Transition metal complexes of a potential anticancer quinazoline ligand

A new heterocycle, namely 2-(furyl)-3-(furfuralimino)-1,2-dihydroquinazolin-4(3H)-one (ffdq) was formed by the ondensation of 2-aminobenzoylhydrazide with furfural and characterized by physico-chemical, spectroscopic, and single crystal X-ray diffraction studies. A series of complexes of ffdq have been synthesized and characterized by physico-chemical, spectroscopic, and thermal studies. According to the i.r. and 1H-n.m.r. spectra ffdq behaves as a bidentate ligand coordinating through quinazoline oxygen and azomethine nitrogen. The FAB-mass spectrum of the Cd(II) complex indicates the monomeric nature of this complex. The X-band e.p.r. spectrum of the Cu(II) complex and thermal stabilities of the Co(II) and Ni(II) complexes are discussed.

Synthesis and characterisation of heterometallic molecular triangles using ambidentate linker: self-selection of a single linkage isomer

The coordination driven self-assembly of discrete molecular triangles from a non-symmetric ambidentate linker 5-pyrimidinecarboxylate (5-pmc) and Pd(II)/Pt(II) based 90◦ acceptors is presented. Despite the possibility of formation of a mixture of isomeric macrocycles (linkage isomers) due to different connectivity of the ambidentate linker, formation of a single and symmetrical linkage somer in both the cases is an interesting observation. Moreover, the reported macrocycles represent the first example of discrete metallamacrocycles of bridging 5-pmc. While solution composition in both the cases was characterised by multinuclear NMR study and electrospray ionization mass spectrometry (ESI-MS), the identity of the assemblies in the solid state was established by X-ray single crystals structure analysis. Variable temperature NMR study clearly ruled out the formation of any other macrocycles by [4 + 4] or [2 + 2] self-assembly of the reacting components.

Self-Assembly of Molecular Prisms via Pt-3 Organometallic Acceptors and a Pt-2 Organometallic Clip

The design and two-component [2 + 3] self-assembly of a series of new organometallic molecular prisms (3a-d) are described. Assemblies 3a,b incorporate 4,4',4'-tris[ethynyl-trans-Pt(PEt3)(2)]triphenylamine (1a) containing a Pt-ethynyl functionality as tritopic planar acceptor and organic ``clips'' 2a and 2b, respectively [where 2a = 1,3-bis(3-pyridyl)isophthalic amide; 2b= 1,3-bis(ethynyl-3-pyridyl)benzene]. In a complementary approach all organic tritopic planar donor ligand 2c [2c 4,4',4'-tris(4-pyridylethynyl)triphenylamine] was assembled with all organometallic ``clip'', 1,8-bis[{trans-Pt(PEt3) (2)(NO3)}ethynyl]anthracene (1b), to obtain prism 3c. A organometallic carbon-centered acceptor, 1,1,1- tris[4-{trans-Pt(PEt3)(2)(NO3)}ethynylphenyl]ethane (1c), has been prepared, and its prism derivative (3d) using an organic `clip'' is prepared. Assemblies (3a-d) were characterized by multinuclear NMR spectroscopy, electrospray ionization mass spectroscopy, and elemental analysis. 3a-d showed fluorescence behavior in solution, and quenching of fluorescence intensity (3a,3c-d) was noticed upon addition of TNT (2,4,6-trinitrotoluene), a common constituent of many commercial explosives. A thin film of the assembly 3d made by spin coating of a solution of 3 x 10(-5) M in DMF on it 1 cm(2) quartz plate showed fluorescence response to the vapor of TNT.

Use of non-specific and specific interactions in the analysis of testosterone and related compounds by capillary electromigration techniques

Determination of testosterone and related compounds in body fluids is of utmost importance in doping control and the diagnosis of many diseases. Capillary electromigration techniques are a relatively new approach for steroid research. Owing to their electrical neutrality, however, separation of steroids by capillary electromigration techniques requires the use of charged electrolyte additives that interact with the steroids either specifically or non-specifically. The analysis of testosterone and related steroids by non-specific micellar electrokinetic chromatography (MEKC) was investigated in this study. The partial filling (PF) technique was employed, being suitable for detection by both ultraviolet spectrophotometry (UV) and electrospray ionization mass spectrometry (ESI-MS). Efficient, quantitative PF-MEKC UV methods for steroid standards were developed through the use of optimized pseudostationary phases comprising surfactants and cyclodextrins. PF-MEKC UV proved to be a more sensitive, efficient and repeatable method for the steroids than PF-MEKC ESI-MS. It was discovered that in PF-MEKC analyses of electrically neutral steroids, ESI-MS interfacing sets significant limitations not only on the chemistry affecting the ionization and detection processes, but also on the separation. The new PF-MEKC UV method was successfully employed in the determination of testosterone in male urine samples after microscale immunoaffinity solid-phase extraction (IA-SPE). The IA-SPE method, relying on specific interactions between testosterone and a recombinant anti-testosterone Fab fragment, is the first such method described for testosterone. Finally, new data for interactions between steroids and human and bovine serum albumins were obtained through the use of affinity capillary electrophoresis. A new algorithm for the calculation of association constants between proteins and neutral ligands is introduced.

