bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enantioselective and nonenantioselective degradation of organic pollutants in the marine ecosystem
Authors: Hühnerfuss Heinrich , Faller Jörn , Kallenborn Roland , König Wilfried A. , Ludwig Peter , Pfaffenberger Bernd , Oehme Michael , Rimkus Gerhard 
Published: January 2005

AbstractEnantiomeric ratios of 11 chiral environmental pollutants determined in different compartments of the marine ecosystem by chiral capillary gas chromatography and chiral high‐performance liquid chromatography allow discrimination between the following processes: enantioselective decomposition of both enantiomers with different velocities by marine microorganisms (α‐HCH, β‐PCCH, γ‐PCCH); enantioselective decomposition of one enantiomer only by marine microorganisms (DCPP); enantioselective decomposition by enzymatic processes in marine biota (α‐HCH, β‐PCCH, trans‐chlordane, cis‐chlordane, octachlordane MC4, octachlordane MC5, octachlordane MC7, oxychlordane, heptachlor epoxide); enantioselective active transport through the “blood–brain barrier” (α‐HCH); nonenantioselective photochemical degradation (α‐HCH, β‐PCCH). © 1993 Wiley‐Liss, Inc.
Disposition kinetics of ML‐1035 sulfoxide enantiomers and the prochiral sulfide in rats
Authors: Kuo Be‐Sheng , Poole James C. , Mandagere Arun K. , Hwang Kin‐Kai 
Published: January 2005

AbstractML‐1035, 4‐amino‐5‐chloro‐2‐[2‐(methylsulfinyl)ethoxy]‐N‐[2‐(diethylamino)ethyl]benzamide, is a sulfoxide compound and a racemic gastroprokinetic agent with a chiral center at the sulfur atom. We have investigated the disposition kinetics of (R)‐ML‐1035 sulfoxide (R) and (S)‐ML‐1035 sulfoxide (S) after the single enantiomers and the racemic mixture were administered to rats in separate experiments. There was no noticeable chiral inversion after either enantiomer dose. Both enantiomers were rapidly absorbed. After dosing with enantiomers or with the racemate, the resulting plasma concentration‐time curve of R was closely parallel to that of S in both intravenous and oral experiments, suggesting that the two enantiomers have approximately the same disposition kinetics. After intravenous enantiomer doses, only S underwent conversion to sulfide, suggesting that sulfidation in the liver is enantioselective. However, the enantioselective sulfidation after intravenous dosing did not introduce a difference in the global plasma disposition profiles between R and S, since the reduction reaction is a minor metabolic process. Other metabolic reactions such as sulfonation and mono‐N‐desethylations were not enantioselective. After oral administration, conversion to sulfide was observed for both enantioners, implicating the existence of a nonhepatic pathway in sulfidation. Administration of a prochiral sulfide dose was associated with an enantioselective sulfoxidation, in which the R/S concentration ratios increased as a function of time. In addition, enantiomeric interaction causing changes in pharmacokinetic parameters was observed after the oral racemate dose, while the interaction is negligible after an intravenous racemate dose, indicating a route dependency in enantiomeric interaction. © 1993 Wiley‐Liss, Inc.
Matrix synthesis of chiral carboxy derivatives: Aldehyde chiral discrimination due to a two‐point coordination of Mg2+
Authors: Beluzhenko Olga V. , Bogdanova Galina V. , Tumenev Vitalii A. , Zhdanov Yurii A. 
Published: January 2005

