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A series of glutarimide derivatives which has two carbonyl coordination sites for intramolecular pentacoordination at silicon with a X(1+n)SiC(3-n)O moiety have been synthesised and characterized. The substituent (leaving group) effects on the Si-O bond exchange between the two coordination sites (resembling a pendulum) have been studied by comparison of the differently substituted (X = F, Cl, OTf, Br and I) structures. The activation parameters for the Si-O bond exchange process were measured by NMR and separately computed and are consistent with the strength of Si-O bond coordination and the nature of the leaving group, X. The temperature-dependent (29)Si NMR spectroscopy is supported by X-ray crystallography and shows that the tetrahedral reactant is converted into pentacoordinate intermediates by intramolecular O-Si association followed by reversion to a tetrahedral geometry by Si-X dissociation. The two association/dissociation patterns offer a model for nucleophilic substitution at a silicon atom. A continuum of structures on the S(N)2 reaction profile from the glutarimide derivatives correlates reasonably well with the structural data obtained from derivatives of lactams, diketopiperazines and quinolones.

The reaction between 2-thiobarbituric acid (H(2)TBA), which was treated with an equimolar amount of potassium hydroxide, in a water with triphenytin chloride in methanol, results in the formation of the {[Ph(3)Sn(O-HTBA)]}(n) (1) complex. Crystals of the hydrated 1 with formula {[Ph(3)Sn(O-HTBA)]·0.7(H(2)O)}(n) were growth from methanol/acetonitrile solution, of the white precipitation, filtered off, from the reaction. The crystal structure of complex 1 has been determined by X-ray diffraction at 120 K. Complex 1 is polymeric. The geometry around the tin(IV) ions is trigonal bi-pyramidal with coordination to three C atoms from phenyl groups and one O atom from a de-protonated HTBA ligand. Complex 1 and the already known [(n-Bu)(3)Sn(O-HTBA)·H(2)O] (2) were evaluated for their in vitro cytotoxic activity (cell viability) against human cancer cell lines: HeLa (cervical), OAW-42 (ovarian), MCF-7 (breast, ER positive), MDA-MB-231 (breast, ER negative), A549 (lung), Caki-1 (renal) and additionally, the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) and normal immortalized human mammary gland epithelial cell line MTSV17 with a Trypan Blue assay. Moreover complex 1 was evaluated for its in vitro cell growth proliferation activity against leiomyosarcoma cells (LMS), MCF-7 and MRC-5 cells with a Thiazolyl Blue Tetrazolium Bromide (MTT) assay. The type of cell death caused by complexes 1 and 2 was also evaluated by use of flow cytometry assay. The results showed that these compounds mediate a strong cytotoxic response to normal and cancer cell lines tested through apoptosis and induce cell cycle arrest in S phase of the cell cycle, suggesting DNA intercalation (direct or indirect) with the complexes. Finally, the influence of these complexes 1 and 2 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Reversed-phase chiral high-performance liquid chromatography (HPLC) is a potentially powerful technique for the enantiomeric resolution of racemic mixtures, although the elution order of enantiomers is only relative and it is necessary to fully characterize reference systems for this method to provide absolute configurational information. The enantiomeric resolution of a series of racemic di-spiro cyclotriphosphazene derivatives, N3P3X2[O(CH2)(3)NH]2 (X = Cl, Ph, SPh, NHPh, OPh) [(1)-(5), respectively] was carried out by reversed-phase chiral HPLC on a commercially available Pirkle-type chiral stationary phase (R,R)-Whelk-01 using 85:15 (v/v) hexane-thf as the mobile phase. The absolute configurations of the resulting enantiomers of compounds (3) (X = SPh) and (5) (X = OPh) were determined unambiguously by X-ray crystallography. For both (3) and (5) it was found that the SS enantiomer eluted before the RR enantiomer, indicating a convenient method to determine the absolute configurations of enantiomers of this series of cyclophosphazene derivatives and providing the first set of enantiomeric reference compounds for cyclophosphazene derivatives. These structures demonstrate an interesting anomaly in that the pair of enantiomers of (3) crystallize in enantiomorphically paired space groups whilst, under the same conditions, the solid-state forms of the enantiomers of (5) form structures in Sohncke space groups that are not enantiomorphous.

