http://www.chemistrycentral.com/ The latest research articles published by Chemistry Central 2012-02-21T00:00:00Z A validated simple, rapid, sensitive and specific square-wave voltammetric technique is described for the determination of acebutolol (AC) following its accumulation onto a hanging mercury drop electrode in a Britton-Robinson universal buffer of pH 7.5. The optimal procedural conditions were: accumulation potential Eacc = 0.8 V versus Ag/AgCl/KCl, accumulation duration tacc = 30 s, pulse-amplitude = 70 mV, scan rate = 100 mV/s, frequency = 30 Hz, surface area of the working electrode = 0.6 mm2 and the convection rate = 2000 rpm. Under these optimized conditions, the adsorptive stripping voltammetry (AdSV) peak current was proportional over the concentration range 5 x 10^-7 - 6 x 10^-6 M (r = 0.999). Recoveries for acebutolol from human plasma and urine were in the range 97-103 % and 96-104 % respectively. The method proved to be precise (intra-day precision expressed as %RSD in human plasma ranged from 2.9 - 3.2 % and inter-day precision expressed as %RSD ranged from 3.4 - 3.8 %) and accurate (intra-day accuracies expressed as % error in human urine ranged from -3.3 - 2.8 % and inter-day accuracies ranged from -3.3 - 1.7 %). The limit of quantitation (LOQ) and limit of detection (LOD) for acebutolol were 1.7 x 10^-7 and 5 x 10^-7 M, respectively. Possible interferences by substances usually present in the pharmaceutical formulations were investigated with a mean recovery of 101.6 +/- 0.64%. Results of the developed square-wave adsorptive stripping voltammetry (SW-AdSV) method were comparable with those obtained by reference analytical method. http://www.journal.chemistrycentral.com/content/6/1/15 Ali F Al-Ghamdi Mohamed M Hefnawy Abdulrahman A Al-Majed Fatallah F Belal Chemistry Central Journal 2012, 6:15 2012-02-21T00:00:00Z ${item.identifier} /content/figures/1752-153X-6-15-toc.gif Chemistry Central Journal 1752-153X 6 15 2012-02-21T00:00:00Z PDF Adsorption of methylene blue (MB) on agar was investigated as a function of temperature (308-328 K), different concentrations of NaCl and HCl and various weight percentages of binary mixtures of ethanol with water. It was observed that the maximum experimental adsorption capacity, qm,exp, in water is up to 50 mg g-1 and decreases with increase in weight percentage of ethanol and NaCl and HCl concentration compared to that of water. Analysis of data using ARIAN model showed that MB adsorbs as monomer and dimer on the surface of agar. Binding constants of MB to agar were calculated using the Temkin isotherm. The process is exothermic in water and other solutions. The mean adsorption energy (E) value indicated binding of MB to agar is chemical adsorption. Kinetics of this interaction obeys from the pseudo-second-order model and diffusion of the MB molecules into the agar is the main rate-controlling step. http://www.journal.chemistrycentral.com/content/6/1/14 Babak Samiey Fatemeh Ashoori Chemistry Central Journal 2012, 6:14 2012-02-17T00:00:00Z ${item.identifier} /content/figures/1752-153X-6-14-toc.gif Chemistry Central Journal 1752-153X 6 14 2012-02-17T00:00:00Z PDF A new simple, rapid and sensitive reversed-phase liquid chromatographic method was developed and validated for the simultaneous determination of sulpiride (SUL) and mebeverine Hydrochloride (MEB) in the presence of their impurities and degradation products. The separation of these compounds was achieved within 6 min on a 250 mm, 4.6 mm i.d., 5 m particle size Waters(R)-C18 column using isocractic mobile phase containing a mixture of acetonitrile and 0.01 M dihydrogenphosphate buffer (45:55) at pH = 4.0. The analysis was performed at a flow rate of 1.0 mL/ min with fluorescence-detection at excitation 300 nm and emission at 365 nm. The concentration-response relationship was linear over a concentration range of 10- 100 ng/ mL for both MEB and SUL with a limit of detection 0.73 ng/ mL and 0.85 ng/ mL for MEB and SUL respectively. The proposed method was successfully applied for the analysis of both MEB and SUL in bulk with average recoveries of 100.22 +/- 0.757% and 99.96 +/- 0.625% respectively, and in commercial tablets with average recoveries of 100.04 +/- 0.93% and 100.03 +/- 0.376% for MEB and SUL respectively. The proposed method was successfully applied to the determination of MEB metabolite (veratic acid) in real plasma simultaneously with SUL. The mean% recoveries (n=3) for both MEB metabolite (veratic acid) and SUL were 100.36 +/- 2.92 and 99.06 +/- 2.11 for spiked human plasma respectively. For real human plasma, the mean% recoveries (n=3)for both MEB metabolite (veratic acid) and SUL were 89.41 and 91.40 respectively. http://www.journal.chemistrycentral.com/content/6/1/13 Mohamed I. Walash Mohie M. KH. Sharaf El-din Nahed M. El-enany Manal I. Eid Shereen M. Shalan Chemistry Central Journal 2012, 6:13 2012-02-14T00:00:00Z ${item.identifier} /content/figures/1752-153X-6-13-toc.gif Chemistry Central Journal 1752-153X 6 13 2012-02-14T00:00:00Z PDF Background: One of the largest challenges in chemistry today remains that of efficiently mining through vast amounts of data in order to elucidate the chemical structure for an unknown compound. The elucidated