An alternative method for the evaluation of docking performance: RSR vs RMSD

A new assessment criterion for docking poses is proposed in which experimental electron density is taken into account when evaluating the ability of docking programs to reproduce experimentally observed binding modes. Three docking programs (Gold, Glide, and Fred) were used to generate poses for a set of 88 protein-ligand complexes for which the crystal structure is known. The new criterion is based on the real space R-factor (RSR), which measures how well a group of atoms-in our case the ligand-fits the experimental electron density by comparing that density to the expected density, calculated from the model (i.e., the predicted ligand pose). The RSR-based measure is compared to the traditional criterion, the root-mean-square distance (RMSD) between the docking pose and the binding configuration in the crystallographic model. The results highlight several shortcomings of the RMSD criterion that do not affect the RSR-based measure. Examples illustrate that the RSR-derived approach allows a more meaningful a posteriori assessment of docking methods and results. Practical implications for docking evaluations and for methodological development work in this field are discussed.     

Three-dimensional molecular mapping of a multiple emulsion by means of CARS microscopy

Multiple emulsions consisting of water droplets dispersed in an oil phase containing emulsifier which is emulsified in an outer water phase (W/O/W) are of great interest in pharmacology for developing new drugs, in the nutrition sciences for designing functional food, and in biology as model systems for cell organelles such as liposomes. In the food industry multiple emulsions with high sugar content in the aqueous phase can be used for the production of sweets, because the high sugar content prevents deterioration. However, for these emulsions the refractive indexes of oil and aqueous phase are very similar. This seriously impedes the analysis of these emulsions, e.g., for process monitoring, because microscopic techniques based on transmission or reflection do not provide sufficient contrast. We have characterized the inner dispersed phase of concentrated W/O/W emulsions with the same refractive index of the three phases by micro Raman spectroscopy and investigated the composition and molecular distribution in water-oil-water emulsions by means of three-dimensional laser scanning CARS (coherent anti-Stokes Raman scattering) microscopy. CARS microscopy has been used to study water droplets dispersed in oil droplets at different Raman resonances to visualize different molecular species. Water droplets with a diameter of about 700 nm could clearly be visualized. The advantages of CARS microscopy for studying this particular system are emphasized by comparing this microscopic technique with conventional confocal reflection and transmission microscopies.     

Controlling the magnetic filaments length by tuning the particle interactions

Initially stable samples of monodisperse superparamagnetic particles were aggregated in the presence of an external magnetic field and different amounts of electrolyte. The aggregation process was monitored using dynamic light scattering (DLS). When the magnetic field was turned off, a significant change of the effective diffusion coefficient was observed at all electrolyte concentrations. This jump was interpreted in terms of filament break-up and additional rotational diffusive modes. Therefore, the length of the magnetic filaments (MF) was determined from the measured average diffusion coefficients applying an adequate theoretical approach. The results prove that the MFs disassemble completely at low electrolyte concentrations. At intermediate amounts of electrolyte added, a partial cluster break-up is observed. Only at high salt concentrations, the chains withstand the absence of the magnetic field. The results show that average filament size can be predicted and controlled by tuning the relative strength of the magnetic and electric interactions.     

Ion transmission in an electrospray ionization-mass spectrometry interface using an S-lens

We present the design and performance of an in-house built electrospray ionization-mass spectrometry (ESI-MS) interface equipped with an S-lens ion guide. The ion source was designed specifically for our ion beam experiments to investigate the chemical reactivity and deposition of the clusters and nanoparticles. It includes standard ESI-MS interface components, such as nanoelectrospray, ion transfer capillary, and the S-lens. A custom design enables systematic optimization of all relevant factors influencing ion formation and transfer through the interface. By varying the ESI voltage and flow rate, we determined the optimal operating conditions for selected silica emitters. A comparison of the pulled silica emitters with different tip inner diameters reveals that the total ion current is highest for the largest tip, whereas a tip with the smallest diameter exhibited the highest transmission efficiency through the ESI-MS interface. Ion transmission through the transfer capillary is strongly limited by its length, but the loss of ions can be reduced by increasing the capillary voltage and temperature. The S-lens was characterized over a wide range of RF frequencies and amplitudes. Maximum ion current was detected at RF amplitudes greater than 50 V peak-to-peak (p/p) and frequencies above 750 kHz, with a stable ion transmission region of about 20%. A factor of 2.6 increase in total ion current is observed for 650 kHz as RF amplitudes reach 400 V p/p. Higher RF amplitudes also focus the ions into a narrow beam, which mitigates their losses when passing through the ion guide.     

