bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface modification of silicone rubber by ion beam assisted deposition (IBAD) for improved biocompatibility
Authors: Song Jeom Sik , Lee Sukmin , Cha Gook Chan , Jung Sung Hee , Choi Seo Yoon , Kim Kyung Hoon , Mun Mu Seong
Published: March 2005

We studied the preparation of antimicrobial silicone rubbers of improved interfacial strength, which could be formed with the ion beam assisted deposition (IBAD) technique for coating metallic or inorganic materials (silver (Ag), Copper (Cu), and Hydroxyapatite(HAp)/TiO2) on the silicone surface. Those coating materials provide high product safety as well as outstanding antimicrobial activity. The deposition methodology is composed of pre‐etching with oxygen gas, vaporizing the coating materials, and post‐treatment with Ar ion. With the evaporation of the coating materials, the Ar beam was focused on the substrate to assist deposition. It was found out that the ion assisting depositions in the IBAD process give a prominent enhancement in adhesion between silicone rubbers and coatings of Ag and Cu. The HAp/TiO2 coating layer was easily dissolved in aqueous saline solution. All deposited layers display high antimicrobial activities against Staphlococcus aureus (ATCC 6538) and Escherichia coil (ATCC 25,922), showing 99.9% reduction of bacteria, respectively. In a cytotoxicity test, the Ag and HAp/TiO2 coated silicone shows a decrease of cytotoxicity, while the Cu coating leads to a slight increase of cytotoxicity. The result on the surface modifications of silicone rubber will be employed in further study for applications of medical or rehabilitation devices. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1095–1101, 2005
Phenomenological modeling of anomalous diffusion in polymers
Authors: Pomerantsev Alexey L.
Published: March 2005

Both normal and anomalous diffusion kinetics are considered in this article. Models of the relaxation, convection, and wetting–drying‐cycle kinetics and some other kinds of diffusion kinetics are evaluated. Analytically tractable solutions (when available) are presented. All calculations have been performed with the new nonlinear regression software Fitter (Moscow, Russia). © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1102–1114, 2005
Thickness‐dependent sorption and effects of physical aging in a polyimide sample
Authors: Punsalan David , Koros William J.
Published: March 2005

The solubility of a relatively noninteracting gas (CH4) was measured and compared for samples of vastly different thicknesses (25.4 vs 0.1 μm) to investigate the possibility of thickness‐dependent sorption and physical aging in glassy polymers. Changes in the sorption due to physical aging in these dense samples were observed and compared. To further compare the tendency of free‐volume relaxations in samples of different thicknesses, a variety of conditioning sorption tests were performed in which increases in the CH4 sorption due to high‐pressure CO2 exposure were observed and then compared after sample degassing. The reduction in CH4 solubility was related to excess free‐volume relaxations, and response comparisons of samples of widely different film thicknesses supported the notion of thickness‐dependent physical aging in glassy polymers. To the authors' knowledge, this was the first direct observation of a significant differences in gas solubility in glassy polymers due to the film thickness and aging time. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1115–1121, 2005
Kinetic study of the degradation of acrylonitrile–acrylamide copolymers
Authors: Hou Chen , Qun Wang , Qu Rong‐Jun , Wang Cheng‐Guo
Published: March 2005

Differential scanning calorimetry was used to investigate the degradation of acrylonitrile–acrylamide copolymers in air. The apparent activation energy of degradation of the copolymers was calculated with the Kissinger method. The effects of the copolymerization conditions on the apparent activation energy of the copolymers were studied. Increasing the dimethylformamide concentration in the solvent mixture led to a rapid increase in the apparent activation energy of degradation of the acrylonitrile–acrylamide copolymers. The apparent activation energy decreased quickly as the comonomer acrylamide concentration increased, and this change became less prominent as the acrylamide/acrylonitrile weight ratio increased beyond 5/95. The apparent activation energy increased as the copolymerization temperature increased. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1017–1020, 2005
Gel formation in diimide‐hydrogenated polymers
Authors: Lin Xingwang , Pan Qinmin , Rempel Garry L.
Published: March 2005

The hydrogenation of diene‐based polymers via diimide is a very attractive alternative to the conventional catalytic hydrogenation route based on gaseous molecular hydrogen. However, serious crosslinking always accompanies it and limits the end‐use properties of the polymers. Gel formation in polymers that are hydrogenated via diimide has been investigated in detail through an inspection of all the chemical reactions involved in the process. The results indicate that hydrogen peroxide decomposition, some reactions related to oxygen, and the redox reaction between hydrogen peroxide and hydrazine are capable of generating radicals. However, radicals generated in the aqueous phase do not appear to initiate the crosslinking of diene‐based polymers in the latex form. It is proposed that the primary radicals giving rise to crosslinking are generated in the polymer phase in situ, and the step responsible for generating these organic radicals is possibly the diimide disproportionation reaction. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1122–1125, 2005
Effect of calcium carbonate on the mechanical and thermal properties of isotactic polypropylene/ethylene vinyl acetate blends
Authors: Öksüz Mustafa , Yıldırım Hüseyin
Published: March 2005