Novel racemic indeno[1,2-e]pyrimido[4,5-b][1,4]diazepine-5,11-diones 3-29 were obtained regioselectivily from the reaction of 5,6-diamino-3,4-dihydropyrimidin-4-ones 1 and 2-arylideneindandiones 2 as reagents. These compounds have been evaluated at the US National Cancer Institute (NCI) for their ability to inhibit approximately 60 different human tumor cell lines, where 5 and 6 presented remarkable activity against 57 and 48 cancer cell lines, respectively, with the most important GI(50) values ranging from 0.49 to 1.46 microM, in vitro assay.

A novel tri-n-butyl(IV) derivative of 2-thiobarbituric acid (HTBA) of formula [(n-Bu)(3)Sn(TBA) H(2)O] (1) has been synthesized and characterized by elemental analysis and (119)Sn-NMR and FT-IR spectroscopic techniques. The crystal structure of complex 1 has been determined by single crystal X-ray diffraction analysis at 120(2) K. The geometry around Sn(IV) is trigonal bipyramidal. Three n-butyl groups and one oxygen atom from a deprotonated 2-thiobarbituric ligand are bonded to the metal center. The geometry is completed with one oxygen from a water molecule. Compound 1 exhibits potent, in vitro, cytotoxicity against sarcoma cancer cells (mesenchymal tissue) from the Wistar rat, polycyclic aromatic hydrocarbons (PAH, benzo[a]pyrene) carcinogenesis. In addition, the inhibition caused by 1, in the rate of lipoxygenase (LOX) catalyzed oxidation reaction of linoleic acid to hyperoxolinoleic acid, has been also kinetically and theoretically studied. The results are compared to that of cisplatin.

Gold-isocyanide complexes XAu(RNC) (X = halide, pseudohalide, R = alkyl, aryl) and water soluble gold-carbene complexes XAuC(NHPh)[MeN(CH(2)CH(2)O)(n)Me] (X = Cl, n = 1-11) have been prepared and evaluated as substrates for the direct laser writing of gold decoration onto ceramics.

The reaction of [Ru2(CO)6Cl4], 1, with excess THZ (1,3-thiazole) in absolute ethanol at 55 degrees C produces fac-[Ru(CO)3Cl2(THZ)], 2, in high yield. [Ru(CO)2Cl2(THZ)2], 3, is formed at higher temperature (ca 70 degrees C) and higher concentration of THZ. The X-ray structures of the new compounds have been determined, and density functional studies performed at the hybrid B3LYP/(Lanl2DZ, Ru; 6-311+G**, CHClNOS) level allowed the estimation of the structures of several conformers as well as that of their relative total electronic energies. Compound 2 is soluble (slowly) in aqueous media, where it reacts with the transport proteins bovine serum albumin (BSA) and human apotransferrin (HTF), and at a lower extent with calf thymus DNA (CT-DNA) and with guanosine-5'-monophosphate (GMP). The complex molecule is adsorbed by certain synthetic acryloyl polymers that have terminal carboxylate functions and is embedded in silica gels when these latter are prepared in the presence of a solution of 2. Ruthenium species are slowly released from the loaded gels into physiological solutions at pH 7.4. The reactivity of 2 with biomolecules and synthetic hydrogels makes it a compound of interest for anticancer and antimetastases tests.

[reaction: see text] A practical synthesis of optically pure alkylphenylvinylphosphine oxides is described, utilizing a nucleophilic displacement at phosphorus to install the vinyl moiety. The products were used to prepare classes of P-stereogenic aminophosphine (PN) and aminohydroxyphosphine (PNO) ligands. Stereocontrol can be exerted at various stages of the synthesis, to provide specific combinations of chirality in the final product. The effect of the stereogenic phosphorus and match-mismatch of chiralities of PNO ligands were examined in the asymmetric ruthenium-catalyzed hydrogen transfer reduction of three aryl ketones.

The synthesis of a series of novel 1-(2-deoxy-4-thio-beta-D-erythro-pentofuranosyl)-(6-azapyrimidine) nucleosides is described. X-ray crystallographic data of the thymidine derivative allowed conformational analysis, which indicated a twist (3T2) sugar conformation. Hydrogen-bonded assemblies for the crystal structure were determined using PLATON software to allow further interpretation of the crystal packing and base interactions. The 6-azapyrimidine nucleosides described were evaluated against a range of viral strains. The thymidine analogue showed pronounced activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and vaccinia virus. This compound lost only 5- to 10-fold of its antiviral activity against thymidine kinase (TK)-deficient HSV-1 and VZV strains. These observations suggest that the compounds may not entirely depend on viral TK-catalyzed phosphorylation for antiviral activity and/or use an alternative metabolic activation pathway, and/or display a unique mechanism of antiviral action by the unmetabolized nucleoside analogue.

