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

Abstract

A ruthenium(II) aquo complex [Ru(dipic)(PPh3)2(OH2)], (1A), bearing O,N,O‐coordinated 2,6‐dipicolinate was synthesized via reaction of [Ru(PPh3)3Cl2] with 2,6‐dipicolinic acid. Crystal structure of 1A was determined. Utilizing 1A as a synthon, three new complexes were synthesized. Reaction of 1A with 1‐methyl‐3‐(2ʹ‐pyridyl)imidazole (IMeCN), afforded [Ru(dipic)(IMeCN)(PPh3)], (2A). Similar reactions of 1A with two pincer ligands, viz. 2,6‐bis(1ʹ‐methyl imidazolyl)pyridine (IMeCNC) and 2,2';6',2"‐terpyridine (trpy), respectively yielded [Ru(dipic)(IMeCNC)(PPh3)], (3A) and [Ru(dipic)(trpy)(PPh3)], (3B). Structure of 2A was optimized by DFT. Structures of 3A and 3B were determined by X‐ray crystallography. In both 3A 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 2A, 3A and 3B was studied and compared. Cytotoxicity of 3A, studied against 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. hPBMC. The comparative cytotoxicity studies indicated that presence of the pincer NHC ligand in 3A, together with presence of the free carboxylate end of N,O‐coordinated dipic ligand, are presumably responsible for its superior cytotoxic behavior.