bluuebunny/crossref_metadata_2025 huggingface dataset:
New insights into the mechanism of molybdenum-catalyzed asymmetric alkylation
Authors: Krska S. W. , Hughes D. L. , Reamer R. A. , Mathre D. J. , Palucki M. , Yasuda Nobuyoshi , Sun Y. , Trost B. M.
Published: October 2007

The major features of the catalytic cycle, including structures of key intermediates, have been determined for the molybdenum-catalyzed asymmetric alkylation. The crystal structure of the π-allyl intermediate exhibits 3-point binding of an anionic ligand. Based on NMR analysis, this species adopts in solution a structure consistent with that observed in the solid state. For the allylic alkylation, the crystal structure predicts the opposite stereochemistry vs. that observed experimentally, which suggests that either the reaction proceeds via a minor isomer (Curtin-Hammett conditions) or with retention of configuration. In addition, CO transfer, promoted by Mo(CO)6, has been found to play a key role in catalyst turnover.
Recent advances in catalyst immobilization using supercritical carbon dioxide
Authors: Leitner Walter
Published: October 2007

Homogeneous organometallic catalysts have a great potential for the development of sustainable synthetic processes. There is, however, an urgent need for the development of new techniques to separate products and catalysts efficiently, allowing for recycling and reuse of the precious catalyst. The unique solvent properties of supercritical carbon dioxide offer new approaches for the immobilization of organometallic catalysts, many of which are suitable for efficient continuous-flow operation. Recent research in this field tries to combine the molecular nature of organometallic catalysts with the reaction-engineering aspect of multiphase catalysis.
Substrate scope in the olefin cyclopropanation reaction catalyzed by m-oxo-bis[(salen)iron(III)] complexes
Authors: Edulji S. K. , Nguyen S. T.
Published: October 2007

The cyclopropanation of various alkenes with different diazoester compounds was investigated using two different μ-oxo-bis[(salen)iron(III)] complexes, [Fe(3,3',5,5'-
t
Bu4salen)]2O and [Fe(salen)]2O. Ethyl diazoacetate (EDA), tert-butyl diazoacetate (
t
BDA), and ethyl diazoacetoacetate (EDAA) were used with mono- and disubstituted terminal olefins (styrene and 1,1-diphenyl ethylene, respectively), internal olefin (trans-β-methyl styrene), and an electron-rich alkene (n-butyl vinyl ether). Moderate-to-good cyclopropanation yields were obtained for most substrates.
Recent advances in transition metal-catalyzed or -mediated cyclization of 2,3-allenoic acids: New methodologies for the synthesis of butenolides
Authors: Ma S.
Published: October 2007

The cyclization reactions of 2,3-allenoic acids or their salts with optically active bases affording butenolides are discussed. Two reaction pathways were observed: (1) intermolecular carbometallation-intramolecular allylation; (2) cyclic oxymetallation-reductive elimination. High efficiency of chirality transfer was realized with the latter case.
3-Halopropenyl esters as precursors of a new class of oxygen-substituted allylic organometallic compounds: Applications in organic synthesis
Authors: Lombardo Marco , Licciulli Sebastiano , Trombini C.
Published: October 2007

3-halopropenyl esters, readily prepared by the addition of acyl halides to acrolein, react with zinc, indium, and chromium(II), thus opening a route to a new class of oxygen-substituted allylic organometallic compounds. Indium and zinc reagents smoothly add to carbonyl compounds, affording alk-1-en-3,4-diol derivatives in a variety of synthetic procedures which include typical Grignard stepwise conditions as well as Barbier one-pot protocols. Using zinc and indium in water or aprotic solvents, simple diastereoselectivity was found to depend on the nature of the carbonyl compound; conjugated aldehydes favor formation of syn-adducts while unconjugated aldehydes favor anti-adducts. Moving to chromium, a reversal of regioselectivity was observed in favor of (Z)-4-hydroxy-enolacetates, flexible protected forms of homoaldols. Chromium complexes are generated in a catalytic cycle based on the combined use of the redox Mn(0)/Cr(III) couple and of TMSCl. When the Cr-catalyzed reaction is carried out in the presence of Jacobsen's Salen ligand, the regiochemical outcome of the reaction is again reversed, and syn-alk-1-en-3,4-diols are formed in high ee's.
Palladium-catalyzed alkylation of unactivated olefins
Authors: Widenhoefer Ross A.
Published: October 2007

The reaction of a 3-butenyl β-diketone with a catalytic amount of PdCl2(CH3CN)2 in dioxane at room temperature led to olefin hydroalkylation and formation of the corresponding 2-acylcyclohexanone in good yield as a single regioisomer. Deuterium-labeling experiments for the hydroalkylation of 7-octene-2,4-dione were in accord with a mechanism involving outer-sphere attack of the pendant enol on a palladium-complexed olefin to form a palladium cyclohexyl species, followed by palladium migration via iterative β-hydride elimination/addition and protonolysis from a palladium enolate complex. In comparison to a 3-butenyl β-diketone, reaction of a 4-pentenyl β-diketone with a catalytic amount of PdCl2(CH3CN)2 in the presence of CuCl2 led to oxidative alkylation and formation of the corresponding 2-acyl-3-methyl-2-cyclohexenone in good yield as a single isomer. Unactivated olefins tethered to less reactive carbon nucleophiles such as β-keto esters, α-aryl ketones, and even dialkyl ketones underwent palladium-catalyzed hydroalkylation in the presence of Me3SiCl or HCl to form the corresponding cyclohexanones in moderate-to-good yield with high regioselectivity.
Heterogeneous asymmetric catalysis
Authors: Lemaire Marc
Published: October 2007