Identification of Isoflavonoid Metabolites in Humans

Epidemiological studies have associated high soy intake with a lowered risk for certain hormone-dependent diseases, such as breast and prostate cancers, osteoporosis, and cardiovascular disease. Soy is a rich source of isoflavones, diphenolic plant compounds that have been shown to possess several biological activities. Soy is not part of the traditional Western diet, but many dietary supplements are commercially available in order to provide the proposed beneficial health effects of isoflavones without changing the original diet. These supplements are usually manufactured from extracts of soy or red clover, which is another important source of isoflavones. However, until recently, detailed studies of the metabolism of these compounds in humans have been lacking. The aim of this study was to identify urinary metabolites of isoflavones originating from soy or red clover using gas chromatography - mass spectrometry (GC-MS). To examine metabolism, soy and red clover supplementation studies with human volunteers were carried out. In addition, the metabolism of isoflavones was investigated in vitro by identification of metabolites formed during a 24-h fermentation of pure isoflavones with a human fecal inoculum. Qualitative methods for identification and analysis of isoflavone metabolites in urine and fecal fermentation samples by GC-MS were developed. Moreover, a detailed investigation of fragmentation of isoflavonoids in electron ionization mass spectrometry (EIMS) was carried out by means of synthetic reference compounds and deuterated trimethylsilyl derivatives. After isoflavone supplementation, 18 new metabolites of isoflavones were identified in human urine samples. The most abundant urinary metabolites of soy isoflavones daidzein, genistein, and glycitein were found to be the reduced metabolites, i.e. analogous isoflavanones, a-methyldeoxybenzoins, and isoflavans. Metabolites having additional hydroxyl and/or methoxy substituents, or their reduced analogs, were also identified. The main metabolites of red clover isoflavones formononetin and biochanin A were identified as daidzein and genistein. In addition, reduced and hydroxylated metabolites of formononetin and biochanin A were identified; however, they occurred at much lower levels in urine samples than daidzein or genistein or their reduced metabolites. The results of this study show that the metabolism of isoflavones is diverse. More studies are needed to determine whether the new isoflavonoid metabolites identified here have biological activities that contribute to the proposed beneficial effects of isoflavones on human health. Another task is to develop validated quantitative methods to determine the actual levels of isoflavones and their metabolites in biological matrices in order to assess the role of isoflavones in prevention of chronic diseases.

Photocytotoxic 3d-Metal Scorpionates with a 1,8-Naphthalimide Chromophore Showing Photoinduced DNA and Protein Cleavage Activity

Ternary 3d-metal complexes of formulation [M(Tp(Ph))(py-nap)](ClO4)(1-3), where M is Co(II) (1), Cu(II) (2), and Zn(II) (3); Tp(Ph) is anionic tris (3-phenylpyrazolyl)borate; and py-nap is a pyridyl ligand with a conjugated 1,8-naphthalimide moiety, have been prepared from the reaction of metal perchlorate with KTp(Ph) and py-nap in CH2Cl2. The complexes have been characterized from analytical and physicochemical data. The complexes are stable in solution as evidenced from the electrospray ionization mass spectrometry data. The complexes show good binding propensity with calf thymus (CT) DNA, giving binding constant (K-b) values of similar to 10(5) M-1 and a molecular ``light-switch'' effect that results in an enhancement of the emission intensity of the naphthalimide chromophore on binding to CT DNA. The complexes do not show any hydrolytic cleavage of DNA. They show poor chemical nuclease activity in the presence of 3-mercaptopropionic acid or hydrogen peroxide (H2O2). The Co(II) and Cu(II) complexes exhibit oxidative pUC19 DNA cleavage activity in UV-A light of 365 rim. The Zn(II) complex shows moderate DNA photocleavage activity at 365 nm. The Cu(II)complex 2 displays photoinduced DNA cleavage activity in red light of 647.1 nm and 676 rim and near-IR light of >750 rim. A mechanistic studyin UV-A and visible light suggests the involvement of the hydroxyl radical as the reactive species in the DNA photocleavage reactions. The complexes also show good bovine serum albumin (BSA) protein binding propensity, giving K-BSA values of similar to 10(5) M-1. Complexes 1 and 2 display significant photoinduced BSA cleavage activity in UV-A light. The Co(II) complex 1 shows a significant photocytotoxic effect in HeLa cervical cancer cells on exposure to UV-A light of 365 nm, giving an IC50 value of 32 mu M. The IC50 value for the py-nap ligand alone is 41.42 mu m in UV-A light. The IC50 value is >200 mu M in the dark, indicating poor dark toxicity of 1. The Cu(II) complex 2 exhibits moderate photocytotoxicity and significant dark toxicity, giving IC50 values of 18.6 mu m and 29.7 mu m in UV-A light and in the dark, respectively.