In vitro anticancer activity and biologically relevant metabolization of organometallic ruthenium complexes with carbohydrate-based ligands

The synthesis and in vitro anticancer activity of dihalogenido(eta6-p-cymene)(3,5,6-bicyclophosphite-alpha-D-glucofuranoside)ruthenium(II) complexes are described. The compounds were characterized by NMR spectroscopy and ESI mass spectrometry, and the molecular structures of dichlorido-, dibromido- and diiodido(eta6-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-alpha-D-glucofuranoside)ruthenium(II) were determined by X-ray diffraction analysis. The complexes were shown to undergo aquation of the first halido ligand in aqueous solution, followed by hydrolysis of a P--O bond of the phosphite ligand, and finally formation of dinuclear species. The hydrolysis mechanism was confirmed by DFT calculations. The aquation of the complexes was markedly suppressed in 100 mM NaCl solution, and notably only very slow hydrolysis of the P--O bond was observed. The complexes showed affinity towards albumin and transferrin and monoadduct formation with 9-ethylguanine. In vitro studies revealed that the 3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D-glucofuranoside complex is the most cytotoxic compound in human cancer cell lines (IC50 values from 30 to 300 microM depending on the cell line).     

Higher manganese silicide nanowires of Nowotny chimney ladder phase

We report the synthesis, structural identification, and electrical properties of the first one-dimensional (1-D) nanomaterials of a semiconducting higher manganese silicide (MnSi(2-x)) with widths down to 10 nm via chemical vapor deposition of the single-source precursor Mn(CO)(5)SiCl(3). The complex Nowotny chimney ladder structure of these homologous higher manganese silicides, also referred to as Mn(n)Si(2n-m), MnSi(1.75), or MnSi(1.8), contributes to the excellent thermoelectric performance of the bulk materials, which would be enhanced by phonon scattering due to 1-D nanoscale geometry. The morphology, structure, and composition of MnSi(2-x) nanowires and nanoribbons are examined using electron microscopy and X-ray spectroscopy. Elaborate select area electron diffraction analysis on single-crystal nanowires reveals the phase to be Mn(19)Si(33), one of a series of crystallographically distinct higher manganese silicides that have a Nowotny chimney ladder structure. Electrical transport study of single nanowires shows that they are degenerately doped with a low resistivity (17 mohms x cm) similar to the bulk.     

Crystal structures of n-BuLi adducts with (R,R)-TMCDA and the consequences for the deprotonation of benzene

Combinations of organolithium compounds and diamine bases have become a powerful tool in synthetic chemistry. Because of the structure-reactivity relationship, the elucidation of reaction mechanisms of these reagents is strongly connected with the structural determination of intermediate species. In mixtures of the diamine TMCDA (N,N,N',N'-tetramethylcyclohexane-1,2-diamine) and n-butyllithium, two different structures, the dimeric [n-BuLi x (R,R)-TMCDA]2 and the aggregate [(n-BuLi)2 x (R,R)-TMCDA]2, can be isolated, depending on the n-BuLi/TMCDA ratio. Thereby, [(n-BuLi)2 x (R,R)-TMCDA]2 is a rare example of an organolithium compound with a ladder arrangement of the central four-membered Li-C-Li-C rings. Two isomers of the ladder structure are formed in the crystal by changing from the enantiomerically pure to racemic TMCDA. As n-BuLi/TMCDA mixtures are also able to deprotonate benzene, these structures give hint to possible mechanisms. Supported by theoretical studies, transition states based on the dimer, the ladder structure, and a hypothetical monomer are discussed.     

Tributylphosphate extraction behavior of bismuthate-oxidized americium

Higher oxidation states of americium have long been known; however, options for their preparation in acidic solution are limited. The conventional choice, silver-catalyzed peroxydisulfate, is not useful at nitric acid concentrations above about 0.3 M. We investigated the use of sodium bismuthate as an oxidant for Am (3+) in acidic solution. Room-temperature oxidation produced AmO 2 (2+) quantitatively, whereas oxidation at 80 degrees C produced AmO 2 (+) quantitatively. The efficacy of the method for the production of oxidized americium was verified by fluoride precipitation and by spectroscopic absorbance measurements. We performed absorbance measurements using a conventional 1 cm cell for high americium concentrations and a 100 cm liquid waveguide capillary cell for low americium concentrations. Extinction coefficients for the absorbance of Am (3+) at 503 nm, AmO 2 (+) at 514 nm, and AmO 2 (2+) at 666 nm in 0.1 M nitric acid are reported. We also performed solvent extraction experiments with the hexavalent americium using the common actinide extraction ligand tributyl phosphate (TBP) for comparison to the other hexavalent actinides. Contact with 30% tributyl phosphate in dodecane reduced americium; it was nevertheless extracted using short contact times. The TBP extraction of AmO 2 (2+) over a range of nitric acid concentrations is shown for the first time and was found to be analogous to that of uranyl, neptunyl, and plutonyl ions.     

The shooting S-estimator for robust regression

To perform multiple regression, the least squares estimator is commonly used. However, this estimator is not robust to outliers. Therefore, robust methods such as S-estimation have been proposed. These estimators flag any observation with a large residual as an outlier and downweight it in the further procedure. However, a large residual may be caused by an outlier in only one single predictor variable, and downweighting the complete observation results in a loss of information. Therefore, we propose the shooting S-estimator, a regression estimator that is especially designed for situations where a large number of observations suffer from contamination in a small number of predictor variables. The shooting S-estimator combines the ideas of the coordinate descent algorithm with simple S-regression, which makes it robust against componentwise contamination, at the cost of failing the regression equivariance property.