The first example of an aromatic diazaarsolyl anion 1 has been synthesised and structurally characterised; the X-ray crystal structure of 1 exhibits planar metallacyclic fragments which link together to generate a coordination polymer via bridging lithium cations.

Four new 2-amidopyrroles and 2,5-diamidopyrroles have been synthesized and their anion complexation properties investigated. The crystal structures of these receptors have been elucidated and reveal hydrogen bonding in the solid state leading to dimer and network formation. Selectivity for oxo-anions has been demonstrated by (1)H NMR titration techniques.

Liquid-crystalline complexes of Pd(II) allow a new approach to the realisation of the biaxial nematic phase.

2-Aminothioisomünchnones, a well-known family of masked dipoles, react with aromatic aldehydes in a domino cascade reaction that produces episulfides (thiiranes) or beta-lactams (2-azetidinones). This sequence is initiated by a [3+2] dipolar cycloaddition followed by ring opening of cycloadducts and intramolecular rearrangement to afford these unusual ring contractions. The nature of the reaction products depends on the structural characteristics of the starting dipole and the experimental conditions. Episulfides are obtained selectively as cis isomers with respect to both aryl groups, whereas beta-lactams are produced as cis/trans mixtures. These structural features were determined unequivocally by X-ray crystallographic analysis. The beta-lactams still possessed a flexible acyclic chain containing sulfur, a salient lead modification of the bioactive cyclic penems and cephems. The preferential production of exo transition structures was rationalized with the aid of computational calculations at the B3LYP/6-31G* level.

In the title compound, C15H18N3+*C7H7O3S-, the phenylene and pyridyl rings are somewhat twisted with respect to each other, forming a dihedral angle of 23.49 (6) degrees. The compound contains a dipolar chromophoric cation, but crystallizes in the centrosymmetric space group P2(1)/n and is thus not expected to display quadratic non-linear optical effects.

Synthesis, structure determination by single-crystal X-ray diffraction, and physical properties are reported and compared for superconducting and semiconducting molecular charge-transfer salts with stoichiometry (BEDT-TTF)(4)[A(I)M(III)(C(2)O(4))(3)].PhCN, where A(I) = H(3)O, NH(4), K; M(III) = Cr, Fe, Co, Al; BEDT-TTF = bis(ethylenedithio) tetrathiafulvalene. Attempts to substitute M(III) with Ti, Ru, Rh, or Gd are also described. New compounds with M = Co and Al are prepared and detailed structural comparisons are made across the whole series. Compounds with A = H(3)O(+) and M = Cr, Fe are monoclinic (space group C2/c), at 150, 120 K a = 10.240(1) A, 10.232(12) A; b = 19.965(1) A, 20.04(3) A; c = 34.905(1) A, 34.97(2) A; beta = 93.69(1) degrees, 93.25(11) degrees, respectively, both with Z = 4. These salts are metallic at room temperature, becoming superconducting at 5.5(5) or 8.5(5) K, respectively. A polymorph with A = H(3)O(+) and M = Cr is orthorhombic (Pbcn) with a = 10.371(2) A, b = 19.518(3) A, c = 35.646(3) A, and Z = 4 at 150 K. When A = NH(4)(+), M = Fe, Co, Al, the compounds are also orthorhombic (Pbcn), with a = 10.370(5) A, 10.340(1) A, 10.318(7) A; b = 19.588(12) A, 19.502(1) A, 19.460(4) A; c = 35.790(8) A, 35.768(1) A, 35.808(8) A at 150 K, respectively, with Z = 4. All of the Pbcn phases are semiconducting with activation energies between 0.15 and 0.22 eV. For those compounds which are thought to contain H(3)O(+), Raman spectroscopy or C=C and C-S bond lengths of the BEDT-TTF molecules confirm the presence of H(3)O(+) rather than H(2)O. In the monoclinic compounds the BEDT-TTF molecules adopt a beta' ' packing motif while in the orthorhombic phases (BEDT-TTF)(2) dimers are surrounded by monomers. Raman spectra and bond length analysis for the latter confirm that each molecule of the dimer has a charge of +1 while the remaining donors are neutral. All of the compounds contain approximately hexagonal honeycomb layers of [AM(C(2)O(4))(3)] and PhCN, with the solvent occupying a cavity bounded by [M(C(2)O(4))(3)](3-) and A. In the monoclinic series each layer contains one enantiomeric conformation of the chiral [M(C(2)O(4))(3)](3-) anions with alternate layers having opposite chirality, whereas in the orthorhombic series the enantiomers form chains within each layer. Analysis of the supramolecular organization at the interface between the cation and anion layers shows that this difference is responsible for the two different BEDT-TTF packing motifs, as a consequence of weak H-bonding interactions between the terminal ethylene groups in the donor and the [M(C(2)O(4))(3)](3-) oxygen atoms.

