bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Biological Evaluation of a Lipid A Derivative That Contains an Aminogluconate Moiety
Authors: Santhanam Balaji , Wolfert Margreet A. , Moore James N. , Boons Geert‐Jan
Published: August 2004

A highly convergent strategy for the synthesis of several derivatives of the lipid A of Rhizobium sin‐1 has been developed. The synthetic derivatives are 2‐aminogluconate 3 and 2‐aminogluconolactone 4, both of which lack C‐3 acylation. These derivatives were obtained by the preparation of disaccharides in which the two amino groups and the C‐3′ hydroxy group could be modified individually with acyl or β‐hydroxy fatty acyl groups. Detailed NMR spectroscopy and MS analysis of 3 and 4 revealed that, even under neutral conditions, the two compounds equilibrate. The synthetic compounds lack the proinflammatory effects of Escherichia coli lipopolysaccharide (LPS), as indicated by an absence of tumor necrosis factor production. Although 3 and 4 were able to antagonize E. coli LPS, they were significantly less potent than the synthetic compound 2, which is acylated at C‐3, and R. sin‐1 LPS; these results indicate that the β‐hydroxy fatty acyl group at C‐3 contributes to the antagonistic properties of R. sin‐1 LPS. Based on a comparison of the biological responses of the synthetic lipid A derivatives with those of the R. sin‐1 LPS and lipid A, the 3‐deoxy‐D‐manno‐octulosonic moieties appear to be important for the optimal antagonization of enteric LPS‐induced cytokine production.
Synthesis and Stereochemical Properties of Chiral Square Complexes of Iron(II)
Authors: Bark Thomas , von Zelewsky Alexander , Rappoport Dmitrij , Neuburger Markus , Schaffner Silvia , Lacour Jérôme , Jodry Jonathan
Published: August 2004

The hexadentate, and ditopic ligand 2,5‐bis([2,2′]bipyridin‐6‐yl)pyrazine yields a chiral, tetrameric, square‐shaped, self‐assembled species upon complexation with Fe2+ ions. The racemate of this complex was resolved with antimonyl tatrate as the chiral auxiliary. The purity of the enantiomer was determined by NMR spectroscopy, by using a chiral, diamagnetic shift reagent, and by circular dichroism (CD). The CD spectrum was also calculated by time‐dependent density functional theory, and the correlation that was found between CD spectrum and configuration was confirmed by X‐ray cristallography. When a “chiralised” version of the ligand was used instead, the corresponding iron complex was obtained in diastereomerically pure form.
Reactions of Hydrated Electrons (H2O)n− with Carbon Dioxide and Molecular Oxygen: Hydration of the CO2− and O2− Ions
Authors: Balaj O. Petru , Siu Chi‐Kit , Balteanu Iulia , Beyer Martin K. , Bondybey Vladimir E.
Published: August 2004

The gas‐phase reactions of hydrated electrons with carbon dioxide and molecular oxygen were studied by Fourier transform ion cyclotron resonance (FT‐ICR) mass spectrometry. Both CO2 and O2 react efficiently with (H2O)n− because they possess low‐lying empty π* orbitals. The molecular CO2− and O2− anions are concurrently solvated and stabilized by the water ligands to form CO2−(H2O)n and O2−(H2O)n. Core exchange reactions are also observed, in which CO2−(H2O)n is transformed into O2−(H2O)n upon collision with O2. This is in agreement with the prediction based on density functional theory calculations that O2−(H2O)n clusters are thermodynamically favored with respect to CO2−(H2O)n. Electron detachment from the product species is only observed for CO2−(H2O)2, in agreement with the calculated electron affinities and solvation energies.
Phenylmalonate‐Containing Copper(II) Complexes: Synthesis, Crystal Structure and Magnetic Properties
Authors: Pasán Jorge , Sanchiz Joaquín , Ruiz‐Pérez Catalina , Lloret Francesc , Julve Miguel
Published: August 2004

Three new copper(II) complexes of formula [Cu(2,2′‐bpy)(Phmal)(H2O)]·2H2O (1), [{Cu(2,2′‐bpym)(Phmal)}]n (2) and [{Cu(phen)(Phmal)}]n·3nH2O (3) (Phmal = phenylmalonate; 2,2′‐bpy = 2,2′‐bipyridine; 2,2′‐bpym = 2,2′‐bipyrimidine; phen = 1,10‐phenanthroline) have been prepared and their structures determined by X‐ray diffraction techniques. Complex 1 is mononuclear whereas 2 and 3 are uniform chain compounds. The copper atoms in 1−3 are distorted square‐pyramidal: two nitrogen atoms from the bidentate nitrogen heterocycle and two carboxylate oxygen atoms from the phenylmalonate ligand build the equatorial plane; the axial position is filled either by a water molecule (1) or a carboxylate oxygen atom from another phenylmalonate group (2 and 3). The values of the intrachain copper−copper separation through the phenylmalonate‐carboxylate bridge in the anti‐syn conformation are 4.6853(7) (2) and 5.014(3) Å (3). The phenyl ring of the Phmal ligand in 1 produces an unusual intramolecular π−π stacking interaction with the CuII−(aromatic 2,2′‐bpy) chelate ring. Intrachain edge‐to‐face phenyl−pyridyl and offset phen−phen‐type interactions occur in 2 and 3, respectively. Magnetic susceptibility measurements of 2 and 3 in the temperature range 1.9−290 K show the occurrence of weak intrachain ferromagnetic interactions between the copper(II) ions through the phenylmalonate‐carboxylate bridge [J = +0.10(1) (2) and +0.31(1) cm−1 (3)]. These values are compared with those reported for malonate‐containing copper(II) complexes with the same exchange pathway through the anti‐syn carboxylate bridge. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis and Characterization of Alkyllanthanum Biphenolate Complexes as Catalysts for Hydroamination/Cyclization and Hydrosilylation
Authors: Gribkov Denis V. , Hampel Frank , Hultzsch Kai C.
Published: August 2004

