The MM2QM tool for combining docking,molecular dynamics,molecular mechanics,and quantum mechanics†

The use of the MM2QM tool in a combined docking + molecular dynamics (MD) + molecular mechanics (MM) + quantum mechanical (QM) binding affinity prediction study is presented, and the tool itself is discussed. The system of interest is Mycobacterium tuberculosis (MTB) pantothenate synthetase in complexes with three highly similar sulfonamide inhibitors, for which crystal structures are available. Starting from the structure of MTB pantothenate synthetase in the “open” conformation and following the combined docking + MD + MM + QM procedure, we were able to capture the closing of the enzyme binding pocket and to reproduce the position of the ligands with an average root mean square deviation of 1.6 Å. Protein–ligand interaction energies were reproduced with an average error lower than 10%. The discussion on the MD part and a protein flexibility importance is carried out. The presented approach may be useful especially for finding analog inhibitors or improving drug candidates. © 2012 Wiley Periodicals, Inc.     

Comparison of contact angle hysteresis of different probe liquids on the same solid surface

Advancing and receding contact angles of water, formamide and diiodomethane were measured on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) layers deposited on three different solid supports—glass, mica and poly(methyl methacrylate). Up to five statistical monolayers were deposited on the surfaces by spreading DPPC solution. It was found that even on five statistical DPPC monolayers, the hysteresis of a given liquid depends on the kind of solid support. Also on the same solid support the contact angle hysteresis is different for each probe liquid used. The AFM images show that the heights of roughness of the DPPC films cannot be the primary cause of the observed hysteresis because the heights are too small to cause the observed hystereses. It is believed that the hysteresis is due to the liquid film present right behind the three-phase solid surface/liquid drop/gas (vapour) contact line and the presence of Derjaguin pressure. The value of contact angle hysteresis depends on both the solid surface and liquid properties as well as on intermolecular interactions between them.     

Sensitive adsorptive stripping voltammetric method for direct determination of trace concentration of lead in the presence of cupferron in natural water samples

This paper reports the use of an adsorptive voltammetric technique for Pb(II) determination using cupferron as a selective complexing agent. After accumulation of the complex onto a hanging mercury drop electrode, the electrode potential was scanned with differential pulse modulation and the reduction current of lead was observed at about??0.5?V. Under optimum conditions (5?×?10^?4?mol?L^?1 cupferron concentration, 0.1?mol?L^?1 acetate buffer (pH 5.5), adsorption at??50?mV for 30?s) the detection limit was 5.1?×?10^?10?mol?L^?1. The relative standard deviation of five measurements for low lead concentration was 3.1%. The accuracy of the method was tested by analysing certified reference material (SPS-WW1 Waste Water). Finally, the method was successfully applied to the determination of Pb(II) in river water samples without any pretreatments.     

Simple and fast voltammetric procedure of U(VI) determination in the presence of high concentrations of surface active substances

In this work, a simple and fast procedure for elimination of interfering surface active substances and for U(VI) adsorptive stripping voltammetric determination was developed. The adsorption in the form of U(VI)-cupferron complexes was performed, because as it was proved before, U(VI) forms with cupferron stable complexes, which were employed in voltammetric procedures. The procedure is based on two steps: the first is an adsorption of surface active substances onto an Amberlite XAD-16 or XAD-7 resin and the second is a voltammetric determination of U(VI) with a pulsed potential of accumulation alternate –0.65–0.3 V with the frequency of 0.5 Hz and then the differential pulse voltammogram was recorded, whereas the potential was scanned from –0.65 to –1.2 V. The detection limit estimated from three times the standard deviation for a low U(VI) concentrations was equal to 1.7 × 10^?10 mol L^?1 (7.2 × 10^?8 g L^?1). The linear range of U(VI) was observed over the concentration range from 5.0 × 10^?10 mol L^?1 (2.1 × 10^?7 g L^?1) to 2.0 × 10^?8 mol L^?1 (8.5 × 10^?6 g L^?1) for an accumulation time of 60 s. The influence of different kinds of surfactants, such as non-ionic, cationic and anionic on the uranium voltammetric signal was studied. The results confirm the possibility of U(VI) determination in water samples containing high concentrations of surface active substances even up to 50 mg L^?1.     

Development of purely structure-based pharmacophores for the topoisomerase I-DNA-ligand binding pocket

Purely structure-based pharmacophores (SBPs) are an alternative method to ligand-based approaches and have the advantage of describing the entire interaction capability of a binding pocket. Here, we present the development of SBPs for topoisomerase I, an anticancer target with an unusual ligand binding pocket consisting of protein and DNA atoms. Different approaches to cluster and select pharmacophore features are investigated, including hierarchical clustering and energy calculations. In addition, the performance of SBPs is evaluated retrospectively and compared to the performance of ligand- and complex-based pharmacophores. SBPs emerge as a valid method in virtual screening and a complementary approach to ligand-focussed methods. The study further reveals that the choice of pharmacophore feature clustering and selection methods has a large impact on the virtual screening hit lists. A prospective application of the SBPs in virtual screening reveals that they can be used successfully to identify novel topoisomerase inhibitors.     

