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.

Photochromic atropisomer generation and conformation determination in a ruthenium bis(bipyridine) phosphonite gamma-cyclodextrin system.

Irradiation of rac-[Ru(bpy)(2)(PhP(OMe)(2))(Cl)]Cl (2) at lambda > 460 nm results in the photochromic generation of a new atropisomer and chirality inversion, via rotation of the PhP(OMe)(2) moiety around the Ru-P bond. However, since the energetic barrier to rotation is low resulting in racemization, it was found that the formation of a supramolecular complex between 2 and gamma-cyclodextrin (gamma-CDx) facilitated the stabilization of the new atropisomeric conformation. On irradiation the bisignate signals in the circular dichroism spectrum of the 2:gamma-CDx complex were converted to an entirely new and distinct circular dichroism spectrum, as a result of a different spatial orientation of the phenyl electronic transition in the PhP(OMe)(2) moiety (the active circular dichroism spectra were found to arise from different g factor values of the Delta-2:gamma-CDx and Lambda-2:gamma-CDx complexes). The new atropisomer formation and subsequent thermally induced interconversion could be further detected by conventional and variable temperature (1)H NMR studies. Determination of the conformation of the new atropisomer was achieved by combining analysis of the changes in the circular dichroism spectra by exciton coupling theory with molecular modeling and DFT calculations.

Stepwise hapticity changes in sequential one-electron redox reactions of indenyl-molybdenum complexes: combined electrochemical, ESR, X-ray, and theoretical studies.

Reduction of the dication [(eta5-Ind)(Cp)Mo[P(OMe)3]2]2+ (1(2+)) and oxidation of the neutral complex (eta3-Ind)(Cp)Mo[P(OMe)3]2 (1) proceed through a one-electron intermediate, 1+. The structures of 1(2+) and 1 have been determined by X-ray diffraction studies, which show the slip-fold distortion angle, Omega, of the indenyl ring increasing from 4.1 degrees in 1(2+) to 21.7 degrees in 1. Cyclic voltammetry and bulk electrolysis were employed to define the thermodynamics and heterogeneous charge-transfer kinetics of reactions 1(2+) + e(-) <==> 1+ and 1+ + e(-) <==> 1: DeltaE1/2 = 113 mV in CH3CN and 219 mV in CH2Cl2/0.1 M [NBu4][PF6]; k(s) = 0.4 cm x s(-1) for 1(2+)/1+ couple, 1.0 cm x s(-1) for 1+/1 couple in CH3CN. ESR spectra of 1+ displayed a surprisingly large hyperfine splitting (7.4 x 10(-4) x cm(-1)) from a single 1H nucleus, and spectra of the partially deuterated indenyl analogue confirmed assignment of a(H) to the H2 proton of the indenyl ring. The related eta5 18-electron complexes [(eta5-Ind)(Cp)Mo(dppe)]2+ (2(2+)) (dppe = diphenylphosphinoethane) and (eta5-Ind)(Cp)Mo(CN)2 (3) may also be reduced in two successive one-electron steps; ESR spectra of the radicals 2+ and 3- showed a similarly large a(H2) (8.7 x 10(-4) and 6.4 x 10(-4) x cm(-1), respectively). Molecular orbital calculations (density functional theory, DFT, and extended Hückel, EH) predict metal-indenyl bonding in 1+ that is approximately midway between that of the eta5 and eta3 hapticities (e.g., Omega = 11.4 degrees ). DFT results show that the large value of a(H2) arises from polarization of the indenyl-H2 by both inner-sphere orbitals and the singly occupied molecular orbital (SOMO) of 1+. The measured ks values are consistent with only minor inner-sphere reorganizational energies being necessary for the electron-transfer reactions, showing that a full eta5/eta3 hapticity change may require only small inner-sphere reorganization energies when concomitant with a pair of stepwise one-electron-transfer processes. The indenyl ligand in 1+ is best described as donating approximately four pi-electrons to Mo by combining a traditional eta3 linkage with two "half-strength" Mo-C bonds.

