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  • 1990-1994  (869)
  • 1980-1984
  • 1991  (869)
  • Organic Chemistry  (822)
  • Gas chromatography
  • Nuclear reactions
  • Physics
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 65 (1991), S. 433-435 
    ISSN: 1432-0738
    Keywords: Analysis ; Blood ; Butoxyacetic acid ; 2-Butoxyethanol ; Gas chromatography ; Glycol ethers ; Man ; Renal clearance ; Toxicokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Venous blood samples from five male volunteers exposed to 20 ppm 2-butoxyethanol (BE) for 2 h were collected at 0, 2, 4, and 6 h from the start of exposure and analyzed by gas chromatography after simultaneous ion-pair extraction and derivatization with pentafluorobenzyl bromide. Butoxyacetic acid (BAA), a major metabolite of BE, was found in all samples except those collected prior to exposure. This is the first time to our knowledge that the analysis of BAA in human blood has been reported. Concentrations of BAA in blood ranged from 22 to 60 μM. These concentrations were about two orders of magnitude lower than those causing swelling and hemolysis of human erythrocytes in vitro. The BAA blood level peaked after 2–4 h. The decrease between 4 and 6 h indicates an average half-time of BAA in blood of about 4 h, which is in accordance with previously observed half-times in urine. The low renal clearance of BAA (22–39 ml/min) indicates extensive binding to blood proteins and poor tubular secretion of the substance. Binding of BAA to blood components is also indicated by the low apparent volume of distribution of approximately 151.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    The astronomy and astrophysics review 3 (1991), S. 1-46 
    ISSN: 1432-0754
    Keywords: Nucleosynthesis ; Nuclear reactions ; Stars: abundances ; Interstellar Medium: abundances ; Cosmology ; Galaxies: evolution of
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Summary The basic scheme of nucleosynthesis (building of heavy elements from light ones) has held up very well since it was first proposed more than 30 years ago by E.M. Burbidge, G.R. Burbidge, A.G.W. Cameron, W.A. Fowler, and F. Hoyle. Significant advances in the intervening years include (a) observations of elemental and a few isotopic ratios in many more extrasolar-system sites, including metal-poor dwarf irregular galaxies, where very little has happened, and supernovae and their remnants, where a great deal has happened, (b) recognition of the early universe as good for making all the elements up to helium, (c) resolution of heavy element burning in stars into separate carbon, neon, oxygen, and silicon burning, with fine tuning of the resulting abundances by explosive nucleosynthesis in outgoing supernova shock waves, (d) clarification of the role of Type I supernovae, (e) concordance between elements produced in short-lived and long-lived stars with those that increased quickly and slowly over the history of the galaxy, and (f) calibration of calculations of the evolution and explosion of massive stars against the detailed observations of SN 1987A. The discussion presupposes a reader (a) with some prior knowledge of astronomy at the level of recognizing what is meant by an A star and an AGB star and (b) with at least a mild interest in how we got to where we currently are.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 62 (1991), S. 603-606 
    ISSN: 1432-1246
    Keywords: Styrene ; Urinary metabolites ; Gas chromatography ; Occupational health
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In support of an occupational investigation of styrene exposure, a capillary gas chromatographic method was developed for the quantitation of the styrene metabolites mandelic and phenylglyoxylic acids. The method was based on that of Guillemin and Bauer [7], in which phenylglyoxylic acid was converted to mandelic acid by reduction before instrumental analysis. The earlier method had to be modified for use with capillary columns; the resulting method was sensitive, selective and reproducible. The detection limit was approximately 0.001 mg/ml urine. Approximately 〈5% relative precision was achieved in the range of 0.05–2 mg/ml urine. Mandelic acid was resolved from other components of urine and from by-products of derivatization.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 63 (1991), S. 27-31 
    ISSN: 1432-1246
    Keywords: Hemoglobin adducts ; Exposure control ; Gas chromatography ; Epoxides ; Alkenes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A method for monitoring exposure to ethylene oxide (EO) and propylene oxide (PO) and their corresponding alkenes through the analysis of adducts to N-terminal valine in hemoglobin (Hb) using gas chromatography (GC) and electron-capture detection has been developed. The method is a further development of the so-called N-alkyl Edman method, which has thus far been carried out using gas chromatography-mass spectrometry (GC/MS). The correlation between GC and GC/MS determinations of adduct levels in human samples was found to be good. The newly developed GC method enables the determination of adducts to Hb from EO and PO down to levels of about 100 pmol/g globin. This adduct level corresponds to the expected increment from ethene in inhaled tobacco smoke in a smoker of about 10 cigarettes/day or from an average exposure to about 50 Wpb EO or 1 Wpm PO during working hours.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    International archives of occupational and environmental health 63 (1991), S. 83-88 
    ISSN: 1432-1246
    Keywords: Toluene diisocyanate, TDI ; Toluenediamine, TDA ; Test chamber ; Gas chromatography ; Mass spectromety ; Biological monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five men were exposed to toluene diisocyanate (TDI) atmospheres for 7.5 h. The TDI atmospheres were generated by a gas-phase permeation method, and the exposures were performed in an 8-m3 stainless-steel test chamber. The mean air concentration of TDI was ca. 40 μg/m3, which corresponds to the threshold limit value (TLV) of Sweden. The inhaled doses of 2,4- and 2,6-TDI were ca. 120 μg. TDI in the test chamber air was determined by an HPLC method using the 9-(N-methyl-aminomethyl)-anthracene reagent and by a continuous-monitoring filter-tape instrument. After hydrolysis of plasma and urine, the related amines, 2,4- and 2,6-toluenediamine 2,4-, and 2,6-TDA), were determined as pentafluoropropionic anhydride (PFPA) derivatives by capillary gas-chromatography using selected ion monitoring (SIM) in the electron-impact mode. The urinary elimination of the TDAs showed a possible biphasic pattern, with rapid first phases for 2,4-TDA (mean t 1/2 for the concentration in urine, 1.9 h) and for 2,6-TDA (mean t 1/2 for the concentration in urine, 1.6 h). The cumulative amount of 2,4-TDA excreted in urine within 28 h ranged from 8% to 14% of the estimated dose of 2,4-TDI, and the cumulative amount of 2,6-TDA in urine ranged from 14% to 18% of the 2,6-TDI dose. The average urinary level of 2,4-TDA was 5 μg/l in the 6 to 8-h sample (range 2.8–9.6 μg/l), and the corresponding value for 2,6-TDA was 8.6 μg/l (range, 5.6–16.6 μg/l). Biological monitoring of exposure to 2,4- and 2,6-TDI by analysis of 2,4- and 2,6-TDA in urine is feasible.
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  • 6
    ISSN: 1438-2199
    Keywords: Amino acids ; Cysteic acid analysis ; Taurine analysis ; Gas chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have reported preparations and gas chromatographic analyses of volatile derivatives of sulfuric acid and taurine (Masuoka et al., 1988; 1989). By extending these studies, we have developed a method for the gas chromatographic determination of cysteic acid. Cysteic acid was converted to the N-isobutoxycarbonyl derivative by the reaction with isobutyl chloroformate in the presence of sodium hydroxide. After desalting with a cation-exchange column, the derivative was converted to the silver salt by reacting with silver oxide. The resulting silver salt was quantitatively esterified with methyl iodide in the presence of dimethyl sulfate and silver oxide. Dimethyl N-isobutoxy-carbonylcysteate [methyl 2-(N-isobutoxycarbonylamino)-3-(methoxysulfonyl) propanoate] formed was analyzed by gas chromatography. The calibration curve was linear up to 5.0µmol per ml of cysteic acid and the recovery was more than 95%.
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  • 7
    ISSN: 1438-2199
    Keywords: Amino acids ; Nonprotein amino acids ; α-Aminoisobutyric acid ; Isovaline ; Screening procedure ; Gas chromatography ; Polypeptide antibiotics (peptaibiotics) ; Filamentous fungi
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Filamentous fungi of the genusHypocrea were grown on malt extract/peptone agar, the mycelia were extracted with dichloromethane/methanol, and the extracts were totally hydrolyzed with 6 N HCl (110°C, 24 h). The amino acids (AA) released from peptides were converted into theirN(O)-pen-tafluoropropionyl 1-propyl esters and investigated by gas chromatography and gas chromatography/mass spectrometry for the presence of the nonprotein AAα-aminoisobutyric acid (Aib) and its homologue isovaline (Iva). In particular Aib served as specific marker compound for a particular group of fungal peptides named peptaibiotics,i.e. peptides containing Aib and having antibiotic activities. Screening of 24 species ofHypocrea revealed that the majority was capable of producing peptaibiotics. The reliability of the screening procedure was shown with the isolation of peptaibiotics fromHypocrea muroiana andHypocrea nigricans. These findings extend the list of genera of fungi already known to produce Aib-containing peptides and also establish that Aib and Iva are fairly common in the biosphere.
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  • 8
    ISSN: 1573-5133
    Keywords: Polychlorinated biphenyl ; DDT ; Gas chromatography ; Mass spectrometry ; Crossopterygii
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Synopsis Gas chromatography coupled with electrolytic conductivity detection and electron capture negative chemical ionization mass spectrometry have been used to identify and quantify organochlorine xenobiotics in tissues from two specimens of the living coelacanth Latimeria chalumnae. Compounds identified include polychlorinated biphenyls (PCB), 4,4′-DDT and its metabolites 4,4′-DDD and 4,4′-DDE. Levels of these compounds in the specimens were observed to be generally related to tissue lipid content. Highest concentrations of the xenobiotics were present in the lipid-rich swim bladder, followed by adipose tissue and liver. Levels ranged from 89 to 510 μg kg−1 for PCB and 210 to 840 μg kg−1 for Σ-DDT (including DDD and DDE) on a wet-weight basis. Organochlorine concentrations in relatively lipid-poor tissues, i.e. muscle and kidney, were lower. Parent DDT contributed significantly to the Σ-DDT burden. PCB congeners containing five to seven chlorines were most prevalent. Component distributions did not match those present in common commercial PCB formulations. However, major congeners observed were similar to those reported for other fishes.
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  • 9
    Electronic Resource
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    Springer
    Chromatographia 31 (1991), S. 31-40 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Resolution of enantiomers ; Thermodynamic analysis ; Enthalpy of interaction ; Extrapolation of net retention time
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The calculation of capacity factors, k′, from net retention times, t′R, and the corresponding dead times, tM, at different temperatures suffers from the limited accuracy of the tM values. If the temperature coefficient racy of the tM values. If the temperature coefficient d ln k′/d (1/T) only is required, it is sufficient to determine net retention times (t′R)p at constant inlet pressure pi for different temperatures, since the temperature dependence of (tM)p can be assumed as (tM)p=A·eB/T, with B being approximately independent of the column inlet pressure and of the nature of the carrier gas. The extrapolation and interpolation of (t′R)p may be either performed by linear regression or graphically with a nomogram for ln (t′R)p versus 1/T. The resolution factor, α, of two components, e.g. enantiomers which are resolved on a chiral stationary phase, can be treated in a similar way. Examples are given for the resolution of enantiomers of two non-proteinogenic amino acids on the new polysiloxane phase L-Chirasil-CPG.