The homochiral, dimeric biphenolate alkyllanthanum complex [La{(R)‐Biphen}{CH(SiMe3)2}]2 can be prepared by facile alkane elimination starting from [La{CH(SiMe3)2}3] and enantiopure (R)‐3,3′‐di‐tert‐butyl‐5,5′,6,6′‐tetramethyl‐1,1′‐biphenyl‐2,2′‐diol [H2{(R)‐Biphen}]. Single‐crystal X‐ray diffraction revealed that the two La{(R)‐Biphen}{CH(SiMe3)2} fragments are connected through bridging phenolate groups of the biphenolate ligands. The two different phenolate groups undergo an intramolecular exchange process in solution leading to their equivalence on the NMR timescale. The biphenolate alkyl complex shows high catalytic activity for hydroamination/cyclization of aminoalkenes, similar to previously known lanthanocene catalysts, but only low enantioselectivity. Addition of THF to [La{(R)‐Biphen}{CH(SiMe3)2}]2 leads to a monomeric tris‐THF adduct [La{(R)‐Biphen}{CH(SiMe3)2}(THF)3] with higher catalytic activity than the THF‐free homochiral dimer in the cyclization of 2,2‐dimethylpent‐4‐enylamine, suggesting that the dimeric structure of the catalyst system prevails under catalytic conditions in the absence of THF. Addition of HN(SiHMe2)2 to [La{(R)‐Biphen}{CH(SiMe3)2}(THF)3] results in the formation of [La{(R)‐Biphen}{N(SiHMe2)2}(THF)3] which is in equilibrium with its homochiral dimer [La{(R)‐Biphen}{N(SiHMe2)2}(THF)]2 at elevated temperatures. The biphenolate alkyl complexes exhibit good catalytic activity and diastereoselectivity in the hydrosilylation of styrene. Hydrosilylation of 1‐hexene and norbornene also proceeds with high diastereoselectivity but rather low activity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Enzymatic synthesis of medium‐chain triacylglycerols by alcoholysis and interesterification of copra oil using a crude papain lipase preparation
Authors: Caro Yanis , Turon Fabrice , Villeneuve Pierre , Pina Michel , Graille Jean
Published: August 2004

We have examined the possibility of producing analogs of medium‐chain triglycerides (MCT) from copra oil, i.e. a triacylglycerol mixture with a high content of medium‐chain fatty acid moieties (C6–C10). A two‐step enzymatic process was used in which copra triacylglycerols were first split with papain lipase by alcoholysis with an alkyl alcohol and then subjected to interesterification with the alkyl esters recovered using papain lipase. Effects of temperature, water activity content, substrate ratio, biocatalyst amount, and alcohol chain length were also investigated. On the one hand, the sn‐3 stereoselectivity of the lipase in the alcoholysis of copra oil with butanol has permitted a direct enrichment of caproic, caprylic and capric moieties in the synthesized butyl esters. Thus, in the batch reactor, the reaction led to about 31% conversion of the oil after 24 h, and the content of C6–C10 acids in the synthesized esters increased from about 16% in the starting oil to almost 42%. A similar enzymatic alcoholysis in a packed‐bed column bioreactor gave 31% conversion of the oil after 120 min of reactor residence time. The reaction was also very selective because the C6–C10 fatty acyl groups represented about half of the newly formed butyl esters, whereas they accounted for only 16% of total fatty acids in the starting oil. On the other hand, the transesterification of the alkyl esters recovered (highly enriched in C6–C10 fatty acyl groups) with native copra oil directly led to an increase in the content of MCT in the oil, from 18 mol‐% at the beginning of the reaction to 61 mol‐% of MCT after a time period of 72 h in the batch reactor.
Temperature and concentration dependent effect of partial glycerides on milk fat crystallization
Authors: Foubert Imogen , Vanhoutte Bert , Dewettinck Koen
Published: August 2004

Two diglycerides (distearin and diolein) and two monoglycerides (monostearin and monoolein) were added to milk fat in a concentration of 0.5% and 1%. The isothermal crystallization behavior was evaluated at 22 °C, 23.5 °C, 25 °C and 26.5 °C by DSC and pNMR. The crystallization kinetic was quantified by means of two models. It was noticed that the effect of the minor components on the crystallization behavior depends on temperature and concentration. The type of esterified fatty acids and the polar head of the amphiphilic molecule determine to what extent partial glycerides influence the nucleation and crystal growth of triglycerides. Moreover the degree of insolubility of partial glycerides in the melt determines which effect (on growth or on nucleation) predominates. Stearic acid based partial glycerides enhance nucleation at low temperatures, while at higher temperatures an interaction with the crystal growth predominates. Oleic acid based partial glycerides have an effect on the nucleation process while no interaction with the crystal growth was observed.
Progress in the analysis of Stratum corneum ceramides
Authors: Raith Klaus , Farwanah Hany , Wartewig Siegfried , Neubert Reinhard H. H.
Published: August 2004

The stratum corneum with its unique structure of corneocytes and intercellular lipid lamellae enables a protection of human and other mammalian skin against transepidermal water loss and harmful substances from the environment. Among these lipids, ceramides play a key role. Several skin disorders such as psoriasis, atopic dermatitis and others show a disturbed barrier function, which can be linked in part to a changed ceramide pattern. Research in dermatology and cosmetic industry requires the use of analytical methods to characterize ceramides. However, the amazing variability of ceramide structures found in stratum corneum makes their analysis a challenge. This is to our knowledge the first review that deals with ceramide analysis. It is focused on stratum corneum ceramides which show much more complexity than intracellular ceramides known to be signal transducers. After a short summary of lipid extraction methods, we discuss the following set of methods: thin‐layer chromatography, gas chromatography, HPLC, LC/MS, mass spectrometry, NMR spectroscopy, vibrational spectroscopy, and X‐ray diffraction. It will be lined out which information about structure, concentration or physical state is available by means of each particular method. Although the focus is clearly on stratum corneum ceramides, some methods of general skin lipid analysis and structure analysis of sphingolipids are also discussed when appropriate.
Synthesis of fatty acid esters from acid oils using lipase B from Candida antarctica
Authors: Tüter Melek , Aksoy H. Ayşe , Gılbaz E. Elif , Kurşun Emel
Published: August 2004

