Synthesis, physicochemical and theoretical studies on new rhodium and ruthenium dimers. Relationship between structure and cytotoxic activity

• Published in: Polyhedron 2018-11, Vol.154, p.263-274
• Main Authors: Masternak, Joanna, Gilewska, Agnieszka, Kazimierczuk, Katarzyna, Khavryuchenko, Oleksiy V., Wietrzyk, Joanna, Trynda, Justyna, Barszcz, Barbara
• Format: Article
• Language: English
• Subjects: Cytotoxicity; Dirhodium(II) complex; DNA interaction; Paddle wheel structure; Ru(II) dimer
• ISSN: 0277-5387
• DOI: 10.1016/j.poly.2018.07.054

Dimeric complexes of the formula (Et3NH)2[Rh2(μ2-L)4] (1) and [((η6-p-cymene)Ru)2(μ-Cl)3]PF6 (2), were synthesized and characterized by means of spectroscopic and physicochemical techniques, including single crystal X-ray diffraction. Antiproliferative activity of the complexes were evaluated against selected cell lines MV-4-11, LoVo, MCF-7 and normal BALB/3T3. Complex 1 is the most active against MV-4-11 with IC50 = 4.02 ± 1.08 µM. Binding of the obtained complexes to CT-DNA and BSA were investigated using UV–Vis and CD measurements. [Display omitted] Two dimeric compounds of the general formulae (Et3NH)2[Rh2(μ2-L)4Cl2] (1) (where L = thiophene-2-carboxylate) and [((η6-p-cymene)Ru)2(μ-Cl)3]PF6 (2) have been synthesized using a new method. The unique anionic complex 1 (space group P bca) has octahedral coordination in which the equatorial positions are occupied by the oxygen atoms of four thiophene-2-carboxylates in a paddle wheel fashion. In complex 2 (space group P1¯), each Ru(II) ion exhibits a pseudo-octahedral, three-legged piano-stool geometry. The electronic structure and absorption spectral features of 1 were also investigated by means of absorption spectroscopy (UV–Vis) and TD-DFT calculations. The biological studies of 1 and 2, such as cytotoxicity, lipophilicity and interactions with DNA and BSA, point on structure-cytotoxic activity relationship of obtained dimers. The results obtained via MTT, SRB assays, UV–Vis and CD spectroscopy, suggest that the rhodium dimer interacts with DNA via groove binding, whereas 2 binds to DNA via electrostatic interactions only. The effect of the dimeric complexes on the cytotoxicity of three human cancer lines, myelomonocytic leukaemia (MV-4-11), colon adenocarcinoma (LoVo) and breast adenocarcinoma (MCF-7), as well as on normal mice fibroblast cells (BALB/3T3), has been screened. Cisplatin was used as a reference drug. As a general observation, the properties reported in this paper suggest that the rhodium complex has considerable potential as an anticancer agent against myelomonocytic leukaemia (IC50 = 4.02 µM).