AbstractTo control stereoselectivity in aldol‐like reactions with chiral carbohydrate templates, we studied the interaction between completely protected dialdo compounds and magnesium enediolates of arylacetic acids. Diastereomeric mixtures of the highly functionalized acids obtained were esterified to isolate individual methyl uronates. It was found that all the diastereomeric esters exhibit Cotton effects of the same positive sign in the 220–230 nm region and so possess the same S configuration of the aryl chiral center C(6). Chiral center C(5) configurational assignments were performed using IR and ORD spectroscopy. We separated and specified four pairs of diastereomeric methyl uronates. It follows that the precursory acids have the same 5R*, 6S (major isomers) and 5S*, 6S (minor isomers) configurations. A tentative mechanism for complexation and possible models of Mg2+ ‐protected dialdose intermediate complexes has been proposed. We have concluded that a kind of orbital steering is realized, accompanied by some “tuning” of molecular assembly conditioned by two‐point coordination between Mg2+ and potential cation‐binding sites in the substrate molecules. Thus it has been demonstrated that reasonable diastereo‐selectivity can be achieved even through the use of small matrix molecules using rather small functional groups, which do not impose any stringent steric requirements. © 1993 Wiley‐Liss, Inc.
γ‐Cyclodextrin as chiral mobile phase additive in the HPLC separation of the atropisomers of some N‐arylthiazoline‐2‐thiones and N‐arylthiazoline‐2‐ones: Attempts to quantify the effect of selected structural parameters
Authors: Roussel Christian , Favrou Anita 
Published: January 2005

AbstractThe effect of the position and type of the substituent on the chromatographic separation of N‐arylthiazoline‐2‐thione and arylthiazoline‐2‐one atropisomers are described in reversed‐phase HPLC using β‐ or ‐β‐cyclodextrin as chiral mobile phase additive. A quantitative approach to experimental design has been developed. © 1993 Wiley‐Liss, Inc.
Synthesis and evaluation of the antidepressant activity of the enantiomers of bupropion
Authors: Musso David L. , Mehta Nariman B. , Soroko Francis E. , Ferris Robert M. , Hollingsworth Elizabeth B. , Kenney Bernard T. 
Published: January 2005

AbstractThe synthesis of the enantiomers of bupropion, (rac)‐2‐tert‐butylamino‐3′‐chloropropiophenone 1 (Wellbutrin®) is described. The enantiomers were compared with the racemate in both the tetrabenazine‐induced sedation model and the inhibition of uptake of biogenic amine assay. No significant differences were found in their potencies to reverse tetrabenazine‐induced sedation in mice or in their IC50 values as inhibitors of biogenic amine uptake into nerve endings obtained from mouse brain. © 1993 Wiley‐Liss, Inc.
Enantioselective detoxication of optical isomers of glycidyl ethers
Authors: Chen Ruth , Nguyen Phuong , You Zhengqing , Sinsheimer Joseph E. 
Published: January 2005

AbstractThe detoxication of the enantiomers of glycidyl 4‐nitrophenyl ether (GNPE), (−)‐(R)‐ and (+)‐(S)‐GNPE, and glycidyl 1‐naphthyl ether (GNE), (−)‐(R)‐ and (+)‐(S)‐GNE, by rat liver glutathione transferase and epoxide hydrolase was studied. Enantioselectivity was observed with both enzymes favoring the (R)‐isomers as determined by the formation of conjugate, diol, and remaining substrate measured by HPLC. Enantiomers of GNE were detoxified by cytosolic epoxide hydrolase but those of GNPE were not. Substantial nonenzymatically formed conjugates of enantiomers of GNPE were detected showing (S)‐GNPE the more reactive of the pair. © 1993 Wiley‐Liss, Inc.
Chiral discrimination of the enantiomers of δ‐phenyl‐δ‐valerolactone by cellulose triacetate: A chromatographic and microcalorimetric study of the thermodynamics
Authors: Wolf Romain M. , Francotte Eric , Hainmüller Justus 
Published: January 2005

AbstractThe resolution of racemic δ‐phenyl‐δ‐valerolactone by chromatography on cellulose triacetate CTA I results in one of the best separations of optical antipodes observed so far on this chiral stationary phase. The thermodynamics of the stereoselective interaction of the enantiomers of δ‐phenly‐δ‐valerolactone have been studied by chromatography at different temperatures and by direct microcalorimetric investigations of the complexation with CTA I. This analysis suggests that the separation process is mainly controlled thermodynamically and that kinetic effects, if any, play a minor role. Microcalorimetric titration experiments indicate that specific (optimum) complexation sites on CTA I for the stronger retained enantiomer of δ‐phenly‐δ‐valerolactone are rapidly saturated, whereas the first eluted enantiomer seems to interact much less selectively with defined interaction sites on the chiral polymer matrix. © 1993 Wiley‐Liss, Inc.
An improved method for the direct chromatographic resolution of abscisic acid enantiomers
Authors: Welch Christopher J. 
Published: January 2005

