👤 Golubeva, Yu. A.

Three copper(II) complexes – [Cu2(bipy)2L4] (1), [Cu2(phen)2L4] (2) and [Cu2(dmphen)2L4]·2H2O (3) – were synthesized based on 5-methyltetrazole (HL) and 2,2′-bipyridine/1,10-phenanthroline derivatives. A crystallographic study revealed that complexes 1–3 have a binuclear structure with coordination polyhedron close to the square pyramid. Stability of the complexes in aqueous solution was studied by UV-Vis spectroscopy and conductometry. In vitro cytotoxicity study was carried out in 2D and 3D cell culture models and showed that complexes 2 and 3 possess cytotoxic activity against tumor cells (A549, Hep2, HepG2, MCF7) with LC50 values exceeding those of the medical drug cisplatin. At the same time, being less active, compound 1 has a selectivity index of 3.1 to hepatocellular carcinoma (HepG2 cell line) compared to non-tumor MRC5 cells. The Hoechst/Propidium iodide staining assay and ROS generation assay on Hep2 cells indicated that the cytotoxic effects of the complexes involved apoptosis induction without ROS accumulation. Show less

Abstract The review is devoted to copper coordination compounds based on 2,2′-bipyridine / 1,10-phenanthroline and diverse N-, O-, S-donor ligands exhibiting cytotoxic properties. Therefore, they can be a starting platform for developing antitumor drugs. The review covers the structural aspects of the complexes, the features of their cytotoxic activity and its mechanism, as well as in vivo studies. Show less

Nickel(II) complexes of 1H-tetrazol-5-acetic acid (H2L) and oligopyridines (1,10-phenanthroline /2,2’-bipyridine derivatives) have been synthesized and characterized by physicochemical methods (elemental and thermogravimetric analysis, powder X-ray diffraction, and IR spectroscopy). The behavior of the complexes in solution was studied by UV–Vis spectroscopy, conductometry, and mass spectrometry. The stability of the complexes over 48 h in aqueous solution and in phosphate-buffered saline was demonstrated using UV–Vis spectroscopy. These compounds were investigated for their cytotoxic and cytostatic activity against HepG2 (hepatocellular carcinoma), and Hep2 (larynx carcinoma) human cancer cell lines. Cytotoxicity was also studied on human non-cancerous cell line MRC-5 (lung fibroblast). All the compounds did not show cytotoxic activity against the tested cell lines in 1–50-µM concentration range. However, compounds showed a cytostatic effect against HepG2 and Hep2 cell lines. The most pronounced cytostatic properties were found for the complex [Ni(dmphen)2L]·2C2H5OH·2H2O (1). In addition, we report three new crystal structures: [Ni(phen)2L]·H2O, [Ni(dmbipy)2L]·2C2H5OH, and [Ni(dmphen)2L]·2C2H5OH·2H2O, where L2– behaves as a bidentate ligand which is coordinated to the Ni(II) ion via N,O atoms. Show less

Herein, we present the synthesis, characterization, and in vitro investigation of cytotoxic activity against cancer (HepG-2, MCF-7) and non-cancerous (Hek-293, MRC-5) cell lines of six copper(II) complexes with 1H-tetrazole-5-acetic acid (H2L) and secondary ligands, such as olygopyridines (dmphen – 4,7-dimethyl-1,10-phenanthroline, phendione – 1,10 phenanthroline-5,6-dione, 5-Cl-phen – 5-chloro-1,10-phenanthroline, phen – 1,10 phenanthroline, dmbipy – 2,2′-bi-4-picoline, bipy – 2,2′-bipyridine). These compounds were characterized by powder X-ray diffraction, IR spectroscopy, elemental, and thermogravimetric analysis. The behavior of the complexes in solution was studied by optical spectroscopy, conductometry, and EPR. The DNA binding constant has been obtained for complex 5 using UV–vis spectroscopy. The antimicrobial activity of the complexes has been investigated against E. coli, S. aureus, P. italicum, and C. steinii. In addition, eight new crystal structures were obtained: [Cu(5-Cl-phen)L]n·0.5DMSO·1.5H2O (3a), [Cu(phen)L]n·2.5nH2O (4·2.5nH2O), [Cu3(phen)2(H2O)(HL)2L2]n·6nH2O (4a), [Cu(dmbipy)L]n (5), [Cu(dmbipy)(HL)2] (5a), [Cu3(dmpiby)2(HL)2L2]n·2nH2O·2nC2H5OH (5b), [Cu(bipy)L]n (6), and [Cu(bipy)(H2O)L] (6a). Show less