Phospholipids of lipid-containing bacteriophages and their transbilayer distribution

In this study we used electro-spray ionization mass-spectrometry to determine phospholipid class and molecular species compositions in bacteriophages PM2, PRD1, Bam35 and phi6 as well as their hosts. To obtain compositional data of the individual leaflets, phospholipid transbilayer distribution in the viral membranes was studied. We found that 1) the membranes of all studied bacteriophage are enriched in PG as compared to the host membranes, 2) molecular species compositions in the phage and host membranes are similar, and 3) phospholipids in the viral membranes are distributed asymmetrically with phosphatidylglycerol enriched in the outer leaflet and phosphatidylethanolamine in the inner one (except Bam35). Alternative models for selective incorporation of phospholipids to phages and for the origins of the asymmetric phospholipid transbilayer distribution are discussed. Notably, the present data are also useful when constructing high resolution structural models of bacteriophages, since diffraction methods cannot provide a detailed structure of the membrane due to high motility of the lipids and lack of symmetric organization of membrane proteins.

Identification and characterization of a library of microheterogeneous cyclohexadepsipeptides from the fungus Isaria

Ten new cyclic hexadepsipeptides, six isariins and four isaridins, from the fungus Isaria have been identified and characterized by high-performance liquid chromatography, coupled to tandem electrospray ionization mass spectrometry (LC-ESIMS/MS). The isariins possess a beta-hydroxy acid residue and five alpha-amino acids, while isaridins contain a beta-amino acid, an alpha-hydroxy acid, and four alpha-amino acids. One- and two-dimensional NMR spectroscopy confirmed the chemical identity of some of the isariin fractions. Mass spectral fragmentation patterns of [M + H](+) ions reveal clear diagnostic fragment ions for the isariins and isaridins. Previously described cyclic depsipeptides, isarfelins from Isaria felina (Guo, Y. X.; Liu, Q. H.; Ng, T. B.; Wang H. X. Peptides 2005, 26, 2384), are now reassigned as members of the isaridin family. Examination of isaridin sequences revealed significant similarities with cyclic hexadepsipeptides such as destruxins and roseotoxins. The structure of an isariin (isariin A) investigated by NMR spectroscopy indicated the presence of a hybrid alpha beta C-11 turn, formed by the beta-hydroxy acid and glycine residues and a (D)Leu-(L)Ala type II' beta-turn. Additionally, the inhibitory effect of isariins and an isaridin on the intra-erythrocytic growth of Plasmodium falciparum is presented.

Search for a Fermiophobic Higgs Boson Decaying into Diphotons in p p-bar Collisions at sqrt{s} = 1.96 TeV

A search for a narrow diphoton mass resonance is presented based on data from 3.0 fb^{-1} of integrated luminosity from p-bar p collisions at sqrt{s} = 1.96 TeV collected by the CDF experiment. No evidence of a resonance in the diphoton mass spectrum is observed, and upper limits are set on the cross section times branching fraction of the resonant state as a function of Higgs boson mass. The resulting limits exclude Higgs bosons with masses below 106 GeV at a 95% Bayesian credibility level (C.L.) for one fermiophobic benchmark model.

Measurement of the WW+WZ production cross section using a matrix element technique in lepton+jets events

We present a measurement of the $WW+WZ$ production cross section observed in a final state consisting of an identified electron or muon, two jets, and missing transverse energy. The measurement is carried out in a data sample corresponding to up to 4.6~fb$^{-1}$ of integrated luminosity at $\sqrt{s} = 1.96$ TeV collected by the CDF II detector. Matrix element calculations are used to separate the diboson signal from the large backgrounds. The $WW+WZ$ cross section is measured to be $17.4\pm3.3$~pb, in agreement with standard model predictions. A fit to the dijet invariant mass spectrum yields a compatible cross section measurement.

