bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational Design of a Minimal and Highly Enriched CYP102A1 Mutant Library with Improved Regio‐, Stereo‐ and Chemoselectivity
Authors: Seifert Alexander , Vomund Sandra , Grohmann Katrin , Kriening Sebastian , Urlacher Vlada B. , Laschat Sabine , Pleiss Jürgen 
Published: February 2009

AbstractMonooxygenase mutants: A minimal and highly enriched CYP102A1 mutant library was constructed by combining five hydrophobic amino acids in two positions. The library was screened with four different terpene substrates. Eleven variants demonstrated either a strong shift or improved regio‐ or stereoselectivity during oxidation of at least one substrate as compared to CYP102A1 wild type.magnified imageA minimal CYP102A1 mutant library of only 24 variants plus wild type was constructed by combining five hydrophobic amino acids (alanine, valine, phenylalanine, leucine and isoleucine) in two positions. Both positions are located close to the centre of the haem group. The first, position 87, has been shown to mediate substrate specificity and regioselectivity in CYP102A1. The second hotspot, position 328, was predicted to interact with all substrates during oxidation and has previously been identified by systematic analysis of 31 crystal structures and 6300 sequences of cytochrome P450 monooxygenases. By systematically altering the size of the side chains, a broad range of binding site shapes was generated. All variants were functionally expressed in E. coli. The library was screened with four terpene substrates geranylacetone, nerylacetone, (4R)‐limonene and (+)‐valencene. Only three variants showed no activity towards all four terpenes, while eleven variants demonstrated either a strong shift or improved regio‐ or stereoselectivity during oxidation of at least one substrate as compared to CYP102A1 wild type.
On the Initiation Mechanism of Syndiospecific Styrene Polymerization Catalyzed by Single‐Component ansa‐Lanthanidocenes
Authors: Perrin Lionel , Sarazin Yann , Kirillov Evgueni , Carpentier Jean‐François , Maron Laurent 
Published: February 2009

AbstractSingle‐site catalysts: Syndiospecific styrene polymerization promoted by single‐site ansa‐lanthanidocene catalysts proceeds selectively in a secondary (2,1) fashion, both at the initiation and propagation steps. The steric hindrance between the phenyl ring of the incoming styrene monomer and the ancillary ligands (Cp′, Flu′), induced by the change of either the bridge or the “active” R ligand in the catalyst precursor, is proposed to control the reactivity of the complexes (see scheme).magnified imageThe mechanism of the initiation step of styrene polymerization promoted by single‐component ansa‐lanthanidocene catalysts [{Cp′XMe2Flu′}Ln(R)(ether)n] (Cp′=C5H4; Flu′=9‐C13H8; X=C or Si; R=allyl=CH2CHCH2 or alkyl=CH2SiMe3; ether=THF or Et2O, n=0,1) has been studied from a combined experimental/theoretical perspective. First, detailed 13C NMR studies conducted on syndiotactic oligostyrenes prepared by chain‐growth polymerization with [{C5H4CMe2Flu′}Nd(η3‐1,3‐C3H3(SiMe3)2)]/Mg(nBu)2 (1:50) have shown that the insertion of styrene in these lanthanidocene systems proceeds selectively in a secondary (2,1) fashion, both at the initiation and propagation steps. Next, DFT studies of styrene insertion have been carried out on three model compounds, [{Cp′CMe2Flu′}Eu(η3‐allyl)(thf)] (I), [{Cp′SiMe2Flu′}Eu(η3‐allyl)(thf)] (II), and [{Cp′CMe2Flu′}Eu(η1‐CH2SiMe3)(thf)] (III), in order to rationalize the influence of the ansa bridge (CMe2 vs. SiMe2) and that of the “active” R ligand (η3‐allyl vs. η1‐CH2SiMe3), previously noticed in styrene polymerization experiments. Dissociation of the THF molecule in precursor I appears not to be a rate‐limiting step and proceeds readily. The steric hindrance between the phenyl ring of the incoming styrene monomer and the ancillary ligands (Cp′, Flu′), induced by the change of either the bridge or the “active” R ligand, is proposed to control the reactivity of the complexes. In all cases, orientation of the styrene phenyl ring toward the most sterically opened Cp′ ligand (as compared to Flu′) and 2,1‐insertion of styrene have been found to be the most thermodynamically and kinetically favorable pathway. Also, in all cases, insertion of the first styrene unit proceeds directly in the η3‐coordinated allyl group. The lack of activity of the ansa‐dimethylsilylene allyl complex and of the ansa‐isopropylidene alkyl complex appears to be mainly due to the thermodynamics of the insertion reaction rather than the height of the activation barrier.
A Chemoenzymatic Approach to Enantiomerically Pure Amines Using Dynamic Kinetic Resolution: Application to the Synthesis of Norsertraline
Authors: Thalén Lisa K. , Zhao Dongbo , Sortais Jean‐Baptiste , Paetzold Jens , Hoben Christine , Bäckvall Jan‐E. 
Published: February 2009