AbstractAn improved method for the direct chromatographic resolution of abscisic acid enantiomers using the commercially available Whelk‐O 1 chiral stationary phase is presented. Previously reported strategies utilized in the chromatographic separation of abscisic acid enantiomers are summarized, and conditions for analytical and semipreparative separations using the Whelk‐O 1 chiral stationary phase are described. This method offers the advantages of rapid analysis time and greatly increased capacity, allowing the resolution of more than 6 mg in 25 min using an analytical column (4.6 mm i.d. × 25 cm length). © 1993 Wiley‐Liss, Inc.
Use of isotopically chiral [4′‐13C]penciclovir and 13C NMR to determine the specificity and absolute configuration of penciclovir phosphate esters formed in HSV‐1‐ and HSV‐2‐infected cells and by HSV‐1‐encoded thymidine kinase
Authors: Hodge R. Anthony Vere , Darlison Sarah J. , Earnshaw David L. , Readshaw Simon A. 
Published: January 2005

AbstractPenciclovir is a potent antiherpesvirus agent which is highly selective due to its phosphorylation only in virus infected cells. Phosphorylation of one of the hydroxymethyl groups of penciclovir (PCV) creates a chiral centre leading to the possible formation of (R)‐ and (S)‐enantiomers. The absolute configuration and stereospecificity of the PCV‐phosphates produced in cells infected with herpes simplex viruses types 1 and 2 (HSV‐1 and HSV‐2), as well as by HSV‐1‐encoded thymidine kinase, were determined using isotopically chiral [4′‐13C]PCV precursors and 13C NMR spectroscopy of the isolated metabolites. The absolute configuration of penciclovir‐triphosphate (PCV‐TP) produced in HSV‐1‐infected cells was shown to be S with an enantiomeric purity of greater than 95%. However, in contrast to HSV‐1‐infected cells in which none of the (R) enantiomer was detected, about 10% of (R)‐PCV‐TP was produced in HSV‐2‐infected cells. Phosphorylation of PCV by HSV‐1‐encoded thymidine kinase was found to give 75% (S)‐ and 25% (R)‐PCV‐monophosphate. The proportion of the (S)‐isomer appears to be amplified in the subsequent phosphorylations leading to the triphosphate. © 1993 Wiley‐Liss, Inc.
Stereoselective cyclooxygenase inhibition in cellular models by the enantiomers of ketoprofen
Authors: Suesa Nuria , Fernandez Maria Francisca , Gutierrez Marta , Rufat Maria Jose , Rotllan Elisabet , Calvo Lidia , Mauleon David , Carganico Germano 
Published: January 2005

AbstractThe pharmacological activity of rac‐ketoprofen and its enantiomers was investigated in vitro using different cellular models. The effect of these compounds on arachidonic acid metabolism was assessed by measuring the inhibition of prostanoid generation under the action of several agonists. Thus, we have evaluated the inhibition of (1) thromboxane B2 synthesis in rabbit platelets and human polymorphonuclear leukocytes (PMNs), (2) prostaglandin E2 synthesis in three cultured cells, namely human umbilical vein endothelial cells (HUVEC), human keratinocytes, and mouse macrophage‐like P388D1 cells. The IC50 values found for (+)‐(S)‐ketoprofen were in the range between 0.1 nM and 0.8 μM, being slightly lower in all models than those found for rac‐ketoprofen (0.4 nM–3 μM). On the other hand, (−)‐(R)‐ketoprofen showed inhibition of cyclooxygenase only at concentrations two or three orders of magnitude higher than those required for the (+)‐(S) enantiomer. These results, obtained with cell types of relevance for inflammatory processes and with compounds of high optical purity, demonstrate that the prostanoid biosynthesis inhibition caused by the drug rac‐ketoprofen is exclusively due to its dextrorotatory enantiomer. © 1993 Wiley‐Liss, Inc.
Warfarin metabolites: Stereochemical aspects of protein binding and displacement by phenylbutazone
Authors: Chan Eli , McLachlan Andrew J. , Rowland Malcolm 
Published: January 2005