Examples of enantioselective catalysts, including homogeneous supported catalysts and biphasic liquid/liquid, are described and compared. In the case of asymmetric hydride transfer, polythiourea was proven to be more efficient for ruthenium-catalyzed reduction of arylketones, although the iridium complexes gave rise to higher ee when using amino sulfonamide bound to a polystyrene matrix. In the case of asymmetric reduction, the modification of the binap allows the formation of a polymer that could be used as a catalyst precursor and exhibits enantioselectivities as high as observed in solution, but easier to separate and recycle. Bisoxazoline bound to silica particules could also be used in copper-catalyzed asymmetric Diels-Alder reaction and cyclopropanation with selectivities similar to that obtained in solution.
Stereoselective chromium- and molybdenum-mediated transformations of arenes
Authors: Kündig E. P. , Cannas Rita , Fabritius C.-H. , Grossheimann Gabriele , Kondratenko Mikhail , Laxmisha Mundruppady , Pache S. , Ratni H. , Robvieux F. , Romanens P. , Tchertchian S.
Published: October 2007

Tricarbonylchromium-mediated dearomatization provides a rapid access to substituted cyclohexadienes. Efficient asymmetric routes to planar chiral arene complexes and to substituted cyclohexadienes have been developed. The article sums up the main features of this chemistry. Highly enantiomerically enriched ortho-substituted benzaldehyde complexes are accessible via asymmetric lithiation followed by trapping with electrophiles. In different solvents, the trimethylsilyl complex exhibits [alpha] values ranging from −174 to +108 for the same enantiomer. Details of two asymmetric syntheses of natural products are given: the alkaloid lasubine I starting from a highly enantiomerically enriched planar chiral arene complex and the marine furanosesquiterpene acetoxytubipofuran. The latter is assembled via asymmetric dearomatization of a benzaldehyde imine complex. Other key steps include an Eschenmoser–Claisen rearrangement and a regio- and diastereoselective Pd-catalyzed allylic substitution. The final section deals with labile arene metal complexes. For the first time, dearomatization reactions mediated by the Mo(CO)3 group have been realized. The reactions show strong analogies to the Cr(CO)3-mediated reactions, but exhibit also marked differences: the arene–Mo bond is stronger, but more labile, and the sequential double additions show different selectivities compared to the chromium analogs.
Voltammetry of drugs at the interface between two immiscible electrolyte solutions
Authors: Alemu Hailemichael
Published: October 2007

In this review, the results of the electrochemical investigations made on the transfer of ionizable drugs at the interface between two immiscible electrolyte solutions (ITIES) in the last decade have been presented. In many of the studies, cyclic voltammetry has been used to investigate the transfer characteristics of the charged species and deduce their partition coefficients, which are very important parameters to infer the lipophilicity of drugs in biological systems. The electrochemical technique allows the precise determination of the distribution of ionic species between two phases in a wider pH range. Such studies point out the complexity of the distribution of ionizable compounds and offer a new approach to relate the structure of such compounds to their passive transport across biological membranes.
Why liquid membrane extraction is an attractive alternative in sample preparation
Authors: Chimuka Luke , Cukrowska Ewa , Jönsson J. Å.
Published: October 2007

The use of liquid membrane-based extractions is increasingly seen as offering an alternative to conventional sample preparation procedures in analysis of chemical species in both environmental and biological media. In this article, emphasis is placed on the attractiveness of liquid membrane-based extraction techniques to a variety of analytical applications such as speciation of metal ions in biological fluids, time-weighted average field sampling, and time-weighted average passive field sampling. Further, the area of designing new and much simpler miniaturized configurations, which is enjoying much attention in liquid membrane-based extraction techniques, is discussed.
Biosensors for environmental applications: Future development trends
Authors: Rodriguez-Mozaz S. , Marco M.-P. , de Alda M. J. Lopez , Barceló D.
Published: October 2007

Biosensors can be excellent analytical tools for monitoring programs working to implement legislation. In this article, biosensors for environmental analysis and monitoring are extensively reviewed. Examples of biosensors for the most important families of envi-ronmental pollutants, including some commercial devices, are presented. Finally, future trends in biosensor development are discussed. In this context, bioelectronics, nanotechnology, miniaturization, and especially biotechnology seem to be growing areas that will have a marked influence on the development of new biosensing strategies in the next future.
Protein adsorption to planar electrochemical sensors and sensor materials
Authors: Lim Caroline , Slack S. , Ufer S. , Lindner E.
Published: October 2007

