bluuebunny/crossref_metadata_2025 huggingface dataset:
Diastereoselective Synthesis of cycloSaligenyl‐Nucleosyl‐Phosphotriesters
Authors: Rios Morales Edwuin H. , Balzarini Jan , Meier Chris
Published: December 2010

A diastereoselective synthesis of cycloSal‐phosphotriesters (cycloSal=cycloSaligenyl) based on chiral auxiliaries has been developed that allows the synthesis of single diastereomers of the cycloSal‐pronucleotides. In previously described synthesis routes, the cycloSal‐compounds were always obtained as 1:1 diastereomeric mixtures that could be separated in only rare cases. However, it was shown that the diastereomers have different antiviral activity, toxicity, and hydrolysis stabilities. Here, first a chiral thiazoline derivative was used to prepare nonsubstituted and 5‐methyl‐cycloSal‐phosphotriesters in 48 and ≥95 % de (de=diastereomeric excess). However, this approach failed to give the important group of 3‐substituted cycloSal‐nucleotides. Therefore, two other chiral groups were discovered that allowed the synthesis of (RP)‐ and (SP)‐3‐methyl‐cycloSal‐phosphotriesters as well. The antiviral activity was found to be five‐ to 20‐fold different between the two individual diastereomers, which proved the importance of this approach.
From Helix to Macrocycle: Anion‐Driven Conformation Control of π‐Conjugated Acyclic Oligopyrroles
Authors: Haketa Yohei , Maeda Hiromitsu
Published: December 2010

Anion‐responsive pyrrole‐based linear receptor oligomers were newly synthesized and their anion‐driven dynamic conformation changes were investigated. Phenylene‐bridged dimers and a tetramer of dipyrrolyldiketone boron complexes as π‐conjugated acyclic anion receptors formed anion‐driven helical structures in the solid and solution states. In fact, single‐crystal X‐ray analyses of the receptor‐anion complexes exhibited various helical structures, such as [1+1]‐ and [1+2]‐type single helices and a [2+2]‐type double helix according to the lengths of oligomers and the existence of terminal aryl substituents. Anion‐binding modes and behaviors of the oligomers in solution state were also examined by 1H NMR and UV/Vis spectra along with ESI‐TOF MS. Differences in the binding modes were observed in the solid and solution states. The oligomers showed augmented anion‐binding constants and anion‐tunable electronic and optical properties in comparison with the monomer receptor. A negative cooperative effect in the tetramer was observed in the second anion binding of the [1+2]‐type single helix due to electrostatic repulsion between two anions captured in the helix. Further, an anion‐template coupling reaction from the linear dimer provided a receptor macrocycle, which was obtained as a Cl− complex with distinct electronic and optical properties. The macrocycle exhibited extremely high anion‐binding constants (>1010 m−1 in CH2Cl2) through multiple hydrogen bonding.
ChemInform Abstract: New Lanthanide Silicates Based on Anionic Silicate Chain, Layer, and Framework Prepared under High‐Temperature and High‐Pressure Conditions.
Authors: Zhao Xinguang , Li Jiyang , Chen Peng , Li Yi , Chu Qingxin , Liu Xiaoyang , Yu Jihong , Xu Ruren
Published: December 2010

The crystal structures of the new lanthanide silicates (III), (VI), and (VIII) with novel three‐dimensional frameworks are determined by single crystal XRD.
ChemInform Abstract: Synthesis and Crystal Structure of the Praseodymium Orthoborate λ‐PrBO3.
Authors: Haberer Almut , Kaindl Reinhard , Huppertz Hubert
Published: December 2010

Single crystals of the title compound are prepared by high temperature/high pressure reaction of Pr6O11, B2O3, and PrF3 in the ratio of 11:6:27 (BN crucible, 3 GPa, 800 °C, 60 min).
ChemInform Abstract: Transition Metal Complexes as Linkages for Assembly of Supertetrahedral T4 Clusters.
Authors: Wang Yu‐Hong , Zhang Ming‐Hui , Yan Yun‐Meng , Bian Guo‐Qing , Zhu Qin‐Yu , Dai Jie
Published: December 2010

(III) and (V) are members of a new type of T4 supertetrahedral compounds.
ChemInform Abstract: Utilization of Aldoses as a Carbonyl Source in Cyclocarbonylation of Enynes.
Authors: Ikeda Keiichi , Morimoto Tsumoru , Kakiuchi Kiyomi
Published: December 2010

The procedure provides a new method to prepare fused cyclopentenones.
ChemInform Abstract: Diastereoselective Synthesis of 1,2‐Disubstituted 2,3,4,5‐Tetrahydro‐1H‐3‐benzazepines by Means of the Stevens Rearrangement.
Authors: Valpuesta Maria , Ariza Manuela , Diaz Amelia , Suau Rafael
Published: December 2010

A number of novel analogues of SCH 23390 and SCH 39166 are prepared using the title reaction.
ChemInform Abstract: Facile Synthesis of Trisubstituted Allenynes by Phosphane‐Mediated Deoxygenation of 2,4‐Pentadiyn‐1‐ol.
Authors: Jiang Huanfeng , Wang Wei , Yin Biaolin , Liu Weibing
Published: December 2010

A variety of propargyl alcohols can be transformed into allenynes in moderate to good yields under mild conditions.
ChemInform Abstract: Bicyclic Phosphine‐Thiazole Ligands for the Asymmetric Hydrogenation of Olefins.
Authors: Li Jia‐Qi , Paptchikhine Alexander , Govender Thavendran , Andersson Pher G.
Published: December 2010

The new complex (I) is found to be a highly efficient catalyst for trisubstituted olefins.
ChemInform Abstract: Organocatalysis in the Stereoselective Bromohydrin Reaction of Alkenes.
Authors: Bar Sukanta
Published: December 2010