The effect of calcium carbonate (CaCO3) on the mechanical properties (with heat treatment) and thermal properties of polypropylene and isotactic polypropylene (i‐PP)/ethylene vinyl acetate (EVA) blends was investigated. CaCO3, in five different concentrations (3, 6, 9, 12l, and 15 wt %), was added to i‐PP/EVA (88/12) to produce ternary composites. The mechanical properties, including the yield and tensile strengths, elastic modulus, Izod impact strength for notch radii of 0.25 and 1 mm, and hardness with and without an annealing heat treatment, and the thermal properties, such as the melting point and melt‐flow index, of the composites were investigated. The annealing heat treatment was carried out at 100°C for three different holding times: 75, 100, and 150 h. On the basis of the results, attempts were made to establish a relationship between the CaCO3 content, the annealing holding time, and the mechanical and thermal properties to obtain the best results. The tensile test results showed that the heat treatment was not effective for the ultimate tensile strength, and the yield strength and tensile strength decreased gradually as the CaCO3 content increased. However, CaCO3 was effective for higher elastic modulus, impact strength, and hardness values. A considerable increase in the elastic modulus was found with a 3% CaCO3 concentration for a holding time of 100 h. The maximum impact strength for a notch radius of 1 mm was obtained with 3% CaCO3 with annealing for a holding time of 100 h, whereas a 9% CaCO3 concentration produced higher toughness values for a notch radius of 0.25 mm. The fracture surfaces also supported the results from the Izod impact tests. Similarly, hardness values increased with the annealing heat treatment and increasing CaCO3 content. However, different holding times showed similar effects on the hardness values. The increased CaCO3 content caused the melting point to increase 5°C, whereas the melt‐flow index showed a sharp decrease as the CaCO3 content increased to 3%. Taking into consideration the mechanical and thermal properties and the annealing holding time, we recommend a CaCO3 concentration of 3% with an annealing heat treatment for 100 h for optimum properties of such ternary composites. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1126–1137, 2005
Prevention of surgical adhesions with barriers of carboxymethylcellulose and poly(ethylene glycol) hydrogels synthesized by irradiation
Authors: Lee Joon‐Ho , Nho Young‐Chang , Lim Youn‐Mook , Son Tae‐Il
Published: March 2005

Biocompatible and biodegradable hydrogels based on carboxymethylcellulose (CMC) and poly(ethylene glycol) (PEG) were prepared as physical barriers for preventing surgical adhesions. These interpolymeric hydrogels were synthesized by a γ‐irradiation crosslinking technique. Sections (1.5 cm × 1.5 cm) of the cecal serosa and an adjacent abdominal wall were abraded with a bone burr until the serosal surface was disrupted and hemorrhagic but not perforated, and the serosa of the cecum was sutured to the abdominal wall 5 mm away from the injured site. The denuded cecum was covered with either CMC/PEG hydrogels or a solution from a CMC/PEG hydrogel. A control rat serosa was not covered. Two weeks later, the rats were killed, and the adhesions were scored on a 0–5 scale. No treatment showed a significantly higher incidence of adhesions than the CMC/PEG hydrogels or solutions from the CMC/PEG hydrogels. This study demonstrated that CMC/PEG hydrogels could prevent intra‐abdominal adhesion in a rat model. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1138–1145, 2005
Bulk polymerization of styrene in the presence of organomodified montmorillonite
Authors: Liu Guodong , Zhang Liucheng , Zhao Dongmei , Qu Xiongwei
Published: March 2005

The effect of montmorillonite (Cloisite 6A) on the bulk polymerization of styrene initiated by benzoyl peroxide (BPO) was studied by the dilatometric determination of the polymerization rates. The bulk polymerization rates increased as the montmorillonite input quantity increased. The effect became greater when the BPO concentration decreased. Under the assumption that clay participated in the radical initiation reaction of the chains, the reaction orders for clay and BPO were determined to be approximately 1.0 and 0.5, respectively. X‐ray diffraction and thermogravimetric analysis studies showed that the structure and properties of the obtained polystyrene (PS)/montmorillonite nanocomposites were greatly affected by the BPO concentration. With lower BPO concentrations, a larger interlayer distance and a higher extent of delamination for the clay were observed in the obtained PS/montmorillonite nanocomposites. The nanocomposites prepared with lower BPO concentrations also showed higher heat‐decomposition‐resistance temperatures. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1146–1152, 2005
Swelling behavior and diffusion studies of high‐water‐retaining acrylamide/potassium methacrylate hydrogels
Authors: Mohan Y. Murali , Murthy P. S. Keshava , Rao K. Madhusudana , Sreeramulu J. , Raju K. Mohana
Published: March 2005

Poly(acrylamide‐co‐potassium methacrylate) hydrogels were prepared by free‐radical simultaneous polymerization with aqueous solutions of acrylamide (AAm) and potassium methacrylate (KMA) with a redox initiator. The copolymerization was performed with eight different compositions of KMA at a fixed concentration of oil‐soluble crosslinkers, including 1,4‐butanediol diacrylate and ethylene glycol dimethacrylate (EGDMA). For every composition of AAm/KMA copolymer, the percentage swelling, swelling equilibrium, and diffusion characteristics were investigated. The copolymers were further studied for deswelling properties. The power law relationships of the hydrogels were evaluated for variation in terms of saline concentration. The AAm/KMA copolymers were confirmed by IR spectroscopy. Thermal studies of hydrogels were performed with differential scanning calorimetry and thermogravimetric analysis. EGDMA was found to be a better crosslinker for obtaining higher swelling and deswelling properties for the AAm/KMA hydrogels. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1153–1164, 2005
Transcriptome profiles for high‐cell‐density recombinant and wild‐type Escherichia coli
Authors: Haddadin Fu'ad T. , Harcum Sarah W.
Published: March 2005