Esterification of corn and sunflower acid oils with straight‐ and branched‐chain alcohols were conducted using lipase B from Candida antarctica (Novozym 435) in n‐hexane. Sunflower acid oil consisted of 55.6% free fatty acids and 24.7% triacylglycerols, while the free fatty acids and triacylglycerols contents of corn acid oil were 75.3% and 8.6%, respectively. After 1.5 h of methanolysis of sunflower acid oil, the highest fatty acid methyl ester content (63.6%) was obtained at 40 °C and the total fatty acid/methanol molar ratio was 1/1, using 15% enzyme based on acid oil weight. The conversion of both acid oils with straight‐ and branched‐chain alcohols was not significantly affected by the chain length of the alcohols. However, the lowest fatty acid methyl ester content (50%) was obtained in the reaction of corn acid oil with methanol. Sunflower acid oil was converted to fatty acid esters using primer alcohols such as n‐propanol, i‐ and n‐butanol, n‐amylalcohols, n‐octanol, and a mixture of amylalcohol isomers, resulting in a fatty acid ester content of about 70% at 40 °C.
C‐Phosphorylated N‐(Trichloroethylidene)sulfonamides: A New Type of Highly Electrophilic Imines
Authors: Rassukana Yuliya V. , Onys’ko Petro P. , Davydova Kateryna O. , Sinitsa Anatolii D.
Published: August 2004

A convenient preparative approach to previously unknown, highly electrophilic C‐phosphorylated N‐arylsulfonylimines 1, based on fairly readily accessible α‐phosphorylated sulfonamides 5, has been developed. Compounds 1 react with trialkyl phosphites or ethyl diphenylphosphinite in the aza‐Perkow reaction scheme to give C,N‐diphosphorylated N‐dichlorovinylsulfonamides 8. On treatment with O‐ and S‐nucleophilic agents (alcohols, thiols, thiophenols), 1 forms addition products 12 and 15, the functionalized derivatives of α‐aminophosphonic acids, while interaction between 1 and mercaptoacetic acid proceeds with intramolecular cyclization of the intermediate adduct to produce the novel 2‐phosphorylated thiazolidinones 17. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis and Radical Polymerization of Various 2‐Cyclopropylacrylates
Authors: Meijere Armin de , Bagutski Viktor , Zeuner Frank , Fischer Urs Karl , Rheinberger Volker , Moszner Norbert
Published: August 2004

Fourteen new alkyl 2‐cyclopropylacrylates 1a−n with various substituents R1−R5 were synthesized from readily available precursors by applying standard transformations such as cyanohydrin formation from an aldehyde, alcoholysis to an α‐hydroxycarboxylic ester, oxidation and Wittig methylenation of an α‐oxocarboxylic ester. Overall yields ranged from 33 to 54%. A new method for the hydrolysis of dimethyl cyclopropanedicarboxylates to the corresponding half‐esters was developed. The α‐oxocarboxylates 7g−n were prepared by dirhodium tetraacetate catalyzed cyclopropanation of alkenes 8g−n with methyl or ethyl diazopyruvate in 32−58% yield. The monomers 1a−n were characterized by 1H, 13C NMR spectroscopy, mass spectrometry and elemental analysis. The radical homopolymerizations of 1a−n were carried out with 2,2′‐azabisisobutyronitrile (AIBN) as initiator in chlorobenzene at 65 °C. The highest polymer yields were obtained in the polymerizations of 1f and 1h or 1k and 1l, i.e. from monomers with an annelated five‐ or six‐membered ring. In the case of 1h and 1k, both the polymer yields (99 and 98%, respectively) and the glass transition temperatures (Tg) of 57 and 93 °C were significantly higher than those observed for the polymer from 1,1‐bis(ethoxycarbonyl)‐2‐vinylcyclopropane (DECVCP), which was used as a benchmark for the monomer reactivities in the radical polymerizations of all the vinylcyclopropane derivatives 1a−n. The bicyclic monomers 1h and 1k also demonstrated drastically improved reactivities in the radical copolymerization with methyl methacrylate when compared to DECVCP. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
A Straightforward Synthesis of 1‐Adamantylmethyl Glycosides, and Their Binding to Cyclodextrins
Authors: Charbonnier Florence , Penadés Soledad
Published: August 2004

A single‐step synthesis of 1‐adamantylmethyl α‐ and β‐glycosides starting from commercially available peracetylated monosaccharides is reported. The α‐ and β‐glucopyranosides 1a and 1b bind to β‐cyclodextrin with association constants in the order of 105 M−1, as determined by 1H NMR spectroscopy. The carbohydrate moiety contributes to the binding depending on the pyranose stereochemistry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Development of a Continuous‐Flow System for Catalysis with Palladium(0) Particles
Authors: Solodenko Wladimir , Wen Hongliang , Leue Stefanie , Stuhlmann Friedrich , Sourkouni‐Argirusi Georgia , Jas Gerhard , Schönfeld Hagen , Kunz Ulrich , Kirschning Andreas
Published: August 2004

