Influence of metal loading and humic acid functional groups on the complexation behavior of trivalent lanthanides analyzed by CE-ICP-MS

The complexation behavior of Aldrich humic acid (AHA) and a modified humic acid (AHA-PB) with blocked phenolic hydroxyl groups for trivalent lanthanides (Ln) is compared, and their influence on the mobility of Ln(III) in an aquifer is analyzed. As speciation technique, capillary electrophoresis (CE) was hyphenated with inductively coupled plasma mass spectrometry (ICP-MS). For metal loading experiments 25 mg L⁻¹ of AHA and different concentrations (c_Ln(Eu+Gd) = 100–6000 μg L⁻¹) of Eu(III) and Gd(III) in 10 mM NaClO₄ at pH 5 were applied. By CE-ICP-MS, three Ln-fractions, assumed to be uncomplexed, weakly and strongly AHA-complexed metal can be detected. For the used Ln/AHA-ratios conservative complex stability constants log β_LnAHA decrease from 6.33 (100 μg L⁻¹ Ln³⁺) to 4.31 (6000 μg L⁻¹ Ln³⁺) with growing Ln-content. In order to verify the postulated weaker and stronger humic acid binding sites for trivalent Eu and Gd, a modified AHA with blocked functional groups was used. For these experiments 500 μg L⁻¹ Eu and 25 mg L⁻¹ AHA and AHA-PB in 10 mM NaClO₄ at pH-values ranging from 3 to 10 have been applied. With AHA-PB, where 84% of the phenolic OH-groups and 40% of the COOH-groups were blocked, Eu complexation was significantly lower, especially at the strong binding sites. The log β-values decrease from 6.11 (pH 10) to 5.61 at pH 3 (AHA) and for AHA-PB from 6.01 (pH 7) to 3.94 at pH 3. As a potential consequence, particularly humic acids with a high amount of strong binding sites (e.g. phenolic OH- and COOH-groups) can be responsible for a higher metal mobility in the aquifer due to the formation of dissolved negatively charged metal-humate species.     

Synthesis and potent cytotoxic activity of 8- and 9-anilinophenanthridine-7,10-diones

A series of 8-anilino and 9-anilinophenanthridine-7,10-diones was prepared and screened against various cancer cell lines to measure anti-proliferative activity. The compounds tested display potent cytotoxic activity in the micromolar and sub-micromolar range. These compounds are promising new leads for developing anticancer compounds.     

Dihydroxy(4-thiomorpholinomethyl)benzoic acid: from molecular asymmetry to diode characteristics

One of the challenges in molecular electronics is to design molecules which can be used as functional units in electronic devices. The subject of our investigations is an asymmetrical molecule, dihydroxy(4-thiomorpholinomethyl)benzoic acid (TMBA), whose structural and electronic properties are characterized. The self-assembly behavior of TMBA on Au(111) surfaces resulting in highly ordered monolayers is obtained using scanning tunneling microscopy (STM). Furthermore, investigations on the electronic properties of the combined metal/molecule system reveal an orbital mediated tunneling process and tunneling decay constants for the carboxylic and thiomorpholino group. Thus, a diode-like character of TMBA is shown to be caused by intrinsic electronic properties of different molecular moieties.     

Microanalytical method development for Fe, Cu and Zn determination in colorectal cancer cells

Microanalytical methods suitable for the determination of Fe, Cu in HT-29 (human colon adenocarcinoma) cells treated with different iron compounds (Fe(II) sulfate, Fe(III) chloride, Fe(III) citrate and Fe(III) transferrin) and cultured in medium supplemented or not with 10% (v/v) fetal calf serum (FCS) by total reflection X-ray fluorescence spectrometry (TXRF) and simultaneous graphite furnace atomic absorption spectrometry (GF-AAS) were developed. The developed TXRF method was also suitable for Zn determination in the samples. The main advantage of the proposed methods is the execution of all sample preparation steps following incubation and prior to the elemental analysis in the same Eppendorf tubes. Sample preparation was performed at microscale (115 μL sample volume) with 65% nitric acid and 30% hydrogen peroxide. According to scanning electron microscopic measurements, the organic matrix of the cell samples could be eliminated to the extent that accurate results were obtained for Cu and Fe by analyzing the same samples by TXRF and GF-AAS. Concerning the iron uptake, HT-29 cells incubated in FCS-free medium contained Fe in cca. 5-50 times higher amounts compared to cells cultured in FCS supplemented medium. Pronounced differences in the iron uptake compared to the iron supply (inorganic vs. organic chelated as well as iron(II) vs. iron(III)) were observed in the case of cell lines incubated in FCS-free medium.     