In electrochemical sensing devices, aimed for acute and chronic in vivo application, the active surface of the sensor is often negligible compared to the overall surface area of the device in contact with the biological host. Consequently, to minimize the perturbation of an implanted sensor on the in vivo environment the chemical composition and surface texturing of the complete device (the active sensor, sensor substrate, and “accessories”) have to be considered. In our work, the adsorption of three abundant proteins (albumin, IgG, and fibrinogen) was determined quantitatively on untreated and modified sensor substrates and sensing membrane surfaces. In this study, a flexible polyimide-based material (Kapton ®) was used as sensor substrate with or without an amorphous diamond-like carbon (DLC) or an amorphous oxygen-containing DLC (o-DLC) coating. The ion-sensitive membranes were cast from high-molecular-weight (HMW) or carboxylated poly(vinyl chloride) (PVC) and were doped with increasing concentrations of highly hydrophilic poly(ethylene oxide) (PEO). The potentiometric characteristics of the potassium-selective membranes cast with up to 6 % PEO were the same as those without PEO. However, the PEO-modified PVC membranes elicited a large amount of protein adsorption, especially in terms of albumin.
Glutamate oxidase advances in the selective bioanalytical detection of the neurotoxic amino acid β-ODAP in grass pea: A decade of progress
Authors: Moges G. , Wodajo N. , Gorton L. , Yigzaw Yirgalem , Kalcher Kurt , Belay Abebaw , Akalu Girma , Nair B. M. , Solomon T.
Published: October 2007

The search for an enzyme as a reagent for selective bioanalytical detection of the neurotoxic amino acid, β-N-oxalyl L-alpha, β-diaminopropionic acid, β-ODAP (found in grass pea, Lathyrus sativus) led to its redox catalytic reaction by glutamate oxidase (GluOx). Homogeneous kinetic studies and an immobilized GluOx reactor-based flow-injection assay were initially made for beta-ODAP with small immobilized GluOx/catalase glutamate destroying prereactors. The method was applied to examine the toxin content in processed grass pea. The kinetics and the equilibrium of the thermal isomerization of β-ODAP to the nontoxic isomer α-ODAP established that GluOx is specific to the neurotoxin. The first ever GluOx-based amperometric biosensor for liquid chromatography (LC) detection was reported in 1997. This biosensor coupled with a refractive index detector improved LC performance. The most recent work with GluOx resulted in MnO2-based screen-printed amperometric biosensor, with offline elimination of glutamate interference by glutamate decarboxylase. A single-shot chemiluminescent sensor developed for hydrogen peroxide is also proposed for β-ODAP with GluOx application. This decade of progress resulted from studies that included four Ph.D. (Ethiopia, Sweden, Austria), four M.Sc. (Ethiopia, Sweden) and Licentiate (Sweden) theses projects, plus one collaborative project in Sweden. The advances in grass pea research may be regarded as a model north–south cooperation for research and education.
Immobilized peptides/amino acids on solid supports for metal remediation
Authors: Malachowski Lisa , Stair J. L. , Holcombe J. A.
Published: October 2007

Recently,a significant amount of work has focused on metal binding by natural systems for various applications. This review will focus on the utility of amino acids, short peptides, and proteins that have been immobilized onto solid supports for use in metal binding. These systems include single amino acids, poly-amino acids, and peptides immobilized onto supports such as silica, polymer resins, and membranes. Also included are the studies involving the use of immobilized amino acids in ion-exchange chromatography.
Electrochemistry and application of a novel monosubstituted squarate electron-transfer mediator in a glucose oxidase-doped poly(phenol) sensor
Authors: Iwuoha E. I. , Williams-Dottin A. R. , Hall L. A. , Morrin A. , Mathebe G. N. , Smyth M. R. , Killard Anthony
Published: October 2007

Electrosynthetic poly(phenol) nanofilms were deposited in situ on platinum electrodes in the presence and absence of glucose oxidase. The synthesis charges and currents of the nonconducting polymer films were recorded at various applied potentials for films grown from 25 –100 mM phenol concentrations. Film parameters such as the standard rate constant for film deposition, film thickness, and surface concentration of the poly(phenol) films were evaluated from the cyclic and step voltammograms of the polymerization process. A novel electron-transfer mediator consisting of monosubstituted 4-hydroxycyclobut-3-ene-1,2-dione (squarate) was used as a mediator for Pt/poly(phenol) nanofilm/GOx amperometric glucose biosensors. Amperometric responses for 3-diphenylamino-4-hydroxycyclobut-3-ene-1,2-dione (diphenylaminosquarate: E°'=of +328 mV/Ag-AgCl at pH 7.0)-mediated systems were measured by both steady-state amperometric and cyclic voltammetry. The sensor sensitivity was calculated to be 558 nA cm−2 (µM)−1.
Use of phytofiltration technologies in the removal of heavy metals: A review
Authors: Gardea-Torresdey J. L. , de la Rosa G. , Peralta-Videa J. R.
Published: October 2007

Biosorption is a relatively new process that has proven very promising in the removal of contaminants from aqueous effluents. Microorganisms as well as plant- and animal-derived materials have been used as biosorbents by many researchers. Biomaterial immobilization and chemical modification improves the adsorption capacity and stability of biosorbents. Biosorption experiments over Cu(II), Cd(II), Pb(II), Cr(III), and Ni(II) demonstrated that biomass Cu(II) adsorption ranged from 8.09 to 45.9 mg g−1, while Cd(II) and Cr(VI) adsorption ranged from 0.4 to 10.8 mg g−1 and from 1.47 to 119 mg g−1, respectively. Mechanisms involved in the biosorption process include chemisorption, complexation, surface and pore adsorption-complexation, ion exchange, microprecipitation, hydroxide condensation onto the biosurface, and surface adsorption. Chemical modification and spectroscopic studies have shown that cellular components including carboxyl, hydroxyl, sulfate, sulfhydryl, phosphate, amino, amide, imine, and imidazol moieties have metal binding properties and are therefore the functional groups in the biomass. Column studies using support matrices for biomass immobilization such as silica, agar, polyacrilamide, polysulfone, alginates, cellulase, and different cross-linking agents have been performed to improve the biomass adsorption capacity and reusability. In this review, the salient features of plant-derived materials are highlighted as potential phytofiltration sources in the recovery of toxic heavy and precious metals.
Selective control and rate enhancement of reactions involving catalytic reduction of organohalides and reduced form of myoglobulin in microemulsions
Authors: Kamau G. N. , Munge B.
Published: October 2007