Heterogeneous catalysis for organic synthesis under continuous‐flow conditions becomes possible by a new reactor‐based approach. Continuous‐flow reactors with a monolithic glass/polymer composite interior are loaded with palladium particles by ion exchange followed by reduction. When incorporated into a continuous‐flow setup (PASSflow) this reactor allows the transfer‐hydrogenation of alkenes, alkynes, nitro‐substituted aromatic compounds and benzyl ethers in the flow‐through mode. In addition, the activity of the catalysts is well suited to achieve Suzuki, Sonogashira and Heck cross‐coupling reactions in the absence of phosphanes or any other ligands, resulting in a greatly simplified purification. As an extension to this concept a bifunctional support was prepared inside the reactor consisting of Pd particles and an ion‐exchange group (hydroxide form). In the Suzuki− Miyaura reaction the reactor serves as a base for immobilisation and activation of the boronic acid as boronate and as a catalyst for promoting the C−C coupling reaction under continuous‐flow conditions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Palladium‐Catalysed Amination of Electron‐Deficient or Relatively Electron‐Rich Benzo[b]thienyl Bromides − Preliminary Studies of Antimicrobial Activity and SARs
Authors: Queiroz Maria‐João R. P. , Begouin Agathe , Ferreira Isabel C. F. R. , Kirsch Gilbert , Calhelha Ricardo C. , Barbosa Sandra , Estevinho Letícia M.
Published: August 2004

Several diarylamines in the benzo[b]thiophene series were prepared in good to high yields by palladium‐catalysed amination of ethyl 3‐bromobenzo[b]thiophene‐2‐carboxylate with anilines and 5‐aminoindole in the presence of Pd(OAc)2, BINAP and Cs2CO3 in toluene. The presence of the ester group at the 2‐position of the benzo[b]thiophene moiety increases the yields and lowers the heating times relative to the reactions performed with 3‐bromobenzo[b]thiophene. When aminopyridines were used instead of anilines, the ligand and the solvent need to be changed to XANTHPHOS and dioxane in the amination reaction. With 2‐aminopyridine a one‐pot C−N coupling and intramolecular cyclization involving the nitrogen atom of the pyridine ring occurred, with loss of ethanol, giving an interesting fluorescent tetracyclic heteroaromatic compound. The antimicrobial activity, the minimal inhibitory concentrations (MICs) and the structure‐activity relationships (SARs) were evaluated. A selectivity with low MICs was observed against Bacillus Cereus, and good results were also obtained against Candida albicans. The acids obtained by hydrolysis of the ester group, as non‐proteinogenic α,β‐unsaturated β‐amino acids, can be incorporated into peptide chains to induce conformational constraints. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of Amino Carba Sugars and Conformationally Restricted Polyhydroxy γ‐Amino Acids from (−)‐Quinic Acid
Authors: Carballido Montserrat , Castedo Luis , González‐Bello Concepción
Published: August 2004

Efficient syntheses of two novel positional stereoisomers of valiolamine, a potent glycosidase inhibitor, and two polyhydroxy γ‐amino acids are reported. The syntheses involve regio‐ and stereoselective azidolysis of epoxides by trimethylsilyl azide with BF3·OEt2 as Lewis acid. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis and Radioiodination of Some 9‐Aminoacridine Derivatives
Authors: Ghirmai Senait , Mume Eskender , Henssen Cecile , Ghaneolhusseini Hadi , Lundqvist Hans , Tolmachev Vladimir , Sjöberg Stefan , Orlova Anna
Published: August 2004

Derivatives of 9‐aminoacridine, namely N‐[ψ‐(acridin‐9‐ylamino)alkyl]‐3‐(trimethylstannyl)benzamides (1), where the alkyl group is propyl (1a) and octyl (1b), and 2‐(acridin‐9‐ylamino)‐3‐(4‐hydroxyphenyl)propionic acid (2), have been synthesized with the aim to use them as precursors in the syntheses of radiolabeled DNA intercalators for biological experiments. It was observed that compounds 1a and 1b can exist in two isomeric forms at room temperature. Radioiodination of the two benzamides 1a and 1b was carried out with the Auger‐emitting nuclide 125I by exchange of the trimethylstannyl group. The optimal conditions for radioiodination of the octyl derivative 1b were established and the labeling yield was found to be as high as 92%, according to TLC analysis in model experiments. Purification of the radioiodinated products gave radiochemical yields of 56% for the propyl and 74% for the octyl compound. The amino acid 2 was directly labeled with 125I at the ortho position to the hydroxyl group by taking advantage of the activated ring. The experiment afforded a very high labeling yield (92%). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Studies in the Cycloproparene Series: Cross‐Conjugated π‐Extended Alkylidenecycloproparenes
Authors: Dixon Gareth M. , Halton Brian
Published: August 2004

The first simple and stable cross‐conjugated π‐extended alkylidenecycloproparenes 5, 6 and 15−22 have been prepared as coloured crystalline derivatives from use of (E,E)‐1,5‐diphenylpenta‐2,4‐dienone, (E,E)‐1,5‐diarylpenta‐1,4‐dien‐3‐ones and (E,E)‐2,5‐(diarylmethylidene)cyclopentanones with the relevant 1,1‐bis(trimethylsilyl)cyclopropa[b]naphthalene. The permanent dipole moments of the compounds have been measured, and the conformational preference of the rotamers assessed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Cover Picture: Chemical Synthesis of GPIs and GPI‐Anchored Glycopeptides (Eur. J. Org. Chem. 17/2004)
Authors: Guo Zhongwu , Bishop Lee
Published: August 2004