Ion pair cooperative binding of potassium salts by new rhenium(I) bipyridine crown ether receptors.

The new rhenium(I) bipyridine crown ether receptors 1-4 have been prepared and their ion pair recognition properties examined. The crystal structure of [1.KCl](2).2H(2)O demonstrates that potassium is coordinated by benzo-18-crown-6 and chloride is hydrogen bonded to the amide groups. Receptor 3 extracts solid KCl and KOAc into chloroform via ion pair complexation. NMR and emission titration studies with receptors 1-4 and KCl/KOAc show that cobound potassium enhances anion binding strength by electrostatic and conformational effects. Significant cooperative interactions are observed between the anion and cation sites for host 4 in CH(3)CN. This molecule coordinates potassium to form a 1:1 intramolecular sandwich complex, which preorganizes the host for acetate binding.

First crystallographic signature of amyloid-like fibril forming beta-sheet assemblage from a tripeptide with non-coded amino acids.

The model tripeptide Boc-beta-Ala(1)-Aib(2)-beta-Ala(3)-OMe 1 [beta-Ala: beta-alanine, Aib: alpha-aminoisobutyric acid] forms an infinite parallel beta-sheet structure through intermolecular interactions in single crystals and from the SEM diagram of this peptide, it is evident that the compound has fibrillar morphology, a characteristic of neurodegenerative disease causing amyloid aggregate.

The binding of difunctional neutral guest molecules by novel bis(tripyrrolyl) cryptands.

Bis(tripyrrolyl) cryptands are prepared via a [2 + 3] Schiff base condensation of formyltripyrrolyls with diamines; an ethyl-spaced hexapyrrole cryptand is shown to bind strongly ethane-1,2-diamine and ethane-1,2-diol in chloroform solution.

Interaction of Ruthenium(II)-dipyridophenazine Complexes with CT-DNA: Effects of the Polythioether Ancillary Ligands.

The complexes [Ru([9]aneS(3))(dppz)Cl]Cl 1 and [Ru([12]aneS(4))(dppz)]Cl(2)2 ([9]aneS(3) = 1,4,7- trithiaciclononane and [12]aneS(4) = 1,4,7,10-tetrathiaciclododecane) were synthesised and fully characterised. These complexes belong to a small family of dipyridophenazine complexes with non-polypyridyl ancillary ligands . Interaction studies of these complexes with CT-DNA (UV/Vis titrations, steady-state emission and thermal denaturation) revealed their high affinity for DNA . Intercalation constants determined by UV/Vis titrations are of the same order of magnitude (10(6)) as other dppz metallointercalators, namely [Ru(II)(bpy)(2)dppz]S(2+). Differences between l and2 were identified by steady-state emission and thermal denaturation studies . Emission results are in accordance with structural data, which indicate how geometric distortions and different donor and/or acceptor ligand abilities affect luminescence. The possibility of noncovalent interactions between ancillary ligands and nucleobases by van der Waals contacts and H-bridges is discussed . Furthermore, complex l undergoes aquation under intra-cellular conditions and an equilibrium with the aquated form l' is attained . This behaviour may increase the diversity of available interaction modes.

The Chatt-Dewar-Duncanson model revisited: X-ray, DFT and NMR studies of rhodium-alkene binding--deviations from structural ideality.

An analysis has been made of deviations from ideal centrosymmetric bonding of alkenes to transition metals in square-planar complexes. Three separate approaches have been employed. Firstly, the geometries obtained for a series of X-ray crystal structures of monosubstituted rhodium-alkene complexes have been obtained. Secondly, DFT computations on closely related rhodium-alkene complexes are reported. Thirdly. the data have been augmented by recourse to the crystal structure serach and retrieval file (CSSR) database to retrieve the X-ray data for square-planar ethene and monosubstituted alkene complexes. The results obtained from these analyses provide a consistent picture. Two distortions from ideality are important: twisting of the alkene about the axis between the metal (M) and the alkene centroid and rolling of the alkene around a cylinder enclosing the metal, such that the two C-M bonds remain equal in length. The presence of both of these is verified through both X-ray structure determinations and DFT calculations. For the rolling distortion, there is a relationship between the electronic character of the substituent on the alkene and the direction of roll. The net effect of this is to place the more nucleophilic carbon of the alkene closer to the square plane. The significance of this for the regiochemistry of the Heck reaction is briefly discussed.

