bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of asymmetric cell divisions: will cnidarians provide an answer?
Authors: Bosch Thomas C.G.
Published: August 2004

Cells in the basal metazoan phylum Cnidaria are characterized by remarkable plasticity in their differentiation capacity. The mechanism controlling asymmetric cell divisions is not understood in cnidarians or in any other animal group. PIWI proteins recently have been shown to be involved in maintaining the self‐renewal capacity of stem cells in organisms as diverse as ciliates, flies, worms and mammals. Seipel et al.1 find that, in the cnidarian Podocoryne carnea, the Piwi homolog Cniwi is transcriptionally upregulated when the polyp generates buds, which will develop into medusae. Since transdifferentiation of striated muscle cells to smooth muscle cells also activated Cniwi expression, Cniwi appears to play a crucial role in differentiation events. The discovery should facilitate elucidation of the poorly understood factors that control asymmetric cell divisions at the beginning of animal evolution. BioEssays 26:929–931, 2004. © 2004 Wiley Periodicals, Inc.
Reduced protein adsorption at solid interfaces by sugar excipients
Authors: Wendorf Janet R. , Radke Clayton J. , Blanch Harvey W.
Published: August 2004

Sugar excipients are shown to reduce the adsorption of ribonuclease A, bovine serum albumin, and hen egg white lysozyme at the liquid–solid interface. The amount of protein adsorbed decreased as the concentration of the sugar increased. At the same sugar concentration, the ability of sugars to reduce protein adsorption followed the trend: trisaccharides > disaccharides > 6‐carbon polyols > monosaccharides. This trend in adsorbed protein amounts among sugars was explained by stabilization of the protein native state in solution by the sugar excipients. The heat of solution of the amorphous saccharide was found to correlate with the amount of protein adsorbed. © 2004 Wiley Periodicals, Inc.
Biooxidation of pyrite by defined mixed cultures of moderately thermophilic acidophiles in pH‐controlled bioreactors: Significance of microbial interactions
Authors: Okibe Naoko , Johnson D. Barrie
Published: August 2004

The oxidative dissolution of pyrite (FeS2) by pure and mixed cultures of moderately thermophilic acidophiles was studied in shake flask cultures and in pH‐controlled bioreactors, incubated at 45°C. Various combinations of seven eubacteria (a Leptospirillum sp. (MT6), Acidimicrobium ferrooxidans, Acidithiobacillus caldus, an Alicyclobacillus sp. (Y004), and three Sulfobacillus spp.) and one archaeon (Ferroplasma sp. MT17) were examined. Pyrite dissolution was determined by measuring changes in soluble iron and generation of acidity, and microbial populations were monitored using a combined culture‐dependent (plate counts) and culture‐independent (fluorescent in situ hybridization) approach. In pure cultures, the most efficient pyrite‐oxidizing acidophile was Leptospirillum MT6, which was unique among the prokaryotes used in being obligately autotrophic. Mixed cultures of Leptospirillum MT6 and the sulfur‐oxidizer At. caldus generated more acidity than pure cultures of the iron‐oxidizer, though this did not necessarily enhance pyrite dissolution. In contrast, a mixed culture of Leptospirillum MT6 and the obligate heterotroph Alicyclobacillus Y004 oxidized pyrite more rapidly and more completely than a pure culture of Leptospirillum MT6, in synchronized bioreactors. Although the autotroph, At. caldus, and the “heterotrophically inclined” iron‐oxidizer, Am. ferrooxidans, were both ineffective at leaching pyrite in pure culture, a mixed culture of the two bacteria was able to accelerate dissolution of the mineral. Concentrations of dissolved organic carbon accumulated to >100 mg/L in some mixed cultures, and the most effective bioleaching systems were found to be consortia containing both autotrophic and heterotrophic moderate thermophiles. A mixed culture comprising the autotrophs Leptospirillum MT6 and At. caldus, and the heterotroph Ferroplasma MT17, was the most efficient of all of those examined. Mutualistic interactions between physiologically distinct moderately thermophilic acidophiles, involving transfer of organic and inorganic carbon and transformations of iron and sulfur, were considered to have critical roles in optimizing pyrite dissolution. © 2004 Wiley Periodicals, Inc.
Estimating the potential refolding yield of recombinant proteins expressed as inclusion bodies
Authors: Ho Jason G. S. , Middelberg Anton P. J.
Published: August 2004

Recombinant protein production in bacteria is efficient except that insoluble inclusion bodies form when some gene sequences are expressed. Such proteins must undergo renaturation, which is an inefficient process due to protein aggregation on dilution from concentrated denaturant. In this study, the protein–protein interactions of eight distinct inclusion‐body proteins are quantified, in different solution conditions, by measurement of protein second virial coefficients (SVCs). Protein solubility is shown to decrease as the SVC is reduced (i.e., as protein interactions become more attractive). Plots of SVC versus denaturant concentration demonstrate two clear groupings of proteins: a more aggregative group and a group having higher SVC and better solubility. A correlation of the measured SVC with protein molecular weight and hydropathicity, that is able to predict which group each of the eight proteins falls into, is presented. The inclusion of additives known to inhibit aggregation during renaturation improves solubility and increases the SVC of both protein groups. Furthermore, an estimate of maximum refolding yield (or solubility) using high‐performance liquid chromatography was obtained for each protein tested, under different environmental conditions, enabling a relationship between “yield” and SVC to be demonstrated. Combined, the results enable an approximate estimation of the maximum refolding yield that is attainable for each of the eight proteins examined, under a selected chemical environment. Although the correlations must be tested with a far larger set of protein sequences, this work represents a significant move beyond empirical approaches for optimizing renaturation conditions. The approach moves toward the ideal of predicting maximum refolding yield using simple bioinformatic metrics that can be estimated from the gene sequence. Such a capability could potentially “screen,” in silico, those sequences suitable for expression in bacteria from those that must be expressed in more complex hosts. © 2004 Wiley Periodicals, Inc.
Establishment of FUT8 knockout Chinese hamster ovary cells: An ideal host cell line for producing completely defucosylated antibodies with enhanced antibody‐dependent cellular cytotoxicity
Authors: Yamane‐Ohnuki Naoko , Kinoshita Satoko , Inoue‐Urakubo Miho , Kusunoki Machi , Iida Shigeru , Nakano Ryosuke , Wakitani Masako , Niwa Rinpei , Sakurada Mikiko , Uchida Kazuhisa , Shitara Kenya , Satoh Mitsuo
Published: August 2004

