Ruthenium p-Cymene Complexes Incorporating Substituted Pyridine–Quinoline-Based Ligands: Synthesis, Characterization, and Cytotoxic Properties
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ABSTRACT:
SUBMITTER: Kokkosi A
PROVIDER: S-EPMC11243419 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Project description:Ruthenium(II) arene complexes of the general formula [RuCl(η6-p-cymene)(diamine)]PF6 (diamine = 1,2-diaminobenzene (1), 2,3-diaminonaphthalene (2), 9,10-diaminophenanthrene (3), 2,3-diaminophenazine (4), and 1,2-diaminoanthraquinone (5) were synthesized. Chloro/aqua exchange was evaluated experimentally for complexes 1 and 2. The exchange process was investigated theoretically for all complexes, revealing relatively fast exchange with no significant influence from the polycyclic aromatic diamines. The calf thymus DNA (CT-DNA) binding of the complexes increased dramatically upon extending the aromatic component of the diamines, as evaluated by changes in absorption spectra upon titration with different concentrations of CT-DNA. An intercalation binding mode was established for the complexes using the increase in the relative viscosity of the CT-DNA following addition of complexes 1 and 2. Theoretical studies showed strong preference for replacement of water by guanine for all the complexes, and relatively strong Ru-Nguanine bonds. The plane of the aromatic systems can assume angles that support non-classical interactions with the DNA and covalent binding, leading to higher binding affinities. The ruthenium arenes illustrated in this study have promising anticancer activities, with the half maximal inhibitory concentration (IC50) values comparable to or better than cisplatin against three cell lines.
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Project description:In this work, the cytotoxic behavior of six ruthenium(II) complexes of stoichiometry [(η6-p-cymene)RuCl2L] (I-VI), L = 4-cyanopyridine (I), 2-aminophenol (II), 4-aminophenol (III), pyridazine (IV), and [(η6-p-cymene)RuClL2]PF6; L = cyanopyridine (V), L = 2-aminophenol(VI) towards three cell lines was studied. Two of them, HeLa and MCF-7, are human carcinogenic cells from cervical carcinoma and human breast cancer, respectively. A comparison with healthy cells was carried out with BGM cells which are monkey epithelial cells of renal origin. The behavior of complex II exhibits selectivity towards healthy cells, which is a promising feature for use in cancer treatment since it might reduce the side effects of most current therapies.
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Project description:A series of ruthenium complexes with chloro-substituted bidentate ligands, proximal-[Ru(tpy)(Cl-pyqu)L] n+ [n = 1 for L = Cl, and n = 2 for L = OH2, tpy = 2,2';6',2''-terpyridine, pyqu = 2-(2'-pyridyl)quinoline] were synthesized and their reversible photoisomerizations and thermal isomerizations were investigated experimentally. The crystal structures of the complexes indicated that introduction of a chloro substituent at the 4- or 4'-position of the pyqu ligand did not change the structure around the metal center from that of the non-substituted complex, proximal-[Ru(tpy)(pyqu)L] n+. In contrast, the 6'-substituted complexes had sterically hindered environments around the metal center. The ruthenium aqua complexes showed reversible photoisomerization between the proximal and distal isomers. The quantum yield for photoisomerization of the 6'-substituted ruthenium aqua complex was almost twice as large as those of the other derivatives. This is explained by weakening of the ligand field on the ruthenium center by introduction of a chloro substituent at the 6'-position. Thermal back isomerization from the distal isomer to the proximal one was observed for the 6'-substituted complex, but such reactions were not observed for the other derivatives. The steric hindrance in the 6'-substituted aqua complex enhanced both thermal isomerization and photoisomerization.
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Project description:A series of half-sandwich arene-ruthenium complexes of the type [(eta(6)-p-cymene) Ru(thiosemicarbazone)Cl](+) have been synthesized and their biological activity investigated. The first structurally characterized arene-ruthenium half-sandwich complex with a thiosemicarbazone ligand is reported.
| S-EPMC2769075 | biostudies-literature
Project description:Two novel series of (salen)ruthenium(iii) complexes bearing guanidine and amidine axial ligands were synthesized, characterized, and evaluated for anticancer activity. In vitro cytotoxicity tests demonstrate that these complexes are cytotoxic against various cancer cell lines and the leading complexes have remarkable cancer-cell selectivity. A detailed study of the guanidine complex 7 and the amidine complex 13 reveals two distinguished modes of action. Complex 7 weakly binds to DNA and induces DNA damage, cell cycle arrest, and typical apoptosis pathways in MCF-7 cells. In contrast, complex 13 induces paraptosis-like cell death hallmarked by massive vacuole formation, mitochondrial swelling, and ER stress, resulting in significant cytotoxicity against human breast cancer cells. Our results provide an extraordinary example of tuning the mechanism of action of (salen)ruthenium(iii) anticancer complexes by modifying the structure of the axial ligands.