This general method for bromohydroxylation and bromomethoxylation of alkenes occurs in the presence of diphenylthiourea as a catalyst and NBS as the halogen source providing the products with excellent anti‐selectivity and yields.
ChemInform Abstract: Enantioselective Synthesis of Allylboronates Bearing a Tertiary or Quaternary B‐Substituted Stereogenic Carbon by NHC‐Cu‐Catalyzed Substitution Reactions.
Authors: Guzman‐Martinez Aikomari , Hoveyda Amir H.
Published: December 2010

Disubstituted as well as trisubstituted alkyl or aryl allylic carbonates are effective substrates.
ChemInform Abstract: New Chiral Imino‐ and Amino‐Sulfoxides as Activators of Allyl Trichlorosilane in the Asymmetric Allylation of Aldehydes.
Authors: De Sio Vincenzo , Acocella Maria Rosaria , Villano Rosaria , Scettri Arrigo
Published: December 2010

Some new sulfoxides such as (I)—(III) are prepared and their catalytic activity in asymmetric allylation of aldehydes is tested.
ChemInform Abstract: Iron‐Catalyzed Suzuki—Miyaura Coupling of Alkyl Halides.
Authors: Hatakeyama Takuji , Hashimoto Toru , Kondo Yoshiyuki , Fujiwara Yuichi , Seike Hirofumi , Takaya Hikaru , Tamada Yoshinori , Ono Teruo , Nakamura Masaharu
Published: December 2010

A novel iron‐catalyzed Suzuki—Miyaura coupling of nonactivated alkyl halides with arylboron compounds is developed.
ChemInform Abstract: Reversible Aqueous Metathesis Reactions for Potential Application in Dynamic Combinatorial Chemistry.
Authors: Hunter Luke , Condie Glenn C. , Harding Margaret M.
Published: December 2010

Allyl sulfides and alkenes undergo reversible olefin metathesis reaction in the presence of Hoveyda—Grubbs catalyst.
ChemInform Abstract: Selective Palladium‐Catalyzed Aminocarbonylation of Aryl Halides with CO and Ammonia.
Authors: Wu Xiao‐Feng , Neumann Helfried , Beller Matthias
Published: December 2010

A new, straightforward, and general access to primary aryl and heteroaryl amides is reported.
ChemInform Abstract: Catalytic Stereoselective Alkene Aziridination with Sulfonimidamides.
Authors: Robert‐Peillard Fabien , Di Chenna Pablo H. , Liang Chungen , Lescot Camille , Collet Florence , Dodd Robert H. , Dauban Philippe
Published: December 2010

Cu‐catalyzed treatment of olefins with the chiral substrate (I) allows stereoselective access to aziridines.
ChemInform Abstract: 2‐(p‐Tolylsulfinyl)benzyl Halides as Efficient Precursors of Optically Pure trans‐2,3‐Disubstituted Aziridines.
Authors: Arroyo Yolanda , Meana Angela , Sanz‐Tejedor M. Ascension , Alonso Ines , Garcia Ruano Jose Luis
Published: December 2010

Base‐mediated treatment of the benzyl iodide (I) with N‐sulfinylaldimines allows a highly efficient access to optically pure trans‐2,3‐disubstituted aziridines.
ChemInform Abstract: Highly Stereoselective Synthesis of trans‐4‐Trifluoromethylsulfonyl‐2,3‐dihydrofurans from Arsonium Ylides and (E)‐α‐Trifluoromethylsulfonyl‐α,β‐unsaturated Ketones.
Authors: Chen Zhenqi , Zhang Jiaping , Chen Jie , Deng Hongmei , Shao Min , Zhang Hui , Cao Weiguo
Published: December 2010

The reaction tolerates a wide range of functional groups at the arsonium ylides and a variety of aromatic and furanyl substituents at the α,β‐unsaturated ketones and proceeds with complete stereoselectivity.
ChemInform Abstract: Lewis Acid Catalyzed Rapid Synthesis of 5‐Hydroxy‐benzo[g]indole Scaffolds by a Modified Nenitzescu Reaction.
Authors: Borthakur Moyurima , Gogoi Shyamalee , Gogoi Junali , Boruah Romesh C.
Published: December 2010

The preparation of the pharmacologically important title compounds (III) (12 examples) involves a Michael addition of acetophenone derivatives to naphthoquinone followed by aza cyclization using urea as source of ammonia.
ChemInform Abstract: One‐Pot Copper‐Catalyzed Synthesis of N‐Functionalized Pyrazoles from Boronic Acids.
Authors: Beveridge Ramsay E. , Fernando Dilinie , Gerstenberger Brian S.
Published: December 2010

The method allows a straightforward synthesis of a broad spectrum of highly substituted, synthetically important pyrazole structures (18 examples),
ChemInform Abstract: 1,1‐Dibromo‐1‐alkenes as Valuable Partners in the Copper‐Catalyzed Direct Alkynylation of Azoles.
Authors: Berciano Beatriz Pacheco , Lebrequier Sabrina , Besselievre Francois , Piguel Sandrine
Published: December 2010

A variety of substituted oxazoles, benzoxazole, benzothiazole, triazole and purine are applied in the reaction with the aromatic, heteroaromatic and olefinic vinyl bromides to afford the alkynylation products with generally moderate to high yields.
ChemInform Abstract: 4‐Isoxazolines and Pyrroles from Allenoates.
Authors: Lopes Susana M. M. , Nunes Claudio M. , Pinho e Melo Teresa M. V. D.
Published: December 2010

By choosing the conditions for the reaction of nitrones, generated in situ from allenoates, with alkynes the isoxazoline or pyrrole products are prepared.
ChemInform Abstract: The Facile One‐Pot Synthesis of N‐Imidoylbenzotriazoles via a Beckmann Rearrangement of Ketoximes.
Authors: Pi Hong‐Jun , Liu Li‐Feng , Jiang Shan‐Shan , Du Wenting , Deng Wei‐Ping
Published: December 2010