AbstractDynamic transformation: A racemization catalyst and the enzyme Candida antarctica lipase B (CALB) were combined in a one‐pot dynamic kinetic resolution (DKR) of primary amines, which were transformed to their corresponding amides in up to 95 % yield and >99 % ee. This chemoenzymatic DKR was also applied to the synthesis of norsertraline (see scheme).magnified imageRacemization catalyst 5 c and the enzyme Candida antarctica lipase B were combined in a one‐pot dynamic kinetic resolution (DKR) of primary amines in which a wide range of amines were transformed to their corresponding amides in up to 95 % isolated yield and >99 % ee. The DKR protocol was applicable with either isopropyl acetate or dibenzyl carbonate as the acyl donor. In the latter case, release of the free amine from the carbamate products was carried out under very mild conditions. The racemization of (S)‐1‐phenylethylamine with several different Ru catalysts was also evaluated. Catalyst 5 c, of the Shvo type, was able to selectively racemize amines and was also compatible with the reaction conditions used for DKR. A racemization study of three different amines with varying electronic properties was also performed. Competitive racemization of a 1:1 mixture of the deuterated and non‐deuterated amine was carried out with 5 c and a primary kinetic isotope effect was observed for all three amines, providing support that the rate‐determining step is β‐hydride elimination. The chemoenzymatic DKR protocol was applied to the synthesis of norsertraline (16) by using a novel route starting from readily available 1,2,3,4‐tetrahydro‐1‐naphthylamine (1 o).
Responsive Metal Complexes: A Click‐Based “Allosteric Scorpionate” Complex Permits the Detection of a Biological Recognition Event by EPR/ENDOR Spectroscopy
Authors: Tamanini Emiliano , Rigby Stephen E. J. , Motevalli Majid , Todd Matthew H. , Watkinson Michael 
Published: February 2009

AbstractClick to detect!Azamacrocyclic complexes with a triazole scorpion ligand may be easily assembled, as shown for a biotin‐functionalised cyclam derivative. Coordination of the triazole to the metal is perturbed by the binding of avidin to the pendant ligand (see scheme). This event can be sensitively detected with EPR and ENDOR spectroscopy, which confirm the loss of the axial triazole nitrogen donor upon avidin binding. This general strategy may have wide applications in imaging and therapeutics.magnified imageChemical sensing is a mature field, and many effective sensors for small anions and cations have been devised. Metal complexes have been used widely for this purpose, but there are fewer reports of their use in the detection of organic and biological analytes. To date metal complexes have been used in sensing via the direct displacement of a pre‐existing ligand by an analyte, or by an adventitious complementarity between the complex and analyte. These strategies do not permit a general approach to the sensing of biological molecules with metal complexes because of the demands to engineer molecular recognition into the complex architecture. We describe a fundamentally new approach to this field—the “allosteric scorpionate” metal complex. The binding partner of a biological analyte is attached to a scorpionate ligand on a metal complex, remote from the metal centre. Binding of the analyte causes a change in the primary coordination sphere at the metal, thereby revealing the presence of the biological molecule. We show that azamacrocyclic complexes with a triazole scorpion ligand may be easily assembled with the [3+2] Huisgens ‘click’ cycloaddition. We demonstrate the synthesis of a biotin‐functionalised cyclam derivative using this methodology. This, and our previously communicated zinc sensor, are to the best of our knowledge the first examples of a triazole being employed as a scorpion ligand on an azamacrocycle. Coordination by the triazole to the metal is perturbed by the binding of avidin to the pendant ligand. This event can be sensitively detected with EPR spectroscopy, and the details of the coordination change probed with ENDOR spectroscopy, confirming the loss of the axial triazole nitrogen donor upon binding to avidin. This represents the first metal complex where remote, ‘allosteric’ coordination of an analyte has been shown to cause a change in the primary coordination sphere of the metal. Since the synthesis is modular and straightforward, other biological ligands may easily be introduced, and the associated binding events may be probed.
D‐Fructose‐6‐phosphate Aldolase in Organic Synthesis: Cascade Chemical‐Enzymatic Preparation of Sugar‐Related Polyhydroxylated Compounds
Authors: Concia Alda Lisa , Lozano Carles , Castillo José A. , Parella Teodor , Joglar Jesús , Clapés Pere 
Published: February 2009