To generate industrially applicable new host cell lines for antibody production with optimizing antibody‐dependent cellular cytotoxicity (ADCC) we disrupted both FUT8 alleles in a Chinese hamster ovary (CHO)/DG44 cell line by sequential homologous recombination. FUT8 encodes an α‐1,6‐fucosyltransferase that catalyzes the transfer of fucose from GDP‐fucose to N‐acetylglucosamine (GlcNAc) in an α‐1,6 linkage. FUT8−/− cell lines have morphology and growth kinetics similar to those of the parent, and produce completely defucosylated recombinant antibodies. FUT8−/−‐produced chimeric anti‐CD20 IgG1 shows the same level of antigen‐binding activity and complement‐dependent cytotoxicity (CDC) as the FUT8+/+‐produced, comparable antibody, Rituxan. In contrast, FUT8−/−‐produced anti‐CD20 IgG1 strongly binds to human Fcγ‐receptor IIIa (FcγRIIIa) and dramatically enhances ADCC to approximately 100‐fold that of Rituxan. Our results demonstrate that FUT8−/− cells are ideal host cell lines to stably produce completely defucosylated high‐ADCC antibodies with fixed quality and efficacy for therapeutic use. © 2004 Wiley Periodicals, Inc.
Change of extracellular cAMP concentration is a sensitive reporter for bacterial fitness in high‐cell‐density cultures of Escherichia coli
Authors: Lin Hongying , Hoffmann Frank , Rozkov Aleksei , Enfors Sven‐Olof , Rinas Ursula , Neubauer Peter
Published: August 2004

Guanosine‐3′,5′‐tetraphosphate (ppGpp) and σS, two regulators of the starvation response of Escherichia coli, have received increasing attention for monitoring cell physiological changes in production processes, although both are difficult to quantify. The kinetics of cAMP formation and degradation were not yet investigated in such processes, although the complex regulation of cAMP by synthesis, release, and degradation in connection with straightforward methods for analysis renders it a highly informative target. Therefore, we followed the cAMP concentration in various nonrecombinant and in four different recombinant glucose‐limited fed‐batch processes in different production scales. The intracellular cAMP concentration increases strongly at the end of the batch phase. Most cAMP is released to the cultivation medium. The rates of accumulation and degradation of extracellular cAMP are growth‐rate‐dependent and show a distinct maximum at a growth rate of about 0.35 h−1. At very low growth rates, below 0.05 h−1, extracellular cAMP is not produced but rather degraded, independent of whether this low growth rate is caused by glucose limitation or by the high metabolic load of recombinant protein production. In contrast to intracellular cAMP, which is highly unstable, analysis of extracellular cAMP is simpler and the kinetics of accumulation and degradation reflect well the physiological situation, including unlimited growth, limitation, and severe starvation of a production host. © 2004 Wiley Periodicals, Inc.
Real‐time update of calibration model for better monitoring of batch processes using spectroscopy
Authors: Kornmann Henri , Valentinotti Sergio , Marison Ian , Stockar Urs von
Published: August 2004

In order to reduce the large calibration matrix usually required for calibrating multiwavelength optical sensors, a simple algorithm based on the addition in process of new standards is proposed. A small calibration model, based on 14 standards, is periodically updated by spectra collected on‐line during fermentation operation. Concentrations related to these spectra are reconciled into best‐estimated values, by considering carbon and oxygen balances. Using this method, fructose, acetate, and gluconacetan were monitored during batch fermentations of Gluconacetobacter xylinus 12281 using mid‐infrared spectroscopy. It is shown that this algorithm compensates for noncalibrated events such as production or consumption of by‐products. The standard error of prediction (SEP) values were 0.99, 0.10, and 0.90 g/L for fructose, acetate, and gluconacetan, respectively. By contrast, without an updating of the calibration model, the SEP values were 2.46, 0.92, and 1.04 g/L for fructose, acetate, and gluconacetan, respectively. Using only 14 standards, it was therefore possible to approach the performance of an 88‐standard‐based calibration model having SEP values of 1.11, 0.37, and 0.79 g/L for fructose, acetate, and gluconacetan, respectively. Therefore, the proposed algorithm is a valuable approach to reduce the calibration time of multiwavelength optical sensors. © 2004 Wiley Periodicals, Inc.
Arabidopsisglycosyltransferases as biocatalysts in fermentation for regioselective synthesis of diverse quercetin glucosides
Authors: Lim Eng‐Kiat , Ashford David A. , Hou Bingkai , Jackson Rosamond G. , Bowles Dianna J.
Published: August 2004