Myoglobin (horse heart, Mb) adsorbed on carbon electrodes or in solution at platinum electrodes was used for electrocatalytic reduction of trans-1,2-dibromocyclohexane (DBCH) and trichloroacetic acid (TCA) in a bicontinuous microemulsion, prepared from sodium didodecyl sulfate (SDS) or hexadecyltrimethylammonium bromide (CTAB), tetradecane, pentanol, and water. Carbon electrodes (glassy carbon, GC, and pyrolytic graphite, PG) exhibited adsorption peaks, whereas platinum (Pt) portrayed diffusion-controlled peaks. Electrode reduction of Mb had E0' at −0.179 ± 0.013 V at GC/SDS, −0.189 ± 0.015 at GC/CTAB, and −0.562 ± 0.018 at Pt/SDS and 0.611 ± 0.008 at Pt/CTAB media.Current efficiencies for electrocatalytic reduction of TCA were higher than that for reduction of dibromocyclohexane. For both substrates, dibromocyclohexane and trichhloroacetic acid, a lowering of overpotential of at least 1.3 V was achieved. Overall, the Pt electrode exhibited higher catalytic efficiencies compared to carbon electrodes, suggesting higher surface concentration and unhindered orientation of the substrate on the Pt electrode. For DBCH, catalytic efficiencies decreased with scan rate, at carbon electrodes as expected for homogeneous solutions, whereas an average value of 2.22 ± 0.42 in SDS and 3.29 ± 0.76 in CTAB microemulsion was obtained at Pt electrodes at a scan rate range of 15 to 3000 mVs−1. Pseudo-first-order rate constants (k') for the rate-determining step (rds) involving reaction of organohalides with catalyst had an average value of 41 ±1 M−1 s−1 for reduction of DBCH/SDS and 4.8 ± 1.0 ×102 M−1 s−1 for reduction of TCA/SDS. Moreover, rate constants were higher in CTAB microemulsion, giving values of 1.5 ±0.016 ×102 and 2.75 ±0.67 × 103 M−1 s−1 for DBCH and TCA, respectively. Positive interfacial charge of the microemulsion conduits influenced catalytic reaction of catalyst and the substrate. Under the conditions of the experiment, no hydrogen evolution was observed at Pt electrodes.
Proteomics principles and challenges
Authors: Marko-Varga G.
Published: October 2007

Proteomics studies rely on high-resolving separation techniques whereby the biological complexity can be unraveled. Both gel-based and liquid-phase separation principles are needed in order to mine deeper into the low abundant area of the proteins expressed in human cell samples. The expression levels that can be reached today with proteomics technology are still only reaching part of all proteins present in complex biological samples. The challenge to be met is not an easy task and will, in many aspects, be determined by the speed and success whereby the analytical field can make milestone progress. Examples will be given from our research group on proteomics studies, as well as principles and challenges within this research area.
Potentiometric detection for high-performance liquid chromatography is a reality: Which classes of organic substances are the targets?
Authors: Nagels L. J.
Published: October 2007

Potentiometric detection in high-performance liquid chromatography (HPLC) is shown to be an underexploited technique. The technique can be of great use to less classical potentiometry targets, such as bioorganics, of low as well as of high molecular weight. The understanding of non-faradaic potentiometry is, however, still problematic. Predicting the selectivity and sensitivity of a potentiometric electrode for organic ionizable substances can be done to a certain extent using QSAR methods. Although many new polymer materials and synthetic receptor molecules for organic ionics are being synthesized, few of them are applied in potentiometric membrane coatings. Hydrophilic organics form an interesting target group for these new materials.
Microbially-assisted dissolution of minerals and its use in the mining industry
Authors: Rawlings D. E.
Published: October 2007

Biomining is currently used successfully for the commercial-scale recovery of metals such as copper, cobalt, and gold from their ores. The mechanism of metal extraction is mainly chemistry-driven and is due to the action of a combination of ferric and hydrogen ions, depending on the type of mineral. These ions are produced by the activity of chemolithotrophic microorganisms that use either iron or sulfur as their energy source and grow in highly acidic conditions. Therefore, metal extraction is a combination of chemistry and microbiology. The mixture of organisms present may vary between processes and is highly dependent on the temperature at which mineral oxidation takes place. In general, relatively low-efficiency dump and heap irrigation processes are used for base metal recovery, while the biooxidation of difficult-to-treat gold-bearing arsenopyrite concentrates is carried out in highly aerated stirred-tank reactors. Bioleaching reactions, the debate as to whether the reactions are direct or indirect, the role of microorganisms, and the types of processes by which metals are extracted from their ores are described. In addition, some new processes under development and the challenges that they present are discussed.
Trends and challenges in biochemical sensors for clinical and environmental monitoring
Authors: Andreescu Silvana , Sadik O. A.
Published: October 2007