candidate compound must be fully consistent with the data and any other competing candidates efficiently eliminated without doubt by using additional data if necessary. It has become increasingly necessary to incorporate an in silico structure generation and verification tool to facilitate this elucidation process. An effective structure elucidation software technology aims to mimic the skills of a human in interpreting the complex nature of spectral data while producing a solution within a reasonable amount of time. This type of software is known as computer-assisted structure elucidation or CASE software. A systematic trial of the ACD/Structure Elucidator CASE software was conducted over an extended period of time by analysing a set of single and double-blind trials submitted by a global audience of scientists. The purpose of the blind trials was to reduce subjective bias. Double-blind trials comprised of data where the candidate compound was unknown to both the submitting scientist and the analyst. The level of expertise of the submitting scientist ranged from novice to expert structure elucidation specialists with experience in pharmaceutical, industrial, government and academic environments. Results: Beginning in 2003, and for the following nine years, the algorithms and software technology contained within ACD/Structure Elucidator have been tested against 112 data sets; many of these were unique challenges. Of these challenges 9% were double-blind trials. The results of eighteen of the single-blind trials were investigated in detail and included problems of a diverse nature with many of the specific challenges associated with algorithmic structure elucidation such as deficiency in protons, structure symmetry, a large number of heteroatoms and poor quality spectral data. Conclusion: When applied to a complex set of blind trials, ACD/Structure Elucidator was shown to be a very useful tool in advancing the computer's contribution to elucidating a candidate structure from a set of spectral data (NMR and MS) for an unknown. The synergistic interaction between humans and computers can be highly beneficial in terms of less biased approaches to elucidation as well as dramatic improvements in speed and throughput. In those cases where multiple candidate structures exist, ACD/Structure Elucidator is equipped to validate the correct structure and eliminate inconsistent candidates. Full elucidation can generally be performed in less than two hours; this includes the average spectral data processing time and data input. http://www.jcheminf.com/content/4/1/5 Arvin Moser Mikhail E Elyashberg Antony J Williams Kirill A Blinov Joseph C DiMartino Journal of Cheminformatics 2012, 4:5 2012-02-09T00:00:00Z 10.1186/1758-2946-4-5 /content/figures/1758-2946-4-5-toc.gif Journal of Cheminformatics 1758-2946 4 5 2012-02-09T00:00:00Z PDF Background: The current chemical space of known small molecules is estimated to exceed 10^60 structures. Though the largest physical compound repositories contain only a few tens of millions of unique compounds, virtual screening of databases of this size is still difficult. In recent years, the application of physicochemical descriptor-based profiling, such as Lipinski's rule-of-five for drug-likeness and Oprea's criteria of lead-likeness, as early stage filters in drug discovery has gained widespread acceptance. In the current study, we outline a kinase-likeness scoring function based on known kinase inhibitors. Results: The method employs a collection of 22,615 known kinase inhibitors from the ChEMBL database. A kinase-likeness score is computed using statistical analysis of nine key physicochemical descriptors for these inhibitors. Based on this score, the kinase-likeness of four publicly and commercially available databases, i.e., National Cancer Institute database (NCI), the Natural Products database (NPD), the National Institute of Health's Molecular Libraries Small Molecule Repository (MLSMR), and the World Drug Index (WDI) database, is analyzed. Three of these databases, i.e., NCI, NPD, and MLSMR are frequently used in the virtual screening of kinase inhibitors, while the fourth WDI database is for comparison since it covers a wide range of known chemical space. Based on the kinase-likeness score, a kinase-focused library is also developed and tested against three different kinase targets selected from three different branches of the human kinome tree. Conclusions: Our proposed methodology is one of the first that explores how the narrow chemical space of kinase inhibitors and its relevant physicochemical information can be utilized to build kinase-focused libraries and prioritize pre-existing compound databases for screening. We have shown that focused libraries generated by filtering compounds using the kinase-likeness score have, on average, better docking scores than an equivalent number of randomly selected compounds. Beyond library design, our findings also impact the broader efforts to identify kinase inhibitors by screening pre-existing compound libraries. Currently, the NCI library is the most commonly used database for screening kinase inhibitors. Our research suggests that other libraries, such as MLSMR, are more kinase-like and should be given priority