Regioselectivity of glycosyltransferases offers an important means to overcome the limitations of chemical synthesis of small molecule glycosides. In this study we explore a large multigene family of UDP‐glucose:glycosyltransferases ofArabidopsisfor their potential as novel biocatalysts for in vitro synthesis and whole‐cell catalysis. We used quercetin as a substrate for this study because the flavonol and its glycosides have important medicinal properties and the metabolite provides a complex structure for regioselective glucosylation. We analyzed the activity of 91 recombinant enzymes for in vitro activity toward quercetin and discovered 29 that are capable of glucosylating the substrate. We demonstrate the first enzymic synthesis of a range of glucosides in vitro, including the 3‐O‐, 7‐O‐, 3′‐O‐, and 4′‐O‐monoglucosides, 3,7‐di‐O‐glucoside, and 7,3′‐di‐O‐glucoside. We also show that the regioselectivity of glucosylation can be maintained when the enzymes are used as whole‐cell biocatalysts inEscherichia coli. © 2004 Wiley Periodicals, Inc.
Brønsted Acidic Ionic Liquids and Their Zwitterions: Synthesis, Characterization and pKa Determination
Authors: Fei Zhaofu , Zhao Dongbin , Geldbach Tilmann J. , Scopelliti Rosario , Dyson Paul J.
Published: August 2004

Imidazolium chlorides with one or two carboxylic acid substituent groups, 1‐methyl‐3‐alkylcarboxylic acid imidazolium chloride, [Me{(CH2)nCOOH}im]Cl (n=1, 3), and 1,3‐dialkylcarboxylic acid imidazolium chloride, [{(CH2)nCOOH}2im]Cl (n=1, 3), have been synthesized via their corresponding acid esters. Deprotonation of the carboxylic acid functionalized imidazolium chlorides with triethylamine affords the corresponding zwitterions [Me{(CH2)nCOO}im] (n=1, 3) and [{(CH2)nCOOH}{(CH2)nCOO}im] (n=1, 3). Subsequent reaction of the zwitterions with strong acids gives the new imidazolium salts [Me{(CH2)nCOOH}im]X (n=1, 3; X=BF4, CF3SO3) and [{(CH2)nCOOH}2im]X (n=1, 3; X=BF4, CF3SO3), which exhibit melting points as low as −61 °C. The solid‐state structures of two of the carboxylic acid functionalized imidazolium salts have been determined by single‐crystal X‐ray diffraction analysis. Extensive hydrogen bonding is present between the chloride and the imidazolium, with eight Cl⋅⋅⋅H interactions below 3 Å. The pKa values of all the salts, determined by potentiometric titration, lie between 1.33 and 4.59 at 25 °C.
Machinable Long PVP‐Stabilized Silver Nanowires
Authors: Jiang Peng , Li Shun‐Yu , Xie Si‐Shen , Gao Yan , Song Li
Published: August 2004

PVP‐capped silver nanowires with a diameter range from 150 to 200 nm and a length range from 50 to 100 μm have been synthesized in large quantity by using a soft‐template liquid‐phase method. The so‐obtained longer and thicker metallic nanowires exhibit fivefold‐twinned structures bound by five {1 0 0} wall‐planes and two spearlike ends around five {1 1 1} facets. X‐ray photoelectron spectroscopy (XPS) investigations show that a strong interaction exists between the carboxyl oxygen atom (CO) of PVP and the Ag core interface. The PVP‐capped Ag nanowires can either self‐assemble into ordered raft structures or form a complicated network, depending on the dispersive solvent employed. In addition, the Ag nanowires can also be specifically bent into various angles, demonstrating their excellent mechanical stability.
Diverted Total Synthesis and Biological Evaluation of Gambierol Analogues: Elucidation of Crucial Structural Elements for Potent Toxicity
Authors: Fuwa Haruhiko , Kainuma Noriko , Tachibana Kazuo , Tsukano Chihiro , Satake Masayuki , Sasaki Makoto
Published: August 2004

Gambierol is a polycyclic ether toxin, which has been isolated from the marine dinoflagellate Gambierdiscus toxicus. A series of gambierol analogues have been prepared from an advanced intermediate of our total synthesis of gambierol and investigated for their toxicity against mice, thus providing the first systematic structure–activity relationships (SAR) of this polycyclic ether class of marine toxin. The SAR studies described herein clearly indicate that 1) the C28C29 double bond within the H ring and the unsaturated side chain are the crucial structural elements required for exerting potent biological activity and 2) the C1 and C6 hydroxy groups, the C30 methyl group, and the C37C38 double bond have little influence on the degree of neurotoxicity against mice.
Synergic Binding of Carbon Monoxide and Cyanide to the FeMo Cofactor of Nitrogenase: Relic Chemistry of an Ancient Enzyme?
Authors: Pickett Christopher J. , Vincent Kylie A. , Ibrahim Saad K. , Gormal Carol A. , Smith Barry E. , Fairhurst Shirley A. , Best Stephen P.
Published: August 2004

The first electrochemical and infra‐red data on the binding of cyanide to the isolated iron–molybdenum cofactor of nitrogenase, FeMoco, is described. It is shown that cyanide stabilises a hitherto unrecognised, low‐spin, EPR‐active (S=${{ 1/2 }}$), superoxidised form of FeMoco, and we provide the first evidence that carbon monoxide and cyanide bind synergically to the oxidised and semireduced states of the isolated cofactor, states which are unreactive to carbon monoxide alone.
New Amphiphilic Silicon(IV) Phthalocyanines as Efficient Photosensitizers for Photodynamic Therapy: Synthesis, Photophysical Properties, and in vitro Photodynamic Activities
Authors: Lo Pui‐Chi , Huang Jian‐Dong , Cheng Diana Y. Y. , Chan Elaine Y. M. , Fong Wing‐Ping , Ko Wing‐Hung , Ng Dennis K. P.
Published: August 2004