The transcriptome profiles for wild‐type (plasmid‐free) and recombinant (plasmid‐bearing) Escherichia coli during well‐controlled synchronized high‐cell‐density fed‐batch cultures were analyzed by DNA microarrays. It was observed that the growth phase significantly affected the transcriptome profiles, and the transcriptome profiles were significantly different for the recombinant and wild‐type cultures. The response of the wild‐type and recombinant cultures to an isopropyl‐1‐thio‐β‐d‐galactopyranoside‐ (IPTG‐) addition was examined, where IPTG induced recombinant protein production in the plasmid‐bearing cultures. The IPTG‐addition significantly altered the transcriptome response of the wild‐type cultures entering the stationary phase. The IPTG‐induced recombinant protein production resulted in a significant down‐regulation of many energy synthesis genes (atp, nuo, cyo), as well as nearly all transcription‐ and translation‐related genes (rpo, rpl, rpm, rps, rrf, rrl, rrs). Numerous phage (psp, hfl) and transposon‐related genes (tra, ins) were significantly regulated in the recombinant cultures due to the IPTG‐induction. These results indicate that the signaling mechanism, associated with the recombinant protein production, may induce a metabolic burden in the form of a phage defense mechanism. Taken together, these results indicated that recombinant protein production initiated a cascade of transcriptome responses that down‐regulated the very genes needed to sustain productivity. © 2005 Wiley Periodicals, Inc.
Uncertainty analysis of penicillin V production using Monte Carlo simulation
Authors: Biwer Arno , Griffith Steve , Cooney Charles
Published: March 2005

Uncertainty and variability affect economic and environmental performance in the production of biotechnology and pharmaceutical products. However, commercial process simulation software typically provides analysis that assumes deterministic rather than stochastic process parameters and thus is not capable of dealing with the complexities created by variance that arise in the decision‐making process. Using the production of penicillin V as a case study, this article shows how uncertainty can be quantified and evaluated. The first step is construction of a process model, as well as analysis of its cost structure and environmental impact. The second step is identification of uncertain variables and determination of their probability distributions based on available process and literature data. Finally, Monte Carlo simulations are run to see how these uncertainties propagate through the model and affect key economic and environmental outcomes. Thus, the overall variation of these objective functions are quantified, the technical, supply chain, and market parameters that contribute most to the existing variance are identified and the differences between economic and ecological evaluation are analyzed. In our case study analysis, we show that final penicillin and biomass concentrations in the fermenter have the highest contribution to variance for both unit production cost and environmental impact. The penicillin selling price dominates return on investment variance as well as the variance for other revenue‐dependent parameters. © 2004 Wiley Periodicals, Inc.
Bioprocess intensification in flow‐through monolithic microbioreactors with immobilized bacteria
Authors: Akay G. , Erhan E. , Keskinler B.
Published: March 2005

Microporous polymers (with porosity up to 90%) with a well‐ prescribed internal microstructure were prepared in monolithic form to construct a flow‐through microbioreactor in which phenol‐degrading bacteria, Pseudomonas syringae, was immobilized. Initially, bacteria was forced seeded within the pores and subsequently allowed to proliferate followed by acclimatization and phenol degradation at various initial substrate concentrations and flow rates. Two types of microporous polymer were used as the monolithic support. These polymers differ with respect to their pore and interconnect sizes, macroscopic surface area for bacterial support, and phase volume. Polymer with a nominal pore size of 100 μm with phase volume of 90% (with highly open pore structure) yielded reduced bacterial proliferation, while the polymer with nominal pore size of 25 μm with phase volume of 85% (with small interconnect size and large pore area for bacterial adhesion) yielded monolayer bacterial proliferation. Bacteria within the 25 μm polymer support remained monolayered, without any apparent production of extracellular matrix during the 30‐day continuous experimental period. The microbioreactor performance was characterized in terms of volumetric utilization rate and compared with the published data, including the case where the same bacteria was immobilized on the surface of microporous polymer beads and used in a packed bed during continuous degradation of phenol. It is shown that at similar initial substrate concentration, the volumetric utilization in the microreactor is at least 20‐fold more efficient than the packed bed, depending on the flow rate of the substrate solution. The concentration of the bacteria within the pores of the microreactor decreases from 2.25 cells per μm2 on the top surface to about 0.4 cells per μm2 within 3 mm reactor depth. If the bacteria‐depleted part of the microreactor is disregarded, the volumetric utilization increases by a factor of 30‐fold compared with the packed bed. This efficiency increase is attributed to the reduction of diffusion path for the substrate and nutrients and enhanced availability of the bacteria for bioconversion in the absence of biofilm formation as well as the presence of flow over the surface of the monolayer bacteria. © 2005 Wiley Periodicals, Inc.
Evaluating environmental and social performance of large Portuguese companies: a balanced scorecard approach
Authors: Dias‐Sardinha Idalina , Reijnders Lucas
Published: March 2005

A thematic balanced scorecard format was used to address environmental and social performance evaluation of 13 large companies operating in Portugal. Financial aspects of environmental and social company activities are also included. Companies were categorized as to their actual performance status using a predefined performance framework. Three categories were found: compliance with the law while emphasizing pollution control, pollution prevention and eco‐efficiency. Management tools and procedural matters were found to be most relevant for categorization. Often, reported information did not allow for quantitative evaluation of environmental burden reduction.

