bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unified QSAR & network‐based computational chemistry approach to antimicrobials. II. Multiple distance and triadic census analysis of antiparasitic drugs complex networks
Authors: Prado‐Prado Francisco J. , Ubeira Florencio M. , Borges Fernanda , González‐Díaz Humberto 
Published: May 2009

AbstractIn the previous work, we reported a multitarget Quantitative Structure‐Activity Relationship (mt‐QSAR) model to predict drug activity against different fungal species. This mt‐QSAR allowed us to construct a drug–drug multispecies Complex Network (msCN) to investigate drug–drug similarity (González‐Díaz and Prado‐Prado, J Comput Chem 2008, 29, 656). However, important methodological points remained unclear, such as follows: (1) the accuracy of the methods when applied to other problems; (2) the effect of the distance type used to construct the msCN; (3) how to perform the inverse procedure to study species–species similarity with multidrug resistance CNs (mdrCN); and (4) the implications and necessary steps to perform a substructural Triadic Census Analysis (TCA) of the msCN. To continue the present series with other important problem, we developed here a mt‐QSAR model for more than 700 drugs tested in the literature against different parasites (predicting antiparasitic drugs). The data were processed by Linear Discriminate Analysis (LDA) and the model classifies correctly 93.62% (1160 out of 1239 cases) in training. The model validation was carried out by means of external predicting series; the model classified 573 out of 607, that is, 94.4% of cases. Next, we carried out the first comparative study of the topology of six different drug–drug msCNs based on six different distances such as Euclidean, Chebychev, Manhattan, etc. Furthermore, we compared the selected drug–drug msCN and species–species mdsCN with random networks. We also introduced here the inverse methodology to construct species–species msCN based on a mt‐QSAR model. Last, we reported the first substructural analysis of drug–drug msCN using Triadic Census Analysis (TCA) algorithm. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010
λ‐Dynamics free energy simulation methods
Authors: Knight Jennifer L. , Brooks Charles L. 
Published: May 2009

AbstractFree energy calculations are fundamental to obtaining accurate theoretical estimates of many important biological phenomena including hydration energies, protein‐ligand binding affinities and energetics of conformational changes. Unlike traditional free energy perturbation and thermodynamic integration methods, λ‐dynamics treats the conventional “λ” as a dynamic variable in free energy simulations and simultaneously evaluates thermodynamic properties for multiple states in a single simulation. In the present article, we provide an overview of the theory of λ‐dynamics, including the use of biasing and restraining potentials to facilitate conformational sampling. We review how λ‐dynamics has been used to rapidly and reliably compute relative hydration free energies and binding affinities for series of ligands, to accurately identify crystallographically observed binding modes starting from incorrect orientations, and to model the effects of mutations upon protein stability. Finally, we suggest how λ‐dynamics may be extended to facilitate modeling efforts in structure‐based drug design. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009
Exploration of density functional methods for one‐electron reduction potential of nitrobenzenes
Authors: Zubatyuk Roman I. , Gorb Leonid , Shishkin Oleg V. , Qasim Mo , Leszczynski Jerzy 
Published: May 2009

AbstractPerformance of the set of density functional approaches for calculation of one‐electron reduction potentials of nitroaromatic compounds was investigated. To select the most precise and affordable method, we selected a set of model molecules and investigated effects of basis set, density functional, and solvation model on the calculation of reduction potentials. It was found that the mPWB1K/TZVP method provides the most accurate gas phase electron affinity values (RMS error is 0.1 eV). This method in conjunction with the PCM (Bondi) method yields also the most accurate difference in solvation energies of neutral oxidized form and anion‐radical reduced form. The final E0 values were calculated with RMS error of 0.10 V, compared with experimental values. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010
Crystal contacts as nature's docking solutions
Authors: Krissinel Evgeny 
Published: May 2009

