Synthesis, structural and theoretical studies of dithiodiglycolamide compounds of palladium(II).

The reaction of palladium(ii) halide with dithiodiglycolamide ligands yielded compounds of the type [PdX2L] (where X = Cl, L = (CH2SCH2CON(i)Pr2)2 (1); L = (CH2SCH2CON(i)Bu2)2 (2); L = (CH2SCH2CONBu2)2 (3); L = C7H6(SCH2CON(i)Bu2)2 (4); X = Br, L = (CH2SCH2CON(i)Bu2)2 (5); X = I, L = (CH2SCH2CON(i)Bu2)2 (6)), whereas palladium(ii) nitrate yielded compounds of the type [PdL2](NO3)2 (where L = (CH2SCH2CON(i)Pr2)2 (7); L = (CH2SCH2CON(i)Bu2)2 (8)). All compounds were characterized by using IR, (1)H NMR spectral techniques and CHN analyses. The structures of compounds 4, 5 and 7 have been determined by using X-ray diffraction methods. The structures show that the ligands bond through the thioether group to the metal centre in all compounds. They show further that the palladium(ii) ion is surrounded by four atoms (two halogens and two thio groups in 4 and 5 and four thio groups in 7) in a square planar arrangement. The dithiodiglycolamide ligand acts as a bidentate chelating ligand and bonds through both the thioether groups to the metal centre, leaving the carbamoyl groups uncoordinated. Theoretical studies reveal that the 1 : 2 compound is energetically more stable and nicely correlates with the IR carbamoyl stretching frequencies as compared to the 1 : 1 compound in which the ligand acts as a tetradentate ligand.

Comparative anti-proliferative activity of some new 2-(arylazo)phenolate-palladium (II) complexes and cisplatin against some human cancer cell lines.

In this study, we report the synthesis of four 2-(arylazo)phenol-Pd(II) complexes and their anti-proliferative property against the human lung cancer (A549), cervical cancer (HeLa), and ovarian teratocarcinoma (PA-1) cell lines with cisplatin as the gold standard. One of the complexes, [Pd(L(2))2], induced robust apoptosis in all the chosen cells, as revealed by annexin-V-positive/propidium iodide dual staining, increased sub-G1 cell cycle population, and significant morphological changes in the treated cells. The Pd complex inflicted mitochondrial dysfunction leading to mitochondrial membrane potential loss, reactive oxygen species generation and release of cytosolic cytochrome c that activated caspase-9 and caspase-3 proteins which finally caused programmed cell death.

Overlapping double turn conformations adopted by tetrapeptides containing non-coded alpha-amino isobutyric acid (Aib) and formation of tape-like structures through supramolecular helix mediated self-assembly.

Single crystal X-ray diffraction studies and solvent dependent (1)H NMR titrations reveal that a set of four tetrapeptides with general formula Boc-Xx(1)-Aib(2)-Yy(3)-Zz(4)-OMe, where Xx, Yy and Zz are coded L-amino acids, adopt equivalent conformations that can be described as overlapping double turn conformations stabilized by two 4-->1 intramolecular hydrogen bonds between Yy(3)-NH and Boc C=O and Zz(4)-NH and Xx(1)C=O. In the crystalline state, the double turn structures are packed in head-to-tail fashion through intermolecular hydrogen bonds to create supramolecular helical structures. Field emission scanning electron microscopic (FE-SEM) images of the tetrapeptides in the solid state reveal that they can form flat tape-like structures. The results establish that synthetic Aib containing supramolecular helices can form highly ordered self-aggregated amyloid plaque like human amylin.

Novel charge transfer supramolecular assemblies with Keggin anions and 2-amino-5-nitropyridine.

Several novel compounds with the non-linear optical chromophore 2-amino-5-nitropyridine (2A5NP) and Keggin polyoxoanions (alpha-isomers), having the general formula (2A5NP)(m)H(n)[XM12O40].xH2O, M = Mo, W, were synthesised. Compounds were obtained with X = P, n = 3, m = 3 and 4 and X = Si, n = m = 4 (x = 2-6). Thus, for each of the anions [PMo12O40]3- and [PW12O40]3- two different compounds were obtained, with the same anion and organic counterpart but with a different stoichiometric ratio. These presented different charge transfer properties and thermal stability. All compounds were characterised by spectroscopic and analytical techniques. The single crystal X-ray diffraction structure of (2A5NP)4H3[PMo12O40].2.5H2O.0.5C2H5OH showed that the water solvent molecules and the organic chromophores are assembled via infinite one-dimensional chains of hydrogen bonds with formation of open channels, which accommodate [PMo12O40]3- and ethanol solvent molecules.