Use of the thematic balanced scorecard format was useful to better understand the strengths and weaknesses of links between objectives and measurements, initiatives and achievements. Improvement as to environmental performance was found to be paralleled by increased social performance, suggesting that a multi‐level ‘sustainability’ performance categorization of these Portuguese companies is feasible. Driving forces for environmental management initiatives were found to differ by category of performance. Copyright © 2005 John Wiley & Sons, Ltd and ERP Environment.
Exploring individual and institutional drivers of proactive environmentalism in the US Wine industry
Authors: Marshall R. Scott , Cordano Mark , Silverman Murray
Published: March 2005

Industry transformation related to environmental stewardship proceeds through multiple stages, and there is as of yet no clear understanding of the importance of certain drivers of transformation at different stages. We bring together previous environmental management research regarding individual‐ and institutional‐level drivers of environmental stewardship to develop a model and series of questions regarding proactive environmental behavior in the US wine industry. A qualitative research method, including interviews and focus groups, is used to test the model. At the early stage of environmental transformation in the wine industry, we find that managerial attitudes and norms, existing regulations, employee welfare and competitive pressures are all strong drivers of proactive environmental behavior. However, our multi‐level analysis suggests that drivers of environmentalism vary in relevance and relative importance and that future environmental management research needs to consider the relationship between drivers of environmentalism and the stage of an industry's environmental transformation. Copyright © 2005 John Wiley & Sons, Ltd and ERP Environment.
Rhetoric and reality of corporate greening: a view from the supply chain management function
Authors: Preuss Lutz
Published: March 2005

The increasingly important economic role of supply chain management provides the backcloth against which this article examines what contribution the function can make to environmental protection. Theoretical perspectives on greener supply are developed and then tested against a sample of manufacturing companies. Environmental policy documents published by the sample companies seem to offer surface evidence for a proactive supply chain management role in environmental protection. Yet a more detailed examination of the three elements that constitute supply chain management – the management of the transformation of materials, the management of information flows and the management of supply chain relationships – finds a suboptimal situation for all three areas. In part this gap can be explained by limits in the technical capabilities of the supply chain. More important, however, are structural constraints that prevent the supply chain manager from actively searching for environmentally friendlier alternatives. Copyright © 2005 John Wiley & Sons, Ltd and ERP Environment.
Target‐Family‐Oriented Focused Libraries for Kinases—Conceptual Design Aspects and Commercial Availability
Authors: Prien Olaf
Published: March 2005

Tailor‐made libraries may increase the likelihood of identifying potential lead candidates in early drug‐discovery phases. That at least 12 commercial vendors offer their services in providing compound collections of tentative kinase inhibitors reflects the growing interest in kinases within the pharmaceutical industry. Some conceptual design approaches for focused library design for the kinase family are reviewed, and the design concepts of these commercialized libraries is discussed.
The Target Discovery Process
Authors: Egner Ursula , Krätzschmar Jörn , Kreft Bertolt , Pohlenz Hans‐Dieter , Schneider Martin
Published: March 2005

In order to minimise attrition rates in drug development projects, a target discovery process is implemented to select and characterise the most suitable candidate kinase targets, before lead identification and lead optimisation are embarked upon. The process consists of 1) target selection, 2) target assessment, and 3) target validation. This rational approach to target discovery, as a prerequisite for lead discovery, ensures that new therapeutic targets fulfil a set of general criteria, as well as indication‐specific, descriptive and functional ones. The approach should ultimately maximise the likelihood of achieving target‐selective inhibition by small‐molecule inhibitors with minimal in vivo side effects and a therapeutic effect based on a sound biological hypothesis.
High‐Throughput Screening for Kinase Inhibitors
Authors: von Ahsen Oliver , Bömer Ulf
Published: March 2005

Following G protein‐coupled receptors (GPCRs), protein kinases have become the second most important class of targets for drug discovery over the last 20 years. While only four kinase inhibitors have reached the market to date (Fasudil for rho‐dependent kinase, Rapamycin for TOR, Gleevec for BCR‐Abl, and Iressa for EGFR), many more are already in clinical development. A historical overview of kinase inhibitors was recently published by Cohen.1 After the previous successes, protein kinases are now regarded as attractive, well‐drugable targets, and the analysis of the human genome has yielded 518 protein kinases.2 We can thus expect screening for protein kinase inhibitors to become even more important in the future. In this review we will focus on the early steps of drug discovery programs producing new lead compounds. We will guide the reader through efficient state‐of‐the‐art assay development and high‐throughput screening of large chemical libraries for protein kinase inhibitors.
Heme Alkylation by Artesunic Acid and Trioxaquine DU1301, Two Antimalarial Trioxanes
Authors: Laurent Sophie A.‐L. , Loup Christophe , Mourgues Sophie , Robert Anne , Meunier Bernard
Published: March 2005

The sesquiterpene Artemisinin, an antimalarial drug that is effective against multidrug‐resistant Plasmodium falciparum strains, contains a 1,2,4‐trioxane, and the endoperoxide function plays a key role in its biological activity. However, its poor solubility means that hemisynthetic derivatives, such as artesunic acid, are preferred for drugs.

The reductive activation of the peroxide function of artemisinin by iron(II)‐heme produces heme derivatives that are alkylated at meso positions by a C‐centered radical derived from artemisinin. We checked if the alkylating ability of trioxane‐based drugs toward heme, which might be related to its parasiticidal activity, is a general feature by comparing the chemical reactivity toward heme of the clinically relevant derivative artesunic acid and DU1301, a drug of the trioxaquine family, that is active against P. falciparum. Both artesunic acid and trioxaquine DU1301 efficiently alkylated the heme macrocycle after activation of their peroxide function by the iron(II) of heme itself and thus gave rise to covalently coupled heme–drug products. This heme–drug adduct formation might be related to the high antimalarial activity of DU1301.
The Effects of Ligand Exchange and Mobility on the Peroxidase Activity of a Bacterial Cytochrome c upon Unfolding
Authors: Worrall Jonathan A. R. , Diederix Rutger E. M. , Prudêncio Miguel , Lowe Christian E. , Ciofi‐Baffoni Simone , Ubbink Marcellus , Canters Gerard W.
Published: March 2005