AbstractThe assumption that crystal contacts reflect natural macromolecular interactions makes a basis for many studies in structural biology. However, the crystal state may correspond to a global minimum of free energy where biologically relevant interactions are sacrificed in favor to unspecific contacts. A large‐scale docking experiment was performed to assess the extent of misrepresentation of natural (in‐solvent) protein dimers by crystal packing. As found, the failure rate of docking may be quantitatively interpreted if both calculation errors and misrepresentation effects are taken into account. The failure rate analysis is based on the assumption that crystal structures reflect thermodynamic equilibrium between different dimeric configurations. The analysis gives an estimate of misrepresentation probability, which suggests that weakly bound complexes with KD ≥ 100 μM (some 20% of all dimers in the PDB) have higher than 50% chances to be misrepresented by crystals. The developed theoretical framework is applicable in other studies, where experimental results may be viewed as snapshots of systems in thermodynamic equilibrium. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010
Drug efficiency indices for improvement of molecular docking scoring functions
Authors: García‐Sosa Alfonso T. , Hetényi Csaba , Maran Uko 
Published: May 2009

AbstractA dataset of protein‐drug complexes with experimental binding energy and crystal structure were analyzed and the performance of different docking engines and scoring functions (as well as components of these) for predicting the free energy of binding and several ligand efficiency indices were compared. The aim was not to evaluate the best docking method, but to determine the effect of different efficiency indices on the experimental and predicted free energy. Some ligand efficiency indices, such as ΔG/W (Wiener index), ΔG/NoC (number of carbons), and ΔG/P (partition coefficient), improve the correlation between experimental and calculated values. This effect was shown to be valid across the different scoring functions and docking programs. It also removes the common bias of scoring functions in favor of larger ligands. For all scoring functions, the efficiency indices effectively normalize the free energy derived indices, to give values closer to experiment. Compound collection filtering can be done prior or after docking, using pharmacokinetic as well as pharmacodynamic profiles. Achieving these better correlations with experiment can improve the ability of docking scoring functions to predict active molecules in virtual screening. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010
PAPER—Accelerating parallel evaluations of ROCS
Authors: Haque Imran S. , Pande Vijay S. 
Published: May 2009

AbstractModern graphics processing units (GPUs) are flexibly programmable and have peak computational throughput significantly faster than conventional CPUs. Herein, we describe the design and implementation of PAPER, an open‐source implementation of Gaussian molecular shape overlay for NVIDIA GPUs. We demonstrate one to two order‐of‐magnitude speedups on high‐end commodity GPU hardware relative to a reference CPU implementation of the shape overlay algorithm and speedups of over one order of magnitude relative to the commercial OpenEye ROCS package. In addition, we describe errors incurred by approximations used in common implementations of the algorithm. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010
Effluent treatment using a bipolar electrochemical reactor with rotating cylinder electrodes of woven wire meshes
Authors: Grau Javier M , Bisang José M 
Published: May 2009

AbstractBACKGROUND: The behaviour of a bipolar electrochemical reactor consisting of one or more rotating cylinder electrodes of woven wire meshes is reported using copper and cadmium deposition from dilute solutions as test reactions.RESULTS: The best performance related to electrode number was determined for copper deposition and was achieved by an arrangement with two bipolar electrodes, for which the conversion in a single pass was approximately 47%. The specific energy consumption was 3.27 kWh kg−1 with a normalised space velocity of 23.05 h−1. The copper powder obtained showed a nodular and dendritic surface morphology. This reactor configuration was also analysed for cadmium deposition, in which hydrogen evolution takes place simultaneously as a side cathodic reaction, considering the effect of flow rate and total current. The maximum conversion per pass for cadmium removal was 38.91%. In this case the reactor with two bipolar electrodes showed a performance similar to that of a monopolar reactor operated at a rotation speed three times higher.CONCLUSION: A continuous electrochemical reactor with two rotating bipolar electrodes of woven wire meshes presents a good performance for copper or cadmium removal from dilute solutions. Copyright © 2009 Society of Chemical Industry
Microscopic studies of the influence of main exposure time on parameters of flexographic printing plate produced by digital thermal method
Authors: Harri Liliya 
Published: May 2009