AbstractD‐Fructose‐6‐phosphate aldolase (FSA) is a key biocatalyst for the alternative synthetic construction of biologically active products with known therapeutic and research interest or novel structures relevant to drug discovery. Novel aldol addition reactions of dihydroxyacetone and hydroxyacetone to a variety of aldehydes catalyzed by FSA are presented (see scheme).magnified imageNovel aldol addition reactions of dihydroxyacetone (DHA) and hydroxyacetone (HA) to a variety of aldehydes catalyzed by D‐fructose‐6‐phosphate aldolase (FSA) are presented. In a chemical‐enzymatic cascade reaction approach, 1‐deoxynojirimycin and 1‐deoxymannojirimycin were synthesized starting from (R)‐ and (S)‐3‐(N‐Cbz‐amino)‐2‐hydroxypropanal, respectively. Furthermore, 1,4‐dideoxy‐1,4‐imino‐D‐arabinitol and 1,4,5‐trideoxy‐1,4‐imino‐D‐arabinitol were prepared from N‐Cbz‐glycinal. 1‐Deoxy‐D‐xylulose was also synthesized by using HA as the donor and either 2‐benzyloxyethanal or 2‐hydroxyethanal as acceptors. In both cases the enzymatic aldol addition reaction was fully stereoselective, but with 2‐hydroxyethanal 17 % of the epimeric product at C2, 1‐deoxy‐D‐erythro‐2‐pentulose, was observed due to enolization/epimerization during the isolation steps. It was also observed that D‐(−)‐threose is a good acceptor substrate for FSA, opening new synthetic possibilities for the preparation of important novel complex carbohydrate‐related compounds from aldoses. To illustrate this, 1‐deoxy‐D‐ido‐hept‐2‐ulose was obtained stereoselectively by the addition of HA to D‐(−)‐threose, catalyzed by FSA. It was found that the reaction performance depended strongly on the donor substrate, HA being the one that gave the best conversions to the aldol adduct. The examples presented in this work show the valuable synthetic potential of FSA for the construction of chiral complex polyhydroxylated sugar‐type structures.
Silver‐Ion‐Mediated DNAzyme Switch for the Ultrasensitive and Selective Colorimetric Detection of Aqueous Ag+ and Cysteine
Authors: Li Tao , Shi Lili , Wang Erkang , Dong Shaojun 
Published: February 2009

AbstractTwo states, two applications! An Ag+‐mediated DNAzyme switch has been designed to detect Ag+ and cysteine with high sensitivity and selectivity. In the closed state, Ag+ turns on the switch through the formation of cytosine–Ag+–cytosine base pairs, whereas adding cysteine turns off the open switch because it competitively binds to Ag+. This feature endows the DNAzyme switch with two sensing applications.magnified image
Structure–Activity Relationships and Binding Mode in the Human Acetylcholinesterase Active Site of Pseudo‐Irreversible Inhibitors Related to Xanthostigmine
Authors: Rizzo Stefano , Cavalli Andrea , Ceccarini Luisa , Bartolini Manuela , Belluti Federica , Bisi Alessandra , Andrisano Vincenza , Recanatini Maurizio , Rampa Angela 
Published: February 2009

AbstractAcetylcholinesterase inhibitors: We extended the AChE inhibitors SAR study to newly synthesized compounds based on the lead compound xantostigmine. Docking and molecular dynamics simulations were carried out to both define a new computational protocol, and to acquire a better understanding of the SAR data. These computations prompted us to evaluate two of the synthesized compounds as inhibitors of AChE‐induced Aβ aggregation.magnified imageStructure–activity relationship studies on acetylcholinesterase (AChE) inhibitors were extended to newly synthesized compounds derived from the lead compound xantostigmine (1). The xanthone ring of compound 1 was replaced with several different scaffolds based on the benzopyran skeleton, linked to the tertiary amino nitrogen through an heptyloxy chain. These modifications resulted in 19 new compounds, most of them showing activity in the nanomolar–subnanomolar range. Docking and molecular dynamics simulations were carried out to both define a new computational protocol for the simulation of pseudo‐irreversibile AChE covalent inhibitors, and to acquire a better understanding of the structure–activity relationships of the present series of compounds. The results of this computational work prompted us to to evaluate the ability of compounds 5 and 13 to inhibit acetylcholinesterase‐induced Aβ aggregation.
Plasmon‐Resonance‐Based Generation of Cathodic Photocurrent at Electrodeposited Gold Nanoparticles Coated with TiO2 Films
Authors: Sakai Nobuyuki , Fujiwara Yusuke , Takahashi Yukina , Tatsuma Tetsu 
Published: February 2009