Compounds (I), C(14)H(20)N(2)O(4)S, and (II), C(12)H(14)N(2)O(3)S(2), are two minor products of the same reaction. Both structures contain identical ester functionalities in similar orientations. Both independent molecules of (I) contain an ethoxycarbothioylamine moiety, whilst (II) possesses a novel exocyclic thione system fused with a pyridine ring.

This report covers initial studies in the coaggregation of nickel (Ni2+) and lanthanide (Ln3+) metal ions to form complexes with interesting structural and magnetic properties. The tripodal amine phenol ligand H3tam (1,1,1-tris(((2-hydroxybenzyl)amino)methyl)ethane) is shown to be particularly accommodating with respect to the geometric constraints of both transition and lanthanide metal ions, forming isolable complexes with both of these ion types. In the solid-state structure of [Ni(H2tam)(CH3CN)]PF6.2.5CH3CN.0.5CH3OH (1), the Ni(II) center has a distorted octahedral geometry, with an N3O2 donor set from the [H2tam]- ligand and a coordinated solvent (acetonitrile) occupying the sixth site. The reaction of stoichiometric amounts of H3tam with the Ni(II) ion in the presence of lanthanide(III) ions provides [LnNi2(tam)2]+ cationic complexes which contain coaggregated metal ions. These complexes are isolable and have been characterized by a variety of analytical techniques, with mass spectrometry proving to be particularly diagnostic. The solid-state structures of [LaNi2(tam)2(CH3OH)1/2(CH3CH2OH)1/2(H2O)]ClO4.0.5CH3OH.0.5CH3CH2OH.4H2O (2), [DyNi2(tam)2(CH3OH)(H2O)]ClO4.CH3OH. H2O(6), and [YbNi2(tam)2(H2O)]ClO4.2.58H2O(9) have been determined. Each complex contains two octahedral Ni(II) ions, each of which is encapsulated by the ligand tam3- in an N3O3 coordination sphere; each [Ni(tam)]-unit caps the lanthanide(III) ion via bridging phenoxy oxygen donor atoms. In 2, La3+ is eight-coordinated, while in 6, Dy(III) is seven- (to "weakly eight-") coordinated, and Yb(III) in 9 has a six-coordination environment. The complexes are symmetrically different, 2 possessing C2 symmetry and 6 and 9 having C1 symmetry. Magnetic studies of 2, 6, and 9 indicate that antiferromagnetic exchange coupling between the Ni(II) and Ln(III) ions increases with decreasing ionic radius of Ln(III).

A series of hydroxylated benzylideneanilines and benzylamines were prepared and tested for inhibition of epidermal growth factor receptor-associated protein tyrosine kinase (PTK) activity in vitro. Molecular modelling and analysis of the biological results lead us to propose a minimal structural pharmacophore for two distinct binding sites within the PTK domain.

A series of spirosuccinimides was synthesized and evaluated for anticonvulsant activity. The study was designed to determine the effect of varying the carbocyclic (ring A) nucleus, while maintaining the heterocyclic ring constant, on anticonvulsant activity. Results indicate that maximum activity was obtained with the ring A comprised of a six-membered spiro ring system, 2a, one methylene group greater than that previously reported for N-(benzyloxy)-2-azaspiro[4.4]nonane-1,3-dione, 1, the prototype analogue. Compound 2a was active in the MES test providing protection at 100 mg/kg, as was the spirododecane analog 2g. X-ray analysis revealed significant differences between active 2a, and the inactive spirooctane analogue, 2f. However these differences could not explain the unexpected activity demonstrated by the spirododecane analog 2g.

