bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamics for reactions of ion pairs in aqueous solution: reactivity of tosylate anion ion paired with the highly destabilized 1‐(4‐methylphenyl)‐2,2,2‐trifluoroethyl carbocation
Authors: Teshima Minami , Tsuji Yutaka , Richard John P. 
Published: January 2010

AbstractThe sum of the rate constants for solvolysis and scrambling of carbon bridging and nonbridging oxygen‐18 at 4‐MeC6H4CH(CF3)OS(18O2)Tos in 50/50 (v/v) trifluoroethanol/water, (ksolv + kiso) = 5.4 × 10−6 s−1, is 50% larger than ksolv = 3.6 × 10−6 for the simple solvolysis reaction of the sulfonate ester. This shows that the ion‐pair intermediate of solvolysis undergoes significant internal return to form reactant. These data give a value of k‐1 = 1.7 × 1010 s−1 for internal return of the carbocation–anion pair to the substrate. This rate constant is larger than the value of k‐1 = 7 × 109 s−1 reported for internal return of an ion pair between the 1‐(4‐methylphenyl)ethyl carbocation and pentafluorobenzoate anion to the neutral ester (4‐MeC6H4CH(CH3)O2CC6F5) in the same solvent. The partitioning of ion pairs to the 1‐(4‐methylphenyl)ethyl carbocation and to the highly destabilized 1‐(4‐methylphenyl)2,2,2‐trifluoroethyl carbocation is compared and contrasted. Copyright © 2010 John Wiley & Sons, Ltd.
The mechanism of the homogeneous, unimolecular gas‐phase elimination kinetic of 1,1‐dimethoxycyclohexane: experimental and theoretical studies
Authors: Rosas Felix , Domínguez Rosa M. , Tosta María , Mora José R. , Márquez Edgar , Córdova Tania , Chuchani Gabriel 
Published: January 2010

AbstractThe gas‐phase elimination of 1,1‐dimethoxycyclohexane yielded 1‐methoxy‐1‐cyclohexene and methanol. The kinetics were determined in a static system, with the vessels deactivated with allyl bromide, and in the presence of the free radical inhibitor cyclohexene. The working temperature was 310–360 °C and the pressure was 25–85 Torr. The reaction was found to be homogeneous, unimolecular, and follows a first‐order rate law. The temperature dependence of the rate coefficients is given by the following Arrhenius equation: log k(s−1) = [(13.82 ± 0.07) – (193.9 ± 1.0)(kJ mol−1)](2.303RT)−1; r = 0.9995. Theoretical calculations were carried out using density functional theory (DFT) functionals B3LYP, MPW1PW91, and PBE with the basis set 6‐31G(d,p) and 6‐31G++(d,p). The calculated values for the energy of activation and enthalpy of activation are in reasonably good agreement with the experimental values using the PBE/6‐31G (d,p) level of theory. Both experimental results and theoretical calculations suggest a molecular mechanism involving a concerted polar four‐membered cyclic transition state. The transition state structure of methanol elimination from 1,1‐dimethoxycyclohexane is characterized by a significantly elongated CO bond, while the CβH bond is stretched to a smaller extent, as compared to the reactant. The process can be described as moderately asynchronic with some charge separation in the TS. Copyright © 2010 John Wiley & Sons, Ltd.
Enantio‐differentiating reactions of a racemic γ‐lactone enolate with chiral esters. A DFT investigation
Authors: Moraleda Delphine , Santelli Maurice 
Published: January 2010

AbstractThe acylation of lithium (±)‐spiro‐γ‐lactone enolate 5 by the O‐protected methyl (−)‐(S)‐lactate or the O‐protected methyl (+)‐(S)‐mandelate occurs through enantio‐differentiating reactions. The (S,S)‐enolate 5 is the most reactive with the lactate whereas the (R,R)‐enolate 5 selectively reacts with the mandelate. According to theoretical calculations at the B3LYP/6‐31G(++)(d,p) level of theory of 40 intermediates of this Claisen condensation, the experimental results are compatible with a previous chelation of the ester by an auxiliary cation lithium arising from the medium. The addition reaction occurs through a chelation process mediated by the counterion of the enolate. More stable tetrahedral intermediates including two lithium cations result from an antiperiplanar transition state. These results clearly demonstrate that the presence of a second lithium cation (the first lithium cation is solvated by di‐isopropylamine and the second one is solvated by a THF molecule or a di‐isopropylamide anion) stabilizes the tetrahedral intermediate and is compatible with an antiperiplanar transition state according to the Felkin–Anh model. Copyright © 2010 John Wiley & Sons, Ltd.
Self‐assembly of daisy chain oligomers from heteroditopic molecules containing secondary ammonium ion and crown ether moieties
Authors: Gibson Harry W. , Yamaguchi Nori , Niu Zhenbin , Jones Jason W. , Slebodnick Carla , Rheingold Arnold L. , Zakharov Lev N. 
Published: January 2010