The cover picture shows a glycosylphosphatidylinositol(GPI‐)anchored protein that is associated with the cell membrane. The insertion of the long lipid chains of GPIs into the membrane bilayers anchors numerous proteins and glycoproteins onto cell surfaces. GPI anchoring is ubiquitous and plays a critical role in the eukaryotic world. The chemical synthesis of some GPIs and GPI‐linked peptides and glycopeptides is summarized in detail in the Microreview by Z. Guo and L. Bishop on p. 3585 ff.
Application of stepwise discriminant analysis to classify commercial orange juices using chiral micellar electrokinetic chromatography‐laser induced fluorescence data of amino acids
Authors: Simó Carolina , Martín‐Alvarez Pedro J. , Barbas Coral , Cifuentes Alejandro
Published: August 2004

The use of chiral amino acids content and stepwise discriminant analysis to classify three types of commercial orange juices (i.e., nectars, orange juices reconstituted from concentrates, and pasteurized orange juices not from concentrates) is presented. Micellar electrokinetic chromatography with laser‐induced fluorescence (MEKC‐LIF) and β‐cyclodextrins are used to determine L‐ and D‐amino acids previously derivatized with fluorescein isothiocyanate (FITC). This chiral MEKC‐LIF procedure is easy to implement and provides information about the main amino acids content in orange juices (i.e., L‐proline; L‐aspartic acid, D‐Asp, L‐serine, L‐asparagine, L‐glutamic acid, D‐Glu, L‐alanine, L‐.arginine, D‐Arg, and the non‐chiral γ‐amino‐n‐butyric acid (GABA), i.e., γ‐aminobutyric acid). From these results, it is clearly demonstrated that some D‐amino acids occur naturally in orange juices. Application of stepwise discriminant analysis to 26 standard samples showed that the amino acids L‐Arg, L‐Asp and GABA were the most important variables to differentiate the three groups of samples. With these three selected amino acids a 100% correct classification of the samples was obtained either by standard or by leave‐one‐out cross‐validation procedures. These classification functions based on the content in L‐Arg, L‐Asp and GABA were also applied to nine test samples and provided an adequate classification and/or interesting information on these samples. It is concluded that chiral MEKC‐LIF analysis of amino acids and stepwise discriminant analysis can be used as a consistent procedure to classify commercial orange juices providing useful information about their quality and processing. To our knowledge, this is the first report about the combined use of chiral capillary electrophoresis and discriminant techniques to classify foods.
Direct enantioseparation of catechin and epicatechin in tea drinks by 6‐O‐α‐D‐glucosyl‐β‐cyclodextrin‐modified micellar electrokinetic chromatography
Authors: Kodama Shuji , Yamamoto Atsushi , Matsunaga Akinobu , Yanai Hiroko
Published: August 2004

Cyclodextrin‐modified micellar electrokinetic chromatography was applied to the enantioseparation of catechin and epicatechin using 6‐O‐α‐D‐glucosyl‐β‐cyclodextrin together with sodium dodecyl sulfate and borate‐phosphate buffer. Factors affecting chiral resolution and migration time of catechin and epicatechin were studied. The optimum running conditions were found to be 200 mM borate‐20 mM phosphate buffer (pH 6.4) containing 25 mM 6‐O‐α‐D‐glucosyl‐β‐cyclodextrin and 240 mM sodium dodecyl sulfate with an effective voltage of +25 kV at 20°C using direct detection at 210 nm. Under these conditions, the resolution (Rs) of racemic catechin and epicatechin were 4.15 and 1.92, respectively. With this system, catechin and epicatechin enantiomers along with other four catechins ((−)‐catechin gallate, (−)‐epicatechin gallate, (−)‐epigallocatechin, (−)‐epigallocatechin gallate) and caffeine in tea samples were analyzed successfully. The difference of migration time between catechin and epicatechin is discussed.
Preparation of a positively charged cellulose derivative chiral stationary phase with copolymerization reaction for capillary electrochromatographic separation of enantiomers
Authors: Chen Xiaoming , Qin Feng , Liu Yueqi , Kong Liang , Zou Hanfa
Published: August 2004

A positively charged chiral stationary phase (CSP) was prepared by chemically immobilizing cellulose 3,5‐dimethylphenylcarbamate onto methacryloyldiethylenetriaminopropylated silica (MCDEAPS) via a radical copolymerization reaction. The prepared CSP was evaluated for enantiomer separation in nonaqueous capillary electrochromatography (CEC). Electroosmotic flow (EOF) generated on the prepared CSP could be significantly improved with introduction of positive charges into the CSP, and separation of enantiomers in CEC has been achieved with mobile phases of ethanol and hexane‐ethanol, respectively. In addition, we investigated the solvent versatility of the immobilized CSP on enantioseparations in CEC and capillary liquid chromatography (CLC) due to the elimination of dissolution of chiral selector in a number of solvents. Chiral resolution of some enantiomers was improved by adopting tetrahydrofuran (THF) and chloroform as mobile‐phase modifiers, respectively.
Enantiomeric resolution of 2‐arylpropionic acid nonsteroidal anti‐inflammatory drugs by capillary electrophoresis: Methods and applications
Authors: Patel Bhavesh K. , Hanna‐Brown Melissa , Hadley Mark R. , Hutt Andrew J.
Published: August 2004

