Quantitative molecular similarity analysis (QMSA) methods for property estimation: a comparison of property-based,arbitrary, and tailored similarity spaces

Three classes of arbitrary quantitative molecular similarity analysis (QMSA) methods have been computed using atom pairs, topological indices, and physicochemical properties. Tailored QMSA models have been developed using a selected number of TIs chosen by ridge regression. The methods have been applied to the K-nearest neighbor based estimation of log P of two sets of chemicals. Results show that the property-based and tailored QMSA methods are superior to the arbitrary similarity methods in estimating log P of both sets of chemicals     

Tin(IV) complex of 3,4-dihydroxybenzaldehyde 4-ethylthiosemicarbazone: Synthesis,spectral studies and molecular modeling

The tin(IV) complex with 3,4-dihydroxybenzaldehyde 4-ethylthiosemicarbazone, [Sn(BETSC)Cl₂] has been synthesised and characterized using elemental analysis, Fourier transform infrared spectroscopy (FT-IR), UV-vis and NMR spectra. Theoretical calculations have also been performed by B3LYP method using LANL2DZ basis set. The assignments of bands observed in FT-IR spectrum for H₂BETSC and its Sn(IV) complex have been made using DFT method. Some significant differences in vibrational structures between the H₂BETSC and [Sn(BETSC)Cl₂] have been observed and discussed. Molecular docking was performed for the ligand H₂BETSC against dihydrofolate reductase (DHFR).     

Quantitative analysis of W-C:H coatings by EPMA,RBS (ERD) and SIMS

Several analytical techniques have been used to characterize homogeneous films of tungsten-containing hydrogenated carbon (W-C: H), deposited on Si with a film thickness of 1–1.5 m. Electron probe microanalysis (EPMA) enables one to determine the major components W (3–43 at %) and C, impurities (< 2 at %) of Ar and O, and the mass thickness (300–1800 g/cm²) of the films. The agreement between the results of EPMA and the data (W-content, mass thickness) provided by Rutherford backscattering spectrometry (RBS) is 5–10% relative. Quantitative analysis of hydrogen in W-C:H films (1–16 at %) is carried out by the technique of elastic recoil detection (ERD). A suitable scheme for the determination of H in W-C: H films by SIMS is proposed, based on monitoring the intensity ratio of HCs⁺/CCs⁺ secondary ions.     

Conformational analysis of dicarbonyl(methylcyclopentadienyl)(2-(diethylamino)-2-oxoethyl)iron(II): a spectroscopic and molecular mechanics study

A combination of NMR and IR spectroscopic techniques was used to examine the conformational preferences of the previously unreported oxaallyliron compound dicarbonyl(methylcyclopentadienyl)(2-(diethylamino)-2-oxoethyl)iron(II) (1). IR studies revealed that 1 existed in n-pentane solutions as an equilibrium between two or more exchanging conformers through a rotation about the Fe---C bond. An additional contribution to the conformational dynamics of 1 was identified due to the resonance component of the amide group. The resonance contribution manifested in the observed restricted rotation about the C---N amide bond. Molecular mechanics calculations were used to model the conformational processes. The calculations predicted that the resonance stabilized conformation was the energetically preferred structure of 1. This agrees with the experimental evidence that identified the influence of resonance on the conformation of 1.     

New salen-type manganese(III) Schiff base complexes derived from meso-1,2-diphenyl-1,2-ethylenediamine: In vitro anticancer activity,mechanism of action,and molecular docking studies

Four new manganese(III) Schiff base complexes (1–4) were synthesized and characterized. The complexes have general formula [MnClL^x] in which L represents a Schiff base ligand derived from condensation of meso-1,2-diphenyl-1,2-ethylenediamine with salicylaldehyde or its 3-OMe-, 5-Br-, or 5-OMe-derivatives (x = 1–4, respectively). The crystal structure of [MnClL¹] (1) was characterized by X-ray crystallography. The in vitro anticancer activity of these complexes was evaluated by MTT and apoptosis assays against human breast (MCF-7) and liver (Hep G2) cancer cells. The complexes exhibited considerable antiproliferative activity against both cell lines (IC₅₀ = 10.8–21.02 μM) comparable to cis-platin, except 4 (MCF-7). The highest activity was found for 1 with IC₅₀ values of 13.62 μM (MCF-7) and 10.8 μM (Hep G2). Flow cytometry experiments showed that 1 induced apoptosis on MCF-7 tumor cell line. Docking simulations using AUTODOCK were also carried out. The results showed that all complexes fitted into the minor groove region of DNA.     