Novel synthetic routes to several new, differentially substituted ruthenium tris(4,4 disubstituted-2,2-bipyridine) complexes.

The stepwise synthesis of several novel Ru(tris(pp)) complexes (pp = 4,4'-disubstituted-2,2'-bipyridine; substituent = H, Me, chiral ester, or chiral amide) is described, where the pp ligands may be the same, or different, in each complex. All of the complexes detailed have been resolved into their pure delta- and lambda-enantiomers or diastereomers. The complexes, which are prepared starting from RuCl3, contain novel ligand architectures, with a range of chiral esters and amides attached to the 4,4'-positions of the bpy ligands. It was postulated that these chiral groups would be capable of inducing chirality at the metal center, but our investigations have shown this not to be the case, and in all reactions completely racemic products were formed. Resolution by chiral HPLC, and the subsequent characterization of the products through NMR, UV-vis, and circular dichroism (CD) spectroscopy, has been carried out; the characteristics of the CD spectra have been discussed with respect to the electron-donating/ withdrawing ability of the groups at the 4,4'-positions. The X-ray crystal structure of the optically pure complex lambda-[Ru(dmbpy)2(4,4'-bis((R)-(+)-alpha-phenylethylamido)-2,2'-bipyridine)] x 2PF6 x 2CHCl3 was obtained and solved using direct methods. This result, in conjunction with the CD spectra, enabled the complete and unambiguous assignment of the stereocenters of all of the novel Ru(tris(bpy)) complexes prepared in this investigation.

Diastereoselective preparation and characterization of ruthenium bis(bipyridine) sulfoxide complexes.

A new concept in the synthesis of optically active octahedral ruthenium complexes was realized for the first time when cis- or trans-Ru(bpy)2Cl, (cis- or trans-1) was reacted with either (R)-(+)- or (S)-(-)-methyl p-tolyl sulfoxide (2 or 3); this novel asymmetric synthesis leads to the diastereoselective formation of the ruthenium bis(bipyridine) complex cis-delta-[Ru(bpy)2(2)Cl]Cl (4) (49.6% de) or cis-lambda-[Ru(bpy)2(3)Cl]Cl (5) (48.4% de), respectively. cis- or trans-Ru(dmbpy)2Cl2 (cis- or trans-6) (dmbpy = 4,4'-dimethyl-2,2'-bipyridine) also reacts with 2 or 3, leading to the diastereoselective formation of cis-delta-[Ru(dmbpy)2(2)Cl]Cl (7) (59.5% de) or cis-lambda-[Ru(dmbpy)2(3)Cl]Cl (8) (57.2% de), respectively. The diastereoselectivity of these reactions is governed solely by the chirality of the sulfoxide nucleophile. This represents the first process by which a sigma-bonded ligand occupying only a single coordination site has had such an important influence on the stereochemical outcome of a ruthenium bis(bipyridine) complex formation. These novel complexes were fully characterized by elemental analysis and IR, UV/vis, and 1H, 13C, and 2D NMR spectroscopy. An investigation into the chiroptical properties of these novel ruthenium bis(bipyridine) sulfoxide complexes has been carried out, and circular dichroism spectra are used to assign absolute stereochemistry.

Crystallographic, X-ray absorption, and IR studies of solid- and solution-state structures of tris(nitrato) N,N,N',N'-tetraethylmalonamide complexes of lanthanides. Comparison with the Americium complex.