The 2‐arylpropionic acids (2‐APAs) are an important group of nonsteroidal anti‐inflammatory drugs. These agents, the majority of which are available as racemates, exhibit stereoselectivity in both their action and disposition. Developments in stereoselective separation science methodology, mainly chromatographic, have facilitated an evaluation of the pharmacological properties of the individual enantiomers of these drugs and contributed to our understanding of both their mode(s) of action and disposition. While a number of electrophoretic techniques, including capillary electrophoresis, capillary electrochromatography and isotachophoresis, have been applied to the stereoselective resolution and stereospecific analysis of these agents using a variety of chiral selectors, e.g., cyclodextrins, oligosaccharides, macrocyclic antibiotics, and proteins, the number of published applications in pharmaceutical and biomedical analysis remains relatively limited. However, the utility of electrophoretic techniques for stereospecific analysis may be illustrated using the 2‐APAs as typical examples of chiral acidic pharmaceuticals. Applications include: determination of enantiomeric composition following biosynthetic stereoselective hydrolysis; examination of both achiral and chiral impurity profiles in bulk drugs and formulated products; determination of enantiomeric impurities in both bulk drugs and formulated products; examination of configurational stability following stress testing of formulated products; determination of enantiomeric composition and metabolite profile in biological fluids following administration of the racemates and individual enantiomers. It may be anticipated that future exploitation of electrophoretic approaches to the stereospecific analysis of these agents will result in further contributions to our understanding of their stereoselective biological properties and therapeutic use.
Chiral capillary electrophoresis: Facts and fiction on the reproducibility of resolution with randomly substituted cyclodextrins
Authors: Schmitt Ulrich , Ertan Mevlut , Holzgrabe Ulrike
Published: August 2004

Comparative enantioseparation of the enantiomers of 1,1'‐binaphthyl‐2,2'‐diyl hydrogen phosphate was performed with cyclodextrin (CD)‐modified capillary electrophoresis (CE). Two single isomers, β‐CD, heptakis(2,3,6‐tri‐O‐methyl)‐β‐CD (TM‐β‐CD), and heptakis(2,6‐di‐O‐methyl)‐β‐CD (DM‐β‐CD) of 98% purity as well as heptakis(2,3‐di‐O‐acetyl)‐β‐CD were used and compared in terms of resolution power to randomly methylated and corresponding acetylated β‐CDs, which were synthesized in our laboratory. The methylated ones were characterized by means of matrix‐assisted laser desorption/ionization‐time of flight‐(MALDI‐TOF) mass spectrometry. By testing defined mixtures of single isomers and comparing their resolution power to randomly substituted CDs of similar degree of substitution we could show, that a simple characterization by the average molecular degree of substitution (DS) is not sufficient. In order to get reproducible results, a clearly defined substitution pattern is necessary, which is not given using randomly substituted CDs. Taken together, a validation of a chiral separation with “undefined” CD derivatives is almost impossible.
A simplified synthesis of polymeric nonparticulate stationary phases with macrocyclic antibiotic as chiral selector for capillary electrochromatography
Authors: Kornyšova Olga , Jarmalavičienė Reda , Maruška Audrius
Published: August 2004

A simplified approach to synthesize nonparticulate (continuous or monolithic) beds with embedded vancomycin chiral selectors for capillary electrochromatography is proposed. In the present approach, N,N'‐diallyltartardiamide monomer with diol functionality is used, which can be readily converted to aldehyde groups via periodate treatment. Parallel to the activation of the polymeric matrix for covalent attachment of vancomycin, the periodate treatment has shown secondary effects on the polymeric bed morphology, namely the increase of the average pore size and porosity of the skeleton. Inversed size‐exclusion chromatography was applied to characterize porosimetric properties of the capillary columns before and after the periodate treatment. Electroosmotic and enantioselective properties of the nonparticulate beds synthesized are presented. The approach is of more general interest attaching different affinity groups to the polymeric matrix and/or enhancing the accessibility to the active sites, for instance, in the molecular imprinting technique.
Enantioselective analysis of primaquine and its metabolite carboxyprimaquine by capillary electrophoresis
Authors: Bortocan Renato , Bonato Pierina S.
Published: August 2004

An enantioselective capillary electrophoresis method for the simultaneous determination of primaquine (PQ) and carboxyprimaquine (CPQ) in rat liver mitochondrial fraction, suitable for in vitro metabolism studies is presented. The drug and metabolite were extracted by liquid‐liquid extraction using ethyl ether. The enantiomers were resolved in a fused‐silica capillary, 50 μm inside diameter (ID) and 24 cm of effective length, using an electrolyte solution consisting of a 20 mmol/L sodium phosphate solution, pH 3.0, and 10% w/v maltodextrin. Hydrodynamic sample injection was used with a 10 s injection time at 50 mbar pressure. The applied voltage was 22 kV and the capillary temperature was controlled at 20°C. Detection was carried out at 264 nm. Under these conditions, the enantiomeric fractions of the drug and of its metabolite were analyzed within 6 min. The extraction procedure was efficient in removing endogenous interferents and low values (<10%) for the coefficients of variation and deviation from theoretical values were demonstrated for both within‐day and between‐day assays. The method described allows the determination of PQ and CPQ enantiomers as low as 100 and 40 ng/mL, respectively. After validation, the method was used for an in vitro metabolism study of PQ. The results showed that the enantiomer (−)‐PQ was preferentially metabolized to (−)‐CPQ.
Heptakis(6‐amino‐6‐deoxy)‐β‐cyclodextrin as a chiral selector for the separation of anionic analyte enantiomers by capillary electrophoresis
Authors: Budanova Natalia , Shapovalova Elena , Lopatin Sergei , Varlamov Valery , Shpigun Oleg
Published: August 2004

A hepta‐substituted β‐cyclodextrin bearing seven amino groups, heptakis(6‐amino‐6‐deoxy)‐β‐cyclodextrin (per‐6‐NH2‐β‐CD) was successfully used as a chiral selector for the enantioseparation of different anionic analytes. The running buffer pH and chiral selector concentration were the studied parameters crucial in achieving the maximum possible enantioresolution. Enantiomeric separation of a mixture of seven carboxybenzyl‐amino acids was achieved in 24 min. Excellent resolution was obtained for carboxybenzyl‐tryptophan (Rs = 11.2).
Enantioseparation using sulfated cyclosophoraoses as a novel chiral additive in capillary electrophoresis
Authors: Park Heylin , Lee Sanghoo , Kang Simook , Jung Yunjung , Jung Seunho
Published: August 2004

