHC/trpy Complexes: Pincer Ligand Induced Hemilability of Dipicolinate and Enhancement of Cytotoxic Property

Abstract A ruthenium(II) aquo complex [Ru(dipic)(PPh 3 ) 2 (OH 2 )], ( 1 A ), bearing O,N,O‐coordinated 2,6‐dipicolinate was synthesized via reaction of [Ru(PPh 3 ) 3 Cl 2 ] with 2,6‐dipicolinic acid. Crystal structure of 1 A was determined. Utilizing 1 A as a synthon, three new complexes were synthesized. Reaction of 1 A with a bidentate NHC‐ligand, viz . 1‐methyl‐3‐(2′‐pyridyl)imidazole ( IMe CN ), afforded [Ru(dipic)( IMe CN )(PPh 3 )], ( 2 A ). Similar reactions of 1 A with two pincer ligands, viz . 2,6‐bis(1′‐methyl imidazolyl)pyridine ( IMe CNC ) and 2,2′;6′,2“‐terpyridine ( trpy ), respectively yielded [Ru(dipic)( IMe CNC )(PPh 3 )], ( 3 A ) and [Ru(dipic)( trpy )(PPh 3 )], ( 3 B ). Structure of 2 A was optimized by DFT method. Structures of 3 A and 3 B were determined by X‐ray crystallography. In both 3 A and 3B the 2,6‐dipicolinate ligand was found to be N,O‐coordinated with one carboxy end remaining unbound to the metal center. Anticancer property of 2 A , 3 A and 3 B was studied and compared. Cytotoxicity of 3 A , studied against three selected cancer cell lines, viz . chronic myelogenous leukemia cell line (K562), hepatocellular carcinoma cell line (HepG2) and breast adenocarcinoma cell line (MCF7), was found to be the most promising. It displayed the best activity against K562, while it did not have any appreciable effect on its normal counterpart, viz . the human peripheral blood mononuclear cells (hPBMC). The comparative cytotoxicity studies indicated that presence of the C,N,C‐coordinated pincer NHC ligand in 3 A , together with presence of the free carboxylate end of N,O‐coordinated dipic ligand, are presumably responsible for its superior cytotoxic behavior.