AbstractThe digital thermal technology of producing flexographic printing plates from photopolymer plates is one of the newest technologies. This technology allows to develop flexographic plates without the use of any solvent. The process of producing flexographic printing plates by the digital thermal method consists of several main stages: back exposure, laser exposure, main exposure, thermal development, post exposure, and light finishing. The studies carried out with the use of optical stereoscopic microscopy allowed to determine the effect of time of main exposure to ultraviolet radiation on the dot area, diameter, and edge factor of halftone dots reproduced on flexographic printing plate produced by the digital thermal method, as well as on the quality of reproducing the surface and on the profiles of free‐standing printing microelements. The results of the microscopic studies performed have allowed to define the criteria of establishing optimum time of main exposure of photopolymer plates used in the digital thermal technology of producing flexographic printing plates. A precise definition of the criteria for determining the optimum time of main exposure will enable to reduce the time‐consuming control tests and to eliminate errors in both the process of manufacturing flexographic printing plates and in the printing process carried out with the use of such plates. Microsc. Res. Tech., 2009. © 2009 Wiley‐Liss, Inc.
Nitrogen heterocyclic analogs of polyaryls
Authors: Buu‐Hoï N. P. , Périn F. , Jacquignon P. 
Published: May 2009

AbstractNitrogen heterocyclic analogs of polyaryls, derived from pyridine, quinoline, benzo[h]‐quinoline, indole, indolizine, and imidazo[1,2‐alpyridine, have been prepared from 1,4‐diacetyl‐ and 1,3,5‐triacetylbenzene and 2,6‐diacetylpyridine, for study of their physical, chemical and biological properties.
Aromaticity in heterocyclic systems III. The structure and proton magnetic resonance spectra of certain imidazo[1,2‐a]pyridines
Authors: Paolini John P. , Robins Roland K. 
Published: May 2009

AbstractA number of improved laboratory procedures for the synthesis of derivatives ofimidazo‐[1,2‐alpyridines are reported. These methods have been employed for the preparation of 5‐chloroimidazo[1,2‐alpyridine (IX), 5‐aminoimidazo[1,2‐a]pyridine (IV), 2‐methyl and 2,3‐dimethyl‐5‐aminoimidazo[1,2‐a]pyridine. The proton magnetic resonance spectra of imidazo[1,2‐a]pyridine (I) have been studied and the bands assigned by a comparison of spectral patterns of simple derivatives. The proton magnetic resonance spectra were then utilized to assign predominant tautomeric structures to imidazo[1, 2‐a]‐2‐pyridone (IIIb), imidazo[1,2‐a]‐(1H)‐5‐pyridone (VIIb) and 5‐aminoimidazo‐[1, 2‐alpyridine (IV). The synthesis of imidazo[1,2‐a]‐(1H)‐5‐pyridone (VII) was accomplished from 5‐chloro‐imidazo[1, 2‐alpyridine (IX) via 5‐benzyloximidazo[1,2‐a]pyridine (X) which was debeneylated catalytically to yield VII. Bromoacetaldehyde and 2‐amino‐4‐chloropyridine gave 7‐chloroimidazo[1,2‐a]pyridine.
1,2,3‐Thiadiazoles as potential antineoplastic agents. I. Synthesis of novel 4‐monosubstituted and 4,5‐disubstituted derivatives
Authors: Looker J. H. , Wilson Leon W. 
Published: May 2009