The effect on the heme environment upon unfolding Paracoccus versutus ferricytochrome c‐550 and two site‐directed variants, K99E and H118Q, has been assessed through a combination of peroxidase activity increase and one‐dimensional NMR spectroscopy. At pH 4.5, the data are consistent with a low‐ to high‐spin heme transition, with the K99E mutation resulting in a protein with increased peroxidase activity in the absence of or at low concentrations of denaturant. Furthermore, the mobility of the polypeptide chain at pH 4.5 for the wild‐type protein has been monitored in the absence and presence of denaturant through heteronuclear NMR experiments. The results are discussed in terms of local stability differences between bacterial and mitochondrial cytochromes c that are inferred from peroxidase activity assays. At pH 7.0, a mixture of misligated heme states arising from protein‐based ligands assigned to lysine and histidine is detected. At low denaturant concentrations, these partially unfolded misligated heme forms inhibit the peroxidase activity. Data from the K99E mutation at pH 7.0 indicate that K99 is not involved in heme misligation, whereas histidine coordination is proven by the data from the H118Q variant.
PTK 787/ZK 222584, a Tyrosine Kinase Inhibitor of all Known VEGF Receptors, Represses Tumor Growth with High Efficacy
Authors: Hess‐Stumpp Holger , Haberey Martin , Thierauch Karl‐Heinz
Published: March 2005

The angiogenesis inhibitor PTK 787/ZK 222584 (PTK/ZK) blocks all known VEGF receptor (VEGFR) tyrosine kinases, including the lymphangiogenic VEGFR3, in the lower nanomolar range. From a panel of 100 kinases only PDGFR, c‐kit, and c‐fms are inhibited beyond those in the nanomolar range. PTK/ZK functions as a competitive inhibitor at the ATP‐binding site of the receptor kinase as shown here in kinetic experiments. The VEGF signal blockade in microvascular endothelial cells (MVEC) results in a blockade of MVEC proliferation (IC50=30 nM), without affecting the proliferation of normal tissue cells and tumor cells. The efficacy of PTK/ZK depends on its continuous presence within the endothelial target cells. Early removal attenuates its antiproliferative activity in vitro. Growth inhibition of endothelial cells is fully reversible as demonstrated by “washout” experiments. Without inhibiting tumor cell proliferation directly, PTK/ZK results in a significant retardation of tumor growth in a number of experimental tumor models of different tissue origin. Combination of PTK/ZK with an antiandrogen revealed additive effects on tumor‐growth inhibition. Treatment efficacy was monitored both by tumor weight and by the determination of serum concentrations of the surrogate marker PSA. PTK/ZK is currently being investigated in patients with different solid tumor types for its therapeutic utility. Preliminary data from phase I/II clinical trials of PTK/ZK as a monotherapy suggested a positive safety and tolerability profile, which we interpret to be a consequence of the high selectivity of the drug for a limited number of kinases. Preliminary response, time to progression, and overall survival data were promising.1 Based on these encouraging results, PTK/ZK is currently in Phase III clinical trials for metastatic colorectal cancer.
Cover Picture: The Target Discovery Process (ChemBioChem 3/2005)
Authors: Egner Ursula , Krätzschmar Jörn , Kreft Bertolt , Pohlenz Hans‐Dieter , Schneider Martin
Published: March 2005

The cover picture shows the target discovery process as implemented at Schering AG for work on kinases. Before a target enters the lead discovery phase, the target candidate has to pass several hurdles to maximise the likelihood of achieving target‐selective inhibition by small‐molecule inhibitors. This target‐discovery process comprises three phases: target identification, drugability assessment and functional target validation. Further details can be found in the article of U. Egner et al. on p. 468 ff.
The Selectivity for Cysteine over Serine in Coenzyme A Biosynthesis
Authors: Strauss Erick , Begley Tadhg P.
Published: March 2005

In the Table of Contents, the ribose moeity of coenzyme A is shown with its stereochemical centre mistakenly inverted. The correct structure appears here.magnified image
Multistate Reactivity in Styrene Epoxidation by Compound I of Cytochrome P450: Mechanisms of Products and Side Products Formation
Authors: Kumar Devesh , de Visser Sam P. , Shaik Sason
Published: March 2005

Density functional theoretical calculations are used to elucidate the epoxidation mechanism of styrene with a cytochrome P450 model Compound I, and the formation of side products. The reaction features multistate reactivity (MSR) with different spin states (doublet and quartet) and different electromeric situations having carbon radicals and cations, as well as iron(III) and iron(IV) oxidation states. The mechanisms involve state‐specific product formation, as follows: a) The low‐spin pathways lead to epoxide formation in effectively concerted mechanisms. b) The high‐spin pathways have finite barriers for ring‐closure and may have a sufficiently long lifetime to undergo rearrangement and lead to side products. c) The high‐spin radical intermediate, 42rad‐IV, has a ring closure barrier as small as the CC rotation barrier. This intermediate will therefore lose stereochemistry and lead to a mixture of cis and trans epoxides. The barriers for the production of aldehyde and suicidal complexes are too high for this intermediate. d) The high‐spin radical intermediate, 42rad‐III, has a substantial ring closure barrier and may survive long enough time to lead to suicidal, phenacetaldehyde and 2‐hydroxostyrene side products. e) The phenacetaldehyde and 2‐hydroxostyrene products both originate from crossover from the 42rad‐III radical intermediate to the cationic state, 42. The process involves an N‐protonated porphyrin intermediate that re‐shuttles the proton back to the substrate to form either phenacetaldehyde or 2‐hydroxostyrene products. This resembles the internally mediated NIH‐shift observed during benzene hydroxylation.
Understanding the Conformational Dependence of Spin–Spin Coupling Constants: Through‐Bond and Through‐Space J(31P,31P) Coupling in Tetraphosphane‐1,4‐diides [M(L)x]2[P4R4]
Authors: Kaupp Martin , Patrakov Alexander , Reviakine Roman , Malkina Olga L.
Published: March 2005

