990 research outputs found
Synthesis and Characterization of New Ethylenediamine Platinum(IV) Complexes Containing Lipophilic Carboxylate Ligands
A series of new ethylenediamine (en) platinum(IV) complexes of the type Pt(IV)enX2A2, with X2â = cyclobutane-1,1-dicarboxylato (CBDCA), dichloro or bis(decanoato) and A = acetato,
dodecanoato, tetradecanoato, hexadecanoato, octadecanoato, adamantanecarboxylato (Ad) or
3α, 12α-diformoxy-5ÎČ-cholato (DFCA) were synthesized and characterized by elemental analysis,
infrared and NMR (1Hâ and â13C) spectroscopic techniques.
Previous platinum(IV) compounds were usually restricted to trans-dihydroxo or trans-dichloro
platinum(IV) complexes. Recently trans-dicarboxylato platinum(IV) complexes with mainly acetate,
trifluoracetate or short-chain carboxylate groups (<11 carbons) in the axial position have been
described in the literature[1,2,3]. In this paper we report on the synthesis and characterization of a new class of ethylenediamine
platinum(IV) compounds that have high lipophilic long-chain carboxylate ligands either in the axial
or equatorial position. The platinum(IV) compounds with the lipophilic trans-carboxylate ligands in
the axial position were prepared by acylation of the trans-dihydroxo platinum(IV) species using an
acyl halide in the presence of pyridine. In contrast to previous publications[1]
the yields were
excellent (up to 94%!)
Synthesis of (N,N'-Bis(2-Hydroxyethyl)Ethane-1,2-Diamine)Malonatoplatinum(II) and X-Ray Crystal Structure of the Cis-R,S-Isomer
Hydroxyethyl substituted amineplatinum(II) and (IV) complexes are an interesting class of platinum based antitumour compounds due to their uncoordinated hydroxy groups. These hydroxy groups could play an important role in the mode of action of such complexes with respect to their ability to act as donor or acceptor for hydrogen bonds. Moreover, their chemistry in solution is of interest because it was found that there is the possibility of an intramolecular attack to form ethanolatoamine chelated species which are responsible for very stable monoadducts with 5'-GMP. Furthermore, there is the possibility of derivatisation at the OH site to form a new series of platinum compounds which may be used for a carrier mediated transport to tumour tissues. In this context a series of (N,N'-bis(2-hydroxyethyl)ethane-l,2-diamine)-platinum(II) complexes has been synthesised. During purification of one of the platinum based compounds, it was possible to isolate (SP-4-3)-R,S-(N,N'-bis(2-hydroxyethyl)ethane-l,2-diamine)malonatoplatinum(ll) and to resolve the structure by single crystal structure analysis. Intra- and intermolecular hydrogen bonds have been found which may explain the spontaneous crystallisation of the cis-R,S isomer and the stabilisation of the boat conformation of the malonatoplatinum(II) six-membered ring
Verhaltensprobleme in alternativen Legehennenhaltungen
In alternativen Haltungssystemen fĂŒr Legehennen stellen Federpicken und Kannibalismus groĂe Probleme dar. Aus der Literatur und Praxis besteht der Hinweis, dass ungĂŒnstige Aufzuchtbedingungen Hauptrisikofaktoren fĂŒr das Auftreten dieser Verhaltensstörungen wĂ€hrend der Legeperiode darstellen könnten. Hypothesenkataloge mit möglichen Risikofaktoren fĂŒr Federpicken und Kannibalismus wurden erstellt und durch Berater und Wissenschaftler bewertet
Comparison of the Antiproliferative Activity of Two Antitumour Ruthenium(III) Complexes With Their Apotransferrin and Transferrin-Bound Forms in a Human Colon Cancer Cell Line
Two ruthenium(III) complexes, namely trans-indazolium[tetrachlorobis(indazole)-
ruthenate(III)], HInd[RuInd2Cl4] and trans-imidazolium[tetrachlorobis(imidazole)-
ruthenate(III)], HIm[RuIm2Cl4] exhibit high anticancer activity in an autochthonous
colorectal carcinoma model in rats. Recently, it has been shown that both complexes bind
specifically to human serum apotransferrin and the resulting adducts have been studied
through spectroscopic and chromatographic techniques with the ultimate goal of preparing
adducts with good selectivity for cancer cells due to the fact that tumour cells express high
amounts of transferrin receptors on their cell surface
Parton distribution functions and quark orbital motion
Covariant version of the quark-parton model is studied. Dependence of the
structure functions and parton distributions on the 3D quark intrinsic motion
is discussed. The important role of the quark orbital momentum, which is a
particular case of intrinsic motion, appears as a direct consequence of the
covariant description. Effect of orbital motion is substantial especially for
polarized structure functions. At the same time, the procedure for obtaining
the quark momentum distributions of polarized quarks from the combination of
polarized and unpolarized structure functions is suggested.Comment: 17 pages, 2 figures, 1 table. Paper is accepted for publication in
Eur.Phys.J.