Abstract1,2,3‐Thiadiazole‐4‐carboxylic acid (IV) has been synthesized by oxidation of 5‐(2‐furyl)‐1,2,3‐thiadiazole‐4‐carboxylic acid (IIb), and converted via the acid chloride (V) to the amide (VI), ethyl ester (VII) and azide (IX). Rearrangement of the azide (IX) in ethanol led to ethyl N‐(1,2,3‐thiadiazol‐4‐yl)carbamate (X) and in benzene or toluene to a complex substance, possibly N,N,N‐tris‐(1,2,3‐thiadiazol‐4‐yl)‐isocyanurate (XI). Ethyl 5‐phenoxy‐1,2,3‐thiadiazole‐4‐carboxylate (XIII), prepared from ethyl (phenoxy‐acetyl)diazoacetate (XII), has been converted to ethyl 5‐formyl‐1,2,3‐thiadiazole‐4‐car‐boxylate methyl phenyl acetal (XVI) via the α ‐halo ether (XIV). The acetal (XVI) underwent partial hydrolysis in dilute acid to yield ethyl 5‐formyl‐1,2,3‐thiadiazole‐4‐car‐boxylate phenyl hemiacetal (XVII) as an oil. Vacuum distillation of XVII gave ethyl 5‐formyl‐1,2,3‐thiadiazole‐4‐carboxylate (XVIII) as an oil. The aldehyde XVIII, but not the hemiacetal XVII, formed a crystalline oxime (XIX) with hydroxylamine.
Naphtho[2,3‐a]quinolizinium derivatives
Authors: Doolittle R. E. , Bradsher C. K. 
Published: May 2009

AbstractThe alkylation of 2‐acetonylpyridines with β‐phenylethyl bromides leads to ketones which may be cyclized to 1‐methyl‐2‐(2‐pyridyl)‐3,4‐dihydronaphthalenes. Aromatization of the dihydronaphthalenes followed by quaternization with chloroacetaldoxime affords salts which may be cyclized to yield the title compounds.
5,6‐Dihydro‐4 H,1,3,4‐oxadiazines. IV. Further studies
Authors: Trepanier D. L. , Spracmanis V. , Tharpe D. S. , Krieger P. E. 
Published: May 2009

AbstractThe scope of the acid‐catalyzed cyclodehydration of 2‐(β‐hydroxyalkyl)carboxylic acid hydrazides into 5, 6‐dihydro‐4H‐1, 3, 4‐oxadiazines has been extended through the use of acidic reagents other than concentrated sulfuric and polyphosphoric acids. Additional data are presented which corroborate previously proposed mechanisms of this reaction.
Nuclear magnetic resonance studies of heteroaromatic systems. Methyl coupling of 2‐substituted picolines, 2‐pyridones and 2‐pyridthiones
Authors: Bell Charles L. , Egan Richard S. , Bauer Ludwig 
Published: May 2009

AbstractThe proton magnetic resonance spectra of all the 2‐amino‐, 2‐chloro‐, 2‐nitropicolines were determined. Long‐range coupling of the methyl groups to all available ortho (four bonds) and para (six bonds) ring protons was found in these picolines. The p.m.r. spectra of all of the ring methyl substituted 2‐pyridones and 2‐pyridthiones were analyzed. In 4‐ and 5‐methyl‐2‐pyridones and the corresponding thiones, selective ring coupling was observed to only one ortho ring proton, viz., to H‐3 and H‐6 respectively. However, in 3‐ and 6‐methyl‐2‐pyridones and analogous thiones, long‐range coupling was visible to both ortho and para ring protons. These long‐range spin‐spin interactions are interpreted in terms of the structures of 2‐pyridones and their thione analogs.
Cinnoline chemistry. XII. The synthesis of 6‐fluoro‐4‐methylcinnoline and other cinnolines as potential antitumor agents
Authors: Castle Raymond N. , Adachi Kikuo , Guither William D. 
Published: May 2009

Abstract6‐Fluoro‐4‐methylcinnoline (IX) has been synthesized in eight steps from 4‐fluoroaniline. A series of styryl and pyridylethenyl cinnolines have been prepared from 6‐fluoro‐4‐methylcinnoline (IX), 4‐methylcinnoline and 4‐methylcinnoline‐2‐oxide. Furthermore, a series of 4‐substituted benzylthiocinnolines have been prepared.
Thiocyanation of amino‐2‐methylbenzothiazoles
Authors: Grandolini Giuliano , Ricci Adolfo , Martani Alfio , Mezzetti Tarcisio 
Published: May 2009