The reaction proceeds via the formation of oxime sulfonates from oximes and MesCl, which upon treatment with benzotriazole generates the desired products with high yields.
ChemInform Abstract: Synthesis of [3.3.1] Bicyclic Compounds by a Broensted Acid Catalyzed Double Intramolecular Michael Addition.
Authors: Mendoza Abraham , Pardo Pilar , Rodriguez Felix , Fananas Francisco J.
Published: December 2010

The target compounds can be easily transformed into cyclooctadiene derivatives.
ChemInform Abstract: Synthesis of 3‐Oxa‐ and 3‐Azabicyclo[4.1.0]heptanes by Gold‐Catalyzed Cycloisomerization of Cyclopropenes.
Authors: Miege Frederic , Meyer Christophe , Cossy Janine
Published: December 2010

The reaction is applied to a wide range of racemic and chiral stereodefined cyclopropenes.
ChemInform Abstract: Base‐Promoted One‐Pot Tandem Reaction of 3‐(1‐Alkynyl)chromones under Microwave Irradiation to Functionalized Amino‐Substituted Xanthones.
Authors: Liu Yang , Huang Liping , Xie Fuchun , Hu Youhong
Published: December 2010

The derivative (IIId) can be coupled with aldehydes to afford fused analogues like (V).
ChemInform Abstract: Iridium‐Catalyzed Annulation of N‐Arylcarbamoyl Chlorides with Internal Alkynes.
Authors: Iwai Tomohiro , Fujihara Tetsuaki , Terao Jun , Tsuji Yasushi
Published: December 2010

The reaction is catalyzed by [IrCl(cod)]2 in the presence of the additional cyclooctadiene in catalytic or equimolar amount and leads to a wide range of bi‐, tri‐ and tetracyclic quinoline derivatives in high yields.
ChemInform Abstract: Asymmetric Broensted Acid Catalysis in Aqueous Solution.
Authors: Rueping Magnus , Theissmann Thomas
Published: December 2010

Employing the principle of hydrophobic hydration, this reaction represents an example of a non‐covalent asymmetric induction conducted in a pure aqueous reaction solvent.
ChemInform Abstract: Ionic Diamine Rhodium Complex Catalyzed Hydroaminomethylation of 2‐Allylanilines.
Authors: Okuro Kazumi , Alper Howard
Published: December 2010

The product distribution depends on the partial pressure of CO and H2 and on the nature of the solvent.
ChemInform Abstract: Nickel‐Catalyzed C—O Activation of Phenol Derivatives with Potassium Heteroaryltrifluoroborates.
Authors: Molander Gary A. , Beaumard Floriane
Published: December 2010

The reaction is general and is applied to a wide range of aromatic and heteroaromatic mesylates and aromatic and heteroaromatic trifluoroborates tolerating many functional groups.
ChemInform Abstract: One‐Step Synthesis of 1‐(4,5‐Diphenylpyrimidin‐2‐yl)thiourea.
Authors: Han Wen‐Yong , Zhang Zun‐Ting , Zhang Ying‐Chun , Xue Dong , Li Gang
Published: December 2010

Cyclocondensation of isoflavones (I) and (IV) with amidinothiourea (II) leads to the formation of previously unknown (diphenylpyrimidinyl)thioureas (III) and (V).
ChemInform Abstract: Dynamic Kinetic Asymmetric Synthesis of Substituted Pyrrolidines from Racemic Cyclopropanes and Aldimines: Reaction Development and Mechanistic Insights.
Authors: Parsons Andrew T. , Smith Austin G. , Neel Andrew J. , Johnson Jeffrey S.
Published: December 2010

The choice of the N‐protecting group (2‐methoxybenzyl) is crucial.
ChemInform Abstract: Radical Addition of Arylboronic Acids to Various Olefins under Oxidative Conditions.
Authors: Dickschat Arne , Studer Armido
Published: December 2010

The reaction of aryl radicals, generated from the boronic acids, with olefins proceeds using Mn(OAc)3 via double olefin addition and aromatic substitution to provides tetrahydronaphthalene derivatives with moderate yields and diastereoselectivities under the inert atmosphere [cf.
ChemInform Abstract: Dolabellane Diterpene and Three Cycloartane Glycosides from Thalictrum squarrosum.
Authors: Yoshimitsu Hitoshi , Miyashita Hiroyuki , Nishida Makiko , Mineno Tomoko , Nohara Toshihiro
Published: December 2010

The plant Thalictrum squarrosum has been used in the traditional Chinese medicine as an antacid.
ChemInform Abstract: Highly α‐Selective Hydrolysis of α,β‐Epoxyalcohols Using Tetrabutylammonium Fluoride.
Authors: Mukerjee Purba , Abid Mohammed , Schroeder Frank C.
Published: December 2010

The ring opening proceeds at the normally believed disfavored α‐position leading to arabino‐ or lyxo‐configured triols with the full retention of the stereoconfiguration.
ChemInform Abstract: Stereoselective Synthesis of 2‐O‐MEM‐2,3‐unsaturated‐β‐O‐glycosides and Elaboration to Useful Synthetic Tools.
Authors: Di Bussolo Valeria , Fiasella Annalisa , Frau Ileana , Favero Lucilla , Crotti Paolo
Published: December 2010

The synthesis of the title compounds proceeds via alcoholytic ring opening of an epoxide, generated from the novel intermediate (II).
ChemInform Abstract: Crotalionosides A‐C, Three New Megastigmane Glucosides, Two New Pterocarpan Glucosides and a Chalcone C‐Glucoside from the Whole Plants of Crotalaria zanzibarica.
Authors: Shitamoto Junko , Matsunami Katsuyoshi , Otsuka Hideaki , Shinzato Takakazu , Takeda Yoshio
Published: December 2010