A novel series of silicon(IV) phthalocyanines substituted axially with one or two 1,3‐bis(dimethylamino)‐2‐propoxy group(s) have been prepared by ligand substitution and alkoxy exchange reactions. Two dicationic and tetracationic phthalocyanines have also been prepared by methylation of two of these compounds. The nonionic phthalocyanines are essentially nonaggregated in common organic solvents and show a weak fluorescence emission, while the methylated derivatives are also nonaggregated, even in aqueous media, and exhibit a strong fluorescence emission. These new phthalocyanines, in particular the unsymmetrical and amphiphilic analogues, are highly potent against HepG2 human hepatocarcinoma cells and J774 mouse macrophage cells with IC50 values down to 0.02 μM. The photodynamic activities are related to the cellular uptake and the efficiency to generate singlet oxygen. A higher positive charge at the phthalocyanine hinders the uptake, reflected by the lower intracellular fluorescence intensity. Fluorescence microscopic studies have also revealed that the unsymmetrical phthalocyanine SiPc[C3H5(NMe2)2O](OMe) (4) has a high and selective affinity to the mitochondria of HepG2 cells.
Enantioselective Cyanosilylation of Ketones by a Catalytic Double‐Activation Method with an Aluminium Complex and an N‐Oxide
Authors: Chen Fu‐Xue , Zhou Hui , Liu Xiaohua , Qin Bo , Feng Xiaoming , Zhang Guolin , Jiang Yaozhong
Published: August 2004

Double‐activation catalysis promises high catalytic efficiency in the enantioselective cyanosilylation of ketones through the combined use of a Lewis acid and a Lewis base. Catalyst systems composed of a chiral salen–Al complex and an N‐oxide have high catalytic turnovers (200 for aromatic ketones, 1000 for aliphatic ones). With these catalysts, a wide range of aliphatic and aromatic ketones were converted under mild conditions into tertiary cyanohydrin O‐TMS ethers in excellent yields and with high enantioselectivities (94 % ee for aromatic ketones, 90 % ee for aliphatic ones). Preliminary mechanistic studies revealed that the salen–Al complex played the role of a Lewis acid to activate the ketone and the N‐oxide that of a Lewis base to activate TMSCN; that is, double activation.
Leukemia incidence following primary breast carcinoma treatment
Authors: Kaplan Henry G. , Malmgren Judith A. , Atwood Mary
Published: August 2004

BACKGROUND

The results of randomized clinical trials have suggested that after receiving radiotherapy and/or chemotherapy, patients with primary breast carcinoma have an increased risk of developing leukemia. In the current study, the authors set out to assess the reported association between breast carcinoma treatment and leukemia risk.

METHODS

A registry of all patients with breast carcinoma who were treated at a community‐based institution since 1989 (updated annually for recurrence and/or vital status) was linked to the National Cancer Institute Surveillance, Epidemiology, and End Results database to confirm complete ascertainment of leukemia cases occurring within this registry population. Incidence rates were calculated for women who were treated for primary Stage 0–III breast carcinoma and had a follow‐up duration of ≥ 24 months (n = 2866). Patients who did not undergo surgery (n = 5), patients for whom chemotherapy records were incomplete or who received nonstandard chemotherapy regimens (n = 69), patients who underwent stem cell transplantation (n = 83), and patients who were lost to follow‐up or who had unknown disease status at follow‐up (n = 81) were excluded from the analysis (total, n = 238).

RESULTS

Among patients diagnosed with breast carcinoma between 1992 and 1999, the crude overall leukemia incidence rate was 0.28%, and the acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS) incidence rate was 0.11%. The average follow‐up duration was 5.46 years (minimum, 2 years). Eight incident cases of leukemia were documented (2 cases of AML, 1 case of acute lymphoblastic leukemia, 1 case of MDS/refractory anemia with excess blasts, 2 cases of chronic myelogenous leukemia, and 2 cases of chronic lymphocytic leukemia). National age‐adjusted overall leukemia incidence rates for the period 1996–1998 predict the occurrence of 9 cases (incidence rate, 0.31%) in the current cohort of women ages 21–94 years. The incidence of leukemia by treatment category was as follows: no surgery/no chemotherapy/no radiotherapy, 2 of 154 patients (1.30%); surgery/no chemotherapy/radiotherapy, 4 of 1403 patients (0.29%); surgery/chemotherapy/no radiotherapy, 0 of 352 patients (0%); and surgery/chemotherapy/radiotherapy, 2 of 957 patients (0.21%).

CONCLUSIONS

In contrast to findings reported from previous randomized clinical trials, the authors did not find evidence of increased posttreatment leukemia incidence in association with the use of chemotherapy, including doxorubicin‐based regimens. Cancer 2004. © 2004 American Cancer Society.
The computation of deterministic bounds to multiplexed MPEG video traffic using z‐characterization
Authors: Poon Wai‐Chung , Lo Kwok‐Tung
Published: August 2004

In this paper, we propose a method called z‐characterization for computing the deterministic bounds of an aggregated MPEG stream at frame level. Traditional deterministic characterization methods like empirical envelope generally suffer from the drawback of high computation complexity. In our approach, the I, P and B sub‐traces of an MPEG trace will be characterized independently such that they possess their own empirical envelopes. By exploiting the periodic group‐of‐pictures (GOP) structure of MPEG video, the I, P and B sub‐envelopes can act as building blocks for computing the characterization of the aggregate stream in real‐time. Experimental results show that our proposed characterization closely bounds the empirical envelope in both homogenous and heterogeneous multiplexing scenarios. Copyright © 2004 John Wiley & Sons, Ltd.
Dinuclear CuII Complexes with a New Phenol‐Based Ligand Bearing Pyridine and Thiophene Substituents: Synthesis, Characterization and Interaction with Catechol Substrates
Authors: Koval Iryna A. , Huisman Mieke , Stassen Arno F. , Gamez Patrick , Roubeau Olivier , Belle Catherine , Pierre Jean‐Louis , Saint‐Aman Eric , Lüken Matthias , Krebs Bernt , Lutz Martin , Spek Anthony L. , Reedijk Jan
Published: August 2004

