Ru(ii)-N-heterocyclic carbene complexes: synthesis, characterization, transfer hydrogenation reactions and biological determination

Abstract

A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl₂(p-cymene)]₂ in dichloromethane under Ar conditions. All new compounds were characterized by spectroscopic and analytical methods. These ruthenium(ii)-NHC complexes were found to be efficient precatalysts for the transfer hydrogenation of ketones by using 2-propanol as the hydrogen source in the presence of KOH as a co-catalyst. The antibacterial activity of ruthenium N-heterocyclic carbene complexes 3a-f was measured by disc diffusion method against Gram positive and Gram-negative bacteria. Compounds 3d exhibited potential antibacterial activity against five bacterial species among the six used as indicator cells. The product 3e inhibits the growth of all the six tested microorganisms. Moreover, the antioxidant activity determination of these complexes 3a-f, using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) as reagent, showed that compounds 3b and 3d possess DPPH and ABTS antiradical activities. From a concentration of 1 mg ml^-1, these two complexes presented a similar scavenging activity to that of the two used controls gallic acid (GA) and butylated hydroxytoluene (BHT). From a concentration of 10 mg ml^-1, the percentage inhibition of complexes 3b and 3d was respectively 70% and 90%. In addition, these two Ru-NHC complexes exhibited antifungal activity against Candida albicans. Investigation of the anti-acetylcholinesterase activity of the studied complexes showed that compounds 3a, 3b, 3d and 3e exhibited good activity at 100 μg ml^-1 and product 3d is the most active. In a cytotoxicity study the complexes 3 were evaluated against two human cancer cell lines MDA-MB-231 and MCF-7. Both 3d and 3e complexes were found to be active against the tested cell lines showing comparable activity with examples in the literature.

Scheme 1. Synthesis of ruthenium–NHC carbene complexes (3a–f).

Fig. 1. Structure of ruthenium–NHC carbene complexes 3(a–f).

Fig. 2. ¹H NMR spectra of Ru(ii)–N-heterocyclic carbene complexes 3a (CDCl₃, 300 MHz).

Fig. 3. ¹³C NMR spectra of Ru(ii)–N-heterocyclic carbene complexes 3a (CDCl₃, 75 MHz).

Fig. 4. DART-TOF-MS of Ru(ii)–N-heterocyclic carbene complexes 3a.

Scheme 2. Mechanism of fragmentation leading to peaks m/z = 225.

Fig. 5. Zone of inhibition of Ru–NHC complexes (3a–f).

Fig. 6. The method of determining the MIC.

Fig. 7. Scavenging activity of compounds 3b and 3d on DPPH radicals.

Fig. 8. Percent inhibition of complexes 3b and 3d as a function of concentration.

Fig. 9. Antifungal activity against Candida albicans.