Technetium dichloride: a new binary halide containing metal-metal multiple bonds

Technetium dichloride has been discovered. It was synthesized from the elements and characterized by several physical techniques, including single crystal X-ray diffraction. In the solid state, technetium dichloride exhibits a new structure type consisting of infinite chains of face sharing [Tc(2)Cl(8)] rectangular prisms that are packed in a commensurate supercell. The metal-metal separation in the prisms is 2.127(2) ?, a distance consistent with the presence of a Tc≡Tc triple bond that is also supported by electronic structure calculations.     

Energetic preference of 8-oxoG eversion pathways in a DNA glycosylase

Base eversion is a fundamental process in the biochemistry of nucleic acids, allowing proteins engaged in DNA repair and epigenetic modifications to access target bases in DNA. Crystal structures reveal end points of these processes, but not the pathways involved in the dynamic process of base recognition. To elucidate the pathway taken by 8-oxoguanine during base excision repair by Fpg, we calculated free energy surfaces during eversion of the damaged base through the major and minor grooves. The minor groove pathway and free energy barrier (6-7 kcal/mol) are consistent with previously reported results (Qi, Y.; Spong, M. C.; Nam, K.; Banerjee, A.; Jiralerspong, S.; Karplus, M.; Verdine, G. L. Nature 2009, 462, 762.) However, eversion of 8-oxoG through the major groove encounters a significantly lower barrier (3-4 kcal/mol) more consistent with experimentally determined rates of enzymatic sliding during lesion search (Blainey, P. C.; van Oijent, A. M.; Banerjee, A.; Verdine, G. L.; Xie, X. S. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 5752.). Major groove eversion has been suggested for other glycosylases, suggesting that in addition to function, dynamics of base eversion may also be conserved.     

11-Step enantioselective synthesis of (-)-lomaiviticin aglycon

Lomaiviticins A and B are complex antitumor antibiotics that were isolated from a strain of Micromonospora. A confluence of several unusual structural features renders the lomaiviticins exceedingly challenging targets for chemical synthesis. We report an 11-step, enantioselective synthetic route to lomaiviticin aglycon. Our route proceeds by late-stage, stereoselective dimerization of two equivalent monomeric intermediates, a transformation that may share parallels with the natural products' biosyntheses. The route we describe is scalable and convergent, and it lays the foundation for determination of the mode of action of these natural products.     

The design, synthesis and photochemical study of a biomimetic cyclodextrin model of photoactive yellow protein (PYP)

The design, synthesis and study of the photophysical and photochemical properties of the first biomimetic cyclodextrin (CD) model of photoactive yellow protein (PYP) are described. This model bears a deprotonated trans-p-coumaric acid chromophore, covalently linked via a cysteine moiety to a permethylated 6-monoamino β-CD. NMR and UV/Visible spectroscopy studies showed the formation of strong self-inclusion complexes in water at basic pH. Steady-state photolysis demonstrated that, unlike the free chromophore in solution, excitation of the model molecule leads to the formation of a photoproduct identified as the cis isomer by NMR spectroscopy. These observations provide evidence that the restricted CD cavity offers a promising framework for the design of biomimetic models of the PYP hydrophobic pocket.     

Trinuclear rhodium hydride complexes

Three novel trinuclear rhodium hydride complexes of the type {[Rh(PP*)H](3)(μ(2)-H)(3)(μ(3)-H)}[BF(4)](2) containing diphosphines Tangphos, t-Bu-BisP* and Me-DuPHOS have been synthesised. The new compounds are very stable. Their structures have been characterized by X-ray analysis in the solid state and by NMR-spectroscopic investigations in solution.