The reaction of the phenol‐based ligand 4‐methyl‐2,6‐bis{[(2‐methylpyridyl)(2‐methylthiophenyl)amino]methyl}phenol(Hpy2th2s), containing pyridine and thiophene substituents, with copper(II) chloride and bromide yields two new dinuclear complexes with the composition [Cu2(py2th2s)X3], where X = Cl or Br. In both complexes, the copper(II) ions are pentacoordinate and bridged by the deprotonated phenolate anion and by one halogen anion. Both complexes exhibit geometric asymmetry, as the coordination environment around one of the two copper ions is square‐pyramidal, whereas the geometry around the other can be best described as a distorted trigonal bipyramid. The complexes were characterized by means of X‐ray single‐crystal diffraction, ligand field and EPR spectroscopy, mass spectrometry, and electrochemically. Magnetic susceptibility measurements indicate an antiferromagnetic coupling between the two metal centers (2J ≈︁ −200 cm−1). The interaction of the complexes with model substrates 3,5‐di‐tert‐butylcatechol and tetrachlorocatechol is reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
A New Synthetic Method and Solution Equilibria for the Chlorotitanate(IV) Anions − Evidence for the Existence of a New Species: [Ti2Cl11]3−
Authors: Robé Emmanuel , Daran Jean‐Claude , Vincendeau Sandrine , Poli Rinaldo
Published: August 2004

TiCl3 is oxidized by SOCl2 in the presence of the appropriate amount of [NEt3Bz]Cl or [PPN]Cl [Bz = benzyl; PPN = bis(triphenylphosphanyl)iminium] to afford the corresponding salts of [Ti2Cl9]−, [Ti2Cl10]2− or [TiCl6]2−. The results of cyclic voltammetric and solution IR studies in the Ti−Cl stretching region are interpreted in terms of a rapid chloride‐redistribution equilibrium between [Ti2Cl10]2− on one side and a mixture of [Ti2Cl9]− and a previously unreported [Ti2Cl11]3− species on the other side. In the solid state, however, a compound with the [PPN]3[Ti2Cl11] stoichiometry exists as a mixture of [PPN]2[Ti2Cl10] and [PPN]2[TiCl6]. The PPN salt of [Ti2Cl9]− has been structurally characterized by X‐ray diffractometry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Mono(alkyne)cobalt Complexes and Electron‐Rich Alkynes − The Formation of an Alkyne‐Bridged Dinuclear Cobalt Complex by a One‐Pot Procedure
Authors: Werz Daniel B. , Gleiter Rolf , Rominger Frank
Published: August 2004

[η2‐Bis(tert‐butylsulfonyl)acetylene](carbonyl)(η5‐trimethylsilylcyclopentadienyl)cobalt (2c) proved to be reactive towards bis(telluro)‐ and bis(seleno)‐substituted alkynes 3 and 4, respectively, to yield push‐pull‐substituted CpCo‐stabilized cyclobutadiene complexes. By utilizing the unsymmetrical diyne 6 and the symmetrical bis(thio)‐substituted triyne 7 it was shown that only the most electron‐rich triple bond was attacked by the electrophilic compound 2c. In the case of 7 a dinuclear CpCo‐stabilized cyclobutadiene complex 14 bridged by one acetylene moiety was obtained. All the reactions could be carried out at room temperature under rather mild conditions. X‐ray investigations of 8, 12, 14a, and 15 show almost equal C−C bond lengths in the cyclobutadiene moieties. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Comparability and reliability of different techniques for the determination of phenolic compounds in virgin olive oil
Authors: Hrncirik Karel , Fritsche Sonja
Published: August 2004

Phenolic compounds represent a unique and functional part of the polar fraction of virgin olive oils. Many different approaches for the analysis of these compounds have been published, which has led to ambiguous results that are difficult to compare. In order to explain the controversial data reported in the literature, extraction techniques (solid‐phase extraction, SPE, and liquid‐liquid extraction, LLE), methods of analysis (HPLC and colorimetric assay) and quantification methods have been re‐investigated with genuine olive oil phenols. The optimized LLE system led to high recovery of the nine major olive oil phenolics (93%) and, in addition, was at least as good as the SPE technique in view of costs, solvent and sample consumption, and analysis time. SPE was shown to be problematic because of the selectivity towards the individual phenolics, particularly the aglycone‐type ones. The proposed LLE/HPLC method was compared with the traditional colorimetric assay (Folin‐Ciocalteu method) by analyzing 23 samples of virgin olive oils. A strong correlation between both methods has been found, suggesting that the colorimetric assay is reasonably valid for a rough prediction of the total phenolic content. In the literature, the level of phenolics is expressed in several different units (reference compound equivalents in case of colorimetric measurements and ppm in HPLC measurements). As these units can differ in orders of magnitude, it is necessary to convert the data to a common base before comparing or combining them.
Analysis of genetic effects and heritabilities for linoleic and α‐linolenic acid content of Brassica napus L. across Chinese environments
Authors: Zhang Haizhen , Shi Chunhai , Wu Jianguo , Ren Yuling , Li Changtao , Zhang Dongqing , Zhang Yaofeng
Published: August 2004

A genetic model for quantitative traits of seed in diploid plant was applied to analyze the main genetic effects and genotype × environment (GE) interaction effects for linoleic and α‐linolenic acid content of rapeseed (Brassica napus L.) by using two year experimental data with 8 parents and their F1 and F2. Results indicated that the performance of linoleic (C18:2) and α‐linolenic acid content (C18:3) of rapeseed were simultaneously controlled by diploid embryo nuclear genes, cytoplasmic genes and diploid maternal plant nuclear genes, and the GE interaction effects for these two seed quality traits were more important than the genetic main effects. The total narrow‐sense heritability was 69.5% and 41.8% for C18:2 and C18:3, respectively, and the GE interaction heritabilities were found to be larger than the general heritabilities for both quality traits. It was suggested by the predicted genetic effects that Huashuang 3 was better than other parents for improving offspring of C18:2 and Youcai 601, Zhongyou 821, Eyouchangjia and Zhong R‐888 for decreasing C18:3.
Degradation of the oxirane ring of epoxidized vegetable oils with solvated acetic acid using cation‐exchange resins
Authors: Campanella Alejandrina , Baltanás Miguel A.
Published: August 2004