Search for Pair Production of Supersymmetric Top Quarks in Dilepton Events from pp̅ Collisions at √s=1.96 TeV

We present the results of a search for pair production of the supersymmetric partner of the top quark (the stop quark $\tilde{t}_{1}$) decaying to a $b$-quark and a chargino $\chargino$ with a subsequent $\chargino$ decay into a neutralino $\neutralino$, lepton $\ell$, and neutrino $\nu$. Using a data sample corresponding to 2.7 fb$^{-1}$ of integrated luminosity of $p\bar{p}$ collisions at $\sqrt{s} = 1.96$ TeV collected by the CDF II detector, we reconstruct the mass of candidate stop events and fit the observed mass spectrum to a combination of standard model processes and stop quark signal. We find no evidence for $\pairstop$ production and set 95% C.L. limits on the masses of the stop quark and the neutralino for several values of the chargino mass and the branching ratio ${\cal B}(\chargino\to\neutralino\ell^{\pm}\nu)$.

Search for a Fermiophobic Higgs Boson Decaying into Diphotons in pp̅ Collisions at √s=1.96 TeV

A search for a narrow diphoton mass resonance is presented based on data from 3.0 fb^{-1} of integrated luminosity from p-bar p collisions at sqrt{s} = 1.96 TeV collected by the CDF experiment. No evidence of a resonance in the diphoton mass spectrum is observed, and upper limits are set on the cross section times branching fraction of the resonant state as a function of Higgs boson mass. The resulting limits exclude Higgs bosons with masses below 106 GeV at a 95% Bayesian credibility level (C.L.) for one fermiophobic benchmark model.

First Measurement of the tt̅ Differential Cross Section dσ/dMtt̅ in pp̅ Collisions at √s=1.96 TeV

We present a measurement of the $\ttbar$ differential cross section with respect to the $\ttbar$ invariant mass, dSigma/dMttbar, in $\ppbar$ collisions at $\sqrt{s}=1.96$ TeV using an integrated luminosity of $2.7\invfb$ collected by the CDF II experiment. The $\ttbar$ invariant mass spectrum is sensitive to a variety of exotic particles decaying into $\ttbar$ pairs. The result is consistent with the standard model expectation, as modeled by \texttt{PYTHIA} with \texttt{CTEQ5L} parton distribution functions.

Search for new particles decaying into dijets in proton-antiproton collisions at √s=1.96 TeV

We present a search for new particles whose decays produce two jets (dijets) using proton-antiproton collision data corresponding to an integrated luminosity of 1.13 fb-1 collected with the CDF II detector. The measured dijet mass spectrum is found to be consistent with next-to-leading-order perturbative QCD predictions, and no significant evidence of new particles is found. We set upper limits at the 95% confidence level on cross sections times the branching fraction for the production of new particles decaying into dijets with both jets having a rapidity magnitude |y|

Late Svecofennian leucogranites of southern Finland : Chronicles of an orogenic collapse

Leucogranite magmatism occurred in southern Finland during the later stages of the Paleoproterozoic Svecofennian orogeny. The leucogranites are considered to have formed from pre-existing crustal rocks that have undergone anatexis in the extensional stage of the orogeny, following continental collision and resultant crustal thickening. The leucogranites have been studied in the field using petrographic and mineralogical methods, elemental and isotope geochemistry on whole rocks and minerals, and U-Pb geochronology. On outcrop scale, these granites typically form heterogeneous, layered, sheet-like bodies that migmatize their country rocks. All of the leucogranites are peraluminous and rich in SiO2, but otherwise display significant geochemical variation. Their Nd isotope composition ranges from fairly juvenile to very unradiogenic, and the Hf isotope composition of their zircon shows a varying degree of mixing in the source, the zircon populations becoming more heterogeneous and generally less radiogenic towards the east. The leucogranites have been dated using U-Pb isotopic analyses, utilizing thermal ionization mass spectrometry, secondary ion mass spectrometry, and laser ablation multicollector ICP mass spectrometry on zircon and monazite. The results show that the granites were emplaced between 1.85 Ga and 1.79 Ga, which is a considerably longer period than has traditionally been perceived for these rocks. The rocks tend to become younger towards the east. Single crystal data also display a wide array of inherited zircons, especially in the eastern part of the leucogranite belt. The most common inherited age groups are ~2.8 2.5 Ga, ~2.1 2.1 Ga, and ~1.9 Ga. Magmatic zircon and monazite usually record similar ages for any one sample.Thermobarometric calculations indicate that the leucogranites in the Veikkola area of southcentral Finland were formed from relatively low-temperature melts, and emplaced at 17-25 km depth, i.e. at mid-crustal level. It is likely that these conditions apply to the Svecofennian leucogranites in general. Large differences in the Hf and Nd isotope compositions, emplacement ages, and distributions of inherited zircon ages show that these granites were formed from different types of source rocks, which probably included both sedimentary and igneous rocks.