Biochemical sensors have emerged as a dynamic technique for qualitative and quantitative analysis of different analytes in clinical diagnosis, environmental monitoring, and food and process control. The need for a low-cost, reliable, ultra-sensitive, and rapid sensor continues to grow as the complexity of application areas increases. New biosensing techniques are emerging due to the need for shorter sample preparation protocols. Such novel biosensor designs make field and bed-site clinical testing simpler with substantial decrease in costs per sample throughputs. In this paper, we will review the recent trends and challenges in clinical and environmental biosensors. The review will focus on immunological, nucleic acid, and cell-based clinical and biological sensors. Special emphasis will be placed on the approaches used for immobilization or biological reagents and low-cost electrochemical biosensors. The promising biosensors for rapid diagnosis of cancer or HIV are also discussed.
In situ poly(ethylene imine) coating of hollow fiber membranes used for microdialysis sampling
Authors: Torto N. , Ohlrogge M. , Gorton L. , Van Alstine J. M. , Laurell Thomas , Marko-Varga G.
Published: October 2007

A method for the in situ modification of hollow fiber membranes used as sampling units for microdialysis probes is presented. The method consists of adsorption-coating, high molecular-weight poly(ethylene imine), PEI, onto membranes, already fitted on microdialysis probes. Modification of membranes was designed to specifically explore the so-called Andrade effects and thus enhance the interaction of membranes with enzyme. The performances of polysulfone, polyethersulfone, and polyamide membranes modified with PEI-enzyme complex were evaluated based on the membrane extraction fraction for maltose and maltotriose and membrane morphology as examined by scanning electron microscopy. Of the membranes tested, the PEI-enzyme complex least affected the performance of the polysulfone membranes. Conversion of maltoheptaose to maltotriose and maltose was increased reproducibly (within a 5 % relative standard deviation) by 50 % for modified membranes compared to the native hollow fiber membranes. The results demonstrate the potential to effectively modify membranes already fitted on a microdialysis probe. Such a procedure can be modified and employed to either promote or reduce membrane–protein interaction for hollow fibers used as microdialysis sampling units or other similar membrane applications.
Definitions of terms relating to reactions of polymers and to functional polymeric materials (IUPAC Recommendations 2003)
Authors: Horie K. , Barón Máximo , Fox R. B. , He J. , Hess M. , Kahovec J. , Kitayama T. , Kubisa P. , Maréchal E. , Mormann W. , Stepto R. F. T. , Tabak D. , Vohlídal J. , Wilks E. S. , Work W. J.
Published: October 2007

The document defines the terms most commonly encountered in the field of polymer reactions and functional polymers. The scope has been limited to terms that are specific to polymer systems. The document is organized into three sections. The first defines the terms relating to reactions of polymers. Names of individual chemical reactions are omitted from the document, even in cases where the reactions are important in the field of polymer reactions. The second section defines the terms relating to polymer reactants and reactive polymeric materials. The third section defines the terms describing functional polymeric materials.
Predicting drug metabolism: Concepts and challenges
Authors: Testa B. , Balmat A.-L. , Long Anthony
Published: October 2007

The paper begins with a discussion of the needs and goals of metabolic predictions in early drug research. Major difficulties toward this objective are examined, mainly the various substrate and product selectivities characteristic of drug metabolism. In a second part, we classify and summarize the major in silico methods used to predict drug metabolism. A discrimination is thus made between “local ”and “global ”systems. In the last part of the paper, the program METEOR is presented and evaluated using the published metabolic data of 10 substrates.
Prion protein as a target for therapeutic interventions
Authors: Liberski P. P.
Published: October 2007

Transmissible spongiform encephalopathies (TSEs), currently known as prion diseases, are neurodegenerative disorders of the central nervous system (CNS) caused by an elusive infectious agent called “prion” (proteinaceous infectious particle). These dis orders include: kuru, Creutzfeldt –Jakob disease (CJD) and its variant (vCJD), Gerstmann–Sträussler–Scheinker (GSS) disease and fatal familial insomnia (FFI) in humans, scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) or mad cow disease, and chronic wasting disease (CWD) in cervids. According to the widely accepted “prion hypothesis”, prion is an aggregate of the abnormal isoform of prion protein (PrPSc). Prion protein is a cell-derived glycoprotein (this normal isoform is called PrPc) encoded by a gene on chromosome 20 in humans (PRNP). In familial forms of TSEs, mutations within the ORF of PRNP are linked to the phenotypic expression of the disease. TSEs are important from public health perspective, and “mad cow disease has created the greatest threat to the safety of human food supply in modern times. vCJD threatens the safety of the blood supply worldwide”. Thus, to search for effective therapy is more than an urgent task. In TSEs, aggregates of PrPSc accumulate in the brain in a form of plaques, or synaptic deposits. The conversion of PrPc into PrPSc and subsequent deposits of PrPSc are targets for therapeutic interventions. These include: tricyclic compounds—acridine and phenothiazine derivatives; quinacrine; anti-PrPSc antibodies; dendrimers; polyethylene antibiotics (amphotericin B, MS-8209); pentosan polysulfate; and dextran sulfate. All these compounds are active in many in vitro and in vivo assays, but not proved definitely active in humans. Thus, albeit interesting and promising, the chemotherapy of TSEs is still in the infant phase.
Structural basis for 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor activation
Authors: Johansen T. N. , Greenwood J. R. , Vogensen S. B. , Krogsgaard-Larsen Povl
Published: October 2007