Vegetable oil epoxides (oxiranes) are customarily manufactured using acetic acid (AA) as oxygen carrier and reactant source, in aqueous/organic media. Further attack of the oxirane ring by AA proceeds in this acid‐catalyzed process, lowering yield. We report a study of the degradation of the ring by water‐solvated AA, using Amberlite IR‐120 as heterogeneous catalyst. The ring opening with solvated AA was found to be first order with respect to the concentration of epoxide groups and second order with respect to the carboxylic acid, with an activation energy of 58.7 ± 0.42 kJ mol−1. This value is within the range found in liquid‐liquid systems (51.3–66.3 kJ mol−1). Yet, using IR‐120, the degradation increases identically either by adding more mass of catalyst or by reducing its particle diameter while keeping the total mass constant, as both situations lead to higher external (exposed) area of the acidic catalyst (i.e., free protons associated to the sulfonic group) on the outer surface of the ion exchange resin beads. These free protons, in turn, become available to catalyze the attack on the oxirane groups of the long‐chain fatty acids, which cannot enter (diffuse) into the gel phase of the resin. Despite the unavoidable presence of surface‐exposed protons, the degradation can be reduced by several orders of magnitude – for similar process conditions – by using this type of heterogeneous catalysts instead of mineral acids.
The prediction of fatty acid structure from selected ions in electron impact mass spectra of fatty acid methyl esters
Authors: Mjøs Svein A.
Published: August 2004

The possibility of fatty acid identification from ions in the mass region of 50–110 amu in electron impact mass spectra has been studied by application of various multivariate techniques. The focus has mainly been on the prediction of the number of double bonds in methylene‐interrupted polyunsaturated fatty acids isolated from marine lipids.

The number of double bonds in these fatty acids could be predicted with high accuracy, both by partial least squares regression on all ions in this region, and by multiple linear regressions on selected subsets of 5–6 ions. The subsets with optimal predictive power have been found, and the ability to distinguish between methylene interrupted polyunsaturated fatty acids and other fatty acids have also been evaluated.
Syntheses of 3‐C‐Methylceramides
Authors: Sawatzki Peter , Kolter Thomas
Published: August 2004

We report on the synthesis of a series of 3‐C‐methylceramide derivatives 2a,b, 12a,b, 13a,b, and 14a,b. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Electron‐Transfer‐Initiated Cascade Cyclizations of Terpenoid Polyalkenes in a Low‐Polarity Solvent: One‐Step Synthesis of Mono‐ and Polycylic Terpenoids with Various Functionalities
Authors: Ozser Mustafa E. , Icil Huriye , Makhynya Yevgeny , Demuth Martin
Published: August 2004

A methodology for the one‐step synthesis of cyclic polyalkene terpenoids in a low‐polarity solvent (dichloromethane) by photoinduced electron transfer (PET) is described. For the efficiency of such processes in low‐polarity solvents, the use of the cationic electron acceptor N‐methylquinolinium hexafluorophosphate is vital. The first direct cyclizations of farnesol and geranylgeraniol to the corresponding all‐trans‐fused 6,6‐ and 6,6,6‐cyclic products are also reported. The mechanism of the termination of the cyclizations is also discussed, isotope‐labeling experiments having shown that it proceeds through reduction of the final radical to the corresponding anion, followed by protonation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
C−C Bond Formation at Ozonide Rings by Substitution of Chlorinated Ozonides
Authors: Griesbaum Karl , Quinkert Ralf‐Olaf , McCullough Kevin J.
Published: August 2004

The TiCl4‐mediated substitution of 3‐chloro‐3,5‐bis(chloromethyl)‐5‐methyl‐1,2,4‐trioxolane (1) with 1‐(trimethylsilyloxy)cyclopentene (4), 2‐methyl‐1‐(trimethylsilyloxy)propene (6) and allyltrimethylsilane (12) gave the corresponding 2‐oxocyclopentyl‐, 1,1‐dimethyl‐2‐oxo‐ethyl‐ and allyl‐substituted ozonides 5, 7 and 13, respectively. Substitution of 3,5‐dichloro‐3,5‐bis(chloromethyl)‐1,2,4‐trioxolane (2) with allyltrimethylsilane (12) gave the diallyl‐substituted ozonide 14. Ozonolysis of the allyl‐substituted ozonide 13 provided the corresponding diozonide 17, and ozonolysis of the diallyl‐substituted ozonide 14 provided the corresponding diozonide 18 and triozonide 19. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Brominated 4‐(Trifluoromethyl)pyrimidines: A Convenient Access to Versatile Intermediates
Authors: Ondi Levente , Lefebvre Olivier , Schlosser Manfred
Published: August 2004

An expedient route to all three monobrominated and all three dibrominated isomers of 4‐(trifluoromethyl)pyrimidine, and to several other halogenated pyrimidines, is described. Key steps are the electrophilic introduction of the halogen in the 5‐position of 2‐ or 4‐pyrimidinones, the bromodeoxygenation of pyrimidinones or thiopyrimidinones using phosphorus tribromide, and the partial debromination of dibromo‐4‐(trifluoromethyl)pyrimidines. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Convenient, Benign and Scalable Synthesis of 2‐ and 4‐Substituted Benzylpiperidines
Authors: Ágai Béla , Proszenyák Ágnes , Tárkányi Gábor , Vida László , Faigl Ferenc
Published: August 2004

