Synthesis, characterization and anticancer activities of cationic η6-p-cymene ruthenium(II) complexes containing phosphine and nitrogenous ligands

Loading...
Thumbnail Image
Date
2022
Authors
Guimaraes, Ivelise D. L.
Marszaukowski, Flávia
Rutka, Priscila B.
Borge, Luis F.
Ribeiro, Renan A. P.
Ricardo de Lazaro, Sergio
Castellen, Patrícia
Sagoe-Wagner, Araba
Golsteyn, Roy M.
Boeré, René T.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
Ruthenium-based anticancer agents have created a center of attention in the field of inorganic medicinal chemistry. The first fully characterized cationic ruthenium(II)-arene complexes [Ru(η6-p-cymene) (PAr3)LNCl]+ with highly lipophilic PAr3 ligands where Ar = 3,5-((CH3)3C)2C6H3– (L1), 3,5-(CH3)2C6H3– (L2), 4-CH3O-3,5-(CH3)2C6H2– (L3) and 4-CH3O-C6H4– (L4) with N = 3-methylpyridine (1–4, respectively), or L4 and 4-methylpyridine (5), or L4 and CH3CN (6) were obtained (yields 67–91%) as solids stable to light and air. Electrical conductance indicates that all the complexes are 1:1 electrolytes in solution. Their composition and purity have been unambiguously established by single-crystal X-ray diffraction, NMR spectroscopy and elemental analysis. The coordination geometries are uniform for all six complexes and each structure consist of a unipositive complex cation bearing the phosphine ligands L1-L4 and LN = 3-methylpyridine, 4-methylpyridine or CH3CN attached to the organometallic fragment. The equivalent unit cell volumes per formula unit decrease with 1 > 3 > 2 > 4 > 5 > 6, accurately reflecting the decreasing sizes of the phosphines L1-L4, and a greater occupied volume for 3-methyl- vs. 4-methylpyridine, and the smallest volume contribution from CH3CN. Electrochemical studies showed mixed electrochemical mechanisms (EC/ECE) from partial substitution of p-cymene by CH3CN ligands from the solvent. A large electrochemical stability window (>2.2 V) for Ru(II) was observed extending beyond the physiological E° range. The complexes were cytotoxic against human cancer cell lines in vitro, and some complexes altered cell morphology.
Description
Accepted author manuscript.
Keywords
Cationic ruthenium-arene , Triarylphosphine , Pyridine derivative , Cyclic voltammetry , Cytotoxicity assays , DFT calculations
Citation
Guimaraes, I. D. L., Marszaukowski, F., Rutka, P. B., Borge, L. F., Ribeiro, R. A. P., Ricardo de Lazaro, S., Castellen, P., Sagoe-Wagner, A., Golsteyn, R. M., Boeré, R. T., & Wohnrath, K. (2022).Synthesis, characterization and anticancer activities of cationic η6-p-cymene ruthenium(II) complexes containing phosphine and nitrogenous ligands. Polyhedron, 224, Article 115980. https://doi.org/10.1016/j.poly.2022.115980