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  • 10
    Electronic Resource
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    Chromatographia 31 (1991), S. 258-262 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Packed columns ; Methyl polysiloxanes immobilization ; Peroxide initiated cross-linking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The free radical cross-linking procedure of stationary phase immobilization introduced by Grob et al. for capillary columns has been adapted for the preparation of column packings on diatomaceous supports. Immobilization of SE-30 and OV-1 on typical gas chromatography supports: Polsorb B-AW, Chromosorb W-AW, Chromosorb G-AW and Gas Chrom Q was investigated. Before immobilization, the supports (excluding Gas Chrom Q) were purified by extraction with 6 M HCl in a Soxhlet extractor and silanized with hexamethyldisilazane vapour at 300°C. The influence of the type and concentration of peroxide on the efficiency of immobilization of the silicone was studied. In order to obtain over 95% immobilization a minimum of 2% w/w of the peroxide in the stationary liquid is required. Properties of packings with immobilized phase were compared with those of related conventional packings. Adsorption activity, column efficiency and thermal stability were used for this comparison.
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  • 11
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Retention indices ; Target factor analysis ; Reproduction, prediction, classification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Using the method of target factor analysis (TFA) described by Malinowski and Howery a computer program has been developed to study different sets of gas chromatographic retention data. Physico-chemical, topological and uniqueness parameters have been found to be basic factors to describe solute behaviour problems. Factor analytical solutions have been used to reproduce the data matrices and to make predictions based on best sets of basic factors. The mean absolute error in the reproduction step is between 1.72 retention index units (i.u.) for a relatively simple matrix consisting of retention indices of alcohols and 7.36 i.u. for a combined data matrix of alcohol, aldehyde and ketone retention indices. TFA has also been used to classify solutes based on their retention behaviour. Alkanes have been classified from cycloalkanes, alkanes from alkenes, and alcohols from aldehydes and ketones using only their retention data and a special kind of uniqueness vector.
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  • 12
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Thin-layer chromatography ; Thermal analysis ; Copper(II) complexes ; Schiff's bases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A study is presented of the thermoanalytical and gas chromatographic (GC) properties of the copper(II) complexes of twenty four tetradenate Schiff's bases. Variations in thermal stability, volatility and GC retention of the complexes are discussed in terms of stereo-electronic effects of the substituents. Although some complexes decomposed extensively during vaporization above 250°C all, apparently, survive chromatography intact at 200°C. Certain complexes were separated as distinct regio-isomers by GC. Fluorinated ligands still appear to be the most suitable derivatizing reagents for Cu(II).
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  • 13
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    Chromatographia 31 (1991), S. 123-128 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Amino acids ; Chiral separations ; Fruit juice adulteration ; Microorganisms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The configurations of free amino acids (AAs) in orange juice beverages (commercial products of satisfactory and unsatisfactory quality), an orange juice concentrate (bulk product suspected of being adulterated), and in an orange juice that has been contaminated by addition ofLactobacillus plantarum as a model for microbial spoilage, were determined, after derivatization, by means of gas-liquid chromatography (GC) using fused-silica capillary columns coated with Chirasil-L-Val or Chirasil-D-Val as stationary phases. AAs were isolated from juices by treatment with Dowex WX8 ion-exchanger and were investigated, by GC, as theirN(O)-pentafluoropropionylorN(O)-trifluoroacetyl 1-propyl esters. It was found that the high quality orange juice beverage contained L-AAs exclusively whereas this juice, after fermentation withLactobacillus, contained free D-Ala (32.7%), D-Val (62.3%), D-Phe (20.0%), D-Glu (24.3%), D-Ser (2.6%), D-Asp (0.8%), and significant amounts of D-Pro [% D=100 D/(D+L)]. D-Ala (8.8%) and D-Ser (4.2%) were found in a sensory and analytically unsatisfactory orange juice beverage, whilst D-Ala (27.5%) and D-Ser (14.3%) were detected in the orange juice concentrate suspected of being adulterated. Although capillary GC on chiral stationary phases is regarded as being highly suitable for the determination of AA enantiomers in fruit juice beverages, detection of D-AAs is currently not considered as conclusive proof of fruit juice adulteration caused by addition of AA racemates since a non-microbial origin of D-AAs in the respective juice, or an original occurrence of D-AAs, in either the free, substituted, or peptide-bonded form in the fruits, cannot be excluded with certainty.
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  • 14
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Gas chromatography ; Polycyclic aromatic hydrocarbons ; Soot and air samples ; Liquid CO2 extraction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The results of the analysis of polycyclic aromatic hydrocarbons (PAH) in soot and similar types of sample are often dependent on the extraction method applied, owing to carbonaceous substances present in these samples. The recoveries of three extraction methods, and ultrasonic ether, a Soxhlet toluene and a Soxhlet extraction with liquid CO2 were compared for a typical soot sample. Additionally the CO2 extraction was optimized with respect to the necessary number of transfers during the extraction and the proper method to remove the CO2 after extraction. Finally, the liquid chromatographic pretreatment of the extract, prior to gas chromatographic analyses of the PAH, was improved.
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  • 15
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    Chromatographia 31 (1991), S. 171-172 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Ethanolamines ; Ethylene glycols ; Wide-bore capillary column
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The GC separation of a mixture of three ethanolamines and four ethylene glycols without any preliminary derivatization, on a wide-bore capillary column coated with Carbowax 20M is described. These high-boiling and polar compounds elute giving simmetrical peaks and show good resolution. The analysis is completed in less than 14 minutes.
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  • 16
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    Chromatographia 31 (1991), S. 173-176 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Stationary phase optimization ; Mobile phase optimization ; Column temperature optimization ; Multifactor optimization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A computer-assisted method is presented for the simultaneous multifactor optimization (stationary phase loading, column temperature and carrier gas flow rate) of the analytical conditions for the optimum separation of multicomponent samples in gas chromatography. The optimization of the separation over the experimental region is based on a special polynomial from twelve preliminary experiments using the resolution as the selection criterion. Computer scanning technique was used for optimum selection in three dimensions. Excellent agreement was obtained between the predicted data and the experimental results.
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  • 17
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    Chromatographia 31 (1991), S. 193-205 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Column liquid chromatography ; Silanol adsorption centres ; Strongly interacting adsorption sites ; Suppression of adsorption activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary In this second part of the review heterogeneity of the silica surface is described and evidence is presented for the existence of a low population of strong adsorption sites. Methods of detection and determination of these strongly interacting sites are discussed. The last part of the review is devoted to the suppression of unwanted adsorption activity. Methods of blockage and special methods for the preparation of HPLC packings are described.
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  • 18
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    Chromatographia 31 (1991), S. 243-246 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Principal component analysis ; Wool wax alcohols ; Sterols
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Capillary gas chromatography with flame ionization detection has been applied to the separation of the components of wool wax alcohols. Twenty-six commercial and non-commercial (laboratory) samples were investigated. Twenty-eight components found in the samples were used as variables for further characterization by a chemometric procedure. Principal component analysis was applied to the differentiation of samples from different sources and obtained by different technologies.
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  • 19
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Chemiluminescence detection ; Phosphine derivatives ; Headspace analysis ; Fluorine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Phosphine, alkylated phosphines and monophosphinate esters are detected with high sensitivity in capillary gas chromatography (GC) by their chemiluminescent reactions with molecular fluorine. Detection limits are estimated to be 1.3 pg, 0.5 pg, 8 pg, and 17 pg for phosphine, trimethyl phosphine, trimethyl phosphinate ester, and triethyl phosphine, respectively. As found earlier with alkylated sulfur, selenium and tellurium compounds, the detector exhibits a linear response. For triethyl phosphine, a linear range of greater than three orders of magnitude was demonstrated. Emission spectra were obtained for the trimethyl phosphine and triethyl phosphine systems. Chemiluminescence emitters include electronically excited HCF, vibrationally excited HF, and an unknown species in the trimethyl phosphine system. Banded emission from vibrationally excited HF and a broad continuum were observed for both trimethyl phosphine and triethyl phosphine; however, HCF emission was observed only for TMP. Under the conditions employed, the principal emitter is HCF for trimethyl phosphine and HF and the unknown emitter for triethyl phosphine. This detector may have important applications in investigations of the biogeochemical cycling of phosphorus.
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  • 20
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    Chromatographia 31 (1991), S. 393-397 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Correlation chromatography ; Spark modulator injector
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A spark modulator has been tested as an injection system for correlation gas chromatography. An air/hydrocarbon vapour mixture was used as the carrier gas. Single negative sample injections were performed using a single spark period. The experiments resulted in negative sample peaks and a positive product peak. The intensity of all peaks showed a characteristic dependence on the spark frequency and power used. Ghostpeaks were absent when a correlation experiment was performed with a high concentration of a test compound in pure air. The signal to noise ratio enhancement however, was lower than the theoretical value. More experiments are necessary to expalain this phenomenon.
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  • 21
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    Chromatographia 31 (1991), S. 457-464 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Organoclay stationary phase ; Bentone ; Ethylbenzene and xylene isomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Several kinds of Bentones which have structures similar to Bentone 34 have been tested and compared for the purpose of improving the resolution of ethylbenzene and xylene isomers by gas chromatography. Bentone SD-3 was found to have higher selectivity toward these close-boiling compounds than the well known stationary phase Bentone 34. Modification effects of some conventional stationary phases which represent the whole range of polarity on the chromatographic property of Bentone SD-3 have been investigated and discussed. A number of new organoclays which have different structures of the organic cation in complexes have been synthesized and their properties evaluated for the separation of positional isomers. A simultaneously high selective organoclay for each component in the aromatic mixture of ethylbenzene and xylene isomers, without assistance of conventional stationary phases, has been described.
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  • 22
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    Chromatographia 31 (1991), S. 453-456 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Organochlorine pesticides ; Polychlorinated biphenyls ; Solid phase extraction ; Mussels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A multi-residue method for the determination of organochlorine pesticides and polychlorinated biphenyls (PCB's) in mussels (Mytilus sp.) is presented. After extraction with acetonitrile, pesticides and PCB's are separated from coextractives by liquid-liquid partition between acetonitrile and water/hexane. Further clean-up is performed using Sep-Pak Florisil cartridges eluting PCB's in the first eluate with hexane and organochlorine pesticides in the second eluate with 15% ethyl ether in hexane. Final determination is carried out by capillary gas chromatography with ECD. Detection limits for different pesticides and PCB's range from 0.02 to 0.3 μg kg−1 and recoveries from standards solutions treated in the same way as the samples averaged 91.5%.
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  • 23
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    Chromatographia 31 (1991), S. 500-504 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Amino acids ; Linearity ; Nitrogen-phosphorus detector
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A significant curvature of the detector response was observed when a Nitrogen-Phosphorus Detector (NPD) was used for the gas chromatographic determination of amino acids. Five calibration standards, over a 16 fold concentration range, were used to calibrate the NPD. A calibration curve of form y=axb was found to be suitable, with coerelation coefficients (r)〉0,997 for all 17 amino acids. A t-test was used to prove that b≠1, i.e. there was significant curvature. This calibration curve reduced calibration errors to less than 6%, compared to more than 40% for linear calibration.