AbstractMALDI‐TOF MS of the heteroditopic compound 2‐(benzylammoniomethyl)dibenzo‐24‐crown‐8 hexafluorophosphate (4) revealed oligomeric “daisy chain” species up to the hexamer. Similar results were obtained for 2‐(6′‐hydroxyhexylammoniomethyl)dibenzo‐24‐crown‐8 hexafluorophosphate (8). The complexations of two substituted dibenzylammonium salts, 2,2′‐dimethyldibenzylammonium hexaflurophosphate (9a) and 2,2′,5‐trimethoxydibenzylammonium hexafluorophosphate (9b), with dibenzo‐24‐crown‐8 were examined as models for slippage systems; association constants are reported for these systems. A crystal structure is reported for the new dimethylbenzylammonoium pseudorotaxane. The trimethoxy analog is shown to be capable of slippage formation of a rotaxane, albeit in low yield. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 975–985, 2010
Is GRP78/BiP a potential salivary biomarker in patients with rheumatoid arthritis?
Authors: Giusti Laura , Baldini Chiara , Ciregia Federica , Giannaccini Gino , Giacomelli Camillo , De Feo Francesca , Delle Sedie Andrea , Riente Lucrezia , Lucacchini Antonio , Bazzichi Laura , Bombardieri Stefano 
Published: January 2010

AbstractPurpose: In the last few years, serum and joint synovial fluid have been extensively analyzed for the proteomic research of rheumatoid arthritis (RA) biomarkers. Nonetheless, to date, there have been no studies investigating salivary biomarkers in this condition. Therefore, aim of this study is to investigate the presence of potential biomarkers of RA in human whole saliva.Experimental design: We combined 2‐DE and MS to analyze the whole saliva protein profile of 20 RA patients in comparison with 20 sex‐ and age‐matched healthy subjects.Results: Eight salivary proteins resulted differentially expressed, namely calgranulin A, calgranulin B, apolipoprotein A‐1, 6‐phosphogluconate dehydrogenase, peroxiredoxin 5, epidermal fatty acid‐binding protein, 78 kDa glucose‐regulated protein precursor (GRP78/BiP), and 14‐3‐3 proteins. It is particularly interesting that chaperone GRP78/BiP showed the greatest increase in RA patients. This finding was validated by Western Blot analysis and the over‐expression of GRP78/BiP appear to be distinctive of RA and drugs treatment independent.Conclusions and clinical relevance: This study provides a rationale for further studies aimed at evaluating any correlation between GRP78/BiP and different clinical/serological aspects of the disease in order to improve the diagnostic algorithms of RA.
Proteomic profile of differentially expressed plasma proteins from dystrophic mice and following suberoylanilide hydroxamic acid treatment
Authors: Colussi C. , Banfi C. , Brioschi M. , Tremoli E. , Straino S. , Spallotta F. , Mai Antonello , Rotili Dante , Capogrossi M. C. , Gaetano Carlo 
Published: January 2010

AbstractPurpose: Histone Deacetylase Inhibitors (DI) ameliorates dystrophic muscle regeneration restoring muscular strength in the mdx mouse model of Duchenne muscular dystrophy (DMD). The further development of these compounds as drugs for DMD treatment is currently hampered by the lack of knowledge about DIs effect in large dystrophic animal models and that of suitable biomarkers to monitor their efficacy.Experimental design: In this study we applied proteomic analysis to identify differentially expressed proteins present in plasma samples from mdx mice treated with the Suberoylanilide hydroxamic acid (SAHA) and relative normal controls (WT).Results: Several differentially expressed proteins were identified between untreated wild type and mdx mice. Among these, fibrinogen, epidermal growth factor 2 receptor, major urinary protein and glutathione peroxidase 3 (GPX3) were constitutively up‐regulated in mdx, while complement C3, complement C6, gelsolin, leukaemia inhibitory factor receptor (LIFr), and alpha 2 macroglobulin were down‐regulated compared to WT mice. SAHA determined the normalization of LIFr and GPX3 protein level while apoliprotein E was de novo up‐regulated in comparison to vehicle‐treated mdx mice.Conclusions and clinical relevance: Collectively, these data unravel potential serological disease biomarkers of mdx that could be useful to monitor muscular dystrophy response to DI treatment.
De novo structure generation using chemical shifts for proteins with high‐sequence identity but different folds
Authors: Shen Yang , Bryan Philip N. , He Yanan , Orban John , Baker David , Bax Ad 
Published: January 2010