The characteristic dependence of J(31P,31P) spin–spin coupling constants of alkali metal tetraphosphane‐1,4‐diides on structure and composition has been analyzed by density functional methods. The computations confirm that the structure of the contact ion pairs is conserved in solution. Calculations on model systems M2P4H4, on naked P4H42− anions, and on models including point charges, show that the role of the cations is mainly structural and to a smaller extent electrostatic. Three of the four J(P,P) coupling constants depend characteristically on the conformation of the anion, which in turn is determined by the substituents R and by cation–anion interactions. Several couplings exhibit a large through‐space component and are thus strongly dependent on the relative orientation of nonbonding electron pairs on the phosphorus atoms involved. This is shown by visualization of coupling pathways using the recently introduced coupling energy density (CED), in combination with the electron localization function (ELF).
Fluorous Base‐Pairing Effects in a DNA Polymerase Active Site
Authors: Lai Jacob S. , Kool Eric T.
Published: March 2005

We describe selective “fluorous” effects in the active site of a DNA polymerase, by using nucleotide analogues whose pairing edges are perfluorinated. The 5′‐triphosphate deoxynucleotide derivatives of DNA base analogues 2,3,4,5‐tetrafluorobenzene (FB) and 4,5,6,7‐tetrafluoroindole (FI), as well as hydrocarbon controls benzene (B) and indole (I), were synthesized and studied as substrates for the DNA Polymerase I Klenow fragment (KF exo−). Modified nucleotides were present in the DNA template or were supplied as nucleoside triphosphates in studies of the steady‐state kinetics of single nucleotide insertion. When supplied opposite the non‐natural bases in the template strand, the hydrophobic nucleoside triphosphates were incorporated by up to two orders of magnitude more efficiently than the natural deoxynucleoside triphosphates. The purine‐like fluorinated indole nucleotide (FI) was the most efficiently inserted of the four hydrophobic analogues, with the most effective incorporation occurring opposite the pyrimidine‐like tetrafluorobenzene (FB). In all cases, the polyfluorinated base pairs were more efficiently processed than the analogous hydrocarbon pairs. A preliminary test of polymerase extension beyond these pairs showed that only the FB base is appreciably extended; the inefficient extension is consistent with recently published data regarding other nonpolar base pairs. These results suggest the importance of hydrophobicity, stacking, and steric interactions in the polymerase‐mediated replication of DNA base pairs that lack hydrogen bonds. These findings further suggest that the enhanced hydrophobicity of polyfluoroaromatic bases could be employed in the design of new, selective base pairs that are orthogonal to the natural Watson–Crick pairs used in replication.
Electronic Properties and Stability of DititaniumIV Substituted α‐Keggin Polyoxotungstate with Heteroatom Phosphorus by DFT
Authors: Guan Wei , Yan Likai , Su Zhongmin , Liu Shuxia , Zhang Min , Wang Xiaohong
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Ab initio Probing of the Aromatic Oxygen Cluster O42+.
Authors: Elliott Ben M. , Boldyrev Alexander I.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
(M4H3X)2B2O2: Hydrometal Complexes (M: Ni, Mg) Containing Double Tetracoordinate Planar Nonmetal Centers (X: C, N)
Authors: Li Si‐Dian , Ren Guang‐Ming , Miao Chang‐Qing
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
The SF5Ox Radicals, x: 0—3.
Authors: Kronberg Marc , von Ahsen Stefan , Willner Helge , Francisco Joseph S.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Electronic Structure of Li2Ga and Li9Al4 Two Solids Containing Infinite and Uniform Zigzag Chains.
Authors: Alemany Pere , Llunell Miquel , Canadell Enric
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Trends in Hydride Formation Energies for Magnesium‐3d Transition Metal Alloys
Authors: Vegge Tejs , Hedegaard‐Jensen Lise S. , Bonde Jacob , Munter Ture R. , Noerskov Jens K.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Structural Reinvestigation of Ammonium Hypophosphite: Was Dihydrogen Bonding Observed Long Ago?
Authors: Marincean Simona , Custelcean Radu , Stein Robin S. , Jackson James E.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
The Structure of α‐Zn4Sb3: Ordering of the Phonon‐Glass Thermoelectric Material β‐Zn4Sb3.
Authors: Nylen Johanna , Andersson Magnus , Lidin Sven , Haeussermann Ulrich
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Crystal Structure of K2V8O21 and Tl2V8O21.
Authors: Tyutyunnik Alexander P. , Zubkov Vladimir G. , Krasil'nikov Vladimir N. , Svensson Gunnar , Sayagues Maria J.
Published: March 2005

For Abstract see ChemInform Abstract in Full Text.
Crystal Structure of RbAl2Tb4F22: A Second Example of Mixed‐Valence Fluoroterbate with a Random Distribution of Tb3+ and Tb4+ Ions.
Authors: Josse Michael , Dubois Marc , El‐Ghozzi Malika , Avignant Daniel
Published: March 2005

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A Novel Approach to Develop Dense Lanthanum Calcium Chromite Sintered Ceramics with Very High Conductivity.
Authors: Kumar A. , Devi P. Sujatha , Maiti H. S.
Published: March 2005

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Transport and Defect Mechanisms in Cuprous Delafossites. Part 1. Comparison of Hydrothermal and Standard Solid‐State Synthesis in CuAlO2.
Authors: Ingram Brian J. , Gonzalez Gabriela B. , Mason Thomas O. , Shahriari Dean Y. , Barnabe Antoine , Ko Donggeun , Poeppelmeier Kenneth R.
Published: March 2005

