Synthesis, characterization, and evaluation of biological activities of new 4′-substituted ruthenium (II) terpyridine complexes: Prospective anti-inflammatory properties

Abstract

The synthesis and characterization of Ru (II) terpyridine complexes derived from 4′ functionalized 2,2′:6′,2″-terpyridine (tpy) ligands are reported. The heteroleptic complexes comprise the synthesized ligands 4′-(2-thienyl)- 2,2′:6′,2″-terpyridine) or (4′-(3,4-dimethoxyphenyl)-2,2′:6′,2″-terpyridine and (dimethyl 5-(pyrimidin-5-yl)isophthalate). The new complexes [Ru(4′-(2-thienyl)-2,2′:6′,2″-terpyridine)(5-(pyrimidin-5-yl)-isophthalic acid)Cl2] (9), [Ru(4′-(3,4-dimethoxyphenyl)-2,2′:6′,2″-terpyridine)(5-(pyrimidin-5-yl)-isophthalic acid)Cl2] (10), and [Ru(4′-(2-thienyl)-2,2′:6′,2″-terpyridine)(5-(pyrimidin-5-yl)-isophthalic acid)(NCS)2] (11) were characterized by 1H- and 13C-NMR spectroscopy, C, H, N, and S elemental analysis, UPLC-ESI-MS, TGA, FT-IR, and UV-Vis spectroscopy. The biological activities of the synthesized ligands and their Ru (II) complexes as anti-inflammatory, antimicrobial, and anticancer agents were evaluated. Furthermore, the toxicity of the synthesized compounds was studied and compared with the standard drugs, namely, diclofenac potassium and ibuprofen, using hemolysis assay. The results indicated that the ligands and the complex 9 possess superior anti-inflammatory activities inhibiting albumin denaturation (89.88–100%) compared with the standard drugs (51.5–88.37%) at a concentration of 500 μg g−1. These activities were related to the presence of the chelating N-atoms in the ligands and the exchangeable chloro- groups in the complex. Moreover, the chloro- and thiophene groups in complex 9 produce a higher anticancer activity compared with its isothiocyanate derivative in the complex 11 and the 3,4-dimethoxyphenyl moiety in complex 10. Considering the toxicity results, the synthesized ligands are nontoxic or far less toxic compared with the standard drugs and the metal complexes. Therefore, these newly synthesized compounds are promising anti-inflammatory agents in addition to their moderate unique broad antimicrobial activity.