Crotalionoside A (Ia), B (Ib), C (II), two pterocarpane glucosides (III) and a chalcone C‐glucoside (IV) are isolated from the MeOH exract of the leaves of the title herb.
ChemInform Abstract: Alsmaphorazines A (Ia) and B (Ib), Novel Indole Alkaloids from Alstonia pneumatophora.
Authors: Koyama Koichiro , Hirasawa Yusuke , Nugroho Alfarius Eko , Hosoya Takahiro , Hoe Teh Chin , Chan Kit‐Lam , Morita Hiroshi
Published: December 2010

Alsmaphorazine A (Ia) inhibits the NO production in LPS‐stimulated J774.1 without affecting the cell viability (IC50 49.2 μM).
ChemInform Abstract: A New Dimeric Alkaloid from the Leaf of Psychotria calocarpa.
Authors: Zhou Hua , He Hong‐Ping , Wang Yue‐Hue , Hao Xiao‐Jiang
Published: December 2010

Psychotriasine(I), composed of two tryptamine‐related moieties containing one indoline and one 1H‐indole chromophore, represents the first example of a dimeric tryptamine‐related alkaloid that contains a free N‐methyltryptamine unit in the molecule.
ChemInform Abstract: Electronically Coupled MM Quadruple Bonded Complexes of Molybdenum and Tungsten
Authors: Chisholm Malcolm H.
Published: December 2010

Review: 52 refs.
ChemInform Abstract: Privileged Chiral Catalysts in Asymmetric Morita—Baylis—Hillman/Aza‐Morita—Baylis—Hillman Reaction
Authors: Wei Yin , Shi Min
Published: December 2010

Review: 70 refs.
ChemInform Abstract: Bifunctional Organometallic Catalysis and Reactivity Using Heterocyclic Phosphines and Metalated Heterocycles
Authors: Grotjahn Douglas B.
Published: December 2010

Review: 76 refs.
ChemInform Abstract: Green Functional Group Transformations by Supported Ruthenium Hydroxide Catalysts
Authors: Yamaguchi Kazuya , Mizuno Noritaka
Published: December 2010

Review: ca. 100 refs
ChemInform Abstract: Biofuels
Authors: Varfolomeev S. D. , Efremenko E. N. , Krylova L. P.
Published: December 2010

Review: 260 refs.
ChemInform Abstract: Inositol Polyphosphates, Diphosphoinositol Polyphosphates and Phosphatidylinositol Polyphosphate Lipids: Structure, Synthesis, and Development of Probes for Studying Biological Activity
Authors: Best Michael D. , Zhang Honglu , Prestwich Glenn D.
Published: December 2010

Review: 330 refs.
ChemInform Abstract: Steroid‐Based Anion Receptors and Transporters
Authors: Brotherhood Peter R. , Davis Anthony P.
Published: December 2010

Review: 60 refs.
ChemInform Abstract: Anion Recognition in Water
Authors: Kubik Stefan
Published: December 2010

Review: 66 refs.
ChemInform Abstract: Tailoring Cyclic Polyamines for Inorganic/Organic Phosphate Binding
Authors: Bazzicalupi Carla , Bencini Andrea , Lippolis Vito
Published: December 2010

Review: 75 refs.
ChemInform Abstract: Boron‐Based Anion Receptors as Sensors
Authors: Galbraith Ewan , James Tony D.
Published: December 2010

Review: 116 refs.
ChemInform Abstract: Physical Methods in Organophosphorus Chemistry
Authors: Slinn Robert N.
Published: December 2010

Review: 196 refs.
ChemInform Abstract: Morphological Changes of Injected Calcium Phosphate Cement in Osteoporotic Compressed Vertebral Bodies
Authors: Heo D. H. , Cho Y. J. , Sheen S. H. , Kuh S. U. , Cho S. M. , Oh S. M.
Published: December 2010

Review: 25 refs.
Entrepreneurial Architecture: A Blueprint for Entrepreneurial Universities
Authors: Nelles Jen , Vorley Tim
Published: December 2010

Universities are increasingly challenged to become more socially and economically relevant institutions. While this phenomenon has prompted a growing literature documenting the evolution of the contemporary university, it remains at once both too broadly conceptualized and overly fragmented. Thus, while these literatures continue to grow, they remain largely undertheorized. This paper employs the concept of “entrepreneurial architecture” as a more nuanced perspective to understand this new mission of contemporary universities. This newly emphasized mission has been politically driven through public policy and funding. While providing a theoretical contribution to the study of the entrepreneurial university/university entrepreneurship, the paper also has broader implications for institutions and policymakers as a pragmatic approach. Copyright © 2010 ASAC. Published by John Wiley & Sons, Ltd.
Improved Inhibitors of Trypanothione Reductase by Combination of Motifs: Synthesis, Inhibitory Potency, Binding Mode, and Antiprotozoal Activities
Authors: Eberle Christian , Lauber Birgit Sophia , Fankhauser Daniel , Kaiser Marcel , Brun Reto , Krauth‐Siegel R. Luise , Diederich François
Published: December 2010

Trypanothione reductase (TR) is an essential enzyme in the trypanothione‐based redox metabolism of trypanosomatid parasites. This system is absent in humans and, therefore, offers a promising target for the development of selective new drugs against African sleeping sickness and Chagas' disease. Over the past two decades, a variety of nonpeptidic small‐molecule ligands of the parasitic enzyme were discovered. A current goal is to decipher the binding mode of these known inhibitors in order to optimize their structures. We analyzed the binding mode of recently reported 1‐(1‐(benzo[b]thiophen‐2‐yl)cyclohexyl)piperidine (BTCP) analogues using computer modeling methods. This led us to conclude that the analogues occupy a different region of the active site than the diaryl sulfide‐based class of inhibitors. A combination of the two motifs significantly increased affinity for the enzyme compared to the respective parent compounds. The newly synthesized conjugates exhibit Kic values for TR as low as 0.51±0.1 μM and high selectivity for the parasitic enzyme over the related human glutathione reductase (hGR), as was predicted by our molecular modeling studies. In vitro studies showed IC50 values in the low micromolar to submicromolar range against Trypanosoma brucei rhodesiense, often in combination with low cytotoxicity against mammalian cells. Interestingly, even stronger activities were found against Plasmodium falciparum.
Waste‐Derived Bioorganic Substances for Light‐Induced Generation of Reactive Oxygenated Species
Authors: Bianco Prevot Alessandra , Avetta Paola , Fabbri Debora , Laurenti Enzo , Marchis Tatiana , Perrone Daniele G. , Montoneri Enzo , Boffa Vittorio
Published: December 2010