A short, scalable and environmentally benign synthesis of 2‐ and 4‐substituted benzylpiperidines has been developed. The method is based on the temperature‐programmed consecutive deoxygenation and heteroaromatic ring saturation of aryl(pyridin‐2‐yl)‐ and aryl(pyridin‐4‐yl)methanols and aryl(pyridin‐4‐yl)methanones in the presence of Pd/C catalyst. The crucial roles of the temperature, the acidity and the substrate structure in the change of selectivity have been demonstrated by isolation of several substituted aryl(piperidine)methanols. The carbinols and ketones were prepared from commercially available pyridinecarbaldehydes or 4‐cyanopyridine and substituted bromobenzenes via organometallic intermediates. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Towards a Total Synthesis of Quinocarcin: Diastereoselective Synthesis of Functionalized Azepino[1,2‐b]isoquinolines
Authors: Koepler Oliver , Laschat Sabine , Baro Angelika , Fischer Peter , Miehlich Burkhard , Hotfilder Marc , le Viseur Christoph
Published: August 2004

1,3‐Disubstituted tetrahydro‐oxazolo‐isoquinolinones 19a,b were obtained from phenylalanine in seven steps and 42% overall yield by Katritzky’s benzotriazole method. The tricyclic oxazolidinone 19a was further converted into amino alcohol 10 by employing a chemoselective reduction of the ester group with LiBH4/MeOH. Compound 10 and the corresponding 1‐unsubstituted tetrahydroisoquinoline alcohol 11 were converted into aldehydes 27 and 33, which cyclized in the presence of different Lewis acids to give the substituted azepino[1,2‐b]isoquinolines 34 and 35, respectively, which are key structural features of the alkaloid quinocarcin. The stereoselectivities of the Lewis‐acid‐catalyzed hetero‐ene reaction are highly dependent on the substitution pattern and the type of Lewis acid. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
N‐Tetrachlorophthaloyl (TCP) Protection for Solid‐Phase Peptide Synthesis
Authors: Cros Esther , Planas Marta , Barany George , Bardají Eduard
Published: August 2004

The N‐tetrachlorophthaloyl‐(TCP‐)amino protecting group has been evaluated for use in solid‐phase peptide synthesis. The TCP group was unaffected by exposure to either piperidine or N,N‐diisopropylethylamine (DIEA), which suggests compatibility with both Fmoc and Boc solid‐phase synthesis protocols. Quantitative TCP removal was achieved by treatment with hydrazine/DMF (3:17) at 35 °C for 30 min or with ethylenediamine/DMF (1:200) at 50 °C for 30 min. Several C‐terminal peptide amides were synthesized successfully by following protocols that use hydrazine/DMF (3:17) at 40 °C for 1 h for repetitive deprotection. Treatment of TCP‐amines with methylamine or with diamines did not give the corresponding amines (deprotected), but rather the appropriate N,N′‐disubstituted tetrachlorophthalamides, which corresponds to a single ring‐opening step. This observation was harnessed to prepare linear and macrocyclic peptide−arene hybrids based on the mild reaction of the parent TCP compound with 1,3‐diaminopropane/DMF (1:49) at 25 °C for 5 min. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Application of Furan as a Diene: Preparation of Condensed 1,3‐Oxazines by Retro‐Diels−Alder Reactions
Authors: Stájer Géza , Miklós Ferenc , Kanizsai Iván , Csende Ferenc , Sillanpää Reijo , Sohár Pál
Published: August 2004

(Di‐exo‐3‐amino‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐yl)methanol (3) was treated with oxo carboxylic acids [p‐toluoylpropionic acid, cis‐ or trans‐(p‐toluoyl)cyclohexanecarboxylic acid, ‐benzoic acid or methanobenzocyclooctenecarboxylic acid] to furnish the oxanorbornene‐fused pyrrolo[1,3]oxazine 4, the isoindolo[1,3]oxazines 5 and 6, and the methanobenzocyclooctenepyrrolo[1,3]oxazine 10, together with the retro‐Diels−Alder products pyrrolooxazinone 7, oxazinoisoindolones 8 and 9, and oxazinopyrrolobenzocyclooctene 11. On reflux in chlorobenzene, furan was released from the oxanorbornene heterocycles 5 and 10 to give the retro‐Diels−Alder products. The structures of the new compounds were established by NMR spectroscopy and also (for 6 and 9) by single‐crystal X‐ray structure determination. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Lithium Bromide, an Inexpensive and Efficient Catalyst for Opening of Epoxide Rings by Amines at Room Temperature under Solvent‐Free Condition
Authors: Chakraborti Asit K. , Rudrawar Santosh , Kondaskar Atul
Published: August 2004

Lithium bromide has been found to be an inexpensive and efficient catalyst for the opening of epoxide rings by amines, and this provides an environmentally friendly method for the synthesis of β‐amino alcohols. Aromatic and aliphatic amines react with cycloalkene oxides to exclusively form trans‐2‐(aryl/alkylamino)cycloalkanols in high yields. A 98−100% selectivity in favour of nucleophilic attack at the benzylic carbon atom of styrene oxide is observed with aromatic amines. However, aliphatic amines exhibit a marginal preference for the reaction at the terminal carbon atom of the epoxide ring in styrene oxide. Non‐styrenoidal, unsymmetrical alkene oxides undergo selective nucleophilic attack at the sterically less hindered carbon atom by aniline. The chelation effect of the Li+ ion enables selective opening of the epoxide ring in 3‐phenoxypropylene oxide in the presence of styrene oxide. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Enantiomeric separation of neutral hydrophobic dihydrofuroflavones by cyclodextrin‐modified micellar capillary electrophoresis
Authors: Lantz Andrew W. , Rozhkov Roman V. , Larock Richard C. , Armstrong Daniel W.
Published: August 2004