in kinase screenings. http://www.jcheminf.com/content/4/1/4 Narender Singh Hongmao Sun Sidhartha Chaudhury Mohamed DM AbdulHameed Anders Wallqvist Gregory Tawa Journal of Cheminformatics 2012, 4:4 2012-02-08T00:00:00Z 10.1186/1758-2946-4-4 /content/figures/1758-2946-4-4-toc.gif Journal of Cheminformatics 1758-2946 4 4 2012-02-08T00:00:00Z PDF The abundant iron sulfide mineral pyrite has been shown to catalytically produce hydrogen peroxide (H2O2) and hydroxyl radical (.OH) in slurries of oxygenated water. Understanding the formation and fate of these reactive oxygen species is important to biological and ecological systems as exposure can lead to deleterious health effects, but also in environmental engineering during the optimization of remediation approaches for possible treatment of contaminated waste streams. This study presents the use of the amino acid phenylalanine (Phe) to monitor the kinetics of pyrite-induced .OH formation through rates of hydroxylation forming three isomers of tyrosine (Tyr) - ortho-, meta-, and para-Tyr. Results indicate that about 50% of the Phe loss results in Tyr formation, and that these products further react with .OH at rates comparable to Phe. The loss of Phe appeared to be pseudo first-order in [Phe] as a function of time, but for the first time showed that rates were much less than first-order as a function of initial substrate concentration, [Phe]. These results can be rationalized by considering that the effective concentration of .OH in solution is lower at higher level of reactant and that an increasing fraction of .OH is consumed by Phe-degradation products as a function of time. A simplified first-order model was created to describe Phe loss in pyrite slurries which incorporates the initial [Phe], a first-order dependence on pyrite surface area, the assumption that all Phe degradation products compete equally for the limited supply of highly reactive .OH, and a flux that is related to the release of H2O2 from the pyrite surface through the Fenton reaction. An empirically derived rate constant, Kpyr, was introduced to describe a variable .OH-reactivity for different batches of pyrite. Both the simplified first-order kinetic model, and a more detailed numerical simulation, yielded results that compare well to the observed kinetic data describing the effects of variations in concentrations of both initial [Phe] and pyrite. This work supports the use of Phe as a useful probe to assess the formation of .OH in the presence of pyrite, and its possible utility for similar applications with other minerals. http://www.geochemicaltransactions.com/content/13/1/3 Shawn C Fisher Martin AA Schoonen Bruce J Brownawell Geochemical Transactions 2012, 13:3 2012-02-07T00:00:00Z 10.1186/1467-4866-13-3 /content/figures/1467-4866-13-3-toc.gif Geochemical Transactions 1467-4866 13 3 2012-02-07T00:00:00Z PDF Background: Sonchus asper (SA) is traditionally used for the treatment of various ailments associated with liver, lungs and kidneys. This study was aimed to investigate the therapeutic potential of nonpolar (hexane, SAHE; ethyl acetate, SAEE and chloroform, SACE) and polar (methanol, SAME) crude extracts of the whole plant. Methods: To achieve these goals, several parameters including free-radical (DPPH * , ABTS * +, H2O2 and * OH) scavenging, iron chelating activity, scavenging of superoxide radicals, total flavonoids and total phenolic content (TPC) were examined. Results: The SA extracts presented a remarkable capacity to scavenge all the tested reactive species with IC50 values being found at the ug ml level. The SAME was shown to have the highest TPCs while lowest IC50 values for the DPPH * , ABTS * + radical scavenging capacities and iron chelating scavenging efficiency, moreover, SAME had best activities in scavenging of superoxide radicals and hydrogen peroxide as well as potently scavenged the hydroxyl radicals. Conclusion: These results suggest the potential of S. asper as a medicine against free-radical-associated oxidative damage. http://www.journal.chemistrycentral.com/content/6/1/12 Rahmat Ali Khan Muhammad Rashid Khan Sumaira Sahreen Mushtaq Ahmed Chemistry Central Journal 2012, 6:12 2012-02-06T00:00:00Z 10.1186/1752-153X-6-12 /content/figures/1752-153X-6-12-toc.gif Chemistry Central Journal 1752-153X 6 12 2012-02-06T00:00:00Z PDF The first RNA World models were based on the concept of an RNA replicase - a ribozyme that was a good enough RNA polymerase that it could catalyze its own replication. Although several RNA polymerase ribozymes have been evolved in vitro, the creation of a true replicase remains a great experimental challenge. At first glance the alternative, in which RNA replication is driven purely by chemical and physical processes, seems even more challenging, given that so many unsolved problems appear to stand in the way of repeated cycles of non-enzymatic RNA replication. Nevertheless the idea of non-enzymatic RNA replication is attractive, because it implies that the first heritable functional RNA need not have improved replication, but could have been a metabolic ribozyme or structural RNA that conferred any function that enhanced protocell reproduction or survival. In this review, I discuss recent findings that suggest