Crystal structure of [3-amino-2-(phenyl-diazenyl)-pyridine]chlorido-(η(6)-p-cymene)-ruthenium(II) chloride.

The title compound, [RuCl(C10H14)(C11H10N4)]Cl is an Ru(II) complex in which an η (6) -p-cymene ligand, two N atoms of 3-amino-2-(phenyl-azo)pyridine and one Cl ion form a piano-stool coordination environment around the metal ion. In the crystal structure, N-H⋯Cl hydrogen bonds play an important role in the formation of the supramolecular zigzag chain along the a-axis direction. Disorder is observed for the isopropyl group with site-occupancy factors refined to 0.78 (5) and 0.22 (5).

Cellular responses of BRCA1-defective and triple-negative breast cancer cells and in vitro BRCA1 interactions induced by metallo-intercalator ruthenium(II) complexes containing chloro-substituted phenylazopyridine.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined by the absence of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Breast cancers with a BRCA1 mutation are also frequently triple-negative. Currently, there is a lack of effective therapies and known specific molecular targets for this aggressive breast cancer subtype. To address this concern, we have explored the cellular responses of BRCA1-defective and triple-negative breast cancer cells, and in vitro BRCA1 interactions induced by the ruthenium(II) complexes containing the bidentate ligand, 5-chloro-2-(phenylazo)pyridine. METHODS: Triple-negative MDA-MB-231, BRCA1-defective HCC1937 and BRCA1-competent MCF-7 breast cancer cell lines were treated with ruthenium(II) complexes. The cytoxoxicity of ruthenium-induced breast cancer cells was evaluated by a real time cellular analyzer (RTCA). Cellular uptake of ruthenium complexes was determined by ICP-MS. Cell cycle progression and apoptosis were assessed using propidium iodide and Annexin V flow cytometry. The N-terminal BRCA1 RING protein was used for conformational and functional studies using circular dichroism and in vitro ubiquitination. RESULTS: HCC1937 cells were significantly more sensitive to the ruthenium complexes than the MDA-MB-231 and MCF-7 cells. Treatment demonstrated a higher degree of cytotoxicity than cisplatin against all three cell lines. Most ruthenium atoms were retained in the nuclear compartment, particularly in HCC1937 cells, after 24 h of incubation, and produced a significant block at the G2/M phase. An increased induction of apoptotic cells as well as an upregulation of p53 mRNA was observed in all tested breast cancer cells. It was of interest that BRCA1 mRNA and replication of BRCA1-defective cells were downregulated. Changes in the conformation and binding constants of ruthenium-BRCA1 adducts were observed, causing inactivation of the RING heterodimer BRCA1/BARD1-mediated E3 ubiquitin ligase activity. CONCLUSIONS: This study has revealed the ability of ruthenium complexes to inhibit cell proliferation, induce cell cycle progression and apoptosis. Ruthenium treatment upregulated the marker genes involved in apoptosis and cell cycle progression while it downregulated BRCA1 mRNA and replication of HCC1937 cells. Our results could provide an alternative approach to finding effective therapeutic ruthenium-based agents with promising anticancer activity, and demonstrated that the BRCA1 RING domain protein was a promising therapeutic target for breast cancers.

2-Amino-5-bromo-pyridin-1-ium (2-amino-5-bromo-pyridine-κN (1))trichloridozincate.

The structure of the title salt, (C5H6BrN2)[ZnCl3(C5H5BrN2)], consists of discrete 2-amino-5-bromo-pyridin-1-ium cations and distorted tetra-hedral (2-amino-5-bromo-pyridine)-tri-chlorido-zincate anions. In the crystal, the complex anions and cations are linked via N-H⋯Cl hydrogen bonds into layers parallel to (101). Short Br⋯Cl contacts of 3.4239 (11) and 3.4503 (12) Šare observed, as well as π-π stacking inter-actions between the pyridine and pyridinium rings, with alternating centroid-to-centroid distances of 3.653 (2) and 3.845 (2) Å.

Bis[5-chloro-2-(phenyl-diazenyl-κN(2))pyridine-κN]bis-(thio-cyanato-κN)iron(II).

In the title complex, [Fe(NCS)(2)(C(11)H(8)ClN(3))(2)], the Fe(II) atom is coordinated by two N atoms from the thio-cyanate ligands and four N atoms from two chelating 5-chloro-2-(phenyl-diazen-yl)pyridine ligands, generating a fairly regular FeN(6) octa-hedral coordination geometry. The thio-cyanate ions are in a cis disposition and the pyridine N atoms are in a trans orientation. In the crystal, a short inter-molecular Cl⋯S contact [3.366 (3) Å] is observed.

Photoactive azoimine dyes: 4-(2-pyridylazo)-N,N-diethylaniline and 4-(2-pyridylazo)-N,N-dimethylaniline: computational and experimental investigation.

4-(2-Pyridylazo)-N,N-dimethylaniline and 4-(2-pyridylazo)-N,N-diethylaniline, two photoactive azoimine dyes, were prepared from the reaction of 2-aminopyridine with N,N-dialkyl-1,4-nitrosoaniline at room temperature. Structural characterizations of these dyes using single crystal X-ray diffraction, (1)H NMR, elemental analysis, mass spectroscopy and IR spectroscopy have been carried out. The X-ray structure indicates a trans configuration around the azo group. The photochemical behavior of these compounds differs from that of 2-phenylazopyridine, the non-dialkylamino substituent compound. The synthesized compounds show emission spectra at room temperature while 2-phenylazopyridine does not. The excitation spectra of these compounds differ from their absorption spectra which can be explained on the basis of the trans to cis photoisomerization which is supported by the TD-PBE0/6-31G(d,p) calculations. Both oxidation of the dialkylamino substituents (-NR(2); R=-CH(3) and -C(2)H(5)) and reduction of -N=N-/-N=N-(-) and -N=N-(-)/-N=N-(2-) were observed in the cyclic voltammogram indicating a π-acidity of both dyes.

N,N-Dimethyl-4-[(2-pyrid-yl)diazen-yl]aniline.

The title compound, C(13)H(14)N(4), adopts a trans configuration about the azo bond. There is a dihedral angle of 12.18 (7)° between the pyridine and benzene rings and the mean plane of the dimethyl-amino substituent is twisted by 6.1 (2)° relative to the benzene ring. In the crystal, weak inter-molecular C-H⋯N hydrogen bonds result in a zigzag arrangement along [010].

Crystal structure of bromo(2,2':6',2"-terpyridine)(2-(phenylazo)-pyridine)ruthenium(II) tetrafluoroborate.

The title compound, C26H20N6BrRu(BF4), crystallizes in the centrosymmetric space group P2(1)/n and consists of discrete complex units. The Ru(II) ion is octahedrally coordinated to one 2,2':6',2"-terpyridine (tpy), one 2-(phenylazo)pyridine (azpy) and a Br atom in trans-axial position at a distance of 2.547(5)A. The shorter Ru-N (azo) distance (1.960(3)A) than the Ru-N(py) distance (2.061(3)A) signifies a strong pi-backbonding, which leads to a longer, N=N (azo) bond (1.304(4)A).