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  • 24
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    Chromatographia 32 (1991), S. 5-12 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Headspace sampling ; GC theory ; Influence of sample volume
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The role of the volume of the sample and the sample vial in equilibrium headspace-gas chromatography is discussed. A new term, thesample phase fraction (ΦS) is introduced. It is shown that if the value of ΦS is kept constant, the vial's volume has no influence on the “sensitivity” of the headspace analysis (which is proportional to the concentration of the analyte in the headspace). In a given headspace sampling system, concentration of the compound of interest in the headspace (c G * ) at equilibrium is related to the value of ΦS: a higher ΦS will increase c G * . However, the influence is important only in the case of low distribution coefficients: in the case of higher distribution coefficients this influence is negligible. This conclusion is also true for small changes in the sample volume in duplicate analyses: exact reproducibility of the sample volume is important only in the case of low distribution coefficient values.
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  • 25
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Supercritical fluid extraction ; GC detectors ; Purity of gases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The usefulness of several grades of carbon dioxide for online supercritical fluid extraction/capillary gas chromatography has been studied. If trace-level work has to be performed, no single grade can be recommended for all modes of detection studied. Good-quality carbon dioxide is available for use with flame ionization and thermionic detectors. With electron-capture detection, however, distinct problems still exist.
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  • 26
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    Chromatographia 32 (1991), S. 579-582 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Flame gas analysis ; Low pressure sampling ; Gas syringes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A new sampling technique is developed for flame samples taken at very low pressure (50 Torr absolute). This technique uses gas syringes. Analysis is by gas chromatography and the compounds of interest are the fixed gases and selected C1 and C2 hydrocarbons and chlorinated hydrocarbons. Linear response factors are obtained for all compounds. This is highly unusual for gas-phase chlorinated hydrocarbon sampling, which is very prone to sample absorption. The sources of experimental error unique to gas syringe use are identified and quantified. One error source is exacerbated by the very low sample pressure and requires special treatment.
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  • 27
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Linear temperature programming ; Calculation of retention indices
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Program temperature retention indices for fifteen nonalkane solutes have been determined by cubic splines, by other procedures found in the literature and by interpolation of the n-alkanes retention time logarithm for eleven temperature programs. A comparison in terms of variance of the differences between PTRI calculated by CS and each of the remaining methods is made for each of the eleven program runs, for each of the three stationary phases used and for many of the programs. The smallest variances obtained result when the Zenkevich, van den Dool & Kratz and Chen et al. methods are tested. The stationary phase polarity is of no relevance since it has no effect on the specific PTRI found by the different methods employed in this work.
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  • 28
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    Chromatographia 32 (1991), S. 211-214 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Retention index of homologous series ; Chain rigidity ; Stationary phase polarity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The rule that addition of a CH2 group to a molecule increases the retention index by 100±3 is subject to a greater uncertainty than ±3 when (a) the stationary phase has very strong intermolecular attractions comparable to the nitriles and the analyte has a polar group in the 1-position, (b) the alkyl chain to which the CH2 is added has 3 or fewer carbons and (c) when a group that is remote from the end of the chain, such as an ester group or a double bond, introduces rigidity in that part of the chain. In cases (a) and (c), it is still true that the retention index increases linearly in a specific homologous series, but it may deviate from 100 units per carbon by as much as 10 or, in the case of nitrile stationary phases, may be as low as 70.
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  • 29
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    Chromatographia 32 (1991), S. 248-258 
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Electron capture detector ; Hypercoulometry ; Secondary polarisation effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary This paper reports measurements of the current characteristics and of the signal corresponding to a constant concentration of Freon F-11 for an electron-capture detector, supplied with a pulse voltage with a changeable pulse duration, amplitude and repetition time. It was found that an additional voltage applied to the detector cathode increased the detector signal by about 50% and that the maximal signal was observed at 5 V. The influence of the polarized voltage on the electron caputure efficiency coefficient (p) measured with two detectors in series was demonstrated and the reliability of the sample mass calculation by means of (p) is discussed.
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  • 30
    ISSN: 1612-1112
    Keywords: Gas chromatography ; Non-equilibrium headspace sampling ; Vegetables and food products ; Flavour compounds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Static headspace sampling combined with gas chromatography using open-tubular (capillary) columns for the characterization of the flavour of raw vegetables and some vegetable products is described. In order to avoid alteration of the composition of the volatiles, the sample was thermostated for a short time only. Although equilibrium between vapour and sample was not established the reproducibility of such conditions is demonstrated. Typical chromatograms are given; the most characteristic compounds present were identified by mass spectrometry.
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  • 31
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    Chirality 3 (1991), S. 2-13 
    ISSN: 0899-0042
    Keywords: drug stereochemistry ; cyclothiazide ; stereoisomerism ; chiral HPLC ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: There is a great deal of current interest in the role and importance of chirality in the development of new drugs, but little attention is being paid to the stereochemistry of older drugs. Indeed, many older chiral drugs were introduced without adequate information on their stereochemical identity or composition. We have examined one such drug, the antihypertensive diuretic agent cyclothiazide. Standard sources of drug information and the research literature do not provide data on the stereochemical composition of clinically used cyclothiazide, although scattered reports indicate that the drug may consist of “several stereoisomers.” Inspection of the chemical structure of the drug, 6-chloro-3,4-dihydro-3-(5-norbornen-2-yl)-2H-l,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide, shows that it can exist as eight stereoisomers that may form four racemates. Using synthesis, fast-atom-bombardment mass spectrometry, gas-liquid chromatography, chiral and nonchiral high-performance liquid chromatography, and nuclear magnetic resonance spectroscopy, we determined that pharmaceutical cyclothiazide is in fact a mixture of the eight stereoisomers in the form of the four racemates. The two racemates with endo configuration at the norbornene moiety predominate over the exo racemates, and small but significant differences in isomer distribution between different batches of the drug were observed. We urge that in studies of older drugs the stereochemical details be considered.
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  • 32
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    Chirality 3 (1991), S. 30-34 
    ISSN: 0899-0042
    Keywords: propafenone ; enantiomers ; α1-acid glycoprotein ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The interaction of propafenone enantiomers with human α1-acid glycoprotein was studied using high-performance liquid chromatography. Each of the two optical antipodes interacted with one class of high-affinity binding sites characterized by Ka(R) = (6.18 ± 0.93) × 105 M-1, n(R) = 1.34 ± 0.09 for the (R)-isomer and Ka(S) = (8.93 ± 1.82) × 105 M-1, n(S) = 0.99 ± 0.08 for the (S)-isomer. Nonspecific binding to secondary low-affinity high-capacity binding site(s) was only slightly greater in the case of the (S)-enantiomer (n′k′(S) = (1.06 ± 0.09) × 104 M-1) compared to the (R)-enantiomer (n′k′(R) = (6.87 ± 0.72) × 103 M-1). It was concluded that both enantiomers interact with common single class of high-affinity binding sites on AAG (along with nonspecific binding) exhibiting only slight stereoselectivity for propafenone.
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  • 33
    ISSN: 0899-0042
    Keywords: enzymatic resolution ; chiral HPLC ; enantiomeric ratio ; enantiomeric excess ; 2-(phenoxy)propionate ; 2-(4-chlorophenoxy)propionate ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: (R)- and (S)-Methyl 2-(phenoxy)propionate and their acids could be separated simultaneously by a Chiralcel OD or OK column, while (R)- and (S)-methyl 2-(4-chlorophenoxy)propionate and their acids were separated concurrently only by an OK column. This is a novel and facile way to measure the enantiomeric excesses of the remaining substrate and product in the reaction of enzymatic resolution; enantiomeric ratios could then be calculated.
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  • 34
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    Chirality 3 (1991), S. 88-89 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 35
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    Chirality 3 (1991), S. 157-157 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 36
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    Chirality 3 (1991), S. 151-155 
    ISSN: 0899-0042
    Keywords: (-)-(R) and (+)-(S) [8] gingerol ; enantiomers synthesis ; chiral stationary phase ; HPLC ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: (+)-(S)-5-Hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-dodecanone 1a commonly named (+)-(S)-[8] gingerol is a natural product known to have cardiotonic activity.1-5 A total synthesis of both enantiomers is described with details for the first time using a general synthetic scheme which was recently outlined in the literature.6 This synthesis relies both on the separation of the diastereoisomers 4a and 4b by simple column chromatography on silica gel and on an HPLC analysis on a chiral phase to determine the optical purity of the enantiomers 8a and 8b of protected [8] gingerol. The gingerol isomers were thus obtained in good chemical yields in greater than 96% enantiomeric excess.
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  • 37
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    Chirality 3 (1991) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 38
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    Chirality 3 (1991), S. 161-164 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 39
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    Chirality 3 (1991), S. 158-158 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 40
    ISSN: 0899-0042
    Keywords: chiral ; chiral solvating agent ; stereochemistry ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The N-(n-butylamide) of (S)-2-(phenylcarbamoyloxy)propionic acid, easily prepared starting from the inexpensive L-ethyl lactate, can be used as convenient chiral solvating agent (CSA) to determine the enantiomeric composition of N-(3,5-dinitrobenzoyl)amino acid methyl esters.
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  • 41
    ISSN: 0899-0042
    Keywords: cellulose triacetate ; tribenzoylcellulose ; methylbenzoylcellulose ; chiral phase ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 2,2,2-Trifluoro-1-(9-anthryl)ethanol (TFAE) has now been widely used as a powerful chiral solvating agent for NMR spectroscopy. In connection with the development of a new general synthesis of halogenoalkylalkanols, starting from the corresponding ketone or aldehyde, we synthesized some halogenoalkyl-1-(9-anthryl)methanol derivatives liable to work as chiral solvating agents. The racemic anthryl derivatives were preparatively resolved into their corresponding enantiomers by chromatography on triacetyl cellulose (CTA I) or on meta-methylbenzoyl cellulose beads as chiral stationary phases. Their effectiveness as chiral solvating agents was measured as the magnitude of the splitting induced in the 1H-NMR spectra of 1-phenylethylamine and of (1-phenylethyl)methyl ether in comparison with splitting caused by TFAE. While TFAE induced the largest splitting for 1-phenylethylamine, 2,2,3,3,3-pentafluoro-1-(9-anthryl)propanol 2 was more effective in the case of (1-phenylethyl)methyl ether, pointing out that depending on the substrate, other derivatives of the TFAE type can be very useful as chiral solvating agents.
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  • 42
    ISSN: 0899-0042
    Keywords: chiral chromatography ; cellulose-based chiral stationary phase ; aromatase inhibitor ; cyclohexylaminoglutethimide and metabolite ; enantiomeric separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Racemic cyclohexylaminoglutethimide (±ChAG) and its acetylated metabolite (±ChAG) were resolved by a direct chromatographic method using a Chiracel OD column without derivatization. Maximum resolutions (R) of 4.89 and 0.74 were obtained for the enantiomers of cyclohexylaminoglutethimide and its acetylated metabolite, respectively.