(S)-Glutamic acid (Glu), the major excitatory neurotransmitter in the central nervous system, operates through ionotropic as well as metabotropic receptors and is considered to be involved in a number of degenerative brain diseases that are currently without any satisfactory therapeutic treatment. Until recently, development of selective Glu receptor agonists had mainly been based on structural optimization of naturally occurring lead compounds structurally related to Glu. Crystallization of the agonist binding domain of the GluR2 subunit of the 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor subtype of ionotropic Glu receptors (iGluRs) in the presence or absence of an agonist has provided important information about ligand-receptor interaction mechanisms. The availability of such binding domain crystal structures has formed the basis for rational design of ligands, especially for the AMPA subtypes of iGluRs.
Search for noncompetitive 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid receptor (AMPAR) antagonists: Synthesis, pharmacological properties, and computational studies
Authors: Chimirri A. , De Sarro G. , Quartarone S. , Barreca M. L. , Caruso R. , De Luca L. , Gitto R.
Published: October 2007

The development of new 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor (AMPAR) negative modulators has received considerable interest due to their crucial role in specific neurological diseases. In recent years, our research group has been engaged in the development of new AMPAR ligands and chemical and biological studies of various 2,3-benzodiazepin-4-(thi)ones (CFMs) and their analogous cyclofunctionalized have been reported. Electrophysiological experiments confirmed that their effects are mediated through the AMPAR complex in a selective and noncompetitive fashion. Moreover, we carried out computational studies which suggested the possible binding site for noncompetitive antagonists; we also developed a 3D ligand-based pharmacophore model in order to map common structural features of highly potent compounds. Our hypothesis was successfully used as a frame work for the design of a new class of allosteric modulators containing a tetrahydroisoquinoline skeleton and led to the discovery of a very potent AMPAR antagonist with marked antiepileptic effects.
Neuropeptide mimetics for pain management
Authors: Lipkowski A. W. , Misicka A. , Carr D. B. , Ronsisvalle G. , Kosson Dariusz , Bonney I. Maszczynska
Published: October 2007

The discovery of numerous endogenous neuropeptides that participate in the formation, transmission, modulation, and perception of pain signals offers numerous strategies for the development of new analgesics. Nevertheless, the same research has not yet replaced opioids as the gold standard of pain treatment. Therefore, one possible avenue of drug development may shift interest from searching for receptor-selective opioids to creating an arsenal of drugs that target multiple opioid and non-opioid sites simultaneously. The presented short review focuses on the development of potential analgesic peptidomimetic compounds based upon opioid neuropeptides and substance P.
New endomorphin analogs with mu-agonist and delta-antagonist properties
Authors: Tóth G. , Keresztes A. , Tömböly Cs. , Péter A. , Fülöp F. , Tourwé D. , Navratilova E. , Varga É. , Roeske W. R. , Yamamura H. I. , Szucs M. , Borsodi A.
Published: October 2007

Endomorphins (endomorphin-1,H-Tyr-Pro-Trp-Phe-NH 2 ,endomorphin-2, Tyr-Pro-Phe-Phe-NH2) are potent and selective µ-opioid receptor agonists. In order to improve the affinity and chemical stability of endomorphins, we have designed, synthesized, and characterized novel analogs with unnatural (2 ',6 '-dimethyltyrosine, Dmt) and/or ß-alicyclic amino acids (ACPC and ACHC). Radioligand binding assay indicated that several of the novel analogs exhibit high affinity for both µ-and d-opioid receptors in rat-or mouse-brain membrane preparations. The most promising derivatives—such as Dmt-Pro-Trp/Phe-Phe-NH2, Dmt-(1 S,2R)-ACPC-Phe-Phe-NH2, and Dmt-(1S,2R)-ACHC-Phe-Phe-NH2 )—were characterized in recombinant cell lines expressing human µ-or d-opioid receptors. Interestingly, while these novel peptides were potent opioid agonists in the functional [35S]GTPgammaS binding assays in Chinese hamster ovary cells expressing the µ-opioid receptors, some behaved as antagonist or inverse agonist in the human d-opioid receptor-expressing CHO cells. Since it has previously been demonstrated that the coadministration of d-antagonists with µ-analgesics attenuates the development of analgesic tolerance, introduction of high-affinity d-antagonist properties into the µ-agonist endomorphins is expected to lead to potent analgesics that produce limited tolerance.
Spacer conformation in biologically active molecules
Authors: Karolak-Wojciechowska J. , Fruzinski A.
Published: October 2007

Based on our contemporary studies on the structures of biologically active molecules, we focus our attention on the aliphatic chain and its conformation. That flexible spacer definitely influenced the balanced position of all pharmacophoric points in molecules of biological ligands. The one atomic linker and two or three atomic spacers with one heteroatom X =O, S, CH2, NH have been taken into account. The conformational preferences clearly depend on the heteroatom X. In the discussion, we utilize our own X-ray data, computation chemistry methods, population analysis, and statistical data from the Cambridge Structural Database (CSD).
Discovery of new anti-inflammatory agents
Authors: Fülöp F. , Lázár László , Szakonyi Z. , Pihlavisto M. , Alaranta Sakari , Vainio P. J. , Juhakoski Auni , Marjamäki Anne , Smith D. J.
Published: October 2007