AbstractProteins with high‐sequence identity but very different folds present a special challenge to sequence‐based protein structure prediction methods. In particular, a 56‐residue three‐helical bundle protein (GA95) and an α/β‐fold protein (GB95), which share 95% sequence identity, were targets in the CASP‐8 structure prediction contest. With only 12 out of 300 submitted server‐CASP8 models for GA95 exhibiting the correct fold, this protein proved particularly challenging despite its small size. Here, we demonstrate that the information contained in NMR chemical shifts can readily be exploited by the CS‐Rosetta structure prediction program and yields adequate convergence, even when input chemical shifts are limited to just amide 1HN and 15N or 1HN and 1Hα values.
Comprehensive modeling and functional analysis of Toll‐like receptor ligand‐recognition domains
Authors: Kubarenko Andriy V. , Ranjan Satish , Colak Elif , George Julie , Frank Martin , Weber Alexander N.R. 
Published: January 2010

AbstractToll‐like receptors (TLRs) are innate immune pattern‐recognition receptors endowed with the capacity to detect microbial pathogens based on pathogen‐associated molecular patterns. The understanding of the molecular principles of ligand recognition by TLRs has been greatly accelerated by recent structural information, in particular the crystal structures of leucine‐rich repeat‐containing ectodomains of TLR2, 3, and 4 in complex with their cognate ligands. Unfortunately, for other family members such as TLR7, 8, and 9, no experimental structural information is currently available. Methods such as X‐ray crystallography or nuclear magnetic resonance are not applicable to all proteins. Homology modeling in combination with molecular dynamics may provide a straightforward yet powerful alternative to obtain structural information in the absence of experimental (structural) data, provided that the generated three‐dimensional models adequately approximate what is found in nature. Here, we report the development of modeling procedures tailored to the structural analysis of the extracellular domains of TLRs. We comprehensively compared secondary structure, torsion angles, accessibility for glycosylation, surface charge, and solvent accessibility between published crystal structures and independently built TLR2, 3, and 4 homology models. Finding that models and crystal structures were in good agreement, we extended our modeling approach to the remaining members of the TLR family from human and mouse, including TLR7, 8, and 9.
Identification of a novel set of scaffolding residues that are instrumental for the inhibitory property of Kunitz (STI) inhibitors
Authors: Khamrui Susmita , Majumder Sudip , Dasgupta Jhimli , Dattagupta Jiban K , Sen Udayaditya 
Published: January 2010

AbstractFor canonical serine protease inhibitors (SPIs), scaffolding spacer residue Asn or Arg religates cleaved scissile peptide bond to offer efficient inhibition. However, several designed “mini‐proteins,” containing the inhibitory loop and the spacer(s) with trimmed scaffold behave like substrates, indicating that scaffolding region beyond the spacer is also important in the inhibitory process. To understand the loop‐scaffold compatibility, we prepared three chimeric proteins ECIL‐WCIS, ETIL‐WCIS, and STIL‐WCIS, where the inhibitory loop of ECI, ETI, and STI is placed on the scaffold of their homolog WCI. Results show that although ECIL‐WCIS and STIL‐WCIS behave like good inhibitors, ETIL‐WCIS behaves like a substrate. That means a set of loop residues (SRLRSAFI), offering strong trypsin inhibition in ETI, act as a substrate when they seat on the scaffold of WCI. Crystal structure of ETIL‐WCIS shows that the inhibitory loop is of noncanonical conformation. We identified three novel scaffolding residues Trp88, Arg74, and Tyr113 in ETI that act as barrier to confine the inhibitory loop to canonical conformation. Absence of this barrier in the scaffold of WCI makes the inhibitory loop flexible in ETIL‐WCIS leading to a loss of canonical conformation, explaining its substrate‐like behavior. Incorporation of this barrier back in ETIL‐WCIS through mutations increases its inhibitory power, supporting our proposition. Our study provides structural evidence for the contribution of remote scaffolding residues in the inhibitory process of canonical SPIs. Additionally, we rationalize why the loop‐scaffold swapping is not permitted even among the members of highly homologous inhibitors, which might be important in the light of inhibitor design.
Curcumin inhibits human lung large cell carcinoma cancer tumour growth in a murine xenograft model
Authors: Su Chin‐Cheng , Yang Jai‐Sing , Lu Chi‐Cheng , Chiang Jo‐Hua , Wu Chang‐Lin , Lin Jen‐Jyh , Lai Kuang‐Chi , Hsia Te‐Chun , Lu Hsu‐Feng , Fan Ming‐Jen , Chung Jing‐Gung 
Published: January 2010