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  • 43
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    Chirality 3 (1991) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 44
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    Chirality 3 (1991), S. 242-253 
    ISSN: 0899-0042
    Keywords: steric effects ; geometric model ; ester hydrolysis ; ester conformation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: With the early aim of quantifying steric consequences of chirality, efforts to define a nonempirical steric parameter of chemical groups are reported. Steric hindrance of a reacting center by any acyclic saturated R group has been characterized by a geometric “axial steric parameter”: the solid angle of R. When the group is a “symmetric top substituent” (i.e., when all the terminal atoms are equivalent), the solid angle matches the solid angle of a cone envelope of R. The definition of this cone is compared with Tolman's definition of a ligand cone in organometallic complexes. The chemical significance of this parameter is shown by an excellent correlation with the Dubois' experimental steric parameter E′s. Modeling steric repulsion by the cone of R, and correcting solid angles for conformational effects, only 3 empirical coefficients are needed to calculate 33 values of E′s with less than 10% error. The cone model is suggested to be relevant within the limits of random and independent free rotations about all the bonds in the C-R group. A separation between “axial cone steric hindrance” and other steric effects is proposed. The basic model and the corrections proposed allow the conformational features of esters to be discussed.
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  • 45
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    Chirality 3 (1991), S. 263-267 
    ISSN: 0899-0042
    Keywords: aloe ; feroxidin ; absolute configuration ; tetralins ; helicity ; Cotton effect ; conformation ; half-chair cyclohexene ring ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The configuration of carbon-8 in feroxidin (1) was proven to be (S) by chemical correlation with (S)-methylsuccinic acid. Previous demonstration that 6-hydroxy and 8-methyl groups are equatorial and pseudoaxial, respectively, in a half-chair conformation of the cyclohexene ring (relative configuration) allowed the absolute stereochemistry of the whole molecule to be established (Fig. 3). The CD spectrum of feroxidin represents the first experimental test confirming the applicability of Snatzke's helicity rules to tetralins m-disubstituted on the aromatic ring.
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  • 46
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    Chirality 3 (1991), S. 285-291 
    ISSN: 0899-0042
    Keywords: macromolecular ; optical activity ; polyisocyanate ; deuterium ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In contrast to random coil polymers, polyisocyanates maintain a highly extended helical conformation in solution. This structural characteristic causes unusually large chiral optical properties to arise from copolymerization of tiny proportions of optically active monomer isocyanates with achiral isocyanates or even from stereospecific placement of deuterium in the side chain of poly(n-hexyl isocyanate). These effects can be understood as phenomenologically related to the optical activity amplification properties of vinyl polymers studied by Pino and his co-workers and ascribed to breaking the energetic degeneracy of the otherwise equally populated left- and right-handed helical states of the backbone. Statistical thermodynamic calculations, based on this model, and analogous to those carried out earlier on the vinyl polymers, allow matching the temperature and molecular weight dependence of the optical activity in poly((R)-1-deuterio-1-hexyl isocyanate) to the approximate responsible energy terms.
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  • 47
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    Chirality 3 (1991), S. 315-317 
    ISSN: 0899-0042
    Keywords: ↕ β6.3-model ; ↕ β-model ; ↕ β7.2-structures ; closed structures ; open structures ; non-conducting dimers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: It is suggested that the conducting transmembrane channels formed by the linear gramicidins A, B and C may be head-to-head (formyl end-to-formyl end) dimers of double-stranded parallel β-helices. This possibility is not in conflict with any of the various experimental findings bearing on the molecular organization of the channels and represents a plausible alternative to Urry's model of a head-to-head dimer of single-stranded β6.3-helices.
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  • 48
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    Chirality 3 (1991), S. 1-1 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 49
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    Chirality 3 (1991), S. 19-23 
    ISSN: 0899-0042
    Keywords: aporphine enantiomers ; serotonin 5-HT1A receptors ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The two enantiomers of the title compound have been prepared by different synthetic routes. Both bind strongly to 5-HT1A receptors from rat forebrain membrane tissue. However, in a guinea pig ileum preparation, the (R)-enantiomer exhibits properties consistent with its being an agonist, whereas the (S)-enantiomer shows no agonist effect, but it blocks the actions of the (R)-enantiomer and of 8-hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT), a 5-HT1A agonist. These data are presented as a rare example of enantiomers which demonstrate opposite pharmacological effects at the same receptor.
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  • 50
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    Chirality 3 (1991), S. 341-344 
    ISSN: 0899-0042
    Keywords: enantioselectivity ; carbonylation ; hydroformylation ; hydroalkoxycarbonylation ; para-substitution ; 2-phenylpropene ; platinum catalyst ; palladium catalyst ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantioselective hydroformylation catalyzed by [(R,R)-Diop]Pt(SnCl3)Cl7 and the enantioselective hydroisopropoxycarbonylation catalyzed by [(R,R)-Diop]PdCl28 or by [(R,R)-Diop-dbp]PdCl29 of some para-substituted 2-phenylpropenes (para substituents = NO2, H, CH3O, Cl, CF3) was investigated in order to recognize possible electronic influences on the regioselectivity and on the enantioface selection which take place in such carbonylation reactions. The catalytic systems used gave no carbonylation products when the nitro compound was the substrate. 7 and 8 show similar regioselectivities, the less branched isomer being exclusively formed for all substrates except p-methoxy-2-phenylpropene which gave small amounts of the alternative regioisomer. The enantioselectivity depends on the σp effect of the substituent in both cases; the differences are, however, rather small and the trend is opposite in the two cases. The regioselectivity displayed by 9 is still in favour of the less branched isomer but it is high only in the case of p-trifluoromethyl-2-phenylpropene. Larger differences with respect to the other catalytic systems were also observed for enantioselectivity but the trend for both regioselectivity and enantioselectivity is not linear.
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  • 51
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    Chirality 3 (1991), S. 355-369 
    ISSN: 0899-0042
    Keywords: enantiomerically pure compounds ; chiral drugs ; enantioselective hydroformylation ; enantioselective catalysts ; biologically active compounds ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The asymmetric hydroformylation reaction represents a potential powerful synthetic tool for the preparation of large number of different chiral products to be used as precursors of several organic compounds endowed with therapeutic activity. Essential and nonessential amino acids, 2-arylpropanoic acids, aryloxypropyl- and β-phenylpropylamines, modified β-phenylethylamines, pheniramines, and other classes of pharmaceuticals are available through enantioselective oxo-reaction of appropriate functionalized olefins; this process is catalyzed by rhodium or platinum complexes with chiral ligands, mainly chelating phosphines, and sometimes affords very high enantiomeric excesses. Furthermore, the application of many simple optically active aldehydes arising from asymmetric hydroformylation as chiral building blocks for the synthesis of complex pharmacologically active molecules such as antibiotics, peptides, antitumor macrocycle compounds, and prostaglandins is conveniently emphasized. The possibility of a future application of this asymmetric process for the production of many synthons to obtain other valuable pharmaceuticals is widely discussed too.
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  • 52
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    Chirality 3 (1991) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 53
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    Chirality 3 (1991), S. 389-392 
    ISSN: 0899-0042
    Keywords: chirality ; origin of life ; Bose condensation ; organic superconductivity ; electroweak interaction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We review a recent paper20 in which a specific enhancement factor (i.e., a phase transition into a condensed Bose mode) is proposed to account for the observed amplification of the ground state energies of the L- and D-amino acid enantiomers; the difference between these energies is assumed to be due to the neutral parity-violating electroweak interaction. This physical effect initially shifts the enantiomer energies by about 3 × 10-19 eV. The proposed phase transition is characterized by a critical temperature Tc, which may be studied theoretically by enlarging the standard electroweak theory to include either the top quark or supersymmetry21. Possible experimental means of finding Tc are discussed.
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  • 54
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    Chirality 3 (1991), S. 418-421 
    ISSN: 0899-0042
    Keywords: chiral bioinversion ; pharmacokinetics ; (+)-(S)-ibuprofen ; (-)-(R)-ibuprofen ; rac-ibuprofen ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Using a pharmacokinetic model recently proposed to explain ibuprofen disposition in man,1 plasma concentrations of pure ibuprofen enantiomers were simulated following oral administration of (-)-(R)-ibuprofen, (+)-(S)-ibuprofen, or rac-ibuprofen. Simulated and literature values for AUC's were used to compare S/R ratios for different cases of the model and for different methods of calculating the fraction of R bioinverted to S. Numerical simulation using STELLA confirmed previous results for different cases of bioinversion. Simulated S/R AUC ratios, for administration of the racemate, ranged from 4.0 (presystemic bioinversion) to 1.66 (systemic bioinversion). Literature values for S/R AUC ratios averaged 1.53±0.2 for administration of the racemate; therefore, systemic bioinversion was concluded to be representative of ibuprofen disposition. Additional simulations of S/R AUC ratios, for administration of (-)-(R)-ibuprofen only, ranged from 1.5 (presystemic bioinversion) to 0.66 (systemic bioinversion). Literature values for S/R AUC ratios averaged 0.50±0.9 for administration of (-)-(R)-ibuprofen only, which again supported conclusions of systemic bioinversion. Using different equations for estimation of fraction of R inverted to S (FR→S), results based on simulated data were identical; however, FR→S values based on literature data were different. Therefore, assumptions made for different FR→S equations do not appear to be rigorous. Calculations of FR→S, based on literature data, averaged 0.52 overall, indicating bioavailability of (+)-(S)-ibuprofen may be similar for a 150 mg dose of (+)-(S)-ibuprofen compared to a 200 mg dose of racemate.
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  • 55
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    Chirality 3 (1991) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 56
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    Chirality 3 (1991), S. 451-453 
    ISSN: 0899-0042
    Keywords: enantioselective ; stereoisomers ; β-blockers ; adrenergic β-receptor blockaders ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: We have studied the stereochemistry of accumulation of the hydrophilic β-adrenoceptor antagonist rac-atenolol by human platelets in vitro. The accumulation was slow, not reaching equilibrium until 90 min at 37°C. The uptake was temperature dependent with the accumulation at 37°C being 3-4 times greater than at 4°C. The accumulation was also stereoselective at 37°C, favoring the active (-)-enantiomer over the (+)-enantiomer by 2.3-fold. Reserpine, but not desipramine, inhibited the platelet accumulation of rac-atenolol enantiospecifically. This uptake profile is different from the platelet uptake of lipophilic β-blockers, which is characterized by nonspecific membrane binding, but similar to the carrier-mediated accumulation of the neurotransmitter norepinephrine by storage granules within the platelet.
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  • 57
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    Chirality 3 (1991), S. 454-459 
    ISSN: 0899-0042
    Keywords: phenytoin ; product inhibition ; p-HPPH ; rat liver microsomes ; ligand-exchange chromatography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Different doses of rac-p-HPPH (0.4 and 4 mg/h) were given repeatedly to rats infused with [14C]phenytoin. The serum levels of 14C-labeled and unlabeled p-HPPH, and [14C]phenytoin were measured by an HPLC method and radiometric analysis. The clearance of phenytoin and p-HPPH was determined by rate of dosing divided by the steady-state concentration. The phenytoin clearance was significantly lower in the high dose p-HPPH injection group than in the low dose group (87 versus 262 ml/h), whereas p-HPPH clearance showed no difference. The formation clearance of [14C]p-HPPH was also significantly lower in rats injected with high dose of p-HPPH (35 versus 169 ml/h). The clearance of other elimination pathways was also lower in rats with high dose of p-HPPH (53 versus 89 ml/h). The serum protein binding of phenytoin was lower in rats injected with high dose of p-HPPH. The result indicated that injections of rac-p-HPPH mainly inhibited on the formation of p-HPPH itself. The formation of (R)-p-HPPH and (S)-p-HPPH in microsomal preparation was measured by a ligand-exchange chromatographic method. The formation of (S)-p-HPPH or (R)-p-HPPH was not only inhibited by the enantiomer itself, but also cross-inhibited by the other enantiomer. To the formation of either (S)-p-HPPH or (R)-p-HPPH, (S)-p-HPPH showed a higher inhibitory activity. The use of rac-p-HPPH to inhibit phenytoin metabolism in vivo involved several mechanisms. In addition to binding displacement on the serum proteins, one is the product inhibition by the respective p-HPPH metabolite, the other is the competitive inhibition by the other p-HPPH enantiomer.