Abstract A novel mononuclear manganese(II) complex with 5-methyltetrazole and 4,7-dimethyl-1,10-phenanthroline is synthesized and characterized by physico-chemical methods (elemental and powder XRD analyses, IR spectroscopy). It is shown by the single-crystal XRD analysis that the coordination environment of the manganese(II) atom is a distorted octahedron. The stability of the complex in an aqueous solution and in phosphate-buffered saline is studied by optical spectroscopy. The cytotoxic activity of the obtained compound is studied on human laryngeal carcinoma cells (Hep-2) and non-cancerous human fibroblasts (MRC-5). The complex exhibits pronounced cytotoxic properties in the studied concentration range: IC50 is 11.1±0.4 µM on the Hep-2 cancer cell line and 0.63±0.05 µM on the MRC-5 line. Show less

Based on bis-hetarylhydrazone H2L, a condensation product of 2,6-diacetylpyridine with 2-hydrazinobenzoxazole, a series of mononuclear copper(II) coordination compounds have been synthesized: [Cu(HL)NO3], [Cu(HL)(H2O)]ClO4, [Cu(HL)X] (X = Br−, X = Cl−). The structure of the compounds has been studied by means of NMR, IR, ESR, X-ray absorption spectroscopy and X-ray single crystal diffraction methods. In the compounds the copper center is in the square pyramidal environment. All compounds have been screened in vitro for their cytotoxic activity against HepG2 and MRC-5 cell lines. The ligand H2L shows no cytotoxicity at tested concentrations (1–100 μM), while all the Cu(II) complexes exhibit significant dose-dependent cytotoxic effects with IC50 values in the range of 1.4–3.0 μM (HepG2 cells). Show less

Abstract The complex [Zn(Phen)(H2O)L2] (I), where HL is 5-benzyltetrazole, Phen is 1,10-phenanthroline, was synthesized. The compound was characterized by standard physicochemical methods (elemental analysis, powder X-ray diffraction, IR spectroscopy). According to X-ray diffraction data (CCDC no. 2220597), zinc coordination environment in the crystal structure of I corresponds to a distorted trigonal bipyramid. The ligand HL is monodentate and is coordinated via tetrazolate ring nitrogen. The stability of complex I was studied by NMR spectroscopy in DMSO. The cytotoxic properties of the compound were assessed against HepG-2 (hepatocellular carcinoma) and MRC-5 (noncancerous human fibroblasts) cells. Complex I exhibits weak cytotoxic properties in the studied concentration range (1–100 µM). Show less

Abstract Five coordination compounds [Cu2(Bipy)2L4]·C2H5OH (Iа, Ib), [Cu2(Dmbipy)2L4] (II), [Cu2(Phen)2L4]·H2O (IIIa), [Cu2(Dmphen)2L4] (IVa), and [Cu2(Phendione’)2L4]·2C2H5OH·2H2O (V) are synthesized from 5-(4-chlorophenyl)-1H-tetrazole (HL), where Bipy is 2,2'-bipyridine, Dmbipy is 4,4'-dimethyl-2,2'-bipyridine, Phen is 1,10-phenanthroline, Dmphen is 4,7-dimethyl-1,10-phenanthroline, and Phendione’ is 6-ethoxy-6-hydroxy-1,10-phenanthrolin-5-one. The crystal structures of the complexes are determined by X-ray diffraction (XRD) of single crystals (CIF files CCDC nos. 2225368 (Ia), 2225369 (Ib), 2225370 (II), 2225372 (IIIa), 2225373 (IVa), and 2225371 (V)). The compounds are binuclear due to the bridging function of the tetrazolate anion, and the coordination number of copper is five in all synthesized complexes. The cytotoxic activity of the complexes against the Hep2 and HepG2 cancer cell lines and non-cancerous human fibroblasts MRC-5 is studied. The complexes exhibit pronounced cytotoxic properties, and compound V has the maximum selectivity index with respect to the cancer cells. Show less

Abstract The crystal structure of the Cu(II) binuclear complex with 5-phenyltetrazole and 4,4'-dimethyl-2,2'-bipyridine (dmbipy), [Cu2(dmbipy)2L4], has been determined. The complex crystallizes in a monoclinic space group P21/c. The distorted square-pyramidal environment of Cu(II) atoms is formed by five nitrogen atoms belonging to three 5-phenyltetrazolate anions and one dmbipy molecule. Due to the presence of the intermolecular interactions π···π and C–H···π, the binuclear molecules combine into a supramolecular layered structure. The bonding energy has been calculated in terms of the density functional theory for two models of the [Cu2(dmbipy)2L4] complex with various coordination modes of the bridging 5-phenyltetrazole. Show less