We have synthesized a series of novel hydrazines and hydrazino alcohols that specifically inhibit vascular adhesion protein-1 (VAP-1), a human endothelial cell adhesion molecule with a well documented role in inflammation. VAP-1 is a semicarbazide-sensitive amine oxidase (SSAO), and the enzyme activity has been demonstrated to have a role in VAP-1 function. An indane hydrazino alcohol was able to reduce clinical symptoms of inflammation in experimental arthritis in rodents and has the potential to be a novel anti-inflammatory drug.
NO donors: Focus on furoxan derivatives
Authors: Gasco Alberto , Fruttero Roberta , Sorba G. , Di Stilo Antonella , Calvino R.
Published: October 2007

The article focuses attention on furoxan derivatives (1,2,5 oxadiazole 2-oxides) as NO donors. Possible mechanisms for NO release from these products in physiological solution and in segments of rabbit femoral artery are briefly considered. The in vitro anti aggregatory activities and the in vitro and in vivo vasodilating properties of a number of furoxans are examined with particular reference to involvement of NO in these actions. The use of the furoxan system to design new NO donor/drug hybrids is discussed in connection with the problem of the balance between NO- and drug dependent activities of the resulting structures. Whether other biological activities (as yet, little studied) of furoxans, such as their antiparasite, antimicrobial, and antitumoral effects, are NO dependent, is a matter still to be explored.
Passive and catalytic antibodies and drug delivery
Authors: Blackburn G. Michael , Rickard J. H. , Cesaro-Tadic S. , Lagos D. , Mekhalfia A. , Partridge L. , Plückthun A.
Published: October 2007

Antibodies are one of the most promising components of the biotechnology repertoire for the purpose of drug delivery. On the one hand, they are proven agents for cell-selective delivery of highly toxic agents in a small but expanding number of cases. This technology calls for the covalent attachment of the cytotoxin to a tumor-specific antibody by a linkage that is reversible under appropriate conditions (antibody conjugate therapy, ACT —“passive delivery”). On the other hand, the linker cleavage can be accomplished by a protein catalyst attached to the tumor-specific antibody (“catalytic delivery”). Where the catalyst is an enzyme, this approach is known as antibody-directed enzyme prodrug therapy (ADEPT). Where the transformation is brought about by a catalytic antibody, it has been termed antibody-directed abzyme prodrug therapy (ADAPT). These approaches will be illustrated with emphasis on how their demand for new biotechnology is being realized by structure-based protein engineering.
Virtual combinatorial chemistry and in silico screening: Efficient tools for lead structure discovery?
Authors: Langer Thierry , Wolber G.
Published: October 2007

In this article, an overview of the most common ligand-based in silico screening techniques is given together with an example on the recent successful application of combined use of pharmacophore modeling, database mining, and biological assays. Additionally, a new approach for structure-based high-throughput pharmacophore model generation is presented. The LigandScout program contains an automated method for creating pharmacophore models from experimentally determined structure data, e.g., publicly available from the Brookhaven Protein Databank (PDB). In a first step, known algorithms were implemented and improved to extract small-molecule ligands from the PDB including assignment of hybridization states and bond orders. Second, from the interactions of the interpreted ligands with relevant surrounding amino acids, pharmacophore models reflecting functional interactions like H-bonds or ionic transfer interactions were created. These models can be used for screening molecular databases for similar modes of actions on the one hand, or for screening one single compound for potential side-effects (reversed screening) on the other hand. The implementation was done using the ilib framework, which also formed the basis of the software tool CombiGen, a fragment-based virtual combinatorial library generation program enabling the user to obtain in silico compound collections with high drug-likeness.
Development of modulators of multidrug resistance: A pharmacoinformatic approach
Authors: Ecker G. F. , Chiba Peter
Published: October 2007

Inhibition of drug efflux pumps such as P-glycoprotein represents a versatile approach for overcoming multidrug resistance in tumor therapy. Although numerous compounds have been identified as being able to inhibit P-glycoprotein, only little is known on the molecular basis of the drug–protein interaction. This article gives an overview of the different pharmacoinformatic approaches we used to develop new propafenone-type modulators of P-glycoprotein. These include 2D-and 3D-QSAR studies, artificial neural networks, and photoaffinity labeling studies.
Hindered nucleoside analogs as antiflaviviridae agents
Authors: Manfredini Stefano , Angusti Angela , Veronese A. C. , Durini Elisa , Vertuani S. , Nalin F. , Solaroli N. , Pricl S. , Ferrone Marco , Mura M. , Piano M. A. , Poddesu B. , Cadeddu Alessandra , Colla P. La , Loddo Roberta
Published: October 2007

Flaviviridae are an important family of viruses, responsible for widely spread diseases such as dengue and West Nile fever and hepatitis C. Despite the severity of the related diseases, no effective antiviral treatments for infection are available. Following our discovery of adenosine-hindered analogs as potent antiflaviviridae agents, we have continued our investigation on guanosine and inosine derivatives, which were evaluated for activity against BVDV, YFV, DENV, and WNV viruses in cell-based assays. The present study allowed us to identify some newer features that led to improve the antiviral potency (down to the µM range) and to selectively inhibit BVDV and YFV viruses. The molecular modeling results were consistent with the hypothesis that test analogs act as RNA-dependent RNA polymerase (RdRp) inhibitors by interacting with a surface allosteric binding pocket.
Solid- and solution-phase synthesis of bioactive dihydropyrimidines
Authors: Dallinger Doris , Stadler A. , Kappe C. O.
Published: October 2007