AbstractThiocyanation of the four amino‐2‐methylbenzothiazole isomers has been studied: in three of these the thiocyano group is oriented ortho to the amino group and consequently three new angular benzobisthiazoles have been obtained. The 7‐thiocyano derivative was obtained from 4 ‐ amino ‐ 2 ‐ methylbenzothiazole. The structure of the benzobis‐heterocycles has been confirmed by NMR spectroscopy.
Reaction of the thiolsulfonate group with the aromatic nucleus: A new ring closure
Authors: Dunbar Joseph E. , Tarnowski Betty H. 
Published: May 2009

AbstractThe double ring closure of N,N‐bis[2‐ (alkyl‐ or arylsulfonylthio)ethyl]anilines to form 2,3,5,6‐tetrahydro[1,4]thiazino[4,3,2‐de][1,4]benzothiazines, a new ring system, is reported. The effects of various benzene ring substituents upon the ring closure are described.
New synthesis routes to 2‐halopyridines. III. 2‐fluoropyridine
Authors: Boudakian Max M. 
Published: May 2009

AbstractThe solvent‐free fluorination of 2‐chloropyridine (III) with alkali metal fluorides and bifluorides was investigated. While complete degradation occurred with potassium fluoride at 315°, the use of potassium bifluoride under identical conditions provided a 74% yield of 2‐fluoro‐pyridine (II). Sodium bifluoride gave only a 3.5% yield of the desired product. These results are discussed in the light of: activation of the substrate, properties of the fluorinating agents, and the stability of 2‐fluoropyridine.
Geometrical isomerism and photochemical behaviour of α‐substituted 2 and 4‐styrylpyridines
Authors: Galiazzo G. , Bortolus P. , Cauzzo G. , Mazzucato U. 
Published: May 2009

Abstractα‐Methyl and α‐phenyl substituted 2 and 4‐styrylpyridines were prepared by classical routes. The geometrical isomers were separated and characterized on the basis of their U.V. absorption spectra and/or of their behaviour under U.V. irradiation which led to photoisomerization and photocyclization products. The last photoreaction, in the case of α‐phenyl derivatives, gave pyridyl‐substituted phenanthrenes and phenyl‐substituted azaphenanthrenes which were isolated and characterized.Spectral, chromatographic and physical properties of trans and cis derivatives and related photocyclization products are given as well as some kinetic data for the photochemical reactions.
The synthesis of 5,6‐dihydro‐6‐methylthiazolo‐[2,3‐b] [1,3] benzodiazepines, 2,3,10,11‐tetrahydro‐10‐methyl‐1H‐cyclopenta[4,5] thiazolo[2,3‐b] [1,3] benzodiazepine, and 7,8,9,10,12,13‐hexahydro‐13‐methylbenzothiazolo[2,3‐b] [1,3]‐benzodiazepine via 1,3,4,5‐tetrahydro‐5‐methyl‐2H‐1,3‐benzodiazepine‐2‐thione
Authors: Elslager Edward F. , Worth Donald F. , Perricone S. C. 
Published: May 2009

AbstractCatalytic reductive scission of 4‐methylcinnoline (V) with Raney nickel afforded o‐amino‐β‐methylphenethylamine (IV) in 57% yield. Treatment of IV with carbon disulfide followed by thermal cyclization of the product furnished 1,3,4,5‐tetrahydro‐5‐methyl‐2H‐1,3‐benzodiazepine‐2‐thione (III). Reaction of III with ethyl chloroacetate, ethyl 2‐bromohexanoate, ethyl 2‐chloroacetoacetate, 2‐bromo‐2′‐methoxyacetophenone, and 2‐bromoacetophenone provided a series of substituted 5,6‐dihydro‐6‐methylthiazolo[2,3‐b][1,3]benzodiazepines. Condensation of III with 2‐chlorocyclopentanone and 2‐chlorocyclohexanone gave 2,3,10,11‐tetrahydro‐10‐methyl‐1H‐cyclopenta[4,5]thiazolo[2,3‐b][1,3]benzodiazepine and 7,8,9,10,12,13‐hexahydro‐13‐methylbenzothiazolo[2,3‐b][1,3]benzodiazepine, respectively. Structure assignments are discussed. None of the compounds possessed appreciable biological activity.
Compounds in the pyrrolo[3,4‐d]pyrimidine series. derivatives with 6‐aryl substituents
Authors: Southwick Philip L. , Madhav R. , Fitzgerald James A. 
Published: May 2009