1-Benzyl-5,5-diphenyl-2,4-dioxo-3-imidazolidineacetic acid (AC), M(r) = 400.434, triclinic, P1, a = 8.7640 (3), b = 11.112 (1), c = 11.323 (2) A, alpha = 102.10 (2), beta = 95.44 (5), gamma = 109.12 (1)., V = 1002.65 (30) A3, Z = 2, Dx = 1.33 g cm-3, F(000) = 420, mu(Mo K alpha) = 0.852 cm-1, T = 293 K, R = 0.066 for 5551 unique observed reflections. The compound crystallizes from ethanol at room temperature in the form of colourless prism. 3-(2,4-Dichlorobenzyl)-5,5-diphenyl-2,4-dioxo-1-imidazolidineacetic++ + acid (AD), M(r) = 469.323, monoclinic, P2(1), a = 8.0399 (7), b = 9.7237 (6), c = 26.9768 (12) A, beta = 94.281 (4)., V = 2102.92 (96) A3, Z = 4, Dx = 1.48 g cm-3, F(000) = 968, mu(Mo K alpha) = 3.417 cm-1, T = 293 K, R = 0.066 for 5677 unique observed reflections. The compound crystallizes from ethanol at room temperature in the form of colourless prisms. Two approaches are employed in trying to understand the known differences in pharmacological activity: an analysis of the molecular geometries, and electronic structure calculations. A detailed analysis is made of the molecular geometries both from the X-ray diffraction results, and following energy minimization with molecular mechanics. The ab initio calculations employ the energy-minimized conformations. Several electronic properties are intercompared for AC, AD and their common parent molecule diphenylhydantoin (DPH). The analyses of geometry and electronic structure indicate dissimilarities between active and inactive compounds which may be linked to differences in the activity.

Aims: To determine the recent incidence of melanoma in the Nelson-Marlborough area of New Zealand and to compare this with a formerly determined incidence from the same area and with published incidences and trends elsewhere in New Zealand and Queensland., Methods: All histopathology reports for the region were examined retrospectively each four weeks and relevant information extracted. In cases of doubt, pathologists were consulted and cases reviewed. Population, demographic and weather information was obtained from statistical records., Results: These showed a doubling of the incidence since the previous survey with a reduction in female incidence. There was marked reduction in the incidence in the age groups 20-39 with an increase in those over 60 years. The number of superficial more easily cured lesions were almost doubled with marked reduction in the more sinister thicker and nodular lesions., Conclusions: The incidence of melanoma in the region is increasing at a rate comparable with other areas but with significant reductions in the incidence of thicker and more advanced melanoma as well as a decreased incidence in those under 40 years of age. The incidence in Nelson-Marlborough still remains very high but is slightly less than that shown for the Tauranga district over a similar period.

Aims: to describe the incidence and thickness of a representative collection of melanomas occurring in recent years in New Zealand., Methods: all pathology reports of primary malignant melanoma of the skin, in defined periods in 1987-9, were collated for four regions of New Zealand., Results: nonMaori incidence rates were 52 and 58 melanomas per 100,000 person years for men and women, respectively. These rates are much higher than the 24 per 100,000 person years for melanoma registrations in 1983-4. The age standardised invasive melanoma rate of 35 per 100,000 person years was higher than those of most Australian states and close to the rate for Queensland in 1986. Preinvasive melanomas comprised 26% of all melanomas. Of invasive melanomas, 58% in men and 55% in women were less than 0.76 mm in thickness; 7% of invasive melanomas in men and 5% in women were at least 3.5 mm thick., Conclusions: increasingly early detection of malignant melanomas in successive years is likely to have contributed to the recent increase in incidence, perhaps to a major degree, but an environmental cause cannot be excluded.

A double-blind controlled trial was performed on the use of topical 5% 5-fluorouracil ointment as a treatment for viral warts. The results showed the 5-fluorouracil to be better than the placebo.

Forty-six patients with herpes zoster were randomised into two groups treated with DMSO alone and 5 percent IDU in DMSO, provided that treatment started within 48 hours of the appearance of a rash. In the IDU group the interval before pain improved was significantly shorter than in the control DMSO group, and significantly fewer new vesicles developed at the three day follow up in the active group compared with the control group. These findings are in agreement with previously published work and confirm the usefulness of Zostrum (5 percent IDU in DMSO) in the treatment of herpes zoster.