Analytical method development for a specific assay method for monomethoxypoly(ethylene glycol)succinimido carbonate (mPEG-SC): A comparison of spectrophotometric, titrimetric and chromatographic methods

Three different quantitative methods, which rely on base-mediated reactions for the purity assessment of the hydrolytically unstable activated ester, mPEG-SC (1) are discussed. In a spectrophotometric assay, controlled base-catalyzed hydrolysis of mPEG-SC (1) affords N-hydroxysuccinimide and its concentration can be determined by UV analysis. Reaction of mPEG-SC (1) with benzylamine and a non-aqueous back titration of the remaining benzylamine can also be used for purity determination of mPEG-SC (1). HPLC analysis of derivatized forms of mPEG-SC (1) affords a potential specific assay for these polymers. The relative attributes and shortcomings of these methods are elaborated. Although the titration assay is intermediate in specificity, the greater precision of the method makes it the preferred method at this stage of development of an HPLC-ELSD or HPLC-UV assay method. The percent relative standard deviation (%R.S.D.) of the titration method was 2.9% as opposed to 8.8% for the HPLC assay. The accuracy of the titration method was shown to be 101 ± 4.0% and was sufficient to justify a blending operation according to FDA cGMP guidelines.     

Rapid multivariate analysis of 3D ToF‐SIMS data: graphical processor units (GPUs) and low‐discrepancy subsampling for large‐scale principal component analysis

Principal component analysis (PCA) and other multivariate analysis methods have been used increasingly to analyse and understand depth‐profiles in XPS, AES and SIMS. For large images or three‐dimensional (3D) imaging depth‐profiles, PCA has been difficult to apply until now simply because of the size of the matrices of data involved. In a recent paper, we described two algorithms, random vector 1 (RV1) and random vector 2 (RV2), that improve the speed of PCA and allow datasets of unlimited size, respectively. In this paper, we now apply the RV2 algorithm to perform PCA on full 3D time‐of‐flight SIMS data for the first time without subsampling. The dataset we process in this way is a 128 × 128 pixel depth‐profile of 120 layers, each voxel having a 70 439 value mass spectrum associated with it. This forms over a terabyte of data when uncompressed and took 27 h to process using the RV2 algorithm using a conventional windows desktop personal computer (PC). While full PCA (e.g. using RV2) is to be preferred for final reports or publications, a much more rapid method is needed during analysis sessions to inform decisions on the next analytical step. We have therefore implemented the RV1 algorithm on a PC having a graphical processor unit (GPU) card containing 2880 individual processor cores. This increases the speed of calculation by a factor of around 4.1 compared with what is possible using a fast commercially available desktop PC having central processing units alone, and full PCA is performed in less than 7 s. The size of the dataset that can be processed in this way is limited by the size of the memory on the GPU card. This is typically sufficient for two‐dimensional images but not 3D depth‐profiles without sampling. We have therefore examined efficient sampling schemes that allow a good approximate solution to the PCA problem for large 3D datasets. We find that low‐discrepancy series such as Sobol series sampling gives more rapid convergence than random sampling, and we recommend such methods for routine use. Using the GPU and low‐discrepancy series together, we anticipate that any time‐of‐flight SIMS dataset, of whatever size, can be efficiently and accurately processed into PCA components in a maximum of around 10 s using a commercial PC with a widely available GPU card, although the longer RV2 approach is still to be preferred for the presentation of final results, such as in published papers. Copyright © 2016 The Authors Surface and Interface Analysis Published by John Wiley & Sons Ltd     

Structural,functional, and evolutionary analysis of late embryogenesis abundant proteins (LEA) in Triticum aestivum: A detailed molecular level biochemistry using in silico approach

LEA (Late Embryogenesis Abundant) proteins are abundant in plants and play a crucial role in abiotic stress tolerance. In our work, we primarily focused on the variations in physiochemical properties, conserved domains, secondary structure, gene ontology and evolutionary relationships among 40 LEA proteins of Triticum aestivum (common wheat). Wheat LEA protein belongs to first 6 classes out of the 13 classes present in LEApdB, the comprehensive database for LEA proteins. Proteins belonging to each LEApdB class have structures and functions distinguished from other classes. The study found three different conserved LEA domains in Triticum aestivum. One important domain was dehydrin, present in wheat proteins of classes 1, 2 and 4, though varied in sequence level, have similar biological processes. The study also found sequence level and phylogenetic similarity between dehydrin domains of class 1 and 4, but distinct from that of LEApdB class 2. This study also demonstrated functional diversity in two class 6 proteins occurred due to many destabilizing mutations in the LEA4 domain that caused alteration of ligand binding and conformational shift from 3₁₀-helix → turn within the domain. The LEA4 domains of these proteins also showed functional similarity and evolutionary relatedness with three other proteins of genus Aegilops, denoting that these proteins in Triticum aestivum were derived from its ancestor Aegilops. The study also assigned LEApdB class 4 to an unclassified LEA protein ‘WZY2-1’ based on amino acid composition, conserved domain, motif architecture and phylogenetic relatedness with class 4 proteins. Our study has revealed a detailed analysis of LEA proteins in Triticum aestivum and can serve as a pillar for further investigations and comparative analysis of wheat LEA proteins with other cereal or plant types.     