AbstractMethods are described for the synthesis of 6,7‐dihydro‐5H‐pyrrolo[3,4‐d]pyrimidines having an aryl substituent in the 6‐position. 4‐Hydroxy‐, 4‐amino, 2‐amino‐4‐hydroxy and 2,4‐diamino derivatives were obtained. The synthetic route involved the preparation of 1‐aryl‐4‐cyano‐ or 4‐carboalkoxy‐3‐pyrrolidinones and 1‐aryl‐4‐cyano‐ or 4‐carboalkoxy‐3‐amino‐3‐pyrrolines as key intermediates.
The NMR spectra of some substituted dibenzothiophenes
Authors: Campaigne E. , Ashby John 
Published: May 2009

AbstractIn order to use the NMR spectra of dibenzothiophenes to determine the position of substitution, a series of compounds has been prepared, most of which are new while some represent an improved method of preparation of previously reported compounds. With the exception of one, the structures of the compounds prepared were not in doubt, however the splitting patterns and chemical shifts presented here will facilitate future structure determinations of dibenzothiophenes.
The hydroxyacetylpiperidines and their N‐benzyl derivatives. The 2‐hydroxymethyl‐2‐piperidyl‐ and 2‐hydroxymethyl‐2‐pyridyl‐1,3‐dioxolanes
Authors: Nielsen Arnold T. , Platt Ernest N. 
Published: May 2009

AbstractThe hydroxyacetylpiperidines, their ethylene ketals, and the N‐benzyl derivatives of these new piperidines have been synthesized. Methylolation of 2‐(2‐ and 4‐pyridyl)‐1,3‐dioxolanes by heating with paraformaldehyde at 185° led to 2‐hydroxymethyl‐2‐(2‐ and 4‐pyridyl)‐i,3‐dioxolanes (7,8, respectively). 2‐Hydroxymethyl‐2‐(3‐pyridyl)‐1,3‐dioxolane (13) was obtained by reaction of 2‐bromomethyl‐2‐(3‐pyridyl)‐1,3‐dioxolane with aqueous sodium hydroxide at 190°. Hydrogenation of these pyridine ketals with rhodium‐charcoal catalyst produced the corresponding piperidine ketals (16,17,18). Acid hydrolysis of the piperidine ketals and their N‐benzyl derivatives led to the hydroxyacetylpiperidines (1,2,3) and their N‐benzyl derivatives (25,26,27). The N‐benzylhydroxyacetylpiperidines undergo rapid hydrogenolysis with palladium‐charcoal catalyst to produce the hydroxyacetylpiperidines. Further hydrogenation produces the piperidyl‐1,2‐ethanediols. The hydroxyacetylpiperidines are somewhat unstable, hygroscopic substances which polymerize with dehydration on standing; in solution they are relatively stable. Their N‐benzyl, ketal, and hydrochloride salt derivatives, on the other hand, represent stable, synthetically useful intermediates from which the reactive trifunctional hydroxyacetylpiperidines may readily be prepared.
Some reactions of 5‐methyl‐11H‐isoindolo[2,1‐α] benzimidazolium salts
Authors: Irick Gether 
Published: May 2009

Abstract5‐Methyl‐11H‐isoindolo[2,1‐α]benzirnidazolium halide (IV), obtained by direct quaternization of the precursor III, underwent facile condensation reactions at its 11‐methylene group similar to those of 11H‐isoindolo[1,2‐b]benzothiazolium cation II. Although the treatment of II with alkali regenerated its precursor I, treatment of IV with alkali caused ring opening to a phthalimidine. Attempted thermal cyclization of 2‐(alkylaminophenyl)phthalimidines, e.g., VII, resulted in dealkylation to produce III.