The limitations of platinum complexes in cancer treatment have motivated the extensive investigation into other metal complexes such as ruthenium. We herein present the synthesis and characterization of a new family of ruthenium compounds 1a-5a with the general formula [Ru(bipy)L][CFSO] (bipy = 2,2'-bipyridine; L = bidentate ligand: N,N; N,P; P,P; P,As) which have been characterized by elemental analysis, ES-MS, H andP-{H} NMR, FTIR and conductivity measurements. The molecular structures of four Ru(ii) complexes were determined by single crystal X-ray diffraction. All compounds displayed moderate cytotoxic activity in vitro against human A2780 ovarian, MCF7 breast and HCT116 colorectal tumor cells. Compound 5a was the most cytotoxic compound against A2780 and MCF7 tumor cells with an IC of 4.75 ± 2.82 μM and 20.02 ± 1.46 μM, respectively. The compounds showed no cytotoxic effect on normal human primary fibroblasts but rather considerable selectivity for A2780, MCF7 and HCT116 tumor cells. All compounds induce apoptosis and autophagy in A2780 ovarian carcinoma cells and some nuclear DNA fragmentation. All compounds interact with CT-DNA with intrinsic binding constants in the order 1a > 4a > 2a > 3a > 5a. The observed hyperchromic effect may be due to the electrostatic interaction between positively charged cations and the negatively charged phosphate backbone at the periphery of the double helix-CT-DNA. Interestingly, compound 1a shows a concentration dependent DNA double strand cleavage. In addition in vivo toxicity has been evaluated on zebrafish embryos unveiling the differential toxicity between the compounds, with LC ranging from 8.67 mg L for compound 1a to 170.30 mg L for compound 2a.
Ruthenium(II) complexes are currently considered a viable alternative to the widely used platinum complexes as efficient anticancer agents. We herein present the synthesis and characterization of half-sandwich ruthenium compounds with the general formula [Ru(p-cymene)(L-N,N)Cl][CF3SO3] (L = 3,6-di-2-pyridyl-1,2,4,5-tetrazine (1) 6,7-dimethyl-2,3-bis(pyridin-2-yl)quinoxaline (2)), which have been synthesized by substitution reactions from the precursor dimer [Ru(p-cymene)(Cl)(μ-Cl)]2 and were characterized by elemental analysis, mass spectrometry, 1H NMR, UV–vis, and IR spectroscopy, conductivity measurements, and cyclic voltammetry. The molecular structure for complex 2 was determined by single-crystal X-ray diffraction. The cytotoxic activity of these compounds was evaluated against human tumor cells, namely ovarian carcinoma A2780 and breast MCF7 and MDAMB231 adenocarcinoma cells, and against normal primary fibroblasts. Whereas the cytotoxic activity of 1 is moderate, IC50 values found for 2 are among the lowest previously reported for Ru(p-cymene) complexes. Both compounds present no cytotoxic effect in normal human primary fibroblasts when they are used at the IC50 concentration in A2780 and MCF7 cancer cells. Their antiproliferative capacity is associated with a combined mechanism of apoptosis and autophagy. A strong interaction with DNA was observed for both with a binding constant value of the same magnitude as that of the classical intercalator [Ru(phen)2(dppz)]2+. Both complexes bind to human serum albumin with moderate to strong affinity, with conditional binding constants (log K b) of 4.88 for complex 2 and 5.18 for complex 1 in 2% DMSO/10 mM Hepes pH7.0 medium. The acute toxicity was evaluated in zebrafish embryo model using the fish embryo acute toxicity test (FET). Remarkably, our results show that compounds 1 and 2 are not toxic/lethal even at extremely high concentrations. The novel compounds reported herein are highly relevant antitumor metallodrug candidates, given their in vitro cytotoxicity toward cancer cells and the lack of in vivo toxicity.