that chemically driven RNA replication may not be completely impossible. http://www.jsystchem.com/content/3/1/2 Jack W Szostak Journal of Systems Chemistry 2012, 3:2 2012-02-03T00:00:00Z ${item.identifier} The path to non-enzymatic RNA replication The original RNA World model is based on the concept of an RNA replicase. However, non-enzymatic RNA replication overcomes some of the problems with this model, and recent findings suggesting that this may have been possible are discussed in this Perspective /content/figures/1759-2208-3-2-toc.gif Journal of Systems Chemistry 1759-2208 3 2 2012-02-03T00:00:00Z PDF This study represents the first report on the development of a novel spectrophotometric method for determination of cinacalcet hydrochloride (CIN) in its tablet dosage forms. Studies were carried out to investigate the reaction between CIN and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 8.5), an orange red-colored product exhibiting maximum absorption peak (lambdamax) at 490 nm was produced. The stoichiometry and kinetic of the reaction were investigated and the reaction mechanism was postulated. This color-developing reaction was employed in the development of a simple and rapid visible-spectrophotometric method for determination of CIN in its tablets. Under the optimized reaction conditions, Beer's law correlating the absorbance with CIN concentration was obeyed in the range of 3 - 100 ug/ml with good correlation coefficient (0.9993). The molar absorptivity (epsilon) was 4.2x105 l/mol/cm. The limits of detection and quantification were 1.9 and 5.7 ug/ml, respectively. The precision of the method was satisfactory; the values of relative standard deviations (RSD) did not exceed 2%. No interference was observed from the excipients that are present in the tablets. The proposed method was applied successfully for the determination of CIN in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 100.80 - 102.23 +/- 1.27 - 1.62%. The results were compared favorably with those of a reference pre-validated method. The method is practical and valuable in terms of its routine application in quality control laboratories. http://www.journal.chemistrycentral.com/content/6/1/11 Ibrahim A Darwish Mona M Al-Shehri Manal A El-Gendy Chemistry Central Journal 2012, 6:11 2012-02-03T00:00:00Z 10.1186/1752-153X-6-11 Determining cinacalcet content in tablets A novel spectrophotometric quality control method has been reported for the determination of pharmaceutical doses of cinacalcet hydrochloride, a selective calcimimetic agent used to treat hyperparathyroidism and hypercalcemia /content/figures/1752-153X-6-11-toc.gif Chemistry Central Journal 1752-153X 6 11 2012-02-03T00:00:00Z PDF Background: Representations of chemical datasets in spreadsheet format are important for ready data assimilation and manipulation. In addition to the normal spreadsheet facilities, chemical spreadsheets need to have visualisable chemical structures and data searchable by chemical as well as textual queries. Many such chemical spreadsheet tools are available, some operating in the familiar Microsoft Excel environment. However, within this group, the performance of Excel is often compromised, particularly in terms of the number of compounds which can usefully be stored on a sheet.SummaryLICSS is a lightweight chemical spreadsheet within Microsoft Excel for Windows. LICSS stores structures solely as Smiles strings. Chemical operations are carried out by calling Java code modules which use the CDK, JChemPaint and OPSIN libraries to provide cheminformatics functionality. Compounds in sheets or charts may be visualised (individually or en masse), and sheets may be searched by substructure or similarity. All the molecular descriptors available in CDK may be calculated for compounds (in batch or on-the-fly), and various cheminformatic operations such as fingerprint calculation, Sammon mapping, clustering and R group table creation may be carried out.We detail here the features of LICSS and how they are implemented. We also explain the design criteria, particularly in terms of potential corporate use, which led to this particular implementation. Conclusions: LICSS is an Excel-based chemical spreadsheet with a difference:* It can usefully be used on sheets containing hundreds of thousands of compounds; it doesn't compromise the normal performance of Microsoft Excel* It is designed to be installed and run in environments in which users do not have admin privileges; installation involves merely file copying, and sharing of LICSS sheets invokes automatic installation* It is free and extensibleLICSS is open source software and we hope sufficient detail is provided here to enable developers to add their own features and share with the community. http://www.jcheminf.com/content/4/1/3 Kevin R Lawson Jonty Lawson Journal of Cheminformatics 2012, 4:3 2012-02-02T00:00:00Z 10.1186/1758-2946-4-3 A chemical spreadsheet in Excel A lightweight open source chemical spreadsheet has been developed that runs within Microsoft Excel and can be used on sheets containing hundreds of thousands of compounds without compromising normal performance /content/figures/1758-2946-4-3-toc.gif Journal of Cheminformatics 1758-2946 4 3 2012-02-02T00:00:00Z PDF