AbstractReversed photoresponse: Indium tin oxide (ITO)/Au nanoparticle (NP)/TiO2 electrodes (see picture) exhibit cathodic photocurrents and positive photopotentials under visible light, whereas ITO/TiO2/Au NP electrodes show an inverted response. This behavior indicates that electron transfer occurs from the plasmon‐excited Au NPs to the TiO2 film. An enhanced O2 photoreduction activity is found for ITO/Au NP/TiO2/Pt electrodes.magnified image
Glucocorticoid‐mediated effects on metabolism are reversed by targeting 11 beta hydroxysteroid dehydrogenase type 1 in human skeletal muscle
Authors: Salehzadeh Firoozeh , Al‐Khalili Lubna , Kulkarni Sameer S , Wang Minghan , Lönnqvist Fredrik , Krook Anna 
Published: February 2009

AbstractBackgroundAdipose tissue and liver play important roles in mediating the metabolic actions of glucocorticoids. However, the effects of glucocorticoids on glucose and lipid metabolism in skeletal muscle are not understood completely. Intracellular glucocorticoid action is dependent on 11 β‐hydroxysteroid dehydrogenase 1 (HSD1), an enzyme that converts cortisone to active cortisol.MethodsWe investigated the direct role of HSD1 in cultured primary human skeletal muscle cells using siRNA and pharmacological inhibitors of the enzyme. Primary human skeletal muscle cells were cultured in the presence of 0.5 µM cortisone or 0.5 µM cortisol for eight days. siRNA was utilized to reduce expression of either HSD1 or pyruvate dehydrogenase kinase (PDK) 4. Effects of pharmacological inhibitors of HSD1 were also studied.ResultsExposure to cortisone or cortisol decreased basal glucose uptake and glucose incorporation into glycogen, but was without effect on the insulin‐stimulated response. Glucocorticoid exposure increased palmitate oxidation, as well as the expression of PDK4. siRNA‐mediated reduction or pharmacological inhibition of HSD1 prevented the effects of cortisone, but not cortisol, on metabolic responses. siRNA‐mediated reduction of PDK4 prevented the effect of cortisol to attenuate glycogen synthesis.ConclusionTargeted reduction or pharmacological inhibition of HSD1 in primary human skeletal muscle cells prevents the effects of cortisone, but not cortisol, on glucose metabolism and palmitate oxidation. Furthermore, the glucocorticoid‐mediated reductions in glucose metabolism are dependent on PDK4. Copyright © 2009 John Wiley & Sons, Ltd.
Adaptive forecasting of the EURIBOR swap term structure
Authors: Blaskowitz Oliver , Herwartz Helmut 
Published: February 2009

AbstractIn this paper we adopt a principal components analysis (PCA) to reduce the dimensionality of the term structure and employ autoregressive (AR) models to forecast principal components which, in turn, are used to forecast swap rates. Arguing in favour of structural variation, we propose data‐driven, adaptive model selection strategies based on the PCA/AR model. To evaluate ex ante forecasting performance for particular rates, distinct forecast features, such as mean squared errors, directional accuracy and directional forecast value, are considered. It turns out that, relative to benchmark models, the adaptive approach offers additional forecast accuracy in terms of directional accuracy and directional forecast value. Copyright © 2009 John Wiley & Sons, Ltd.
Facial identity and facial expression matching in 5–12‐year‐old children and adults
Authors: Karayanidis Frini , Kelly Megan , Chapman Prudence , Mayes Angela , Johnston Pat 
Published: February 2009

AbstractFacial identity and facial expression matching tasks were completed by 5–12‐year‐old children and adults using stimuli extracted from the same set of normalized faces. Configural and feature processing were examined using speed and accuracy of responding and facial feature selection, respectively. Facial identity matching was slower than face expression matching for all age groups. Large age effects were found on both speed and accuracy of responding and feature use in both identity and expression matching tasks. Eye region preference was found on the facial identity task and mouth region preference on the facial expression task. Use of mouth region information for facial expression matching increased with age, whereas use of eye region information for facial identity matching peaked early. The feature use information suggests that the specific use of primary facial features to arrive at identity and emotion matching judgments matures across middle childhood. Copyright © 2009 John Wiley & Sons, Ltd.
Late Quaternary landscapes in Central Australia: sedimentary history and palaeoecology of Puritjarra rock shelter
Authors: Smith M. A. 
Published: February 2009