Urban waste‐derived bioorganic substances (UW‐BOS) have shown promise as chemical auxiliaries for a number of technological applications in the chemical industry and in environmental remediation. In this study, the application of these substances in the photodegradation of organic pollutants is addressed. The experimental work is specifically focused on the photolysis mechanism promoted by AC8, a UW‐BOS isolated from a 2:1 w/w mixture of food and green residues, composted for 110 days, using 4‐chlorophenol (4‐CP) as probe molecule. The production of ⋅OH and the 1O2 is monitored by EPR spectroscopy. The correlation between radical species evolution and photodegradation of 4‐CP is investigated. The effect of 1O2 and ⋅OH scavengers on the 4‐CP degradation process is also checked. The results suggest that the role of these species in the photodegradation of 4‐CP depends on AC8 concentration. AC8 is thereby proven to be a photosensitizer for applications in environmental remediation. The results on AC8 further support the use of urban bio‐waste as a versatile source of chemical auxiliaries of biological origin for use in diversified applications.
Pharmacophore inference and its application to computational drug discovery
Authors: Wallach Izhar
Published: December 2010

Pharmacophores are fundamental tools in the process of rational drug discovery. Pharmacophores are associated with binding sites of proteins and characterize the arrangement of chemical and physical features that govern the modes of interactions of different ligands within the binding sites. Methods designed to infer pharmacophores computationally have been successfully applied in drug discovery pipelines. Virtual high‐throughput screening (HTS), lead optimization, and de novo drug design are just a few areas in which pharmacophores are actively used. This review surveys different computational methods to elucidate pharmacophores and discuss their utilization in drug discovery applications. Drug Dev Res 72: 17–25, 2011. © 2010 Wiley‐Liss, Inc.
Mechanistic disease modeling as a useful tool for improving CNS drug research and development
Authors: Geerts Hugo
Published: December 2010

Despite tremendous advances in the basic understanding of CNS diseases, successful clinical drug development in psychiatry and neurology has been limited, putting huge pressure on remaining CNS R&D programs in pharmaceutical companies. In this report, it is proposed that re‐engineering parts of the pharmaceutical Research and Development process by integrating complex modeling and simulation approaches, similar to the aerospace and micro‐electronics industry, has the potential to increase the clinical predictability of animal models and to reduce the attrition rate in clinical drug development. This report will present top‐down Mechanistic Disease Modeling approaches in relation to bottom‐up Systems Biology with specific emphasis on CNS drug R&D. Both combine basic research data with human clinical outcome, but in contrast to System Biology that generically models intracellular pathways and protein‐protein networks, Mechanistic Disease Modeling models the emergent properties of neuronal cell firing activity in large interacting neuronal networks. Such an outcome is much closer to physiological and behavioral processes that drive actual clinical scales. Also illustrated here are some practical applications in the area of Alzheimer's disease and schizophrenia for CNS Research and Development, such as guiding multitarget drug discovery, evaluating both the harmful and beneficial off‐target human effects of candidate drugs, as well as exploring the effect of co‐medications and functional genotypes on the candidate drug efficacy and sensitivity analysis for responder identification. Drug Dev Res 72: 66–73, 2011. © 2010 Wiley‐Liss, Inc.
Molecular similarity and diversity approaches in chemoinformatics
Authors: Khanna Varun , Ranganathan Shoba
Published: December 2010

Combinatorial synthesis and high‐throughput screening (HTS) are playing increasingly important roles in chemoinformatics. This review gives an overview of the strategies available for library design and compound selection. Although the traditional approach of diversity‐oriented library design continues to be an important criterion in lead generation, nevertheless, pharmacokinetic properties are also widely recognized in compound selection for generating lead libraries. We summarize all the current molecular similarity and diversity methods employed in chemoinformatics to design lead libraries for in silico drug discovery. We have also included a section on popular molecular descriptors and similarity/diversity coefficients. Recent developments, include multi‐optimization design algorithms to select suitable molecules, such as Pareto‐optimization, representing a compromise between several competing objectives, have also been discussed in the context of virtual screening and library design. Drug Dev Res 72: 74–84, 2011. © 2010 Wiley‐Liss, Inc.
Is conformational sampling of drug‐like molecules a solved problem?
Authors: Chen I‐Jen , Foloppe Nicolas
Published: December 2010

With computational tools, it has become straightforward to obtain three‐dimensional (3D) conformers for drug‐like molecules, even for large numbers of compounds. This underpins many downstream molecular modeling activities. We summarize the principles behind the methods, explain why considering multiple conformers per compound is necessary, and discuss the tests used to assess the computed conformers. It leads us to suggest that conformational sampling per se is essentially a solved problem for small drug‐like compounds, and that efforts should focus on improving the energy models. Drug Dev Res 72: 85–94, 2011. © 2010 Wiley‐Liss, Inc.
Fragment and protein simulation methods in fragment based drug design
Authors: Klon Anthony E. , Konteatis Zenon , Meshkat Siavash N. , Zou Jinming , Reynolds Charles H.
Published: December 2010