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  • 58
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    Chirality 3 (1991), S. 212-219 
    ISSN: 0899-0042
    Keywords: oxazepam ; demoxepam ; 3-O-acyl-1-(N,N-dimethylcarbamyl)oxazepam ; 1-(N,N-dimethylcarbamyl)oxazepam ; 3-O-(N,N-dimethylcarbamyl)oxazepam ; camazepam ; norcamazepam ; 1,3-O-bis(N,N-dimethylcarbamyl)oxazepam ; kinetics of racemization ; enantioselectivity of esterases ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Three N,N-dimethylcarbamyl derivatives of oxazepam {1-(N,N-dimethylcarbamyl)oxazepam, 3-O-(N,N-dimethylcarbamyl)oxazepam, and 1,3-O-bis(N,N-dimethylcarbamyl)oxazepam} and a 3-O-acyl-1-(N,N-dimethylcarbamyl)-oxazepam were synthesized from either oxazepam or demoxepam. Enantiomeric pairs of these derivatives and of camazepam were resolved by high-performance liquid chromatography on at least two of three commercially available chiral stationary phase columns employed. Absolute configurations of resolved enantiomers were established by comparing their circular dichroism spectra to those of enantiomeric oxazepams with known absolute stereochemistry. Similar to those of oxazepam, enantiomers of 1-(N,N-dimethylcarbamyl)oxazepam undergo rapid racemization (t½ 1.9 min at 23°C and 0.9 min at 37°C) in an aqueous solution at pH 7.5. The (R)-enantiomer of rac-3-O-acyl-1-(N,N-dimethylcarbamyl)oxazepam was hydrolyzed ∼4.6-fold faster than the (S)-enantiomer by esterases in rat liver microsomes, whereas the (S)-enantiomer was hydrolyzed ∼43-fold faster than the (R)-enantiomer by esterases in rat brain S9 fraction.
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  • 59
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    Chirality 3 (1991), S. 233-241 
    ISSN: 0899-0042
    Keywords: circular dichroism ; 1(S),1′(S)-dimethylbisheptylsulphosuccinate sodium salt ; spectroscopy ; optical activity ; surfactant ; chiroptical properties ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Four chiral analogues of the surfactant Aerosol-OT (AOT) have been synthesized and characterized. All of them form reverse micelles in apolar solvents in the w0 range 0-30 (w0 = [water]/[tenside]). Reverse micellar solutions have been investigated by UV absorption and circular dichroism spectroscopies with the aim of clarifying whether the formation of the macromolecular micellar structure induces the appearance of new chromophoric bands or perturbs the existing ones. Methanolic solutions of the surfactants, in which no micellar aggregates are formed, were taken as references. One of the products 1(S),1′(S)-dimethylbisheptylsulphosuccinate sodium salt (MH-AOT) was capable of forming reverse micelles of relatively high water content (w0 up to 40) and this process was accompanied by a specific increase in the intensity of the circular dichroism band associated with the ester absorbance of the molecule. As no concomitant changes were seen in the UV absorbance spectrum, it was concluded that this observation reflected conformational events occurring within the surfactant rather than chromophoric perturbation. These results are qualitatively similar to those found recently for lecithin reverse micelles which, however, form gels at sufficiently high water contents. The chiroptical properties of these supramolecular aggregates are compared with those of covalent macromolecular systems such as polypeptides.
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  • 60
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    Chirality 3 (1991), S. 257-262 
    ISSN: 0899-0042
    Keywords: chiral photochemistry ; excitation transfer ; optical activation ; circular dichroism ; dissymmetry factor ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The physics involved in photochemistry with circularly polarized light, the warnings on its inherent limitations, as well as some examples of application on organic molecules are briefly reviewed.
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  • 61
    ISSN: 0899-0042
    Keywords: asymmetric polymerization ; stereospecific polymerization ; optically active polymer ; helix ; (+)-tartaric acid ; L-proline ; (+)-(S)-2-(1-pyrrolidinylmethyl)pyrrolidine ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Polymerization of diphenyl-2-pyridylmethyl methacrylate was carried out with the complexes of organolithium compounds with 22 chiral ligands. Helix-sense-selectivity of the polymerization was largely affected by a slight structural difference of chiral ligands. (+)-(S)-2-(1-Pyrrolidinylmethyl)pyrrolidine was the most effective ligand in producing a one-handed helical polymer with narrow molecular weight distribution.
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  • 62
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    Chirality 3 (1991), S. 307-314 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The preparation is reported of two side chain polyacrylate samples 1a,b containing a sulfide group linked to the mesogenic core. By oxidation with a preferentially chiral oxaziridine, samples 1a,b were chemoselectively and enantioselectively converted to the corresponding sulfoxide containing polymers 2a,b with an estimated 20% asymmetric induction. The mesophasic behaviour of the parent and oxidized polymer samples is analyzed by thermal and optical techniques. The modification of the prochiral sulfide groups into chiral sulfoxide groups slightly depresses the propensity of the resulting polymers to give stable and persistent mesophases.
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  • 63
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    Chirality 3 (1991), S. 318-323 
    ISSN: 0899-0042
    Keywords: nuclear magnetic resonance ; circular dichroism ; β-turn conformation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Poly(X-Gly-Gly), simple structural models for the hydrophobic, proline-devoid, regions of elastin, have been synthesized and studied by circular dichroism and NMR spectroscopies. The results gave evidence of type II β-turns as the only ordered structure present in the polymers. The stability of the turns has been shown to decrease on hydration and to increase in the series Leu 〈 Ala 〈 Val 〈 Ile.
    Additional Material: 7 Ill.
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  • 64
    ISSN: 0899-0042
    Keywords: asymmetric synthesis ; enantioselectivity ; diastereoselectivity ; double stereodifferentiation ; chiral ferrocenyl ligands ; bis(1,3-diketonato)oxovanadium(IV) complexes ; oxazolines ; dihydropyrones ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The notion of internal (or intramolecular) cooperativity of chirality is reviewed on the basis of various examples of diastereoisomeric ferrocenylphosphine ligands used in the gold(I)-catalyzed aldol reaction. It was found that the stereochemical outcome of this reaction strongly depends on the specific combination of the absolute configuration of the different stereogenic centers present in the ligand. Thus, individual chirotopic segments in these ligand molecules can act either in a cooperative or noncooperative manner in determining both diastereo-and enantioselectivity. Furthermore, several examples of application of the strategy of double stereodifferentiation (external, or intermolecular cooperativity of chirality) in the gold(I)-catalyzed aldol reaction and the vanadium(IV)-catalyzed hetero Diels-Alder condensation are presented. Based on our work it is apparent that, whether the diastereoselectivity of these two reactions is controlled by the catalyst or by a chiral substrate, cannot be predicted and very much depends on the nature of every individual reactant. Thus, it was found that in both reactions the chiral aldehyde substrate usually has a strong impact on the diastereoselectivity, leading to interesting patterns of double asymmetric induction. On the other hand, chiral isocyanoacetate and chiral-activated dienes, respectively, showed little or no effect on the stereochemical outcome of the reactions.
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  • 65
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    Chirality 3 (1991), S. 376-385 
    ISSN: 0899-0042
    Keywords: circular dichroism ; detection system ; chromatography ; chiral discrimination ; enantiomeric excess ; elution order ; dissymmetry factor ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A circular dichroism-based detection system presents several advantages in the HPLC analysis of chiral compounds because of the selective monitoring of optically active molecules. Its use allows reliable determination of enantiomeric excesses and elution order. To this end, the application of empirical, semiempirical, and nonempirical methods to get stereochemical information from the CD signal is reported. Furthermore, recording the CD spectra on line and evaluation of the dissymetry factor make the CD detection very powerful in characterizing the stereochemistry of chiral eluates.
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  • 66
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    Chirality 3 (1991) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 67
    ISSN: 0899-0042
    Keywords: debrisoquine ; nortriptyline ; desipramine ; polymorphism ; phenocopy ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 1A single oral dose (50 mg) of quinidine significantly increased the debrisoquine metabolic ratio in six healthy volunteers. For four of the volunteers the metabolic ratio changed to that typical of the poor metaboliser (PM) phenotype.2The effect of quinidine in producing debrisoquine oxidation “poor metaboliser” phenocopies persisted for at least 3 days but had disappeared by 1 week.3The debrisoquine metabolic ratios for the same six subjects were not significantly altered by the oral administration of quinine (200 or 400 mg), the dia-stereoisomer of quinidine.4The plasma pharmacokinetic parameters of both nortriptyline and desipramine in healthy volunteers were all changed to those more typical of the debrisoquine PM phenotype following the concomitant administration of quinidine (50 mg).5It is concluded that quinidine, but not its diastereoisomer quinine, is a potent selective inhibitor of the in vivo oxidation of debrisoquine and can produce an artifactual PM phenocopy in persons who are phenotypically extensive metaboliser (EM) phenotype status. The clinical implications of this observation are discussed.
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  • 68
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    Chirality 3 (1991), S. 43-55 
    ISSN: 0899-0042
    Keywords: beads ; polymer ; enantiomer ; chiral phase ; interaction ; alcohol ; diol ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Cellulose-based stationary phases are known to be very efficient and versatile chiral sorbents for the chromatographic resolution of racemates. Except for microcrystalline cellulose triacetate (CTA I), basically all other cellulose-based phases have been prepared by coating of ca. 20% weight polymer on a wide pore silica gel used as a carrier. In this work we describe the preparation of benzoylcellulose (TBC) beads in the pure polymeric form (without inorganic carrier) from an emulsion of the organic polymer. The new material has been fully characterized and used as a chiral stationary phase for the resolution of various classes of racemic compounds such as benzylic alcohols or acetate derivatives of aliphatic alcohols and diols. The structural variety of the separated solutes as well as the irrational influence of the aromatic substituent in different classes of aryl compounds suggest that multiple interaction sites are involved in the complexation, making a prediction of the separation difficult. The benzoyl cellulose beads exhibit a very high loading capacity, which is particularly useful for preparative purposes as demonstrated for selected examples.