Discovery of potential inhibitors targeting the kinase domain of polynucleotide kinase/phosphatase (PNKP): Homology modeling,virtual screening based on multiple conformations,and molecular dynamics simulation

In recent years, the level of interest has been increased in developing the DNA-repair inhibitors, to enhance the cytotoxic effects in the treatment of cancers. Polynucleotide kinase/phosphatase (PNKP) is a critical human DNA repair enzyme that repairs DNA strand breaks by catalyzing the restoration of 5’-phosphate and 3’-hydroxyl termini that are required for subsequent processing by DNA ligases and polymerases. PNKP is the only protein that repairs the 3′-hydroxyl group and 5′-phosphate group, which depicts PNKP as a potential therapeutic target. Besides, PNKP is the only DNA-repair enzyme that contains the 5′-kinase activity, therefore, targeting this kinase domain would motivate the development of novel PNKP-specific inhibitors. However, there are neither crystal structures of human PNKP nor the kinase inhibitors reported so far. Thus, in this present study, a sequential molecular docking-based virtual screening with multiple PNKP conformations integrating homology modeling, molecular dynamics simulation, and binding free energy calculation was developed to discover novel PNKP kinase inhibitors, and the top-scored molecule was finally submitted to molecular dynamics simulation to reveal the binding mechanism between the inhibitor and PNKP. Taken together, the current study could provide some guidance for the molecular docking based-virtual screening of novel PNKP kinase inhibitors.     

Shellfish waste-derived mesoporous chitosan for impressive removal of arsenic(V) from aqueous solutions: A combined experimental and computational approach

Novel shellfish waste-derived chitosan (CS) has been developed to adsorb As(V) from simulated wastewater under evaluating adsorption process parameters. The coexistence of some competing ions, like SiO₃^2-, Cl^-, NO₃^– and PO₄^3- as well as the regeneration capacity of the spent adsorbent, was explored. The experimental data were modeled using several kinetics and isotherm models to understand the mechanism related to the uptake process. As(V) uptake was relatively rapid and highly dependent on pH. The Avrami-fractional-order expression supported data best, while the Liu equation described well isotherm data at pH 5.0. The maximum uptake capability (Liu) was 12.32 mg/g, and the highest removal performance (99 %) was obtained at optimum pH 5.0. Molecular dynamics simulations were performed to more clearly illuminate the atomic-level interactions between arsenic species and CS surface in both acidic and basic mediums. After four adsorption–desorption cycles, CS exhibited more than 90 % As(V) removal efficiency. The results of this study indicates that low cost shellfish derived chitosan is promising for efficient removal of As(V) from water body and can be used to remove other pollutants from watewater.     

A series of 1-D zinc(II) coordination polymers with 3-D supramolecular networks: synthesis,structural investigation,and NBO analysis

Abstract

N,N′-Bis(pyridin-4-ylmethylene)naphthalene-1,5-diamine (L) acts as a bipyridine analogue linker ligand towards {Zn₇(μ₄-O)₂(OAc)₁₀}, {Zn₂(NCS)₂(OAc)₂}, and {Zn(N₃)₂} nodes and allows construction of three new 1-D coordination polymers, the linear chain [Zn₇(μ₄-O)₂(OAc)₁₀(L)]_n (1), [Zn(NCS)(OAc)(L)]_n (2) in ladder-type geometry and the zigzag chain [Zn(N₃)₂(L)]_n (3). Structural characterization reveals that in 1 acetate anionic ligands connect seven Zn(II) ions through the bridging coordination modes μ₃-η¹,η² and μ₂-η¹,η¹. The resulting heptanuclear node is located on an inversion center and therefore consists of four crystallographically distinct cations; their coordination spheres correspond to distorted octahedra or tetrahedra. The Zn(II) ions in polymer 2 exhibit distorted trigonal bipyramidal {ZnN₃O₂} coordination; μ₂-η¹,η¹ coordinated acetate and terminal thiocyanate ligands lead to inversion-symmetric [Zn₂(NCS)₂(OAc)₂] secondary building units (SBU), which are further linked by the N,N′-bipyridine analogue L. Terminal coordination of two anionic azide ligands and the bridging bipyridine L result in coordination polymer 3, in which the cations adopt distorted tetrahedral {ZnN₄} coordination. In all crystalline solids 1–3, adjacent 1-D chains interact through π–π stacking and non-classical (C???H···O, C???H···π) hydrogen bonds, leading to 3-D supramolecular architectures. Differences in their 3-D arrangement are due to variations in the anionic co-ligands, subtle conformational differences in the semi-rigid linker and the variable coordination sphere about the zinc cations. Thermogravimetric investigations indicate differences in both thermal stability and decomposition mode. Natural bond orbital (NBO) analysis provides a convenient basis for investigating the intramolecular bonding interactions and delocalization effects in these molecular systems. Finally, solids 1–3 exhibit intense luminescence at room temperature.     