Highly sulfated cyclosophoraoses (HS‐Cys) were synthesized by the chemical modification of a family of neutral cyclosophoraoses isolated from Rhizobium leguminosarum bv. trifolii. The HS‐Cys were then analytically characterized using Fourier transform‐infrared spectroscopy and elemental analysis. These HS‐Cys were successfully used as a novel chiral additive, in low‐pH aqueous background electrolytes, for capillary electrophoretic separation of five basic chiral drugs such as arterenol, atenolol, isoproterenol, propranolol, and metoprolol.
Assessment of the N‐oxidation of deprenyl, methamphetamine, and amphetamine enantiomers by chiral capillary electrophoresis: An in vitro metabolism study
Authors: Szökő Éva , Tábi Tamás , Borbás Tímea , Dalmadi Balázs , Tihanyi Károly , Magyar Kálmán
Published: August 2004

A chiral capillary electrophoresis method using hydroxypropyl‐β‐cyclodextrin as chiral selector was developed and validated for the quantification of the N‐oxygenated metabolites of deprenyl, methamphetamine, and amphetamine enantiomers, formed in vitro. The influence of various parameters (selector concentration, buffer pH, temperature, polymer additive, etc.) on the simultaneous separation of the optical isomers of the parent drugs and their metabolites has been evaluated. The buffer pH had the greatest impact on the separation selectivity of the N‐oxygenated compounds. Linear calibration curves were obtained over the concentration range of 2.5–50 μM for the enantiomers of amphetamine‐hydroxylamine, methamphetamine‐hydroxylamine, and deprenyl‐N‐oxide. The inter‐ and intra‐assay precision and accuracy varied by less than 15% for all analytes at concentrations of 5, 10, and 30 μM, and less than 20% at the lower limit of quantitation (2.5 μM). The sample extraction recovery ranged between 109 and 129% at the three concentration levels. The drug enantiomers were incubated with recombinant human flavin‐containing monooxygenase enzymes (FMO3 and FMO1), and human liver microsomes, respectively. The enantioselectivity of the substrate preference, as well as the stereoselective formation of the new chiral center upon the oxidation of the prochiral tertiary nitrogen of deprenyl were assessed. FMO1, the extrahepatic form of the enzyme in man, was shown to be more active in the N‐oxygenation of both deprenyl and methamphetamine isomers than FMO3. Deprenyl enantiomers and S‐methamphetamine were substrates of human recombinant FMO3. Conversion of amphetamine to its hydroxylamine derivative could not be observed on incubation with either FMO1 or FMO3. Formation of the new chiral center on the nitrogen, during N‐oxidation of the tertiary amine deprenyl, was found stereoselective. The two FMO isoforms have shown opposite preference in the formation of this chiral center. Methamphetamine‐hydroxylamine formed from methamphetamine was further transformed by FMO, amphetamine‐hydroxylamine was identified as the product of a demethylation reaction.
Influence of (hydroxy)alkylamino substituents on enantioseparation ability of single‐isomer amino‐β‐cyclodextrin derivatives in chiral capillary electrophoresis
Authors: Iványi Róbert , Jicsinszky László , Juvancz Zoltán , Roos Natascha , Otta Klára , Szejtli József
Published: August 2004

A family of single‐isomer amino‐β‐cyclodextrin (amino‐β‐CD) derivatives containing an amino or (hydroxy)alkylamino group in one of the primary positions has been synthesized. The steric effect and hydrogen bond forming ability of the different substituents on enantioseparation of acidic enantiomers has been studied by capillary electrophoresis (CE). Three enantiomeric model compounds (mandelic acid, cis‐permethrinic acid, and cis‐deltamethrinic acid) having significantly different apparent complex stability constants with β‐CD were applied in the experiments. Dependence of separation selectivity, resolution as well as mobility difference on chiral selector concentration (0.1–20 mM, pH 6.0) was investigated. Each amino‐β‐CD showed higher enantioselectivity than the native β‐CD. One hydroxyalkyl group attached to the primary amino N‐atom significantly increased both the enantioselectivity and the resolution compared to the primary amino‐β‐CD, while two hydroxyalkyl moieties decreased them due to the predominance of steric hindrance. The value of the apparent complex stability constants obtained suited well the mobility difference model (by Wren). On the other hand, the optimum selector concentrations calculated according to the model were slightly lower than the experienced concentrations giving the maximum enantioresolution of enantiomers.
Optimization and validation of an enantioselective method for a chiral drug with eight stereo‐isomers in capillary electrophoresis
Authors: Jimidar M. Ilias , Vennekens Tom , Van Ael Willy , Redlich Dirk , De Smet Maurits
Published: August 2004

Highly selective capillary electrophoresis (CE) screening methods were applied to find a satisfactory separation of a chiral drug with eight stereoisomeric compounds. The initial separation conditions were further optimized using response surface modelling by applying a Box‐Behnken experimental design. This approach resulted in a rapid and efficient optimization of the buffer concentration, the concentration of two cyclodextrins, and the run voltage, in order to obtain final separation conditions of the method. Further optimization and validation of the system in terms of sensitivity and robustness resulted in a method that is suitable for quality control release purposes.
Ultrashort partial‐filling technique in capillary electrophoresis for infinite resolution of tramadol enantiomers and its metabolites with highly sulfated cyclodextrins
Authors: Rudaz Serge , Le Saux Thomas , Prat Josiane , Gareil Pierre , Veuthey Jean‐Luc
Published: August 2004