Fragment‐based drug design (FBDD) has become an important and successful approach to drug discovery. In this review, we discuss two classes of simulation technologies that we routinely employ as part our of computational FBDD efforts. The first class centers on simulation methods in torsion space to develop high‐quality protein models suitable for FBDD. These algorithms allow for fast molecular dynamics and modal Monte Carlo simulations. The torsion space dynamics techniques have been applied to develop models for the bound conformations of a variety of proteins including the HIV‐1 protease, p38 MAP kinase, and the 5′‐AMP‐activated protein kinase. The second class of simulations is comprised of the Grand Canonical Monte Carlo and systematic sampling methods, which are used to explore the interactions of individual fragments with the protein target. Previously published validation studies for the binding of molecules to T4 lysozyme and the p38 MAP kinase are discussed. We review previous work to computationally assemble whole molecules from fragment binding data, a potential bottleneck in the FBDD approach. One effect of the fragment simulations is that an approximate value for the free energy of binding of a given molecule with the protein may be computed from the fragment simulations, with an estimated standard error approaching 1 kcal/mol, which is comparable to the performance of a variety of other methods reported in the literature. Drug Dev Res 72:130–137, 2011.  © 2010 Wiley‐Liss, Inc.
In silico subtractive genomics for target identification in human bacterial pathogens
Authors: Barh Debmalya , Tiwari Sandeep , Jain Neha , Ali Amjad , Santos Anderson Rodrigues , Misra Amarendra Narayan , Azevedo Vasco , Kumar Anil
Published: December 2010

Target identification is the first step in the drug and vaccine discovery process;in silicosubtractive genomics is widely used in this process. Using this approach, in recent years, a large number of targets have been identified for bacterial pathogens that are either drug resistant or for which no suitable vaccine is available; most such reports concern a specific pathogen. Thein silicomethod reduces the time as well as the cost of target screening. Although a powerful technique that can be applied to a wide range of pathogens, there are many pitfalls in the analysis and interpretation of the data. We review this approach, including targets that have been identified with this technique and various other aspects, including advantages and disadvantages. We also discuss our own experiences using this technology. Drug Dev Res 72: 162–177, 2011. © 2010 Wiley‐Liss, Inc.
Scientific literature mining for drug discovery: a case study on obesity
Authors: Rajpal Deepak K. , Kumar Vinod , Agarwal Pankaj
Published: December 2010

Obesity is currently an epidemic that affects almost 15% of the global adult population. The complex metabolic processes involved in energy homeostasis, which are regulated by signals from multiple sources, present a challenging problem for drug discovery. In the current analysis, we present bibliometric and data‐mining approaches based on categorizing literature according to medical subject headings (MeSH) to examine “hot” and “cold” trends, which indicate emerging areas of scientific research within obesity. This trend analysis corrects for increase in the overall size of obesity publications. A “hot” trend within obesity research is a concept on which publications are growing statistically faster than the background rise in obesity publications. In addition to growth in the number of publications associated with gastrointestinal weight‐loss surgery and clinical studies in obesity, there is increasing research in the fields of adipose tissue, islet cell, and enteroendocrine biology as observed by a significant increase in the number of publications during the period 2005–2009, when compared to 2000–2004. However, the number of the publications in the area of hypothalamic and nervous system research in obesity appears to be cooling off. Extending the same concept of trend analysis to genes, we present a list of obesity‐related genes that show “hot” trends suggesting emerging molecular mechanisms for obesity. Finally, we present a list of key scientific publications associated with obesity, one from each year over the last decade, which have the highest number of citations. Drug Dev Res 72: 201–208, 2011. © 2010 Wiley‐Liss, Inc.
Mapping drug architecture by MoStBioDat: rapid screening of intramolecular hydrogen bonded motifs in catechols
Authors: Bak Andrzej , Magdziarz Tomasz , Kurczyk Agata , Polanski Jaroslaw
Published: December 2010

Computer‐assisted simulations are important for present‐day chemical investigations, producing large amount of structural data. In molecular design, we calculate molecular descriptors for factual or virtual structures in chemical space attempting to predict their chemical properties and evaluate potential biological effects. In the current study, we investigated the application of the MoStBiodat software platform for the extensive screening of spatial arrangement and conformational analysis locating intramolecular hydrogen‐bonded motifs in catechols. We compared the experimentally determined structural data to those that are simulated using virtual structural data. The relevant topological incoherence among structural and molecular data coming from different sources is thus revealed. Drug Dev Res 72: 209–218, 2011.  © 2010 Wiley‐Liss, Inc.
Heterogeneous Catalytic Reactions “On Water” by Using Stable Polymeric Alkynylcopper(I) Pre‐Catalysts: Alkyne/Azide Cycloaddition Reactions
Authors: Buckley Benjamin R. , Dann Sandra E. , Heaney Harry , Stubbs Emma C.
Published: December 2010

Dinuclear alkynylcopper(I) complexes have been found to be the active pre‐catalysts in copper‐catalysed cycloaddition of azides and terminal alkynes (CuAAC). These copper(I) ladderane polymers are used in “on water” CuAAC reactions, with loadings as low as 1 mol‐%.
Population dynamics of methanogens during acidification of biogas fermenters fed with maize silage
Authors: Munk Bernhard , Bauer Christoph , Gronauer Andreas , Lebuhn Michael
Published: December 2010

Limitations in the supply of essential trace elements for methanogenic Archaea can arise in biogas production from renewable resources in flow‐through systems particularly when no manure is added. Without compensating supplementation, primarily Co and Na+ can become limiting in long‐term mono‐digestion of maize silage at threshold values of ca. 0.03 and 10 mg/L, respectively. These deficiencies apparently triggered process acidification. Using molecular biological methods (PCR‐SSCP and quantitative real‐time PCR), microbial population dynamics were monitored qualitatively and quantitatively at distinct stages during the experiments, investigating mcrA/mrtA, coding for a subunit of the key enzyme of methanogenesis. An exponential correlation between mcrA/mrtA copies and methane productivity was obtained. Members of obligatley acetoclastic Methanosaetaceae were found only at low acetate concentrations (below 1 g/L). At organic loading rates>1 g volatile solids/(L×d) and without acidification symptoms, obligately hydrogenotrophic (oh) Methanobacteriales and versatile Methanosarcinaceae were dominating, and an abundance of up to 1010 methanogens per mL fermenter content was determined. In the acidified process, however, ca. 4 orders of magnitude less methanogens were detected, and Methanomicrobiales (oh), more specifically Methanospirillum hungatei or Methanoculleus spp., were dominating. Species diversity at the DNA level was highest at efficient process performance without stress symptoms and at a relatively low organic loading rate (1–2 g volatile solids/(L×d)). According to the quantitative real‐time PCR data, the process was not sustained below an availability of 10−8 to 10−9 μg Co per methanogenic cell.
Operational modeling of a sustainable gas supply chain
Authors: Bekkering Jan , Broekhuis Ton A. , van Gemert Wim J. T.
Published: December 2010

