Joel M. Gichumbi

Synthesis, characterization, and cytotoxic and antimicrobial activities of ruthenium(II) arene complexes with N,N-bidentate ligands

Abstract Three new complexes, [(η6-C6H6)RuCl(C5H4N-2-CH=N-Ar)]PF6 (Ar = phenylmethylene (1), (4-methoxyphenyl)methylene (2), and phenylhydrazone (3)), were prepared by reacting [(η6-C6H6)Ru(μ-Cl)Cl]2 with N,N′-bidentate ligands in a 1 : 2 ratio. Full characterization of the complexes was accomplished using 1H and 13C NMR, elemental and thermal analyses, UV–vis and IR spectroscopy and single crystal X-ray structures. Single crystal structures confirmed a pseudo-octahedral three-legged, piano-stool geometry around Ru(II), with the ligand coordinated to the ruthenium(II) through two N atoms. The cytotoxicity of the mononuclear complexes was established against three human cancer cell lines and selectivity was also tested against non-cancerous human epithelial kidney (HEK 293) cells. The compounds were selective toward the tumor cells in contrast to the known anti-cancer drug 5-fluoro uracil which was not selective between the tumor cells and non-tumor cells. All the compounds showed moderate activity against MCF7 (human breast adenocarcinoma), but showed low antiproliferative activity against Caco-2 and HepG2. Also, antimicrobial activities of the complexes were tested against a panel of antimicrobial-susceptible and -resistant Gram-negative and Gram-positive bacteria. Of special interest is the anti-mycobacterial activity of all three synthesized complexes against Mycobacterium smegmatis, and bactericidal activity against resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus ATCC 43300.

Synthesis, characterization, antiproliferative, and antimicrobial activity of osmium(II) half-sandwich complexes

Abstract New osmium(II)-arene complexes [(η6-C6H6)OsCl(C5H4N-2-CH=N-C6H5X)](PF6) (X = p-flouro (1), p-chloro (2), p-methyl (3)) were synthesized by reaction of the corresponding bidentate N,N′-ligands with the osmium-arene precursor [(η6-C6H6)Os(μ-Cl)Cl]2 in a 2:1 ratio. These complexes were characterized by UV–Vis, IR, 1H, 13C NMR spectroscopy, and elemental analysis and, for compound 1, a single crystal X-ray structure was also obtained. The complexes were investigated for antiproliferative activity in vitro against MCF-7 (human breast adenocarcinoma), Caco-2 (human epithelial colorectal adenocarcinoma), and HepG2 (human hepatocellular carcinoma) tumor cell lines. To test their selectivity, the non-tumor HEK293 (human embryonic kidney) cell line was used. The compounds were selective toward the tumor cell lines when compared to the known anticancer drug 5-fluorouracil which displayed low selectivity. The compounds were substantially more active against Caco-2 than 5-fluorouracil. They also showed moderate activity against the other two tumor cell lines. In addition, the antimicrobial activity of complex 2 was explored against a panel of antimicrobial-susceptible and -resistant Gram-negative and Gram-positive bacteria. Complex 2 showed anti-mycobacterial activity against Mycobacterium smegmatis and bactericidal activity against drug-resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus ATCC 43300.

Synthesis, characterization, anticancer and antimicrobial study of arene ruthenium(II) complexes with 1,2,4-triazole ligands containing an α-diimine moiety

Abstract The reaction of the ruthenium arene dimers [(η6-arene)Ru(μ-Cl)Cl]2 (where arene=benzene or p-cymene) with the ligands 4-benzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L1), 2-methoxybenzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L2), 4-methylbenzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L3) and indole-3-carbaldehyde-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L4) in a 1:2 ratio gives the new complexes [(η6-arene)RuCl(L)]+ [arene=C6H6 (with L=L1(1), L2(3), L4(7), with PF6− as a counter ion, and L4 (6), with Cl− as a counter ion) or p-cymene with L=L1(2), L2(4), L3(5), L4(8) with PF6− as a counter ion]. All complexes were fully characterized using 1H and 13C NMR, elemental analyses, UV/Vis and IR spectroscopy. The single crystal X-ray structures of ligand L2 and complex 1 have been determined. The structure of 1 has the Ru atom coordinated with the arene group and to the N,N′-bidentate ligand and to the Cl atom. The arene group occupies the apex, while the ligand and the Cl atom are at the base of a pseudo-octahedral three-legged piano stool. The cytotoxicity of these mononuclear complexes was established in the human epithelial colorectal adenocarcinoma cell line (Caco-2) and for selectivity in the non-cancerous human embryonic kidney cell line (HEK293), using 5-fluorouracil (5-FU) as the reference anticancer drug. Compounds 1 and 7 were relatively inactive toward the Caco-2 tumor cells (IC50>200), while complexes 2–5 showed moderate anti-proliferative properties (IC50>100–200). Compound 6, however, displayed better anti-proliferative properties with an IC50 value lower than that of the reference drug, 5-FU, and was therefore further investigated for its antimicrobial activity against six Gram-positive and four Gram-negative bacteria.

Crystal structure of chlorido-(η6–1-isopropyl-4-methyl benzene)-(1-(pyridin-2-yl)-N-(p-tolyl)methanimine-κ2N,N′)ruthenium(II) hexafluorophosphate(V), C23H26ClF6N2PRu

Abstract C23H26ClF6N2PRu, triclinic, P1̅ (no. 2), a = 8.9950(6) Å, b = 11.1669(8) Å, c = 12.4128(9) Å, α = 80.520(2)°, β = 87.5360(10)°, γ = 86.3200(10)°, V = 1226.59(15) Å3, Z = 2, Rgt(F) = 0.0267, wRref(F2) = 0.0622, T = 173(2) K.

Crystal structure of chlorido-(N-(2,5-dichlorophenyl)-1-(pyridin-2-yl)methanimine-κ2N,N′)(η6-1-isopropyl-4-methyl benzene) ruthenium (II) tetrafluoroborate, C22H22Cl3N2BF4Ru

Abstract C22H22Cl3N2BF4Ru, monoclinic, P21/n (no. 14), a = 15.067(5) Å, b = 10.409(5) Å, c = 16.503(5) Å, β = 112.75(5)°, V = 2386.9(16) Å3, Z = 4, Rgt(F) = 0.0211, wRref(F2) = 0.0535, T = 173 K.

Crystal structure of (η6-benzene)-(N-(2,6-dimethylphenyl)-1-(pyridin-2-yl)methanimine-κ2N,N′)ruthenium(II) perchlorate monohydrate, C20H20Cl2N2O5Ru

Abstract C20H20Cl2N2O5Ru, monoclinic, P1̅ (no. 2), a = 8.7921(2) Å, b = 11.2515(3) Å, c = 11.7014(3) Å, α = 103.752(1)°, β = 107.296(1)°, γ = 98.562(1)°, V = 1043.01(5) Å3, Z = 2, Rgt(F) = 0.0198, wRref(F2) = 0.0553, T = 173 K.

Crystal structure of 3,6-di-2-pyridinyl-4-pyridazine carbonitrile, C15H9N5

Abstract C15H9N5, monoclinic, P21/c (no. 14), a = 8.9817(4) Å, b = 11.5791(19) Å, c = 12.065(2) Å, β = 102.289(4)°, V = 1226.03(3) Å3, Z = 4, Rgt(F) = 0.0533, wRref(F2) = 0.1512, T = 173(2) K.