The enantiomeric separations of several very hydrophobic dihydrofuroflavones were performed and optimized using cyclodextrin‐modified micellar capillary electrophoresis. Overall, the greatest enantiomeric peak‐to‐peak separations for the greatest number of flavones were obtained with hydroxypropyl‐γ‐cyclodextrin. The effects of cyclodextrin and sodium dodecyl sulfate concentration and pH were examined in order to optimize the separation conditions. The ratio of surfactant‐to‐cyclodextrin concentration affected the chiral discrimination of the system significantly, with increases in the derivatized cyclodextrin concentration generally enhancing resolution. Higher efficiencies were obtained with lower concentrations of surfactant and cyclodextrin, although enantioseparation optimization often required higher concentrations to be used. A highly acidic pH was necessary to effectively suppress the electroosmotic flow when operating in the reversed polarity mode. Experiments utilizing the normal polarity mode and higher pH produced no separations.
Enantioselectivity of structurally modified poly(sodium undecenoyl‐L‐leucinate) by insertionof Triton X‐102 surfactant molecules
Authors: Tarus Jepkoech , Jernigan Thomasas , Morris Kevin , Warner Isiah M.
Published: August 2004

The effectiveness of Triton X‐102 (TX‐102), as a structural modifier of the polymeric surfactant sodium undecanoyl‐L‐leucinate (L‐SUL) was investigated for enhanced enantiomeric recognition of various chiral compounds in micellar electrokinetic chromatography (MEKC). Increasing concentrations of TX‐102 were separately added into the micellar solutions of L‐SUL and then polymerized to form poly‐L‐SUL. The resulting polymers were purified by use of 3500 molecular‐weight‐cutoff (MWCO) dialysis membranes. Fluorescence and pulsed field gradient‐nuclear magnetic resonance (PFG‐NMR) techniques were used to elucidate the structural effects of TX‐102 on poly‐L‐SUL. Evaluation of data from fluorescence measurements suggested an increase in polarity with increasing concentration of TX‐102. However, the polarity decreased at higher concentrations of TX‐102. Evaluation of data from PFG‐NMR suggested an increase in hydrodynamic radius upon increasing the concentration of TX‐102. The racemates of coumarinic and phenythiohydantoin amino acid derivatives, and pindolol were used as test analytes in MEKC. A notable increase in resolution and capacity factors of the test analytes was observed when the modified poly‐L‐SUL was used in MEKC measurements. Examination of the data obtained from fluorescence, PFG‐NMR, and MEKC suggests a strong correlation between the polarity and the hydrodynamic radii of TX‐102 modified micelles and the enantiomeric resolution of the test analytes.
Single‐isomer sulfated α‐cyclodextrins for capillary electrophoresis: Hexakis(2,3‐di‐O‐methyl‐6‐O‐sulfo)‐α‐cyclodextrin, synthesis, analytical characterization, and initial screening tests
Authors: Li Shulan , Vigh Gyula
Published: August 2004

The third, concluding member of the family of single‐isomer, fully sulfated α‐cyclodextrins, the sodium salt of hexakis(2,3‐di‐O‐methyl‐6‐O‐sulfo)‐α‐cyclodextrin (HxDMS), has been synthesized on the kilogram scale, completing the nine‐member array of the single‐isomer, 6‐O‐sulfo CDs now available. HxDMS was tested for the capillary electrophoretic (CE) resolution of the enantiomers of nonelectrolyte, weak acid and weak base analytes contained in our CD screening kit. HxDMS complexed differently with many of the analytes tested than either its larger‐ring analogs, heptakis(2,3‐di‐O‐methyl‐6‐O‐sulfo)‐β‐CD (HDMS) and octakis(2,3‐di‐O‐methyl‐6‐O‐sulfo)‐γ‐CD (ODMS) or its same‐ring, but differently substituted analogs, hexakis(6‐O‐sulfo)‐α‐CD (HxS) and hexakis(2,3‐di‐O‐acetyl‐6‐O‐sulfo)‐α‐CD (HxDAS). For all analytes, the effective mobilities and separation selectivities as a function of the background electrolyte concentration of HxDMS followed the trends that were found for the other single‐isomer, 6‐O‐sulfo CDs.
Chiral separation of N‐imidazole derivatives, aromatase inhibitors, by cyclodextrin‐capillary zone electrophoresis. Mechanism of enantioselective recognition
Authors: Foulon Catherine , Danel Cécile , Vaccher Marie‐Pierre , Bonte Jean‐Paul , Vaccher Claude , Goossens Jean‐François
Published: August 2004

Baseline separation of ten new, substituted [1‐(imidazo‐1‐yl)‐1‐phenylmethyl)] benzothiazolinone and benzoxazolinone derivatives with one chiral center was achieved using cyclodextrin‐capillary zone electrophoresis (CD‐CZE). A method for the enantiomeric resolution of these compounds was developed using neutral CDs (native α‐, β‐, γ‐CDs or α‐, β‐, γ‐hydroxypropyl (HP)‐CDs) as chiral selectors. Operational parameters including the nature and concentration of the chiral selectors, pH, ionic strength, organic modifiers, temperature, and applied voltage were investigated. The use of neutral CDs provides enantiomeric resolution by inclusion of compounds in the CD cavity. The HP‐α‐CD and HP‐β‐CD were found to be the most effective complexing agents and allowed efficient enantiomeric resolutions. Optimal separation of N‐imidazole derivatives was obtained using 50 mM phosphate buffer at pH 2.5 containing either HP‐α‐CD or HP‐β‐CD (7.5–12.5 mM) at 25°C, with an applied field of 0.50 kV·cm−1 giving resolution factors Rs superior to 1.70 with migration times of the second enantiomer less than 13 min. The same enantiomer migration order observed for all molecules can be related to a close interaction mechanism with CDs. The influence of structural features of the solutes on Rs and tm was studied. The lipophilic character (log kw) of the solutes and the apparent and averaged association constants of inclusion complexes for four compounds with the six different CDs led us to rationalize the enantioseparation mechanisms. The conclusions were corroborated with reversed‐phase high‐performance liquid chromatography (HPLC) on chiral stationary phases (CSPs) based on CDs.