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Transport and Defect Mechanism in Cuprous Delafossites. Part 2. CuScO2 and CuYO2.
Authors: Ingram Brian J. , Harder Bryan J. , Hrabe Nikolas W. , Mason Thomas O. , Poeppelmeier Kenneth R.
Published: March 2005

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Tin Nanoparticle Loaded Graphite Anodes for Li‐Ion Battery Applications.
Authors: Wang Yong , Lee Jim Y. , Deivaraj Theivanayagam C.
Published: March 2005

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Preparation of Carbon‐Supported PtNi Nanoparticles via the Single Source Molecular Precursor Approach.
Authors: Deivaraj T. C. , Lee Jim Yang
Published: March 2005

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Chemical and Electrochemical Li‐Insertion into the Li4Ti5O12 Spinel.
Authors: Aldon L. , Kubiak P. , Womes M. , Jumas J. C. , Olivier‐Fourcade J. , Tirado J. L. , Corredor J. I. , Perez Vicente C.
Published: March 2005

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Photodissociation Dynamics of SOCl2.
Authors: Chichinin Alexei , Einfeld Tina S. , Gericke Karl‐Heinz , Grunenberg Joerg , Maul Christof , Schaefer Lars V.
Published: March 2005

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Synthesis, Structural Characterization, and Computanional Study of the Strong Oxidant Salt [XeOTeF5] [Sb(OTeF5)6]×SO2ClF.
Authors: Mercier Helene P. A. , Moran Matthew D. , Sanders Jeremy C. P. , Schrobilgen Gary J. , Suontamo R. J.
Published: March 2005

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Confirmation of the Semivacant Wells—Dawson Polyoxotungstate Skeleton. The Structure of [Ce{X(H4)W17O61}2]19‐ (X: P, As) Indicate the Probable Location of Internal Protons.
Authors: Belai Nebebech , Dickman Michael H. , Pope Michael T. , Contant Roland , Keita Bineta , Mbomekalle Israel‐Martyr , Nadjo Louis
Published: March 2005

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Novel Topotactic Conversion of an Organically Templated Vanadyl Phosphate Framework into Layered Structures.
Authors: Asnani Minakshi , Sharma Sanjeev , Lofland Samuel E. , Ramanujachary Kandalam V. , Buffat Philippe A. , Ramanan Arunachalam
Published: March 2005

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Syntheses, Structures, and Ion‐Exchange Properties of the Three‐Dimensional Framework Uranyl Gallium Phosphates, Cs4 [(UO2)2(GaOH)2(PO4)4] ×H2O and Cs[UO2Ga(PO4)2].
Authors: Shvareva Tatiana Y. , Sullens Tyler A. , Shehee Thomas C. , Albrecht‐Schmitt Thomas E.
Published: March 2005

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Crystalline, Mixed‐Valence Manganese Analogue of Prussian Blue: Magnetic, Spectroscopic, X‐Ray and Neutron Diffraction Studies.
Authors: Decurtins Silvio , et al. et al.
Published: March 2005

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Incorporation Transition Metal Complexes into Tetrathioarsenates(V): Syntheses, Structures, and Properties of Two Unprecedented [Mn(dien)2]n [Mn(dien)AsS4]2n×4nH2O and [Mn(en)3]2[Mn(en)2AsS4] [As3S6].
Authors: Fu Ming‐Lai , Guo Guo‐Cong , Cai Li‐Zhen , Zhang Zhang‐Jing , Huang Jin‐Shun
Published: March 2005

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A Relative of Sr4Fe6O13 with Double Perovskite Layers: Bi4Sr14Fe24O56, m = 2‐Members of a Potential Series [(Sr,Bi)2Fe4O7‐δ] [(Sr,Bi)2Fe2O6]m.
Authors: Lepoittevin C. , Malo S. , Hervieu M. , Grebille D. , Raveau B.
Published: March 2005

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A Chiral Electrophilic Selenium Reagent to Promote the Kinetic Resolution of Racemic Allylic Alcohols.
Authors: Tiecco Marcello , Testaferri Lorenzo , Santi Claudio , Tomassini Cristina , Bonini Rosaria , Marini Francesca , Bagnoli Luana , Temperini Andrea
Published: March 2005

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C2‐Symmetric Fluorous Diamines and Diimines as Ligands for Metal‐Catalyzed Asymmetric Cyclopropanation of Styrene.
Authors: Shepperson Ian , Quici Silvio , Pozzi Gianluca , Nicoletti Marcello , O'Hagan David
Published: March 2005

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Coordination Chemistry and Asymmetric Catalysis with a Chiral Diphosphonite.
Authors: van der Vlugt Jarl Ivar , Paulusse Jos M. J. , Zijp Eric J. , Tijmensen Jason A. , Mills Allison M. , Spek Anthony L. , Claver Carmen , Vogt Dieter
Published: March 2005

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Synthesis of Vicinal Diols from Various Arenes with a Heterocyclic, Amino or Carboxyl Group by Using Recombinant Escherichia coli Cells Expressing Evolved Biphenyl Dioxygenase and Dihydrodiol Dehydrogenase Genes.
Authors: Misawa Norihiko , Nakamura Ryoko , Kagiyama Yukiko , Ikenaga Hiroshi , Furukawa Kensuke , Shindo Kazutoshi
Published: March 2005

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Iridium‐Catalyzed Addition Reactions of Ethynylsilane to Quinolines and Isoquinolines Activated by Acyl Chloride.
Authors: Yamazaki Yusuke , Fujita Ken‐ichi , Yamaguchi Ryohei
Published: March 2005