Fatty Acid Ethyl Esters (FAEE): A New,Green and Renewable Solvent for the Extraction of Carotenoids from Tomato Waste Products

Currently there is a drive towards the minimisation and reclamation of valuable materials from the waste products of the food and beverage industry. This can be achieved through the extraction of residual nutraceuticals from such materials. Tomato pomace contains carotenoids and other chemicals which can be extracted directly into edible oils to improve the health-giving properties of such oils. We report here a novel green solvent, fatty acid ethyl esters (FAEE), which is significantly more effective than sunflower oil and hexane for the extraction of lycopene and beta-carotene from tomato skin waste. FAEE are a non-toxic renewable resource that is environmentally friendly and to our knowledge has never been used as a vegetal extraction fluid. The efficiency of FAEE extraction was significantly improved relative to both sunflower oil and hexane under ultrasound-assisted extraction (UAE) conditions. In addition, FAEE have the additional and significant advantage that once enriched with the extracted nutraceuticals can be used directly as a food additive.     

A new six-coordinate organotin(IV) complex of OP[NC5H10]3: A comparison with an analogous five-coordinate complex by means of X-ray crystallography,Hirshfeld surface analysis and DFT calculations

A new six-coordinate organotin(IV)-phosphoric triamide complex of OP[NC₅H₁₀]₃ = OP was synthesized ([Cl₂Sn(CH₃)₂(OP)₂], 1) and characterized by X-ray crystallography and spectroscopic methods (FT-IR, UV–Vis, and ¹H/¹³C/³¹P-NMR). The crystal structures of 1 and the analogous previously reported five-coordinate complex [Cl₂Sn(CH₃)₂(OP)] (IZOVIE) were compared on a structural level and by computational means using Hirshfeld surface analysis, density functional theory calculations and the atom in molecule method. The investigation of intermolecular interactions in the crystal structures of the two complexes by the Hirshfeld surface method indicates that in the absence of normal hydrogen bonds, the chlorine-based interactions H?Cl/Cl?H (for 1 and IZOVIE) and Cl?Sn/Sn?Cl (for IZOVIE) play a determinant role in the molecular assemblies. However, the prominent contacts are of H?H type. From calculated electronic parameters such as bond order, Mulliken charge and electron delocalization energy, it was found that the Sn-OP contact has a lower strength in IZOVIE than in 1, suggesting more ionic character of the metal-oxygen contact in five-coordinate complex IZOVIE. Furthermore, we discuss the similarities and differences of the two complexes 1 and IZOVIE derived from the same ligand OP by density functional theory calculations to present an insight into the organotin(IV)-phosphoric triamide coordination chemistry affected by different geometries and coordination numbers.     

ESI,APCI, and MALDI tandem mass spectrometry of poly(methyl acrylate)s: A comparison study for the structural characterization of polymers synthesized via CRP techniques and the software application to analyze MS/MS data

Research in polymer science and engineering is moving from classical methodologies to advanced analytical strategies in which mass spectrometry (MS)‐based techniques play a crucial role. The molecular complexity of polymers requires new characterization tools and approaches to elucidate the detailed structural information. In this contribution, a comparison study of poly(methyl acrylate)s (PMA) using different tandem mass spectrometry techniques (ESI, APCI, and MALDI MS/MS) is reported to provide insights into the macromolecular structure with the aid of a special MS/MS data interpretation software. Collision‐induced dissociation (CID) was utilized to examine the fragmentation pathways of PMAs synthesized via various controlled radical polymerization techniques. All three mass spectrometry techniques are used to analyze structural details of PMAs and the labile end‐groups are determined based on the fragmentation behavior in CID. Fragmentation products were identified which are characteristics for the cleavage between the polymer chain and the end‐group. The application of a tailor‐made software is shown to analyze complex MS/MS data, and it is proven that this kind of software will be helpful for polymer scientists to identify fragmentation products obtained by tandem mass spectrometry similar to the fields of proteomics, metabolomics, genomics, and glycomics. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

ChemInform Abstract: Sm2Si3O3N4 and Ln2Si2.5Al0.5O3.5N3.5 (Ln: Ce,Pr, Nd,Sm, Gd) — A Novel Synthetic Approach for the Preparation of N-Containing Melilites and X-Ray Single-Crystal Structure Determination.

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