AbstractThe in vitro human serum albumin binding characteristics of the enantiomers of the major metabolites of warfarin [6‐hydroxywarfarin (6‐HW), 7‐hydroxywarfarin (7‐HW), (S)‐warfarin alcohols [(S,S)‐ and (S,R)‐WA], and (R,S)‐warfarin alcohol [(R,S)‐WA]] have been studied, using a stereospecific HPLC assay. Warfarin metabolites are less bound both within plasma and a 40 g/liter solution of human serum albumin than the enantiomers of warfarin. The reduced warfarin metabolites have a lower fraction unbound [1.33% for (S,R)‐WA, 2.09% for (S,S)‐WA, and 1.04% for (R,S)‐WA] than hydroxylated metabolites [3.24% for (R)‐6‐HW, 4.26% (S)‐6‐HW, 4.49% for (R)‐7‐HW and 4.27% for (S)‐7‐HW] to HSA. Phenylbutazone produced a concentration‐dependent increase in the unbound fraction of all metabolites. It was possible to predict the unbound fraction of warfarin metabolites based on the unbound fraction of warfarin enantiomers. © 1993 Wiley‐Liss, Inc.
Enantioselective inhibitory effect of nicardipine on the hepatic clearance of propranolol in man
Authors: Vercruysse Isabelle , Belpaire Frans , Wynant Pascal , Massart Désiré L. , Dupont Alain G. 
Published: January 2005

AbstractThe influence of a single oral dose of 30 mg nicardipine on the pharmacokinetics of (R)‐ and (S)‐propranolol, given orally as rac‐propranolol 80 mg, was studied in 12 healthy volunteers. The plasma concentrations were higher for the (S)‐enantiomer than for the (R)‐enantiomer. The Clo and the Cl′intr of (S)‐propranolol were significantly lower than the Clo and Cl′intr of (R)‐propranolol. The unbound fraction of (R)‐propranolol was significantly higher than that of (S)‐propranolol. Coadministration of nicardipine significantly increased the AUC and Cmax and significantly decreased the Clo and Cl′intr for unbound drug of (R)‐ and (S)‐propranolol. These changes were more important for (R)‐ than for (S)‐propranolol. The protein binding was not altered by nicardipine. The enantioselective effect of nicardipine on the metabolic clearance of propranolol appears to be due to an interaction at the level of the metabolizing enzymes. The effect on blood pressure of rac‐propranolol was little affected when nicardipine was coadministered with rac‐propranolol, and its bradycardic effect was reduced. © 1994 Wiley‐Liss, Inc.
On the other hand: The stereoselectivity of drug action at ion channels
Authors: Triggle David J. 
Published: January 2005

AbstractIon channels are pharmacological receptors with specific drug binding sites. These binding sites define specific structure–function relationships for the actions of drug classes. Interpretation of these structure–function relationships may be complex because of state‐dependent drug‐channel interactions. These state‐dependent interactions determine affinity and access of drug to binding sites and may result in both quantitative and qualitative changes in structure–function relationships including stereoselectivity. A channel‐active drug may exhibit antagonist or activator properties according to membrane potential and the stereoselectivity of interaction may also change with channel state. © 1994 Wiley‐Liss, Inc.
Current regulatory (draft) guidance on chiral medicinal products: Canada, EEC, Japan, United States
Authors: Rauws Adalbert Gerard , Groen Kees 
Published: January 2005