Biogas production from codigestion of cattle manure and biomass can have a significant contribution to a sustainable gas supply when this gas is upgraded to specifications prescribed for injection into the national gas grid and injected into this grid. In this study, we analyzed such a gas supply chain in a Dutch situation. A model was developed with which the cost price per m was presented as a function of scale level (m/hr). The hypothesis that transport costs increase with increasing scale level was confirmed although this is not the main factor influencing the cost price for the considered production scales. For farm‐scale gas supply chains (approximately 150–250 m/h green gas), a significant improvement is expected from decreasing costs of digesters and upgrading installations, and efficiency improvement of digesters. In this study also practical sustainability criteria for such a supply chain were investigated. For this reason, the digestate from the digester should be used as a fertilizer. For larger scale levels, the number of transport movements and energy use in the supply chain seem to become a limiting factor with respect to sustainability.
Energy balance of a two‐phase anaerobic digestion process for energy crops
Authors: Zielonka Simon , Lemmer Andreas , Oechsner Hans , Jungbluth Thomas
Published: December 2010

This article deals with the digestion of energy crops in a two‐phase biogas process based on an anaerobic leach‐bed reactor combined with an anaerobic filter. The biogas process is a microbiological conversion of biomass into methane and carbon dioxide. This process is carried out by different microorganisms and can be divided into four steps which normally take place in only one digester. To be able to digest difficult energy crops by mono‐digestion and to meet the different needs of the several bacteria, which take part in the four‐step process of the methane production, the process was divided into two phases: (i) an anaerobic batch leach‐bed phase, where the leachate was produced and (ii) an anaerobic filter, where the organic fraction of the leachate was converted into biogas. Considering the results of the experiments, the two‐phase digestion of energy crops exhibited stable digestion behavior. No biological imbalance of the process, e.g. due to a sudden change of substrate, was detected either in the leach bed or in the anaerobic filter. Variation in suitability for two‐phase fermentation with an anaerobic batch leach‐bed reactor was observed for various substrates. The different substrates varied in their influence on acid formation and concentration as well as an influence on the course of the pH value.Therefore, an effect on the distribution of energy to the phases could be observed.
Combined mechanical enzymatic pretreatment for an improved substrate conversion when fermenting biogenic resources
Authors: Ellenrieder Johannes , Schieder Doris , Mayer Wolfgang , Faulstich Martin
Published: December 2010

Anaerobic digestion of lignocellulosic fractions of biogenic resources in biogas plants performs slowly and incompletely leaving fibrous residues. Thus, this work focused on a combined mechanical and enzymatic pretreatment of maize and grass silage to achieve a partial hydrolysis of the substrates and a higher biogas yield. To get an intensive disintegration, the refiner technology was used. For subsequent enzymatic hydrolysis, several commercially available enzyme preparations were tested, and their effect on solid substrate degradation, viscosity and pumpability of the suspensions was investigated. Experiments were performed in laboratory fermenters as well as in pilot scale (1 m3) at a biogas plant. The most promising enzymatic pretreatments with respect to their effect on the fermentation process were tested in 20‐L semicontinuously operated laboratory scale digesters. On maize silage, a dry mass (DM) reduction up to 40% with an amylase‐based preparation was achieved. Equal results were obtained with a cellulase preparation on grass silage. Yet, due to the high demand of enzyme, the economical feasibility was doubtful. Laboratory semicontinuous fermentation experiments, therefore, were performed on maize silage. At a substrate load of 1.5–2.0 kg organic DM (oDM)/(m3 d), a good biogas yield of about 0.7 LN (liter norm)/g oDM and methane yield of about 0.4 LN/g oDM were obtained. However, at the chosen fermentation conditions at 37°C and 25 days hydraulic retention time, no positive effect of the enzymatic prehydrolysis on the biogas yield of fine grinded substrate could be established.
Factors controlling sediment yield in China's Loess Plateau
Authors: Xin Zhongbao , Yu Xinxiao , Lu X. X.
Published: December 2010

The Loess Plateau in China, an area with some of the highest sediment yield in the world, contributes predominant proportion of the sediments found in the Yellow River. We examined sediment yield and its control variables in the plateau based on a multi‐year dataset from 180 gauging stations in areas varying in size from 102 to 104 km2. Various morphometric, hydrologic, climatic and land cover variables were estimated in order to understand and predict the variations in sediment yield. The results show a spatial pattern of sediment yield exhibiting an obvious zonal distribution and a coupling between precipitation and vegetation cover that fits the Langbein–Schumm law. A critical threshold of precipitation and vegetation cover was observed among the relationships of sediment yield and precipitation/vegetation cover. A multiple regression equation with three control variables, i.e. vegetation cover, percentage of cultivated loess and annual runoff, explains 65% of the total variation in sediment yield. For the loess dominated basins, where the cultivated loess accounts for more than 60% of the total area, annual runoff was the dominant variable, explaining 76% of the observed variation in sediment yield. The established equation could be a valuable tool for predicting total sediment yield in the Loess Plateau. Copyright © 2010 John Wiley & Sons, Ltd.
ICI mitigation and diversity gain for OFDM systems in time‐varying multipath fading channels
Authors: Chen Shaoping , Dai Guangfa , Rao Wengui
Published: December 2010