AbstractCurcumin can decrease viable cells through the induction of apoptosis in human lung cancer NCI‐H460 cells in vitro. However, there are no reports that curcumin can inhibit cancer cells in vivo. In this study, NCI‐H460 lung tumour cells were implanted directly into nude mice and divided randomly into four groups to be treated with vehicle, curcumin (30 mg/kg of body weight), curcumin (45 mg/kg of body weight) and doxorubicin (8 mg/kg of body weight). Each agent was injected once every 4 days intraperitoneally (i.p.), with treatment starting 4 weeks after inoculation with the NCI‐H460 cells. Treatment with 30 mg/kg and 45 mg/kg of curcumin or with 8 mg/kg of doxorubicin resulted in a reduction in tumour incidence, size and weight compared with the control group. The findings indicate that curcumin can inhibit tumour growth in a NCI‐H460 xenograft animal model in vivo. Copyright © 2010 John Wiley & Sons, Ltd.
Protective effect of bilberry (Vaccinium myrtillus L.) extracts on cultured human corneal limbal epithelial cells (HCLEC)
Authors: Song Juxian , Li Yiqing , Ge Jian , Duan Yongheng , Sze Stephen Cho‐Wing , Tong Yao , Shaw Pang‐Chui , Ng Tzi‐Bun , Tsui Kam Chuen , Zhuo Yehong , Zhang Kalin Yanbo 
Published: January 2010

AbstractThe use of bilberry (Vaccinium myrtillus L.) as a food and medicine for improving human vision has a long history all over the world. However, there is lack of convincing evidence from rigorous clinical trials or scientific research. This study investigated the effects of different concentrations of bilberry extracts on the cell viability, cell cycle and the expression of hyaluronic acid and glycosaminoglycans of cultured human corneal limbal epithelial cells. The data showed that bilberry extracts had no cytotoxicity to the corneal limbal epithelial cells at a wide range of concentrations (10−9–10−4 M, equalized to the content of cyanidin‐3‐O‐glucoside). Bilberry extract (10−6, 10−5 and 10−4 M) increased cell viability after 48 h incubation. The number of cells decreased in G0/G1 phase and increased prominently in S and G2/M phases after treatment with bilberry extracts at a high concentration (10−4 M). The expression of glycosaminoglycans increased prominently after incubation with bilberry extracts (10−7 and 10−4 M) for 48 h while no significant changes were observed for the expression of hyaluronic acid. The results indicated that bilberry extract may be beneficial for the physiological renewal and homeostasis of corneal epithelial cells. Copyright © 2010 John Wiley & Sons, Ltd.
Antimethicillin‐resistant Staphylococcus aureus (MRSA) activity of ‘pacific propolis’ and isolated prenylflavanones
Authors: Raghukumar Raghavendra , Vali Leila , Watson Dave , Fearnley James , Seidel Véronique 
Published: January 2010

AbstractThe need to discover and develop alternative therapies to treat methicillin‐resistant Staphylococcus aureus (MRSA) infections is timely. This study was undertaken to purify and identify some anti‐MRSA constituents from propolis, a natural product from the beehive traditionally used in folk medicine for its antimicrobial properties. A crude extract of propolis originating from the Solomon Islands (‘Pacific propolis’) was screened, using an agar dilution assay, in vitro against 15 MRSA clinical isolates. Results revealed activity worthy of further investigation, and subsequent purification work on this crude extract afforded 23 fractions. Further purification of active fractions led to the isolation of compounds 1–4, characterized upon analysis of their spectroscopic data (1D‐ and 2D‐NMR, MS) and by comparison with the literature, as the prenylflavanones propolin H (1), propolin G (2), propolin D (3), and propolin C (4). This study is the first to report the anti‐MRSA activity of ‘Pacific propolis’ and the presence of prenylflavanones in the propolis sample selected. The anti‐MRSA activity of propolin D (3) (MIC 8–16 mg/L) and propolin C (4) (MIC 8–32 mg/L) is reported for the first time. Copyright © 2010 John Wiley & Sons, Ltd.
Quantitative aspects of analyzing small molecules – monitoring singly or doubly charged ions? A case study of ximelagatran
Authors: Allard Erik , Tröger Rikard Åslund , Arvidsson Björn , Sjöberg Per Johan Ragnar 
Published: January 2010