AbstractThe rapid development of stereospecific analytical, synthetic, and preparative methods has profoundly changed the prospects for development and application of chiral medicinal products. This has induced regulatory agencies, e.g., in Canada, the EEC, Japan, and the United States, to prepare guidance on this subject. The present draft documents are discussed, with emphasis on the two most important cases: (1) New racemates: How many extra requirements are justified? (2) Development of a single enantiomer from an approved racemate: how few are acceptable? At the moment the opportunities for early harmonisation are favourable and the formulation of one international guidance document seems feasible. © 1994 Wiley‐Liss, Inc.
The effects of desipramine and iprindole on levels of enantiomers of fluoxetine in rat brain and urine
Authors: Aspeslet Launa J. , Baker Glen B. , Coutts Ronald T. , Torok‐Both George A. 
Published: January 2005

AbstractThe antidepressant fluoxetine (FLU) and its N‐demethylated metabolite, norfluoxetine (NFLU), each contains a chiral center. The combination of FLU and desipramine (DMI), another antidepressant, has been reported to be useful in treatment of depression, to dramatically increase plasma levels of DMI and also to produce more rapid β‐adrenergic receptor down‐regulation in brain than caused by DMI alone. We have now begun studies on the effects of this drug combination on the levels of FLU and NFLU enantiomers in the rat. In addition, the combination of FLU and iprindole (IPR) was also investigated. Male Sprague–Dawley rats were treated intraperitoneally with either normal saline vehicle, DMI (5 mg/kg/day), (R,S)‐FLU (10 mg/kg/day) or DMI (5 mg/kg/day) + (R,S)‐FLU (10 mg/kg/day) for 4 days. Following the last treatment, 24 h urine samples were collected. Rats were sacrificed and brains were removed. For the IPR study, rats were pretreated with either saline or IPR‐HCl (11.2 mg/kg) and then treated 1 h later with (R,S)‐FLU. After 5 h, the rats were sacrificed and brains were removed. Brain and urine samples were analyzed by gas chromatography with electron‐capture detection for free (R)‐ and (S)‐FLU and (R)‐ and (S)‐NFLU after extraction and reaction with (−)‐(S)‐N‐(trifluoroacetyl)prolyl chloride. The results from the brains of the rats treated with DMI/FLU indicate that levels of the enantiomers of both FLU and NFLU were significantly increased over those seen in the animals receiving (R,S)‐FLU alone. In the IPR/FLU treated rats, an increase in the brain levels of both (R)‐ and (S)‐FLU was noted when compared with rats receiving (R,S)‐FLU alone; however, there appeared to be no increase in the brain levels of NFLU enantiomers. © 1994 Wiley‐Liss, Inc.
Diphenylethanediamine (DPEDA) derivatives as chiral selectors: IV. A comparison of 3,5‐dinitrobenzoylated (S,S)‐ and (S,R)‐DPEDA‐derived chiral stationary phases with Pirkle's standard (R)‐phenylglycine‐derived phase in normal phase HPLC
Authors: Maier Norbert M. , Uray Georg , Kleidernigg Oliver P. , Lindner Wolfgang 
Published: January 2005

AbstractUndecanoyl bound 3,5‐dinitrobenzoyl‐(S,R)‐1,2‐diphenylethane‐1,2‐diamine [(1S,2R)‐DNB‐DPEDA] as chiral selector (SO) has been synthesized and used as a chiral stationary phase (CSP II) for normal‐phase enantioselective HPLC. It is compared with the already published diastereomeric (1S,2S)‐DNB‐DPEDA‐derived CSP I and with the “standard” Pirkle DNB‐(R)‐phenylglycine‐derived CSP III. Chromatographic data for about 100 racemic analytes reveal that CSP II is able to separate especially well enantiomers of derivatized aromatic carboxylic acids and analytes having a benzyl substituent bound at the chiral center. However, CSP I was found to be superior to CSP II and III in its general applicability and its ability to resolve enantiomers of heterocyclic drugs. © 1994 Wiley‐Liss, Inc.
Experimental studies of competition between enantiomers in chiral liquid chromatography through their system peaks
Authors: Levin Shulamit , Abu‐Lafi Saleh 
Published: January 2005