To fine-tune the design of optimized donor ligands for nuclear waste actinide selective extraction, both electronic and molecular structures of the actinide complexes that are formed must be investigated. In particular, to achieve the selective complexation of transplutonium 3+ ions versus lanthanide 3+ ions is one of the major challenges, given the chemical similarities between these two f-element families. In this work, the structure of solvent-phase M(NO3)3(TEMA)2 complexes (Ln = Nd, Eu, Ho, Yb, Lu, Am; TEMA = N,N,N',N'-tetraethylmalonamide) was investigated by liquid-phase spectroscopic methods among which extended X-ray absorption fine structure played a major role. In addition, the crystal structures of the species Nd(NO3)3(TEMA)2 and Yb(NO3)3(TEMA)2 have been determined by X-ray diffraction. Nd(NO3)3(C11N2O2H22)2 crystallizes in the monoclinic system (P2(1) space group; a = 11.2627(4) A, b = 20.5992(8) A, c = 22.2126(8) A; alpha = gamma = 90 degrees, beta = 102.572(1) degrees; Z = 6), and Yb(NO3)3(C11N2O2H22)2 crystallizes in the orthorhombic system (P2(1)2(1)2(1) space group; a = 9.3542(1) A, b = 18.1148(2) A, c = 19.7675(2) A; alpha = beta = gamma = 90 degrees; Z = 4). In the solvent phase, the metal polyhedron was found to be similar to that of the solid-state complex Nd(NO3)3(TEMA)2 for M = Nd to Ho. For M = Yb and Lu, a significant elongation of one nitrate oxygen bond was observed. Comparison with measurements on the Am(NO3)3(TEMA)2 complex in ethanol has shown the similarities between the Nd3+ and Am3+ coordination spheres.

Detection of creatinine by a designed receptor.

An artificial receptor has been designed to bind creatinine with a color change (chromogenic response) caused by proton transfer from one end of the receptor to the other. The receptor was synthesized and found to extract creatinine from water into chlorocarbon solvents. The color change in the organic layer is specific for creatinine relative to other organic solutes, and it is selective for creatinine relative to sodium, potassium, and ammonium ions. The chromogenic mechanism is revealed by x-ray crystal structures of creatinine, the free receptor, and the complex, showing "induced fit" binding resulting from electronic complementarity between host and guest.

Effects of molecular substitution patterns on the cytochrome P-450-dependent metabolism of 2,2',3,5,5',6- and 2,2',3,4,4',6-hexachlorobiphenyl by rat liver microsomal monooxygenases.

The metabolism by rat hepatic microsomal cytochrome P-450-dependent monooxygenases of several model substrates that are specific for individual isoforms of cytochrome P-450 and the metabolism by these monooxygenases of two structurally related isomers of hexachlorobiphenyl was studied. The most striking result was that 2,2',3,5,5',6-hexachlorobiphenyl was metabolised in vitro at the rate of 4.5 pmol/mg microsomal protein per min, whereas the other isomer 2,2',3,4,4',6-hexachlorobiphenyl was not metabolised at detectable rates. This finding provides strong evidence for a regioselective oxidative attack by cytochrome P-450-dependent monooxygenase with preferential insertion of oxygen at meta-para unsubstituted carbon atoms. Investigations into the mechanism of this oxidative attack suggest that the ortho hydrogen atom at carbon atom C-6' of 2,2',3,4,4',6-hexachlorobiphenyl was associated with a lower charge (0.075 e) compared with the meta or para hydrogen atoms at carbon atom C-3' and C-4' of 2,2',3,5,5',6-hexachlorobiphenyl (0.086 e). In addition, measurement of the main C-C bond length using MOPAC calculations and X-ray crystalographic data suggests significant differences in the bond-length distance, with the main bond lengths of 1.390, 1.385 and 1.374 A, respectively, for bridgehead to ortho (C1-C2), for ortho to meta (C2-C3), and for meta to para bonds. These results provide evidence that the preferential meta-para oxidative attack is linked to a shorter carbon-carbon bond length and a more positive charge distribution of the corresponding hydrogen atoms.