Bulnesia sarmientoi Supercritical Fluid Extract Exhibits Necroptotic Effects and Anti-Metastatic Activity on Lung Cancer Cells.

Bulnesia sarmientoi (BS) has long been used as an analgesic, wound-healing and anti-inflammatory medicinal plant. The aqueous extract of its bark has been demonstrated to have anti-cancer activity. This study investigated the anti-proliferative and anti-metastatic effects of BS supercritical fluid extract (BSE) on the A549 and H661 lung cancer cell lines. The cytotoxicity on cancer cells was assessed by an MTT assay. After 72 h treatment of A549 and H661 cells, the IC50 values were 18.1 and 24.7 µg/mL, respectively. The cytotoxicity on MRC-5 normal cells was relatively lower (IC50 = 61.1 µg/mL). BSE arrested lung cancer cells at the S and G2/M growth phase. Necrosis of A549 and H661 cells was detected by flow cytometry with Annexin V-FITC/PI double staining. Moreover, the cytotoxic effect of BSE on cancer cells was significantly reverted by Nec-1 pretreatment, and BSE induced TNF-α and RIP-1 expression in the absence of caspase-8 activity. These evidences further support that BSE exhibited necroptotic effects on lung cancer cells. By wound healing and Boyden chamber assays, the inhibitory effects of BSE on the migration and invasion of lung cancer cells were elucidated. Furthermore, the chemical composition of BSE was examined by gas chromatography-mass analysis where ten constituents of BSE were identified. α-Guaiene, (-)-guaiol and ß-caryophyllene are responsible for most of the cytotoxic activity of BSE against these two cancer cell lines. Since BSE possesses significant cytotoxicity and anti-metastatic activity on A549 and H661 cells, it may serve as a potential target for the treatment of lung cancer.

Weak antiferromagnetic coupling for novel linear hexanuclear nickel(II) string complexes (Ni6 12+) and partial metal-metal bonds in their one-electron reduction products (Ni6 11+).

The preparation, crystal structures, magnetic properties and electrochemistry of novel linear hexanuclear nickel string complexes (Ni6(12+)) and their corresponding 1-e(-) reduction products (Ni6(11+)) are reported. In these complexes, the hexanickel chain is in a symmetrical arrangement (approximately D(4) symmetry) and is helically supported by four bpyany(2-) ligands [bpyany(2-) = the dianion of 2,7-bis(alpha-pyridylamino)-1,8-naphthyridine]. The Ni6(12+) complexes show that the two terminal nickel ions have high-spin states (S = 1) and the four inner ones have low-spin states (S = 0). The two terminal nickel ions exhibit weak antiferromagnetic coupling of ca.-5 cm(-1). All of Ni6(12+) complexes display three reversible redox couples at about -0.70, -0.20 and +1.10 V (vs. Ag/AgCl). The first reduction wave at about -0.20 V suggests facility of 1-e(-) reduction for the Ni(6)(12+) compounds. The reaction of Ni(6)(12+) complexes with hydrazine afforded the 1-e(-) reduction products (Ni6(11+)). As far as we are aware, the shortest bond distance of 2.202 A with a partial metal-metal bond was observed in Ni6(11+) compounds. The magnetic results of these Ni6(11+) compounds are in agreement with a localized model, in which the two terminal nickel ions are in a spin state of S = 1 whereas the central Ni3-Ni4 pair in a spin state of S = 1/2. The N6(11+) compounds show relatively strong antiferromagnetic coupling of about 60 cm(-1) between the terminal and the central dinickel ions.

Novel linear hexanuclear cobalt string complexes (Co6(12+)) and one-electron reduction products (Co6(11+)) supported by four bpyany2- ligands.

The new ligand, 2,7-bis(alpha-pyridylamino)-1,8-naphthyridine (H2bpyany), was synthesized by the reaction of 2,7-dichloro-1,8-naphthyridine with 2-aminopyridine in the presence of t-BuOK under palladium(0)-catalyzed conditions. The preparation and characterization of novel hexacobalt string complexes, [Co6(mu6-bpyany)4(NCS)2](PF6)n (n=1 (1); n=2 (2)) and [Co6(mu6-bpyany)4(OTf)2](OTf)n (n = 2 (3); n = 1 (4)) are presented. The crystal structures for compounds have been determined by X-ray crystallography. Compounds 1 and 4 have the Co6 11+ configurations and are air-stable. Compounds 2 and 3 with Co6 12+ configurations are structurally similar to 1 and 4, respectively. The electrochemistry of 1 displays four redox couples at E1/2= -0.55, +0.38, +0.91, and +1.18 V (vs. Ag/AgCl). The magnetic data show that compounds 1 and 4 are in a spin state of S = 1/2, and 2 and 3 in a spin state of S = 1. The results of the EHMO calculations on compounds 1 and 2 are in agreement with their magnetic measurements.

Synthesis, structures, magnetism and electrochemical properties of triruthenium-acetylide complexes.

A series of triruthenium complexes with arylacetylide axial ligands Ru(3)(dpa)(4)(C(2)X)(2)(BF(4))(y)(dpa = dipyridylamido; X = Fc, y= 0 (1); X = Ph, y= 0 (2); X = PhOCH(3), y= 1 (3); X = PhC(5)H(11), y= 1 (4); X = PhCN, y= 0 (5); X = PhNO(2), y= 0 (6)) have been synthesized. The crystal structures show that the Ru-Ru bond lengths (2.3304(9)-2.3572(5)A) of these compounds are longer than those of Ru(3)(dpa)(4)Cl(2)(Ru-Ru=2.2537(1)A). This is ascribed to the formation of the stronger pi-backbonding from metal to axial ligand which weakens the Ru-Ru interactions and the bond order is reduced in the triruthenium unit. Cyclic voltammetry and differential pulse voltammetry show that compound exhibits electronic coupling between the two ferrocenyl units with DeltaE(1/2) close to 100 mV. Compounds 2-6 display three triruthenium-based reversible one-electron redox couples, two oxidations and one reduction, and the electrode potentials shift upon varying the substituents. A linear relationship is observed when the Hammett constants are plotted against the redox potentials.

Porphyrin-triarylamine conjugates: strong electronic communication between triarylamine redox centers via the porphyrin dication.

A set of porphyrin-triarylamine hybrids have been synthesized in good yield by Sonogashira palladium-catalyzed cross-coupling reactions between the zinc complex of 5,15-diethynyl-10,20-dimesitylporphyrin and the appropriate iodophenyldiarylamines. The crystal structure of porphyrin 1 shows that the dihedral angle between the acetylene-bonded benzene rings and the porphyrin macrocycle is 20.0 degrees. Such a structural characteristic enables effective electronic perturbations within the molecule. The electronic spectra are red-shifted and display a broad Soret band and an intense Q band relative to those of meso-substituted tetraarylporphyrins. These conjugates display four oxidations and one reduction. All the electrochemical reactions involve one-electron transfer. The first and second oxidations are reversible and can be assigned to the porphyrin-centered reactions. The third and fourth ones, separated by about 270 mV, correspond to the triarylamine units. The comproportionation constant (Kc) is calculated to be 3.67x10(4). The electron coupling between the triarylamine moieties, at a separation of >23 A, is remarkably strong. The electrochemical results and the absorption spectra show that the electronic characteristics of these porphyrins can be significantly modulated by the triarylamine substituents via the conjugated carbon-carbon triple bond. Variations of the substituents on the triarylamines can fine-tune the electronic properties of these molecules.