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  • 69
    ISSN: 0899-0042
    Keywords: molecular recognition ; chiral recognition ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Molecular dynamics simulations were performed on complexes of (S)-methyl N-(2-naphthyl)alaninate (NAP) with the enantiomers of N-(3,5-dinitrobenzoyl)leucine n-propylamide (DNB), which are used as models for chiral stationary-phase systems developed by Pirkle and co-workers. These studies were undertaken to qualitatively examine (pictorially) the role of entropic effects in these systems. The results of the dynamics calculations were used to refine the search for low-energy conformers. The structures were refined by the use of BioDesign's molecular mechanics method implemented in Biograf. The results of the structural refinements support our previous observation that the SR complex can achieve the same three primary interactions which are observed in the SS structure (i.e., two intermolecular hydrogen bonds and pi stacking) without a significant increase in energy. In addition, these primary interactions are conserved during molecular dynamics simulations with the occurrence of conformations which differ only in the rotational states of the alkyl side chains and ester group (which bears two potential hydrogen bond acceptors utilized in both the homo- and heterochiral complexes). The major difference in the two complexes is the relative position of the sec-butyl group and hydrogen atom on DNB's chiral center, both of which are outside the primary interaction region. All other local minima which have different relative pi orientations (“front-back,” “back-back,” and “back-front” as defined herein) are not sufficiently populated to make more than a negligible contribution to the statistical (time- or energy-averaged) analysis of the (SS)- and (SR)-NAP-DNB complexes. Thus the entropic effects observed in this study (e.g., alkyl side chain or ester group rotations) do not show evidence of qualitative differential effects on the maintenance of the same three primary interactions by both the homo- and heterochiral complexes. The reliability of the present study, which provides pictorial representations of the entropic effects, is not sufficient to determine whether the entropic effects observed herein are sufficient to achieve enantiomeric discrimination alone or in conjunction with other factors (e.g., conformational strain energy). Thus, all of the computational studies we have performed to date (i.e., our previous studies, which include strain energy and through-space field effects, and the present study, which includes entropic effects) show no evidence of any qualitative difference in the homo- and heterochiral complexes in terms of maintaining the same three “contact points”.
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  • 70
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    Chirality 3 (1991), S. 71-75 
    ISSN: 0899-0042
    Keywords: crystal structure ; aldosterone conformation ; correction of assigned configuration ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In the presence of dilute alkali at room temperature aldosterone undergoes rearrangement to form 11β,18:18,21-diepoxy-20,21-dihydroxy-4-pregnen-3-one (V). X-Ray crystallographic analysis demonstrates that isomers of both 18R, 20S, 21S and 18R, 20S, 21R configuration are formed rather than the 18R, 20R, 21R isomer postulated on the basis of examination of 1H-NMR spectra. The spectra appears to be consistent with the major component of the mixture. The 20S configuration observed is in agreement with the chirality assigned to the degradation product obtained when the same alkaline solution of aldosterone is subjected to reflux. The crystals of (V) are monoclinic P21, Z = 4 with a = 20.891(2), b = 6.3848(5), c = 16.067(2)Å, β = 122.09°(1) with two molecules in the asymmetric unit. Molecule A has the 20S,21S configuration and the molecules in the second site are a mixture of the 20S, 21S and 20S, 21R configuration in the ratio of 3:2.
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  • 71
    ISSN: 0899-0042
    Keywords: warfarin ; human liver ; competitive inhibitor ; chiral interactions ; kinetics ; enantiomers ; racemate ; drug metabolism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Inhibition of the metabolism of (S)-warfarin, the more pharmacologically active enantiomer of the racemic drug, by (R)-warfarin was investigated in microsomes obtained from three human livers. In each case the production of both (S)-6- and (S)-7-hydroxywarfarin was found to be competitively inhibited by (R)-warfarin. The Kis for inhibition of (S)-6- and (S)-7-hydroxylation by (R)-warfarin ranged from 7.0 to 8.4 μM and from 6.0 to 6.9 μM, respectively, while the Kms for the 6- and 7-hydroxylation of (S)-warfarin ranged from 3.6 to 3.8 μM and from 3.3 to 3.9 μM, respectively. In contrast, except for the 4′-hydroxylation pathway (S)-warfarin was found to be a weak inhibitor of the metabolism of (R)-warfarin. Possible implications of these findings include the following: (1) the kinetic parameters defining the interactions of two enantiomers of a racemic drug with the cytochrome P-450s or other macromolecular systems in the living organism can only be properly defined from experiments with the pure enantiomers, (2) an enantiomer of a racemic drug may contribute significantly to biological effect not by its inherent activity but by altering the pharmacokinetics of the eutomer, and (3) enantiomeric interactions are not easily detected unless directly sought and may be relatively common.
    Additional Material: 4 Ill.
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  • 72
    ISSN: 0899-0042
    Keywords: chiral derivatization ; pharmacokinetics ; enantiospecific assay ; fluorescent derivatization ; flunoxaprofen ; acyl glucuronides ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The major biotransformation pathway for the chiral lipid-regulating agent beclobrate is conversion to the corresponding carboxylic acid, which is then metabolized to the acyl glucuronide. An enantiospecific assay for biological material was developed that is based on chiral derivatization with N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide (EDAC) and the primary amine S-FLOPA, a new chiral coupling component for carboxylic acids derived from the 2-arylpropionic acid S-flunoxaprofen. Conversion of beclobric acid to the acyl chloride prior to coupling with the amine is also feasible. From plasma or urine beclobric acid was extracted into n-hexane/ethanol (9:1) at pH 4 after addition of sodium chloride. Clofibric acid was used as internal standard. Derivatization with EDAC/FLOPA was performed under addition of 1-hydroxybenzotriazole in anhydrous dichloromethane containing trace amounts of pyridine (ambient temperature/2 h reaction time). The chromatographic separation was performed on a silica gel stationary phase (Zorbax Sil) using n-hexane-chloroform-ethanol (100:10: 0.75, by vol) as mobile phase [flow rate, 2 ml/min; fluorescence detection, 305/355 nm; elution order of the derivatives, (-) before (+)]. Coefficients of variation were between 1.3 and 9.3% for both plasma and urine. Limit of quantification was 20-25 ng/ml for plasma based on a sample volume of 0.2 ml. Application of the assay in a pilot pharmacokinetic study showed significant differences between the kinetics of the two enantiomers. In plasma and urine, the concentrations of the dextrorotatory enantiomer exceeded those of the levorotatory enantiomer significantly.
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  • 73
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    Chirality 3 (1991), S. 76-83 
    ISSN: 0899-0042
    Keywords: chiral flavour compounds ; chiral cyclic acetals NMR data ; diastereoisomer/enantiomer separation ; crystal structure elucidation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The synthesis of several 2-alkoxy-5-alkyl-tetrahydrofurans is of interest in our investigations of structure-function relationships of chiral flavour compounds. For the preparation of the enantiomeric acetals the unambiguous configurational assignment of the cis and trans series of these compounds is indispensable. By means of crystalline acetal derivatives the absolute structure of a model compound in the cis and the trans configuration is revealed by X-ray measurement and correlated with the corresponding cis and trans configurated aroma compounds. The first complete structure elucidation of the class of 2-alkoxy-5-alkyltetrahydrofurans has been carried out.
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  • 74
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    Chirality 3 (1991) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 75
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    Chirality 3 (1991), S. 165-169 
    ISSN: 0899-0042
    Keywords: ibuprofen ; enantiomer ; stereoselectivity ; chiral inversion ; pharmacokinetics ; dog ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Inversion of inactive (R)-ibuprofen to active (S)-ibuprofen has been suggested to occur presystemically only. In order to investigate the site of inversion in dogs we administered both enantiomers either intravenously or intraduodenally (10 mg/kg) to adult, male beagle dogs (n = 3) in a crossover design. Plasma, urine, and bile were collected for up to 6 h and analyzed stereospecifically by HPLC, according to a previously published method. Pharmacokinetic parameters were calculated using a linear computer program. Absorption after intraduodenal administration occurred rapidly, resulting in maximum plasma concentrations 0.2 h after giving the enantiomer. Approximately 70% of the (R)-enantiomer (according to AUC) was inverted to the S-enantiomer independent of route of administration. No R-ibuprofen could be detected in plasma after (S)-ibuprofen administration. Mean residence time was found to be 2 to 3 times longer for (S)-than for (R)-ibuprofen. Total systemic clearance from plasma was twice as high for (R)- than for (S)-ibuprofen. There were no differences between plasma clearances after intravenous and intraduodenal administration. Between 8 and 17% of dose was recovered in bile [especially as free and conjugated (S)-ibuprofen] and 3-12% in urine [as (S)-ibuprofen, hydroxy- and carboxyibuprofen, free and conjugated forms]. Small amounts of (R)-ibuprofen were detected in bile after intraduodenal administration of (R)-ibuprofen only (1.8% of dose). In short, the unidirectional inversion of R-ibuprofen appears to occur systemically rather than presystemically in dogs.
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  • 76
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    Chirality 3 (1991), S. 188-195 
    ISSN: 0899-0042
    Keywords: fast analysis times ; enantiomers ; chiral stationary phase ; Pirkle-concept ; achiral derivatization ; rapid screening ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A Pirkle-concept chiral stationary phase (CSP) derived from N-(1-naphthyl)leucine was evaluated for developing methods to reduce analysis times and investigating techniques in the rapid screening of a variety of chiral compounds over a given chiral selector. The effects of reduced column lengths and elevated temperatures were studied to shorten analysis times.
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  • 77
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    Chirality 3 (1991), S. 208-211 
    ISSN: 0899-0042
    Keywords: neuroleptic ; dopamine ; receptor ; enantioselectivity ; schizophrenia ; stereochemistry ; isomers ; racemate ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The relative configuration of the enantiomers of thioridazine was defined to explore the stereochemistry associated with the selective binding of (-)-thioridazine to dopamine D-1 receptors and (+)-thioridazine to D-2 receptors. Using a seven-step stereoconservative synthesis, (-)-(S)-2-piperidinecarboxylic acid was converted to (-)-(S*)-2-(2-chloroethyl)-1-methylpiperidine, a literature (-)-thioridazine synthetic precursor. Accordingly, (-)- and (+)-thioridazine are the (S)- and (R)-enantiomers, respectively.
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  • 78
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    Chirality 3 (1991), S. 221-222 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 79
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    Chirality 3 (1991), S. 484-491 
    ISSN: 0899-0042
    Keywords: propylene sulfide ; cadmium thiolate ; stereospecific polymerization ; living polymerization ; anionic polymerization ; ring-opening polymerization ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The polymerization of racemic methylthiirane in homogeneous phase, initiated by bis(isopropyl-S-cysteinato) cadmium is a living process. The resulting polymers are isotactic and optically active at partial conversion. The optical purity of the residual monomer may reach 27% at half conversion. The propagation occurs mainly on one valency of Cd, however oligomers grow slowly on the second valency. The stereoregularity of the polymer chain appears only when the length of the oligomer becomes high enough, making possible a bicoordination of the Cd counterions. The stereoregularity of the polymer is characterized by the molar fraction σ of isotactic diads which varies from 0.5 for atactic chains - formed at the beginning - to about one for isotactic segments formed for longer chains. The stereospecifictity also depends on temperature of propagation and on initiator concentration. The kinetics observed (zero order in monomer and one-half in Cd) are explained by monomer coordination before insertion and dimeric association of the thiolate end groups. The enantioasymmetric process observed results from an unbalance in the number of the two different types of active sites and possibly from a difference in their reactivities. Enantioasymmetry has been found to decrease significantly when the dielectric constant ε of the medium increases.