AbstractPuritjarra rock shelter provides a long record of late Quaternary vegetation in the Australian arid zone. Analysis of the sedimentary history of this rock shelter is combined with reanalysis of charcoal and phytolith records to provide a first‐order picture of changing landscapes in western Central Australia. These show a landscape responding to increasing aridity from 45 ka with deflation of clay‐rich red palaeosols (<45 ka) and sharp declines in grassland and other vegetation at 40–36 ka, and at the beginning of the Last Glacial Maximum (LGM) (24 ka). Vegetation in the catchment of the rock shelter recovered after 15 ka with expansion of both acacia woodland and spinifex grasslands, registering stronger summer rainfall in the interior of the continent. By 8.3 ka re‐vegetation of local palaeosols and dunes had choked off sediment supply to the rock shelter and the character of the sediments changed abruptly. Poaceae values peaked at 5.8 ka, suggesting the early–mid Holocene climatic optimum in Central Australia is bracketed between 8.3 and 5.8 ka. Local vegetation was disrupted in the late Holocene with a sharp decline in Poaceae at 3.8 ka, coinciding with an abrupt intensification of ENSO. Local grasslands recovered over the next two millennia and by 1.5 ka the modern vegetation appears to have become established. Copyright © 2009 John Wiley & Sons, Ltd.
Assessment of antiradical potential of Calluna vulgaris (L.) Hull and its major flavonoid
Authors: Deliorman‐Orhan Didem , Şenol Sezer , Kartal Murat , Orhan Ilkay 
Published: February 2009

AbstractBACKGROUND: Antioxidant capacity of the chloroform, ethyl acetate, n‐butanol and water fractions of the aerial parts of Calluna vulgaris (L.) Hull (Ericaceae) has been assessed in this study. Antioxidant capacity of the plant was screened by assays of 2,2‐diphenyl‐β‐picrylhydrazyl, superoxide anion and hydrogen peroxide scavenging, metal‐chelating activity and reducing power. Butylated hydroxyanisole was used as reference in all assays; ethylene diamine tetraacetic acid was also used as reference in the assay of metal‐chelating activity. Total phenolic contents of the fractions were determined by the Folin–Ciocalteu method.RESULTS: Liquid chromatography/diode array detection/mass spectrometry was used for phytochemical identification of the fractions. Kaempferol‐3‐O‐β‐D‐galactoside was found to be the major constituent in the ethyl acetate fraction (37.1 ± 0.9%), followed by the n‐butanol fraction (4.6 ± 0.1%). High occurrence of antioxidant capacity, with the exception of metal‐chelating activity, was observed in the ethyl acetate and chloroform fractions as well as in kaempferol‐3‐O‐β‐D‐galactoside.CONCLUSION: Calluna vulgaris and its major flavonoid, kaempferol‐3‐O‐β‐D‐galactoside, show high antioxidant capacity in various assays. As far as is known, this is the first report on antioxidant capacity of C. vulgaris and its major flavonoid. Copyright © 2009 Society of Chemical Industry
Yield and quality of early potato cultivars in relation to the use of glufosinate‐ammonium as desiccant
Authors: Gonnella Maria , Ayala Osman , Paradiso Annalisa , Buono Vito , De Gara Laura , Santamaria Pietro , Serio Francesco 
Published: February 2009

AbstractBACKGROUND: Glufosinate‐ammonium (GA) is used for chemical vine killing of potato crop before harvest. Over two years we tested the effect of GA, applied at 0.48 kg ha−1 of active ingredient, on desiccation of haulms, yield and some qualitative traits of tubers of three cultivars of early potatoes, a typical crop of southern Italy and large areas of the Mediterranean countries.RESULTS: Seven days after treatment desiccation reached 90% of leaves for all cultivars. At harvest, the highest desiccation percentage of haulms was 85% in Spunta. The desiccant did not affect yield in either year during which the analysis was carried out, but it increased the percentage of tubers in the range of 35–70 mm in diameter. In the first year, the treatment decreased dry matter and vitamin C content and increased free sugar concentration in tubers. In the second year, no negative effects on the nutritional traits were observed. Strong differences were found on yield and quality between the two years as a result of the different climatic conditions.CONCLUSION: In the two experiments GA had no influence on yield, but increased the percentage of potato tubers in the 35–70 mm range. From a qualitative standpoint in 2004 the chemical vine‐killing treatment had some negative effects (decreased dry matter and vitamin C content, increased free sugar concentrations), whereas no such negative effects were observed in 2005. Copyright © 2009 Society of Chemical Industry