Controlled assembly of SNAP-PNA-fluorophore systems on DNA templates to produce fluorescence resonance energy transfer
The SNAP protein is a widely used self-labeling tag that can be used for tracking protein localization and trafficking in living systems. A model system providing controlled alignment of SNAP-tag units can provide a new way to study clustering of fusion proteins. In this work, fluorescent SNAP-PNA conjugates were controllably assembled on DNA frameworks forming dimers, trimers, and tetramers. Modification of peptide nucleic acid (PNA) with the O6-benzyl guanine (BG) group allowed the generation of site-selective covalent links between PNA and the SNAP protein. The modified BG-PNAs were labeled with fluorescent Atto dyes and subsequently chemo-selectively conjugated to SNAP protein. Efficient assembly into dimer and oligomer forms was verified via size exclusion chromatography (SEC), electrophoresis (SDS-PAGE), and fluorescence spectroscopy. DNA directed assembly of homo- and hetero-dimers of SNAP-PNA constructs induced homo- and hetero-FRET, respectively. Longer DNA scaffolds controllably aligned similar fluorescent SNAP-PNA constructs into higher oligomers exhibiting homo-FRET. The combined SEC and homo-FRET studies indicated the 1:1 and saturated assemblies of SNAP-PNA-fluorophore:DNA formed preferentially in this system. This suggested a kinetic/stoichiometric model of assembly rather than binomially distributed products. These BG-PNA-fluorophore building blocks allow facile introduction of fluorophores and/or assembly directing moieties onto any protein containing SNAP. Template directed assembly of PNA modified SNAP proteins may be used to investigate clustering behavior both with and without fluorescent labels which may find use in the study of assembly processes in cells
Crystallization behavior of iron- and boron-containing nepheline (Na2 OâAl2 O3 â2SiO2 ) based model high-level nuclear waste glasses
This study focuses on understanding the relationship between iron redox, composition, and heatâtreatment atmosphere in nephelineâbased model highâlevel nuclear waste glasses. Glasses in the Na2OâAl2O3âB2O3âFe2O3âSiO2 system with varying Al2O3/Fe2O3 and Na2O/Fe2O3 ratios have been synthesized by meltâquench technique and studied for their crystallization behavior in different heating atmospheresâair, inert (N2), and reducing (96%N2â4%H2). The compositional dependence of iron redox chemistry in glasses and the impact of heating environment and crystallization on iron coordination in glassâceramics have been investigated by Mössbauer spectroscopy and vibrating sample magnetometry. While iron coordination in glasses and glassâceramics changed as a function of glass chemistry, the heating atmosphere during crystallization exhibited minimal effect on iron redox. The change in heating atmosphere did not affect the phase assemblage but did affect the microstructural evolution. While glassâceramics produced as a result of heat treatment in air and N2 atmospheres developed a golden/brown colored ironârich layer on their surface, those produced in a reducing atmosphere did not exhibit any such phenomenon. Furthermore, while this ironârich layer was observed in glassâceramics with varying Al2O3/Fe2O3 ratio, it was absent from glassâceramics with varying Na2O/Fe2O3 ratio. An explanation of these results has been provided on the basis of kinetics of diffusion of oxygen and network modifiers in the glasses under different thermodynamic conditions. The plausible implications of the formation of ironârich layer on the surface of glassâceramics on the chemical durability of highâlevel nuclear waste glasses have been discussed
A novel EGFR inhibitor acts as potent tool for hypoxia-activated prodrug systems and exerts strong synergistic activity with VEGFR inhibition in vitro and in vivo
Small-molecule EGFR inhibitors have distinctly improved the overall survival especially in EGFR-mutated lung cancer. However, their use is often limited by severe adverse effects and rapid resistance development. To overcome these limitations, a hypoxia-activatable Co(III)-based prodrug (KP2334) was recently synthesized releasing the new EGFR inhibitor KP2187 in a highly tumor-specific manner only in hypoxic areas of the tumor. However, the chemical modifications in KP2187 necessary for cobalt chelation could potentially interfere with its EGFR-binding ability. Consequently, in this study, the biological activity and EGFR inhibition potential of KP2187 was compared to clinically approved EGFR inhibitors. In general, the activity as well as EGFR binding (shown in docking studies) was very similar to erlotinib and gefitinib (while other EGFR-inhibitory drugs behaved different) indicating no interference of the chelating moiety with the EGFR binding. Moreover, KP2187 significantly inhibited cancer cell proliferation as well as EGFR pathway activation in vitro and in vivo. Finally, KP2187 proved to be highly synergistic with VEGFR inhibitors such as sunitinib. This indicates that KP2187releasing hypoxia-activated prodrug systems are promising candidates to overcome the clinically observed enhanced toxicity of EGFR-VEGFR inhibitor combination therapies
- âŠ