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  • 80
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    Chirality 3 (1991), S. 227-232 
    ISSN: 0899-0042
    Keywords: DNA ; liquid crystal ; ethidium ; circular dichroism ; X-ray diffraction ; optical microscopy ; intercalation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The influence of the intercalation of ethidium bromide (EB) on the characteristics of the DNA cholesteric and hexagonal mesophases is studied by optical microscopy, circular dichroism, and X-ray diffraction. The distance between DNA rods in the hexagonal phase is not modified by the presence of EB whereas the pitch of the cholesteric mesophase is considerably shortened by the dye. This seems to be related to the stereochemical effect of the intercalation rather than to the presence of a random distribution of the positive charge of the dye.
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  • 81
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    Chirality 3 (1991), S. 223-226 
    ISSN: 0899-0042
    Keywords: enantiomers ; diastereomers ; chirality ; circularly polarized radiation ; circular dichroism ; parity violation ; electroweak interaction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Fischer demonstrated (1890-1919) that functional biomolecules are composed specifically of the D-sugars and the L-amino acids, and that in the laboratory synthetic reactions of such molecules propagate with chiral stereoselectivity. Given a primordial enantiomer, biomolecular homochirality followed without the intervention of the chiral natural force conjectured by Pasteur (1860), except prebiotically. Polarized solar radiation and other classical chiral forces were proposed as agencies generating a prebiotic enantiomeric excess, but the forces then known were found to be evenhanded on a time and space average, exemplifying parity conservation (1927). The weak nuclear force, shown to violate parity (1956), was unified with electromagnetism in the electroweak force (1970). Ab initio estimations including the chiral electroweak force indicate that the L-amino acids and the D-sugars are more stable than the corresponding enantiomers. The small energy difference between these enantiomer pairs, with Darwinian reaction kinetics in a flow reactor, account for the choice of biomolecular handedness made when life began.
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  • 82
    ISSN: 0899-0042
    Keywords: tumor necrosis factor-α ; secondary structure ; circular dichroism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The circular dichroism (CD) spectrum of tumor necrosis factor-α has been measured into the vacuum UV to 168 nm. Analysis of the CD for secondary structure is in good agreement with X-ray diffraction results, but the analysis is somewhat unstable. Adding the CD of this protein together with its X-ray determined secondary structure to the basis set should improve subsequent analyses of CD spectra for other all-β proteins.
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  • 83
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    Chirality 3 (1991), S. 268-276 
    ISSN: 0899-0042
    Keywords: absolute configuration ; peptidomimetics ; retro-inverso modifications ; 2-aminocyclopentanecarboxylic acid ; nuclear magnetic resonance (NMR) ; nuclear Overhauser effect ; bioactive peptides ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A modern method is reported for the assignment of absolute configuration for peptidomimetics in bioactive peptides by use of 1H-NMR parameters in solution. Four peptide systems incorporating either retro-inverso modifications or 2-aminocyclopentanecarboxylic acid (2-Ac5c) as a peptidomimetic for proline are discussed. (1) Two 14-membered cyclic dermorphin analogs Tyr-c[D-A2bu-Phe-gPhe-(S and R)-mLeu] with a reverse amide bond between gPhe and mLeu residues where gPhe denotes a gem-diamino analog of Phe and mLeu refers to a malonyl analog of Leu. (2) Two cyclic hexapeptides related to somatostatin, c[gSar6-(S and R)-mPhe7-D-Trp8-Lys9-Thr10-Phe11], with a reverse amide bond between the gSar and mPhe residues where the gSar and mPhe denote the gem-diamino and malonyl analogs of the Sar and Phe residues, respectively. The superscript numbers refer to positions in native somatostatin. (3) Cyclic hexapeptide somatostatin analogs containing 2-Ac5c [trans-(1S,2S)-2-Ac5c, trans-(1R,2R)-2-Ac5c, cis-(1R,2S)-2-Ac5c, and cis-(1S,2R)-2-Ac5c] in place of proline c[(2-Ac5c)6-Phe7-D-Trp8-Lys9-Thr10-Phe11]. (4) Morphiceptin related analogs incorporating a cis-2-Ac5c residue as shown in Tyr-cis-2-Ac5c-Phe-Val-NH2. The methodology described in this investigation could be applied to a wide variety of peptide systems.
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  • 84
    ISSN: 0899-0042
    Keywords: photochromic polymers ; chiral polymers ; stereoregular polymers ; 4-methacryloxyethylenoxyazobenzene ; (-)-menthyl methacrylate ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Copolymers of the photochromic monomer 4-methacryloxyethylenoxyazobenzene with the optically active comonomer (-)-menthyl methacrylate, having different stereoregularity, were investigated in order to obtain a better understanding of the relationship between microstructure and photochromism in synthetic macromolecules. No appreciable effect was observed by copolymer composition, sequence distribution, and microtacticity on the photoinduced trans → cis isomerization of the azobenzene side chains. This last, however, is reflected in changes of the chiroptical properties, type and entity of the photoinduced variation being dependent on chain structure. The long spacer separating the azo chromophore from the main chain limits the extent of chiroptical properties dependence on irradiation.
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  • 85
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    Chirality 3 (1991), S. 324-330 
    ISSN: 0899-0042
    Keywords: bis(μ-methyl-1,3-dimethyl-η3-allylnickel) ; menthyl phosphines ; menthoxy phosphines ; carbon monoxide ; parity control ; complementarity control ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Bis(μ-methyl-1,3-dimethyl-η3-allylnickel) reacts in the presence of phosphorus(III) ligands (phosphines, phosphites) with CO to give 3-methyl-(E)-4-hexen-2-one. Systematic experiments were performed using chiral ligands containing menthyl or menthoxy groups and different achiral groups on the P atom to determine the influence of ligand structure and concentration on the direction and extent of chiral induction in this ketone synthesis. It could be shown that reversion of enantioselectivity can be obtained not only by the obvious method of reversing the absolute configuration of the ligand (“parity control”) but also by modifying the nonchiral substituents of the phosphorus ligand (“complementarity control”). The synthesis, physical, and spectroscopic properties of several new menthyl phosphines and phosphites are reported.
    Additional Material: 6 Ill.
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  • 86
    ISSN: 0899-0042
    Keywords: iridium ; asymmetric hydrogenation ; dehydroamino acid esters ; enamide complexes ; resolution ; homogeneous catalysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The reaction of chiral diphosphines with a configurationally pure cationic bis-enamide complex of iridium, bis(menthyl (Z)-α-benzamidocinnamate)-iridium tetrafluoroborate, is described. When the reactant ligand is racemic then kinetic resolution occurs with high specificity under the appropriate conditions. Since the iridium diphosphine complex is catalytically inactive in homogeneous hydrogenation, the residual enantiomer may be reacted with bis(norbornadiene)-rhodium tetrafluoroborate to produce an active catalyst. This effects the hydrogenation of methyl (Z)-α-acetamidocinnamate in optical yields comparable with those obtained separately with the enantiomerically pure ligand rhodium complex. The reaction of pure (+)- or (-)-enantiomer of bis(menthyl (Z)-α-benzamidocinnamate)-iridium tetrafluoroborate with enantiomerically pure diphosphines has been studied. Invariably one hand of the diphosphine reacts rapidly with a given enantiomer of the iridium complex to give a stable diphosphine iridium enamide complex in which the original configuration of the coordinated olefin is maintained. The other combination of enantiomers reacts much more slowly, in keeping with the kinetic resolution work, and produces an enamide complex which is unstable in solution, isomerising to a second diastereomer. Since the absolute configuration of the iridium bis-enamide complex has been established by X-ray crystallography, this experiment affords a method of determining the configuration of rhodium enamide complexes in asymmetric hydrogenation (assuming structural homology between Rh and Ir). In all cases the disfavoured enamide complex was the one involved in the catalytic pathway.
    Additional Material: 5 Ill.
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  • 87
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    Chirality 3 (1991), S. 370-375 
    ISSN: 0899-0042
    Keywords: enantioselective catalysis ; (2S)-ethyl-2-hydroxy-4-phenylbutyrate ; (S)-ethyl lactate ; α-hydroxy esters ; (2S,3S)-NORPHOS ; rhodium diphosphine catalyst ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantioselective hydrogenation of several α-keto acid derivatives with rhodium diphosphine catalysts has been investigated using a random screening approach. The neutral rhodium catalyst prepared in situ from bis(2,5-norbornadiene rhodium chloride) and NORPHOS has been found to be an excellent catalyst for preparing aliphatic α-hydroxy esters in high optical purities. The reaction parameters for the hydrogenation of ethyl 2-oxo-4-phenyl-butyrate, an intermediate for the ACE inhibitor Benazepril, were optimized and the best optical yields obtained were 96%.
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  • 88
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    Chirality 3 (1991), S. 387-388 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 1 Ill.
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  • 89
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    Chirality 3 (1991), S. 480-483 
    ISSN: 0899-0042
    Keywords: biscarbamoylpiperidine ; stereoisomer separation ; enantioselectivity ; circular dichroism ; α1-acid glycoprotein ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: α,α′-Bis[3-(N,N-diethylcarbamoyl)piperidino]-p-xylene dihydrobromide, a novel antiplatelet agent, was resolved into three isomers A, B, and C, on a chiral α1-acid glycoprotein analytical column using a mobile phase of 0.025 M phosphate buffer containing 0.025 M tetrabutylammonium hydrogen sulfate, at a pH of 6.5. The effect of molarity, temperature, pH, flow rate, and organic modifiers on the enantioselectivity was examined. Based on circular dichroic spectra at 220 nm, A and C appear to be the (-)- and (+)-enantiomers, respectively, and B the meso diastereomer. Attempts at resolution using Pirkle type columns gave unsatisfactory results. It appears that both hydrophobic and polar interactions between the compound and the stationary phase are important determinants of resolution.
    Additional Material: 5 Ill.
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  • 90
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    Chirality 3 (1991), S. 503-505 
    ISSN: 0899-0042
    Keywords: racemisation of an S-enantiomeric Schiff base ligand ; potassium isocyanato-{N-salicylidene-(RS)-alaninato}cuprate(II) ; EPR spectrum ; basalcrystallographic data ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Copper(II) N-salicylidene-(S)-alaninate trihydrate reacting as the S-enantiomeric parent compound with KOCN in hot diluted methanol yielded by slow crystallisation from the cooled reaction mixture (in the course of 1 day) the racemic product K[Cu{sal-(RS)-ala}(NCO)]. The parameters of the axial type EPR spectrum in X-band region and the LF band position in the electronic spectrum are typical of an axially distorted square pyramidal coordination of the Cu(II) atom in this complex. The spectral properties of the complex cuprate prepared and its basal crystallographic data are consistent with those of the earlier studied15 K2[Cu2{sal-(RS)-ala}2(μ-NCO)2] synthetized by using [Cu{sal-(RS)-ala}(H2O)].H2O as the racemic parent complex in the reaction mixture with KOCN.