The possibility to enhance resolution to infinite value in chiral capillary electrophoresis is attained as soon as the apparent mobility of one enantiomer becomes opposite to the other. This could be achieved on the basis of the carrier ability of multiple charged chiral selectors such as highly sulfated cyclodextrin (HS‐CD). With tramadol and its phase I metabolites selected as model compounds, the HS‐γ‐CD was found to be the most appropriate chiral selector. The CD concentration was determined where one enantiomer still migrated as a cation while the other migrated in the opposite side. Besides the chiral selector concentration, secondary parameters such as buffer concentration appeared to be critical to reach infinite resolution. The latter was achieved with partial filling technique using ultrashort separation zones (a few mm). In order to better understand the interaction mechanism between the selected CD and the analytes, the classical affinity capillary electrophoresis method, although not fully satisfactory because of ionic strength variations within a series of mobility shift measurements, was applied to estimate complexation constants and complex mobilities. The results obtained point to the prevailing role of complex mobility differences in the enantioselectivity mechanism.
QALY maximisation and people's preferences: a methodological review of the literature
Authors: Dolan Paul , Shaw Rebecca , Tsuchiya Aki , Williams Alan
Published: August 2004

In cost‐utility analysis, the numbers of quality‐adjusted life years (QALYs) gained are aggregated according to the sum‐ranking (or QALY maximisation) rule. This requires that the social value from health improvements is a simple product of gains in quality of life, length of life and the number of persons treated. The results from a systematic review of the literature suggest that QALY maximisation is descriptively flawed. Rather than being linear in quality and length of life, it would seem that social value diminishes in marginal increments of both. And rather than being neutral to the characteristics of people other than their propensity to generate QALYs, the social value of a health improvement seems to be higher if the person has worse lifetime health prospects and higher if that person has dependents. In addition, there is a desire to reduce inequalities in health. However, there are some uncertainties surrounding the results, particularly in relation to what might be affecting the responses, and there is the need for more studies of the general public that attempt to highlight the relative importance of various key factors. Copyright © 2004 John Wiley & Sons, Ltd.
In vitro study of human vascular endothelial cell function on materials with various surface roughness
Authors: Xu Chengyu , Yang Fang , Wang Shu , Ramakrishna Seeram
Published: August 2004

In recent years, creating a biodegradable polymer scaffold with an endothelialized surface has become an attractive concept for replacement of small‐diameter blood vessels. Toward this end, a better understanding of the interaction between endothelial cells and biodegradable polymer substrates is particularly important. Surface roughness of biomaterials is one of the important parameters that affect cell behavior. In this study, human vascular endothelial cells were cultured on electrospun and solvent‐cast poly(L‐lactic acid) substrates with different surface roughness. Cell responses were evaluated via both qualitative examinations of cell morphology changes as well as quantitative assessment of cell adhesion and proliferation rate on the different substrates. The results proved that endothelial cell function was enhanced on the smooth solvent‐cast surface rather than on the rough electrospun surface of poly(L‐lactic acid). Together with our previous findings that electrospun substrates favor vascular smooth muscle cell behavior, it is possible to design a unique three‐dimensional scaffold for application of tissue‐engineered small‐diameter vessel replacement by combining the fabrication technique of solvent casting and electrospinning. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 154–161, 2004
Characteristics of polyethylene wear particles isolated from synovial fluid after mobile‐bearing and posterior‐stabilized total knee arthroplasties
Authors: Minoda Yukihide , Kobayashi Akio , Iwaki Hiroyoshi , Miyaguchi Masatsugu , Kadoya Yoshinori , Ohashi Hirotsugu , Takaoka Kunio
Published: August 2004

The size, shape, and number of polyethylene wear particles found in synovial fluids of patients 1 year after implantation of 22 well‐functioning total knee prostheses (11 contemporary mobile‐bearing type, 11 posterior‐stabilized type) were determined. Polyethylene wear particles were isolated from synovial fluids and examined by scanning electron microscopy. Particle size (equivalent circle diameter) was 0.81 ± 0.12 μm (mean ± standard error) in mobile‐bearing types and 0.78 ± 0.08 μm in posterior‐stabilized types. Particle shape (aspect ratio) was 1.94 ± 0.13 in mobile‐bearing types and 2.30 ± 0.22 in posterior‐stabilized types. Total numbers of particles were (1.75 ± 1.02) × 108 in mobile‐bearing and (1.16 ± 0.57) × 108 in posterior‐stabilized types. The differences in these parameters between the two groups were not statistically significant. In the early stages after surgery, contemporary mobile‐bearing types were comparable to posterior‐stabilized types in terms of polyethylene wear‐particle generation. The present results do not support the proposition that has been put forward in the literature; namely, that the contemporary mobile‐bearing design has an advantage, in terms of the polyethylene wear rate. These data suggest that the advantage of complete conformity in the femoro‐tibial articulating surface of contemporary mobile‐bearing design may be offset by wear of the mobile undersurface and slot, apart from the articulating surface. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 71B: 1–6, 2004
The effect of basis set superposition error on the convergence of intermolecular interaction energies for deprotonated complexes
Authors: Masamura Masao
Published: August 2004

The intermolecular interaction energies of the deprotonated hydrogen‐bonded complexes F−(HF), F−(H2O), F−(NH3), Cl−(HF), SH−(HF), H2P−(HF), OH−(H2O), OH−(H2O)2, OH−(NH3), Cl−(H2O), SH−(H2O), H2P−(H2O), Cl−(NH3), SH−(NH3), H2P−(NH3), Cl−(HCl), Cl−(H2S), Cl−(PH3), SH−(H2S), SH−(PH3), and H2P−(PH3) were calculated with correlation consistent basis sets at the MP2, MP4, QCISD(T), and CCSD(T) levels. When the basis set is smaller, the counterpoise‐uncorrected intermolecular interaction energies are closer to the complete basis set limit than the counterpoise‐corrected intermolecular interaction energies. The counterpoise‐uncorrected intermolecular interaction energies obtained at the MP2/aug‐cc‐pVDZ level of theory are close to the interaction energies obtained at the extrapolated complete basis set limit in most of the complexes. Also, we investigate the accuracy of the other levels. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1771–1778, 2004