Ruthenium-based drugs exhibit interesting properties as potential anticancer pharmaceuticals. We herein present the synthesis and characterization of a new family of ruthenium complexes with formulas [{Ru(bipy)}(μ-L)][CFSO] (L = bptz, 1a) and [{Ru(bipy)}(μ-L)][CFSO] (L = arphos, 2a; dppb, 3a; dppf, 4a), which were synthesized from the Ru(II) precursor compound cis-Ru(bipy)Cl. The complexes were characterized by elemental analysis, mass spectrometry, H andP{H} NMR, IR spectroscopy, and conductivity measurements. The molecular structures for three Ru(II) compounds were determined by single-crystal X-ray diffraction. The newly developed compounds interact with CT-DNA by intercalation, in particular, 2a, 3a, and 4a, which also seemed to induce some extent of DNA degradation. This effect seemed to be related with the formation of reactive oxygen species. The cytotoxic activity was evaluated against A2780, MCF7, and MDAMB231 human tumor cells. Compounds 2a and 4a were the most cytotoxic with activity compared to cisplatin (∼2 μM, 72 h) in the A2780 cisplatin sensitive cells. All the compounds induced A2780 cell death by apoptosis, however, to a lesser extent for compounds 4a and 2a. For these compounds, the mechanism of cell death in addition to apoptosis seemed to involve autophagy. In vivo toxicity was evaluated using the zebrafish embryo model. LC estimates varied from 5.397 (3a) to 39.404 (1a) mg/L. Considering the in vivo toxicity in zebrafish embryos and the in vitro cytotoxicity in cancer cells, compound 1a seems to be the safest having no effect on dechirionation and presenting a good antiproliferative activity against ovarian carcinoma cells.
We present a novel family of polyhalide salts of Bi(III) with the general formula [Dim][BiX], where Dim is the diimidazolium cation (CHN) and X is Cl, Br, or I. Single-phase materials are easily obtained by means of a mild solution chemistry method performed at room temperature. This [Dim][BiX] family exhibits a crystal structure based on halobismuthate [BiX] dimers, built by distorted {BiX} octahedra interconnected by edge sharing, and sandwiched between two diimidazolium cations. The optical band gaps displayed by these materials (1.9-3.2 eV) allow their classification as semiconductors. Additionally, the three halides display photoluminescence with emission in the visible range. The behavior of [Dim][BiI] is particularly interesting, as it shows an optical band gap of 1.9 eV, a broad band photoluminescence emission, and a relatively long emission lifetime of 190 ns. Moreover, the iodide and bromide compounds also exhibit a reversible solid state thermochromism, being the first example of a bromobismuthate with this property. The diimidazolium cations play an important structural role by stabilizing the crystal structure and balancing the charges of the [BiX] dimers. Furthermore, density functional theory calculations suggest that they play a key role in the thermochromic behavior. Therefore, compounds [Dim][BiX] (X = Cl, Br, or I) represent a very versatile family in which the optical band gap can be tuned by changing the halide or temperature. This makes them promising new materials for different optoelectronic applications, in particular for obtaining new solar absorbers.
Treatment of the chloride-bridged complex [Pd{2, 2 C 6 H 2 C(H)=N(Cy)-C6,N}(m-Cl)] 2 (1) with 1,1bis(diphenylphosphino)ethene (vdpp) and NH 4 PF 6 or NaClO 4 in 1:2 molar ratio afforded the mononuclear cyclometallated palladium(II) complexes [Pd{2,4-(OMe 2 )C 6 H 2 C(H)=N(Cy)-C6,N}{(Ph 2 P) 2 C=CH 2 -P,P 0 }](X) (2, X ¼ PF 6 ; 3, X ¼ ClO 4 ). The structure of 2 has been determined by X-ray diffraction analysis. Reaction of 2 with acetylacetone in the presence of anhydrous sodium carbonate yielded in high yield the addition product [Pd{2,4-(MeO) 2 C 6 H 2 C(H)=N(Cy)-C6,N}{(Ph 2 P) 2 CHCH 2 CH(COMe) 2 -P,P 0 }](PF 6 ) (4). The 31 P-{ 1 H} NMR spectrum showed a greater 2 J(PP) coupling constant than the one observed for the starting complex. Reaction of 2 with diethyl malonate afforded a 7:3 mixture of the addition product [Pd{2,4-(MeO) 2 C 6 H 2 C(H)=N(Cy)-C6,N}{(Ph 2 P) 2 CHCH 2 CH(COOEt) 2 -P,P 0 }](PF 6 ) (5) and the starting complex. The desired addition compound could be isolated in pure form by treatment of 3 with diethyl malonate yielding [Pd{2,4-(MeO) 2 C 6 H 2 C(H)=N(Cy)-C6,N}{(Ph 2 P) 2 CHCH 2 CH(COOEt) 2 -P,P 0 }](ClO 4 ) ( 16). The reaction of 2 with asymmetric nucleophiles such as methyl acetoacetate, ethyl propionylacetate, ethyl acetoacetate, methyl 4chloroacetoacetate, 1,1,1-trifluoroacetylacetone and thenoyltrifluoroacetone afforded the corresponding addition derivatives, [Pd{2, 2 C 6 H 2 C(H)=N(Cy)-C6,N}{(PH 2 P) 2 CHCH 2 CH(COR 1 )(COR 2 )-P,P 0 }]-(PF 6 ) (R 1
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