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  • 91
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    Chirality 3 (1991), S. 495-502 
    ISSN: 0899-0042
    Keywords: circular dichroism ; spectroscopy ; surfactant ; optical activity ; phosphatidylcholine ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The ultraviolet absorbance and circular dichroism (CD) spectra of lecithin reverse micelles and gels were investigated in order to establish whether the formation of these noncovalent macromolecular aggregates, which was induced by the addition of water to solutions of lecithin in organic solvents, was accompanied by specific spectroscopic changes. Systems containing the synthetic short-chain lecithins, 1,2-hexanoyl-, 1,2-diheptanoyl-, 1,2-dioctanoyl-, and 1,2-dinonaoyl-sn-glycero-3-phosphatidylcholines were used as models for the long-chain lecithins, soybean phosphatidylcholine and palmitoyl-oleoyl-phosphatidylcholine. All the molecules studied had asymmetric centres, formed reverse micelles under appropriate conditions, and, while both the long-chain lecithins also formed gels, none of the short-chain molecules did. As well as having CD spectra that were simpler to interpret, spectroscopic observations on solutions of the short-chain lecithins could be carried out over a large water content range. The ester chromophore of these compounds was shown to be highly sensitive to variation in both the solvent environment and the temperature, and components of both direct solvent effects and conformational change upon the addition of water were detected in the spectra.The spectra of the longer chain lecithins were complicated by the presence of double bonds although, here again, it was found that significant changes occurred as the water content increased, as monitored by the ester chromophore. However, no specific effect that could be ascribed to gelation alone was detected.The overall picture that emerged was that the ester chromophore of anhydrous micelles gave rise to a specific negative band in the CD spectrum (λmax ≈ 210 nm) whereas a positive CD signal (λmax ≈ 233 nm) was associated with the same chromophore in filled (i.e., hydrated) micelles. The two signals correspond to two different conformational states of the lecithin molecule, the hydrated state being not only more conformationally restricted but also providing a less polar environment for the ester groups, while the addition of water to the system shifts the conformational equilibrium. These observations have been interpreted as showing that only a limited range of lecithin conformation is compatible with the formation of the micellar structure and that it is this constraint, together with those introduced by the overall geometry of the aggregated state, that gives rise to the changes observed in the CD spectrum.
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  • 92
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    Chirality 3 (1991), S. 84-87 
    ISSN: 0899-0042
    Keywords: diabrotica ; stereocontrol ; inversion ; template ; chiral building blocks ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A highly stereospecific synthesis of the title compound (2R,8R)-8-methyl-2-decanol (I) has been devised via 16 simple steps. The required chirons (5 and 11) were prepared from easily accessible templates viz. (R)-methyl citronel-late and (S)-glutamic acid. This on Grignard coupling furnished the ketal (12) which was converted to the desired epoxide (14) and subsequently reduced to furnish the alcohol (2R,8R)-I. Its corresponding (2S)-epimer was prepared by total stereoselective inversion of its C-2 center. The title compounds are the parent alcohols of the pheromone components of the female rootworms.
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  • 93
    ISSN: 0899-0042
    Keywords: methylphenidate ; enantioselectivity ; blood esterases ; hydrolysis ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enantioselective in vitro hydrolysis of methylphenidate (MPH) by the blood esterases of seven mammalian species is reported. The species included rats, rabbits, dogs, cattle, horses, monkeys, and humans. In vitro incubations up to 8 h were carried out in plasma, red blood cells, and whole blood of the various species. Enantioselective differences were evident among the different species on comparison of the data obtained from the three biological fluids. The esterases present in plasma appeared to show greater activity in the hydrolysis of MPH in all species where comparison with the other two biofluids was possible. Only in the case of humans did esterases present in plasma and red blood cells demonstrate opposite enantioselectivity in the hydrolysis of MPH. Thus after 8 h incubation, the RR-MPH/SS-MPH ratios in plasma and red blood cells were 0.31 and 1.16, respectively.
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  • 94
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    Chirality 3 (1991), S. 124-128 
    ISSN: 0899-0042
    Keywords: enantiomers ; warfarin ; phenprocoumon ; complexes ; HPLC ; fluorescent enhancement ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The fluorescences of warfarin and phenprocoumon are enhanced following complexation with β-cyclodextrin; (+)-(R)- and (-)-(S)-phenprocoumons have different affinities for this cyclodextrin, whereas the corresponding enantiomers of warfarin have similar binding constants. Apparently, hemiketal formation in the case of warfarin minimizes chiral discrimination. This is confirmed using a β-cyclodextrin bonded chromatography column on which the phenprocoumon enantiomers are separated, whereas those of warfarin are not.
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  • 95
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    Chirality 3 (1991), S. 136-138 
    ISSN: 0899-0042
    Keywords: solvent generated HPLC systems ; β-cyclodextrin derivatives ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The paper demonstrates that the technique of solvent generated liquid--solid chromatography can be used to create normal phase systems for chiral separations. The chiral adsorption layer was generated by pumping a binary hexane:ethanol eluent containing a small fraction of permethylated β-cyclodextrin through a column packed with microparticulate silica. This technique leads to columns with good time stability and reproducibility. The possibility of generating normal phase systems with permethylated β-cyclodextrin as chiral component via the mobile phase broadens the range of phase system which can be used to separate enantiomers by HPLC.
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  • 96
    ISSN: 0899-0042
    Keywords: conformational analysis ; nonbonded interactions ; metallocene/methylalumoxane systems ; 1-pentene ; styrene ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantioselectivity found in homogeneous isospecific Ziegler-Natta catalysts for the insertion of 1-alkenes in metal-deuterium or in metalisobutyl bonds is discussed from a theoretical point of view. Nonbonded energy calculations, based on a model of the catalytic site previously proposed by us, indicate that the strong enantioselectivity found in the insertion of 1-alkenes in a metal-isobutyl bond is drastically reduced in the presence of a metal-deuterium bond. In particular, a weak enantioselectivity in favour of a monomer coordinated with the opposite chirality (lower for the case of 1-butene, higher for the case of styrene) is shown to occur in the latter case.
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  • 97
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    Chirality 3 (1991), S. 91-93 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Additional Material: 2 Ill.
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  • 98
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    Chirality 3 (1991), S. 104-111 
    ISSN: 0899-0042
    Keywords: stereochemistry ; sulfation ; enantioselectivity ; inhibition ; chiral ; mechanism ; stereoselective ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Aryl sulfotransferase IV catalyzes the 3′-phosphoadenosine-5′-phosphosulfate (PAPS)-dependent formation of sulfuric acid esters of benzylic alcohols. Since the benzylic carbon bearing the hydroxyl group can be asymmetric, the possibility of stereochemical control of substrate specificity of the sulfotransferase was investigated with benzylic alcohols. Benzylic alcohols of known stereochemistry were examined as potential substrates and inhibitors for the homogeneous enzyme purified from rat liver. For 1-phenylethanol, both the (+)-(R)-and (-)-(S)-enantiomers were substrates for the enzyme, and the kcat/Km value for the (-)-(S)-enantiomer was twice that of the (+)-(R)-enantiomer. The enzyme displayed an absolute stereospecificity with ephedrine and pseudoephedrine, and with 2-methyl-1-phenyl-1-propanol; that is, only (-)-(1R,2S)-ephedrine, (-)-(1R,2R)-pseudoephedrine, and (-)-(S)-2-methyl-1-phenyl-1-propanol were substrates for the sulfotransferase. In the case of 1,2,3,4-tetrahydro-1-naphthol, only the (-)-(R)-enantiomer was a substrate for the enzyme. Both (+)-(R)-2-methyl-1-phenyl-1-propanol and (+)-(S)-1,2,3,4-tetrahydro-1-naphthol were competitive inhibitors of the aryl sulfotransferase-catalyzed sulfation of 1-naphthalenemethanol. Thus, the configuration of the benzylic carbon bearing the hydroxyl group determined whether these benzylic alcohols were substrates or inhibitors of the rat hepatic aryl sulfotransferase IV. Furthermore, benzylic alcohols such as (+)-(S)-1,2,3,4-tetrahydro-1-naphthol represent a new class of inhibitors for the aryl sulfotransferase.
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  • 99
    ISSN: 0899-0042
    Keywords: hexahydro-difenidol enantiomers ; muscarinic receptor subtypes M1, M2, M3 and M4 ; stereoselective interaction ; difenidol ; dicyclidol ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: (R)-Hexahydro-difenidol has a higher affinity for M1 receptors in NB-OK 1 cells, pancreas M3 and striatum M4 receptors (pKi 7.9 to 8.3) than for cardiac M2 receptors (pKi 7.0). (S)-Hexahydro-difenidol, by contrast, is nonselective (pKi 5.8 to 6.1). Our goal in the present study was to evaluate the importance of the hydrophobic phenyl, and cyclohexyl rings of hexahydro-difenidol for the stereoselectivity and receptor selectivity of hexahydro-difenidol binding to the four muscarinic receptors. Our results indicated that replacement of the phenyl ring of hexahydro-difenidol by a cyclohexyl group (→ dicyclidol) and of the cyclohexyl ring by a phenyl moiety (→ difenidol) induced a large (4- to 80-fold) decrease in binding affinity for all muscarinic receptors. Difenidol had a significant preference for M1, M3, and M4 over M2 receptors; dicyclidol, by contrast, had a greater affinity for M1 and M4 than for M2 and M3 receptors. The binding free energy decrease due to replacement of the phenyl and the cyclohexyl groups of (R)-hexahydro-difenidol by, respectively, a cyclohexyl and a phenyl moiety was almost additive in the case of M4 (striatum) binding sites. In the case of the cardiac M2, pancreatic M3, or NB-OK 1 M1 receptors the respective binding free energies were not completely additive. These results suggest that the four (R)-hexahydro-difenidol “binding moieties” (phenyl, cyclohexyl, hydroxy, and protonated amino group) cannot simultaneously form optimal interactions with the M1, M2, and M3 muscarinic receptors. When each of the hydrophobic groups is modified, the position of the whole molecule, relative to the four subsites, was changed to allow an optimal overall interaction with the muscarinic receptor.
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  • 100
    ISSN: 0899-0042
    Keywords: chiral separation ; diastereomer ; racemate ; (+)-α-(1-naphthyl)ethylamine derivatives ; enantioselective ; drug disposition ; toxicokinetic studies ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A stereospecific HPLC bioanalytical method was developed for quantitation of the enantiomers of MK-0571, a leukotriene D4 receptor antagonist. The procedure involves the addition of an internal standard analog to the biological matrix followed by extraction of the free acids into ethyl acetate. The acids are subsequently reacted with the homochiral reagent, (+)-(R)-α-(1-naphthyl)ethylamine (NEA) to form diastereomers. Following removal of excess reagent and side products by a dilute acid wash, the NEA-MK-0571 diastereomers are separated on a phenyl urea chiral column using a mobile phase containing hexane, isopropanol, and acetonitrile and are detected with a fluorescence detector. The sensitivity of the method is such that 50 ng of each enantiomer can be quantitated. In the 0.05 to 10 μg range the recoveries of the enantiomers of MK-0571 from plasma were 100.4 ± 7.9% and 100.0 ± 7.2%. NMR and mass spectral data confirmed the structure of the derivative. The method has been utilized in drug safety evaluation studies to demonstrate enantioselectivity in disposition of the enantiomers of MK-0571 in rats and monkeys but not in mice.
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