In orthogonal frequency division multiplexing (OFDM) systems, channels' rapid variations cause intercarrier interference (ICI), resulting in performance degradation. Although ICI caused by channels' variations makes the reliable signal detection difficult, it also introduces Doppler diversity, which can be exploited to improve the system performance. In this paper, an ICI mitigation and Doppler‐multipath diversity technique based on fractionally sampling at the receiver is proposed for OFDM systems over time‐varying multipath fading channels. To reduce the computation burden of minimum mean‐square error (MMSE) equaliser with successive detection (SD), an efficient algorithm is presented by using the property of matrix decomposition. The algorithm avoids direct or recursive computation of matrix inversion, thereby reducing the computation complexity and ensuring numerical stability. Simulations show that the proposed techniques can collect both Doppler and multipath diversity gains with moderate complexities. Copyright © 2010 John Wiley & Sons, Ltd.
The present status of the NATM in contracts – tendering / Gegenwart der NÖT im Bauvertrag – Ausschreibung
Authors: Herdina Johann
Published: December 2010

Although the expert circle of NATM users has demonstrated that they are technically capable of using the NATM successfully under almost any conditions, there are repeated difficulties concerning the handling of contracts. The construction contract with flexible provisions regarding classification and the invoicing of common costs as the basis for a collaborative project implementation has been subjected to extreme stress recently by various construction companies. The expectations of the contractor concerning tendering are not identical to the tender documents currently in use in the market. The article explains the differences and proposes a way of overcoming such problems in the future. The author maintains that in his view three main points could lead to an improvement of contract implementation:

· The appointment of contractors only for a plausible total price,

· Consultants as a partner of the client and

· The provision of a behaviour code for NATM construction measures.

Während die Fachgemeinschaft der NÖT‐Anwender bewiesen hat, dass sie technisch in der Lage ist, bei fast allen Randbedingungen die NÖT erfolgreich anzuwenden, ergeben sich auf der vertraglichen Seite immer wieder Abwicklungsschwierigkeiten. Der flexible Bauvertrag bezüglich Klassifizierung und Gemeinkostenabrechnung als Grundlage für eine partnerschaftliche Projektabwicklung zwischen Bauherren und Auftragnehmern wurde in letzter Zeit bei verschiedenen Baumaßnahmen äußerst strapaziert. Die Erwartungshaltung des Auftragnehmers zur Ausschreibung ist nicht ident mit den aktuell am Markt befindlichen Ausschreibungsunterlagen. Im Artikel werden die Unterschiede dargelegt, und es wird versucht, einen Weg aufzuzeigen, wie in Zukunft die Probleme überwunden werden können, wobei der Autor festhält, dass aus seiner Sicht drei wesentliche Punkte zur Verbesserung der vertraglichen Abwicklung führen können:

· Beauftragung von Firmen nur zur einem plausiblen Gesamtpreis,

· Planer als Partner des Bauherrn und

· Festlegen eines Verhaltenskodex für NÖT‐Baumaßnahmen.
The present status of the NATM in contracts – construction / Gegenwart der NÖT im Bauvertrag – Ausführung
Authors: Sachs Manfred
Published: December 2010

Since the start of the worldwide success of the new Austrian tunnelling method in the middle 1960s, not only our society but also tunnelling have experienced fundamental change in many areas. The increasing influence of law and bureaucracy have led to the situation where today's tunnelling contracts have become extensive, intricate and disputed compared to former times. Collaboration as among colleagues has been replaced by the collective shedding of responsibility. The creation of tender documents, processing of the tenders and the construction of the works are all subject to the principle of lowest price, which is forced on the clients by law. Tender documents often contain errors and the tenders are not seldom speculative and under‐priced. This inevitably leads to disputes during the construction phase.

The NATM is, however, a construction method, which needs flexible contract arrangements between partners, competent professionals, slender structures and short decision routes on the tunnel site in order to fulfil its entire potential. In contrast to this, tunnel sites today are often characterised by senseless administrative work and irrelevant reciprocal controls. The rapid development and increasing automation of machines and the development of construction materials still offer great chances for the NATM in the future. The future of the tendering and award arrangements, however, should be reconsidered and the training of managers capable of making decisions should be encouraged, in order to recreate the old team spirit of tunnellers on the site.

Seit der Einführung der Neuen Österreichischen Tunnelbauweise in der Mitte der 1960er Jahre erlebt der Tunnelbau in vielen Bereichen eine grundlegende Veränderung. Die zunehmende Verrechtlichung und die fortschreitende Bürokratisierung haben dazu geführt, dass die heutigen Tunnelbauverträge im Vergleich zu früher umfangreich, umständlich und widersprüchlich geworden sind. Sowohl die Erstellung der Ausschreibungsplanung als auch die Angebotsbearbeitung bis hin zur Ausführung leiden unter dem Billigstbieterprinzip, dem die Bauherrn gesetzlich unterworfen sind. Die Ausschreibungen sind meist mangelhaft, die Angebote nicht selten spekulativ und unterpreisig. Die NÖT aber ist eine Bauweise, die zur vollen Entfaltung ihres Potenzials eine flexible partnerschaftliche Vertragsgestaltung, kompetente Mitarbeiter, schlanke Strukturen und kurze Entscheidungswege auf der Baustelle benötigt. Im Gegensatz dazu sind die Baustellen heute von sinnlosem Verwaltungsaufwand und oft unsinniger gegenseitiger Kontrolle geprägt. Die rasante Entwicklung und die zunehmende Automatisierung von Maschinen und die Weiterentwicklung von Baustoffen bieten auch in Zukunft große Chancen für die NÖT. Allerdings ist in Zukunft der Vergabemodus zu überdenken und die Ausbildung entscheidungskompetenter Führungskräfte zu fördern, um den alten Teamgeist der Tunnelbauer auf den Baustellen wieder herzustellen.