AbstractPrecision, reproducibility and lower limit of quantitation (LLOQ) are important characteristics of a quantitative method. We have investigated these properties for Ximelagatran (Xi), which has a high tendency to form doubly charged ions in electrospray ionization (ESI), by studying the percentage of doubly charged species formed when varying the formic acid (FA) concentration, analyte concentration, amount of organic modifier and flow rate. It was found that the percentage of [Xi + 2H]2+ can be controlled to be more than 90% or less than 10% by varying the amount of FA present, and that the change between these values is dramatic. Furthermore, the percentage of [Xi + 2H]2+ formed decreases with increased analyte concentration and increased flow rate. No apparent relationship with the amount of organic modifier was found. The results have the implication that, by carefully controlling the selected parameters, the LLOQ, precision and reproducibility can be improved. We have compared the fragmentation of the singly and doubly charged species and concluded that the [Xi + 2H]2+ ion is more inclined to undergo fragmentation than [Xi + H]+. As a consequence, unusual instrumental settings had to be used for the experiments. The fragmentation patterns are to a great extent similar, but the doubly charged species is more inclined to generate low‐mass product ions. Copyright © 2010 John Wiley & Sons, Ltd.
Fast and automated characterization of major constituents in rat biofluid after oral administration ofAbelmoschus manihotextract using ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry and MetaboLynx
Authors: Guo Jianming , Shang Er‐xin , Duan Jin‐ao , Tang Yuping , Qian Dawei , Su Shulan 
Published: January 2010

AbstractIn drug metabolism research, the setting up of a complex series of mass spectrometry experiments and the subsequent analysis of the large amounts of data produced are often time‐consuming. In this paper, we describe a strategy using ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry (UPLC/QTOFMS) with automated data analysis software (MetaboLynx™) for fast analysis of the metabolic profile of flavonoids inAbelmoschus manihot. Rat plasma and urine samples collected 1 h and 0–12 h after oral administration ofAbelmoschus manihotwere analyzed by UPLC/QTOFMS within 15 min. The post‐acquisition data were processed using MetaboLynx. With key parameters carefully set, MetaboLynx is able to show the presence of a wide range of metabolites with only a limited requirement for manual intervention and data interpretation time. A total of 16 and 38 metabolites were identified in plasma and urine compared with blank samples. The results indicated that methylation and glucuronidation after deglycosylation were the major metabolic pathways of flavonoid glycosides inAbelmoschus manihot. The present study provided important information about the metabolism of flavonoid glycosides inAbelmoschus manihotwhich will be helpful for fully understanding the mechanism of action of this herb. Furthermore, this work demonstrated the potential of the UPLC/QTOFMS approach using MetaboLynx for fast and automated identification of metabolites from Chinese herbal medicines. Copyright © 2010 John Wiley & Sons, Ltd.
Empirical approach to false discovery rate estimation in shotgun proteomics
Authors: Goloborodko Anton A. , Mayerhofer Corina , Zubarev Alexander R. , Tarasova Irina A. , Gorshkov Alexander V. , Zubarev Roman A. , Gorshkov Mikhail V. 
Published: January 2010

AbstractEstimation of false discovery rate (FDR) for identified peptides is an important step in large‐scale proteomic studies. We introduced an empirical approach to the problem that is based on the FDR‐like functions of sets of peptide spectral matches (PSMs). These functions have close values for equal‐sized sets with the same FDR and depend monotonically on the FDR of a set. We have found three of them, based on three complementary sources of data: chromatography, mass spectrometry, and sequences of identified peptides. Using a calibration on a set of putative correct PSMs these functions were converted into the FDR scale. The approach was tested on a set of ∼2800 PSMs obtained from rat kidney tissue. The estimates based on all three data sources were rather consistent with each other as well as with one made using the target‐decoy strategy. Copyright © 2010 John Wiley & Sons, Ltd.