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C—C Double Bond Cleavage of Linear α,β‐Unsaturated Ketones.
Authors: Lim Sung‐Gon , Jun Chul‐Ho
Published: March 2005

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Ring‐Closing Metathesis in Biphasic BMI×PF6 Ionic Liquid/Toluene Medium: A Powerful Recyclable and Environmentally Friendly Process.
Authors: Clavier Herve , Audic Nicolas , Mauduit Marc , Guillemin Jean‐Claude
Published: March 2005

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Stoichiometric and Catalytic Reductive Aldol Cyclizations of Alkynediones Induced by Stryker′s Reagent.
Authors: Chiu Pauline , Leung Sze Kar
Published: March 2005

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A New Class of Substrates for the Nucleophilic 5‐endo‐trig Cyclization, 1‐Trifluoromethylvinyl Compounds: Synthesis of Indoline and Pyrrolidine Derivatives.
Authors: Ichikawa Junji , Mori Takashi , Iwai Yu
Published: March 2005

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Rhodium(II)‐Catalyzed Inter‐ and Intramolecular Enantioselective Cyclopropanations with Alkyl‐Diazo(triorganylsilyl)acetates.
Authors: Mueller Paul , Lacrampe Fabienne
Published: March 2005

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Alanine/Chlorochromic Acid/Silica Gel: An Efficient and Selective Reagent for the Oxidation of Organic Functional Groups.
Authors: Salehi Peyman , Khodaei Mohammad Mehdi , Rostami Amin
Published: March 2005

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Expeditious α‐Hydroxylation of Ketones in Water Using Microwave Irradiation.
Authors: Lee Jong Chan , Yoo Eun Sang , Park Jin Young
Published: March 2005

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Selective Reduction of the Nitro‐Group Using Co2(CO)8—H2O.
Authors: Lee Hee‐Yoon , An Mihyun
Published: March 2005

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Fe2(SO4)3‐Mediated Coiodination of Alkenes with Acetic Acid: A Convenient and Regioselective Eco‐Friendly Preparation of β‐Iodoacetates.
Authors: de Mattos Marcio C. S. , Sanseverino Antonio Manzolillo
Published: March 2005

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Iron‐Catalyzed Dechlorination of Aryl Chlorides.
Authors: Guo Haiqing , Kanno Ken‐ichiro , Takahashi Tamotsu
Published: March 2005

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A Highly Effective (Triphenyl phosphite)palladium Catalyst for a Cross—Coupling Reaction of Allylic Alcohols with Organoboronic Acids.
Authors: Kayaki Yoshihito , Koda Takashi , Ikariya Takao
Published: March 2005

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Boron Trifluoride Etherate Mediated Dehydrogenative Nucleophilic Addition Reaction of Aliphatic Ethers in the Presence of Acetal Affording α,β‐Unsaturated Carbonyl Compounds.
Authors: Jobashi Takashi , Takano Masaomi , Hino Tetsuo , Maeyama Katsuya , Fugami Keigo , Ozaki Hiroyuki , Ogino Kenji , Yonezawa Noriyuki
Published: March 2005

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Isomerization and Ring‐Closing Metathesis for the Synthesis of 6‐, 7‐ and 8‐Membered Benzo‐ and Pyrido‐Fused N,N‐, N,O‐ and N,S‐Heterocycles.
Authors: van Otterlo Willem A. L. , Morgans Garreth L. , Khanye Setshaba D. , Aderibighe Blessing A. A. , Michael Joseph P. , Billing David G.
Published: March 2005

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A Catalytic Amount of Nickel(II) Chloride Hexahydrate and 1,2‐Ethanedithiol is a Good Combination for the Cleavage of Tetrahydropyranyl (THP) and tert‐Butyldimethylsilyl (TBS) Ethers.
Authors: Khan Abu T. , Islam Samimul , Choudhury Lokman H. , Ghosh Subrata
Published: March 2005

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An Efficient Protocol for the Preparation of MOM Ethers and Their Deprotection Using Zirconium(IV) Chloride.
Authors: Sharma G. V. M. , Reddy K. Laxma , Lakshmi P. Sree , Krishna Palakodety Radha
Published: March 2005

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Bismuth(III) Nitrate Supported onto Silica Gel, a New Catalyst for Acetylation of Alcohols and Phenols under Microwave Irradiation.
Authors: Asadolah Karim , Heravi Majid M.
Published: March 2005

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Convenient Magnesiation of Aromatic and Heterocyclic Rings Bearing a Hydroxy Group in Presence of LiCl.
Authors: Kopp Felix , Krasovskiy Arkady , Knochel Paul
Published: March 2005

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Palladium‐Catalyzed Mizoroki—Heck‐Type Reactions Using Telluronium Salts.
Authors: Hirabayashi Kazunori , Nara Yoshiko , Shimizu Toshio , Kamigata Nobumasa
Published: March 2005

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Radical Alkenylation of α‐Halo Carbonyl Compounds with Alkenylindiums.
Authors: Takami Kazuaki , Yorimitsu Hideki , Oshima Koichiro
Published: March 2005

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Sugar Recognition by Triethylbenzene‐Based C3‐Symmetric Hosts.
Authors: Cho Hong‐Kwan , Kim Hae‐Jo , Lee Kwan Hee , Hong Jong‐In
Published: March 2005

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Synthesis and Guest Binding Properties of Cyclophanes Containing Two Benzo[b]furan Rings.
Authors: Park Kwanghee Koh , Kim Sun‐Hyuk , Park Joon Woo
Published: March 2005

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