With the emergence of high-throughput screening in the pharmaceutical industry over a decade ago, synthetic chemists were faced with the challenge of preparing large collections of molecules to satisfy the demand for new screening compounds. The unique exploratory power of multicomponent reactions such as the Biginelli three-component reaction was soon recognized to be extremely valuable to produce compound libraries in a time- and cost-effective manner. The present review summarizes synthetic advances from our laboratories for the construction of Biginelli libraries via solution-and solid-phase strategies that are amenable to a high-throughput or combinatorial format.
Synthesis of naturally occurring o-heterocyclic compounds of biological activity
Authors: Antus Sándor , Gulácsi Katalin , Juhász László , Kiss Loránd , Kurtán Tibor
Published: October 2007

The total synthesis of (−)-cabenegrin A-I was achieved via (−)-6aR,11aR maackiain, which was obtained by optical resolution of racemic maackiain using S-(−)-alpha-methylbenzyl isocyanate. The synthesis of rac-maackiain was performed both with the Heck oxyarylation of 7-benzyloxy-2H-chromene and the BF3OEt2 mediated ring closure of isoflavan-4-ol derivatives, the latter of which provided much higher yields. The first enantioselective synthesis of trans-6aS,11aR-pterocarpan and its conversion to cis-6aS,11aS -ptarocarpan was also presented starting from racemic 2'-benzyloxyflavanone. Their stereochemistry was deduced by circular dichroism (CD) as well as by X-ray analysis of the ketal intermediate.
Glossary of terms used in toxicokinetics (IUPAC Recommendations 2003)
Authors: Nordberg M. , Duffus J. , Templeton D. M.
Published: October 2007

This glossary contains definitions of 365 terms frequently used in the multidisciplinary field of toxicokinetics. The glossary is compiled primarily for chemists who find themselves currently working in toxicology and requiring a knowledge of the expressions used in toxicokinetics,especially in relation to hazard and risk assessment. Some medical terms are included, where relevant, because of their frequent occurrence in the toxicological literature and because chemists would not normally be expected to be familiar with them. There are three annexes,one containing a list of abbreviations and acronyms used in toxicokinetics, one containing a list of abbreviations and acronyms of names of international bodies and legislation that are relevant to toxicology and chemical safety, and one giving sources for further reading.
Quantities, terminology, and symbols in photothermal and related spectroscopies (IUPAC Recommendations 2004)
Authors: Terazima M. , Hirota N. , Braslavsky S. E. , Mandelis Andreas , Bialkowski S. E. , Diebold G. J. , Miller R. J. D. , Fournier Danièle , Palmer R. A. , Tam A.
Published: October 2007

This paper presents quantities, terminology, and symbols of terms related to photothermal phenomena and used in photothermal and related spectroscopies. The terms used in the literature to describe photothermal phenomena and methods are reviewed, and a glossary of terms is given. The origins of photothermal phenomena, as well as the relations among various photothermal effects, are summarized. The listed terms cover the terminology in transient grating, transient lens, photoacoustic spectroscopy, photothermal radiometry, calorimetry, interferometry, deflection, reflection, and other related spectroscopies, which use or are related to photothermal effects.
Electrochemical detection in liquid flow analytical techniques: Characterization and classification (IUPAC Technical Report)
Authors: Tóth K. , Stulík K. , Kutner W. , Fehér Zs. , Lindner E.
Published: October 2007

Liquid flow analytical techniques are classified, and definitions are provided of flow-injection analysis, segmented flow analysis, flow titration, continuous monitoring, liquid chromatography, and capillary electrophoresis. Electrochemical detection and flow through detection cells are characterized with respect to the surface and bulk detection. The detector performance is discussed in terms of its principal analytical parameters, such as detection limit and dynamic concentration range, as well as its dynamic characteristics, such as the response time, sampling frequency, transport lag, and long-term stability. Moreover, different detection modes are critically evaluated, including both potentiostatic and galvano-static techniques. Factors influencing sensitivity and detection limit, which include electronic and hydrodynamic approach, are also discussed. Different detector designs are critically reviewed, and the special features of electrochemical detectors for flow analytical techniques are emphasized.
Piezoelectric chemical sensors (IUPAC Technical Report)
Authors: Buck R. P. , Lindner E. , Kutner W. , Inzelt György
Published: October 2007

Piezoelectric chemical and electrochemical sensors are classified. Basic terms and definitions related to piezoelectric materials and sensing devices, electric transducers, and analytical measurements with piezoelectric chemical sensors are provided. In addition, the more essential response equations are presented.
Critical evaluation of the state of the art of the analysis of light elements in thin films demonstrated using the examples of SiOXNY and AlOXNY films (IUPAC Technical Report)
Authors: Dreer Sabine , Wilhartitz P.
Published: October 2007

The quantitative analysis of thin films containing light elements is very important in improving the coating processes and technological properties of the products. In order to review the state of the art of modern analytical techniques for such applications, the model systems SiOXNY and AlOXNY were selected. Over 1000 abstracts were screened, and the relevant literature was evaluated to give a comprehensive overview of instruments, analytical procedures and results, film types, deposition methods, and investigation goals. From more than 150 citations, the limitations, drawbacks, and pitfalls of the different methods were extracted and reviewed critically, while in addition, improvements were proposed where possible. These suggestions are combined with the newest results of investigation by the authors of this paper. Recommendations concerning the optimized combination of analytical methods for different analytical problems have been worked out on the basis of all results. Analysis of various multicomponent systems containing light elements demonstrated the applicability of the different methods of analysis in combination to all film systems with related compositions.