Alkali metal cation complexation by 1,3-alternate,mono-ionisable calix[4]arene-benzocrown-6 compounds

Alkali metal cation extraction behaviour for two series of 1,3-alternate, mono-ionisable calix[4]arene-benzocrown-6 compounds is examined. In Series 1, the proton-ionisable group (PIG) is a substituent on the benzo group of the polyether ring that directs it away from the crown ether cavity. In Series 2, the PIG is attached to one para position in the calixarene framework, thereby positioning it over the crown ether ring. Competitive solvent extraction of alkali metal cations from aqueous solutions into chloroform shows high Cs⁺ efficiency and selectivity. Single-species extraction pH profiles of Cs⁺ for Series 1 and 2 ligands with the same PIG are very similar. Thus, association of Cs⁺ with the calixcrown ring is more important than the position of the PIG relative to the crown ether cavity. Solid-state structures of two unionised ligands from Series 2 are presented. Also described is a crystal containing two different ionised ligand–Cs⁺ complexes.     

Thermal properties of vitrified llw hospital waste incineration ash

The low level nuclear waste (LLW) resulting from the use of radioactive isotopes in medicine, industry, laboratories, and other purposes can be immobilized by vitrification, using methods applied in the nuclear power industry. Borosilicate glass is providing the very suitable medium for the majority of the species present in these wastes. Management of LLW waste begins with combustion reducing their amount. The paper presents the results of model studies of vitrification of hospital waste by incorporating it into the composition of boro-aluminosilicate glass, similar to those used in nuclear power industry. The proposed borosilicate waste glass composition was: SiO₂-56.0, B₂O₃-15.0, Na₂O-21.0, and Al₂O₃-8.0 (mass %). The ashes were mixed in different amount with the glass frit and then remelted to obtain homogenous melt which was vitrified. The influence of the main ash components on the thermal properties of the vitrified waste was studied using DSC and heating microscopy methods. The glass transformation, crystallization and melting temperatures, and Hruby glass stability against crystallization parameter were determined. The correlations between ΔC _p , T _g, and K _H were observed and discussed.     

Electrocatalytic properties of platinum nanocenters electrogenerated at ultra-trace levels within zeolitic phosphododecatungstate cesium salt matrices

A unique preparation method of obtaining stable composite film (with ultra-low platinum content) highly active towards oxygen reduction and hydrogen oxidation is presented here. The matrix for platinum centers consists of high-surface-area zeolite-type acidic salt of cesium phosphododecatungstate (Cs_2.5H_0.5PW₁₂O₄₀) admixed with carbon (Vulcan XC-72) carriers. Platinum nanoparticles were deposited on the working electrode modified with matrix via corrosion of platinum counter electrode during cyclic voltammetry experiment conducted in acid electrolyte containing chloride ions. The results obtained from rotating disk voltammetry revealed that the composite film containing Pt nanoparticles at very low loadings (on the level of 2–5 μg cm^?2) demonstrated remarkable electrocatalytic activity towards both oxygen reduction and hydrogen oxidation, particularly, when compared to the performance of the Cs_2.5H_0.5PW₁₂O₄₀-free system (i.e., containing only Vulcan support) prepared and examined under analogous conditions. The phenomenon should be primarily ascribed to the mesoporous nature of the matrix enabling immobilization and stabilization of small catalytic nanoparticles (1–2 nm diameters) inside the pores as well as to high surface acidity of the polyoxometalate-based salt providing proton-rich environment at the electrocatalytic interface.     

Functionalization of polyurethanes by incorporation of alkyne side-groups to oligodiols and subsequent thiol–yne post-modification

A versatile and upscalable method for the synthesis of polyurethanes (PUs) bearing pendant functionalities at the hard–soft segment interface from easily accessible commercial oligodiols is described. Reactive alkyne groups were introduced to polytetrahydrofuran (PTHF), poly(ε-caprolactone) (PCL) and polydimethylsiloxane (PDMS) diols by cationic ring-opening polymerization of glycidyl propargyl ether using these oligodiols as macroinitiators. The resulting oligodiols, with alkyne side groups located at both chain ends, were subsequently reacted with 1,4-butanediol and hexamethylene diisocyanate for the synthesis of PUs, containing several pendant alkyne groups between the soft and hard segments. The functionalized PUs based on different soft segments (PTHF, PCL or PDMS) have been further modified via metal-free thiol–yne chemistry. Proper reaction conditions were found for quantitative radical thiol–yne coupling reactions with benzyl mercaptan and thioglycerol.