AbstractCompetition between the (+)‐ and (−) enantiomers of 2,2,2‐trifluoro‐1‐(9‐anthryl) ethanol as mobile phase additives was indicated by the chromatographic behavior of their system peaks. Two types of chiral stationary phases were used, one based on dinitrobenzoylphenylglycine and the other on dinitrobenzylphenylethylamine plus tartaric acid. The racemic mixture was used as the mobile phase additive and k′ of their system peaks was studied as a function of the mixture concentration in the mobile phase in both cases. A shift in k′ of the two system peaks was observed and considered as an indication that competition occurred. The areas of the two system peaks were also studied as a function of the concentration of the enantiomers in the samples, using two different compositions of the mobile phase. The dependency of system peaks' area on the sample composition indicated whether competition between the enantiomers occurred. One mobile phase contained 0.1 mM of the racemic mixture, where the area of the two retained system peaks behaved independently, i.e., only the peak corresponding to the enantiomer was affected by its presence in the sample. The other mobile phase contained 0.75 mM of the racemic mixture, and both peaks were affected by the injection of any one of the enantiomers. The interdependency of the system peaks' area on both the enantiomers indicated that their distribution in the chiral system was interrelated due to mutual interactions. A quantitative treatment of the interdependency and competition was excluded, due to the irreversible adsorption of the two enantiomers on the chiral stationary phase after using overloading concentrations. This irreversible adsorption was visualized by the appearance of two retained system peaks of the two residual enantiomers. These system peaks were detected only when the sample contained pure enantiomers due to competition between the enantiomer in the sample with the residual enantiomers in the stationary phase. © 1994 Wiley‐Liss, Inc.
Stereoselective hydrolysis of ICRF‐187 (dexrazoxane) and ICRF‐186 by dihydropyrimidine amidohydrolase
Authors: Hasinoff Brian B. 
Published: January 2005

AbstractThe enzymatic ring‐opening hydrolyses of the doxorubicin cardioprotective agents (+)‐(S)‐ICRF‐187 (dexrazoxane), (−)‐(R)‐ICRF‐186, and rac‐ICRF‐159 by the enzyme dihydropyrimidine amidohydrolase (DHPase) have been studied. ICRF‐187 underwent enzymatic ring‐opening hydrolysis by DHPase 4.5 times faster than did ICRF‐186. It was also shown that DHPase opens only one ring of ICRF‐186 and does not act on this one‐ring open hydrolysis product, as has been observed for ICRF‐187. Differences in the rates at which the two optical isomers are acted upon by DHPase suggest that they could have differing protective effects. © 1994 Wiley‐Liss, Inc.
Stereoselectivity of the in vitro metabolism of thalidomide
Authors: Knoche Beate , Blaschke Gottfried 
Published: January 2005

AbstractThe stereoselective metabolism of the former sedative thalidomide and the metabolism of its analogue EM 12 were studied in vitro with liver homogenates. In our study we focused on hydroxylated nonhydrolyzed metabolites of thalidomide. An analytical HPLC method was developed to determine these metabolites directly. The investigations showed a highly stereoselective biotransformation of thalidomide. 5‐Hydroxy thalidomide was preferentially formed by (−)‐(S)‐thalidomide, whereas (+)‐(R)‐thalidomide was metabolized to two hitherto unknown compounds (Met A and B). Mass spectrometry of these metabolites Met A and B indicated that oxidation or hydroxylation took place in the glutarimide moiety. Biotransformation studies with the more stable thalidomide analogue EM 12 revealed four new metabolites (Met CF) whose quantities differed in the selected liver homogenate. © 1994 Wiley‐Liss, Inc.
Evaluation of enantiomeric purity of selected amino acids in honey
Authors: Pawlowska Maria , Armstrong Daniel W. 
Published: January 2005

AbstractHighly sensitive and accurate HPLC methods were used for the determination of total amounts of proline, leucine and phenylalanine and their enantiomeric ratios in a variety of different honey samples. Significant amounts of D‐leucine and D‐phenylalanine and relatively low concentrations of D‐proline have been found in honeys of different botanical and geographical origins. It is suggested that the enantiomeric ratios of amino acids could be used to test for storage effects, age, and the quality of the processing of the honey. © 1994 Wiley‐Liss, Inc.