21-deoxycortisone (17alpha-hydroxy-4-pregnene-3,11,20-trione).

The title compound, C21H28O4, a synthetic glucocorticoid, crystallizes with a single molecule in the asymmetric unit. Ring A is almost in a half-chair conformation, rings B and C are almost in chair conformations, and ring D is between a twist and a 13beta-envelope conformation. The A/B ring junction is quasi-trans, whereas the B/C and C/D ring junctions both approach trans characteristics. The molecule as a whole is slightly convex towards the beta side, with an angle of 9.60 (2) degrees between the C10-C19 and C13-C18 vectors. Molecular-packing and hydrogen-bonding (both intra- and intermolecular) interactions play a major role in the structural association of the compound.

Different supramolecular hydrogen bond structures and significant changes in magnetic properties in dinuclear mu 2-1,1-N3 copper(II) complexes with very similar tridentate Schiff base blocking ligands.

Three new basal-apical, mu(2)-1,1-azide bridged complexes, [CuL(1)(N(3))](2) (1), [CuL(2)(N(3))](2) (2) and [CuL(3)(N(3))](2) (3) with very similar tridentate Schiff base blocking ligands [L(1) = N-(3-aminopropyl)salicylaldimine, L(2) = 7-amino-4-methyl-5-azahept-3-en-2-one and L(3) = 8-amino-4-methyl-5-azaoct-3-en-2-one) have been synthesised and their molecular structures determined by X-ray crystallography. In complex 1, there is no inter-dimer H-bonding. However, complexes 2 and 3 form two different supramolecular structures in which the dinuclear entities are linked by strong H-bonds giving one-dimensional systems. Variable-temperature (300-2 K) magnetic susceptibility measurements and magnetization measurements at 2 K reveal that complexes and have antiferromagnetic coupling while has ferromagnetic coupling which is also confirmed by EPR spectra at 4-300 K. Magnetostructural correlations have been made taking into consideration both the azido bridging ligands and the existence of intermolecular hydrogen bonds in complexes 2 and 3.

Oestrogenic activity of parabens in MCF7 human breast cancer cells.

Parabens (4-hydroxybenzoic acid esters) have been recently reported to have oestrogenic activity in yeast cells and animal models. Since the human population is exposed to parabens through their widespread use as preservatives in foods, pharmaceuticals and cosmetics, we have investigated here whether oestrogenic activity of these compounds can also be detected in oestrogen-sensitive human cells. We report on the oestrogenic effects of four parabens (methylparaben, ethylparaben, n-propylparaben, n-butylparaben) in oestrogen-dependent MCF7 human breast cancer cells. Competitive inhibition of [3H]oestradiol binding to MCF7 cell oestrogen receptors could be detected at 1,000,000-fold molar excess of n-butylparaben (86%), n-propylparaben (77%), ethyl-paraben (54%) and methylparaben (21%). At concentrations of 10(-6)M and above, parabens were are able to increase expression of both transfected (ERE-CAT reporter gene) and endogenous (pS2) oestrogen-regulated genes in these cells. They could also increase proliferation of the cells in monolayer culture, which could be inhibited by the antiestrogen ICI 182,780, indicating that the effects were mediated through the oestrogen receptor. However, no antagonist activity of parabens could be detected on regulation of cell proliferation by 17 beta-oestradiol at 10(-10)M. Molecular modelling has indicated the mode by which paraben molecules can bind into the ligand binding pocket of the crystal structure of the ligand binding domain (LBD) of the oestrogen receptor alpha (ERalpha) in place of 17beta-oestradiol; it has furthermore shown that two paraben molecules can bind simultaneously in a mode in which their phenolic hydroxyl groups bind similarly to those of the meso-hexoestrol molecule. Future work will need to address the extent to which parabens can accumulate in hormonally sensitive tissues and also the extent to which their weak oestrogenic activity can add to the more general environmental oestrogen problem.