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Project description:With the aim of exploring the anticancer properties of organometallic compounds with bioactive ligands, Ru(arene) compounds of the antibacterial quinolones nalidixic acid (2) and cinoxacin (3) were synthesized, and their physicochemical properties were compared to those of chlorido(?(6)-p-cymene)(ofloxacinato-?(2)O,O)ruthenium(II) (1). All compounds undergo a rapid ligand exchange reaction from chlorido to aqua species. 2 and 3 are significantly more stable than 1 and undergo minor conversion to an unreactive [(cym)Ru(?-OH)(3)Ru(cym)](+) species (cym = ?(6)-p-cymene). In the presence of human serum albumin 1-3 form adducts with this transport protein within 20 min of incubation. With guanosine 5'-monophosphate (5'-GMP; as a simple model for reactions with DNA) very rapid reactions yielding adducts via its N7 atom were observed, illustrating that DNA is a possible target for this compound class. A moderate capacity of inhibiting tumor cell proliferation in vitro was observed for 1 in CH1 ovarian cancer cells, whereas 2 and 3 turned out to be inactive.
| S-EPMC3086571 | biostudies-literature
Project description:A new family of ruthenium(II) complexes with sterically expansive ligands for targeting DNA defects was prepared, and their luminescent responses to base pair mismatches and/or abasic sites were investigated. Design of the complexes sought to combine the mismatch specificity of sterically expansive metalloinsertors, such as [Rh(bpy)2(chrysi)](3+) (chrysi = chrysene-5,6-quinone diimine), and the light switch behavior of [Ru(bpy)2(dppz)](2+) (dppz = dipyrido[3,2-a:2',3'-c]phenazine). In one approach, complexes bearing analogues of chrysi incorporating hydrogen-bonding functionality similar to dppz were synthesized. While the complexes show luminescence only at low temperatures (77 K), competition experiments with [Ru(bpy)2(dppz)](2+) at ambient temperatures reveal that the chrysi derivatives preferentially bind DNA mismatches. In another approach, various substituents were introduced onto the dppz ligand to increase its steric bulk for mismatch binding while maintaining planarity. Steady state luminescence and luminescence lifetime measurements reveal that these dppz derivative complexes behave as DNA "light switches" but that the selectivity in binding and luminescence with mismatched/abasic versus well-matched DNA is not high. In all cases, luminescence depends sensitively upon structural perturbations to the dppz ligand.
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Project description:The synthesis of ruthenium complexes incorporating an overcrowded pentaarylcyclopentadienyl ligand has been investigated, and higher efficiency has been reached using chlorine-functionalised precursors when compared with their brominated counterparts. A new methodology for the preparation of chlorocyclopentadienes has been developed which is well adapted for highly sterically hindered compounds and works with either electron rich or poor systems.
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Project description:Reaction of Ru3(CO)12 with two equiv of 6-bromopyridine alcohols 6-bromopyCHROH [(R = C6H5 (L1); R = 4-CH3C6H4 (L2); R = 4-OMeC6H4 (L3); R = 4-ClC6H4 (L4); (R = 4-CF3C6H4 (L5); R = 2-OMeC6H4 (L6); R = 2-CF3C6H4 (L7)] and 6-bromopyC(Me)2OH (L8) in refluxing xylene afforded novel trinuclear ruthenium complexes [6-bromopyCHRO]2Ru3(CO)8 (1a-1g) and [6-bromopyC(Me)2O]2Ru3(CO)8 (1h). These complexes were characterized by FT-IR and NMR spectroscopy as well as elemental analysis. The structures of all the complexes were further confirmed by X-ray crystallographic analysis. In the presence of tert-butyl hydroperoxide (TBHP) as the source of oxidant, complexes 1a-1h displayed high catalytic activities for oxidation of primary and secondary alcohols and most of oxidation reactions could be completed within 1 h at room temperature.
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Project description:The complexes cis-[Ru(quin)(dppm)2]PF6 and cis-[Ru(kynu)(dppm)2]PF6 (quin = quinaldate; kynu = kynurenate; dppm = bis(diphenylphosphino)methane) were prepared and characterized by elemental analysis, electronic, FTIR, 1H, and 31P{1H} NMR spectroscopies. Characterization data were consistent with a cis arrangement for the dppm ligands and a bidentate coordination through carboxylate oxygens of the quin and kynu anions. These complexes were not able to intercalate CT-DNA as shown by circular dichroism spectroscopy. On the other hand, bovine serum albumin (BSA) binding constants and thermodynamic parameters suggest spontaneous interactions with this protein by hydrogen bonds and van der Waals forces. Cytotoxicity assays were carried out on a panel of human cancer cell lines including HepG2, MCF-7, and MO59J and one normal cell line GM07492A. In general, the new ruthenium(II) complexes displayed a moderate to high cytotoxicity in all the assayed cell lines with IC50 ranging from 10.1 to 36 µM and were more cytotoxic than the precursor cis-[RuCl2(dppm)2]. The cis-[Ru(quin)(dppm)2]PF6 were two to three times more active than the reference metallodrug cisplatin in the MCF-7 and MO59J cell lines.
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