bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of pirprofen enantiomers with human serum albumin
Authors: Oravcová J. , Mlynárik V. , Bystrický S. , Šoltés L. , Szalay P. , Boháčik Ľ. , Trnovec T. 
Published: January 2005

AbstractThe interaction of pirprofen enantiomers with human serum albumin (HSA) was investigated by means of high‐performance liquid chromatography (HPLC), circular dichroism (CD), and 1H NMR spectroscopy. HPLC experiments indicated that both pirprofen enantiomers were bound to one class of high‐affinity binding sites (n(+) = 1.91 ± 0.13, K(+) = (4.09 ± 0.64) × 105 M−1, n(‐) = 2.07 ± 0.13, K(‐) = (6.56 ± 1.35) × 105 M−1) together with nonspecific binding (n′K′(+) = (1.51 ± 0.21) × 104 M−1, n′K′(‐) = (0.88 ± 0.13) × 104 M−1). Slight stereoselectivity in specific binding was demonstrated by the difference in product n(+)K(+) = (0.77 ± 0.08) × 106 M−1 vs. n(‐)K(‐) = (1.30 ± 0.21) × 106 M−1, i.e., the ratio n(‐)K(‐)/n(+)K(+) = 1.7. CD measurements showed changes in the binding sites located on the aromatic amino acid side chains (a small positive band at 315 nm and a pronounced negative extrinsic Cotton effect in the region 250–280 nm). The protein remains, however, in its predominantly alpha‐helical conformation. The 1H NMR difference spectra confirmed that both pirprofen enantiomers interacted with HSA specifically, most probably with site II on the albumin molecule.
Stereoselective accumulation of the β‐receptor blocking drug atenolol by human platelets
Authors: Walle T. , Webb J. G. , Walle U. K. , Bagwell E. E. 
Published: January 2005

AbstractWe 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.
Production of a chiral polyester by Pseudomonas oleovorans grown with 5‐phenyl‐2,4‐pentadienoic acid
Authors: Antoun Safwat , Grizzi Ilaria , Lenz Robert W. , Fuller R. Clinton 
Published: January 2005

AbstractPseudomonas oleovorans has been previously shown to produce a polyester containing a phenyl pendant group when grown with 5‐phenylpentanoic acid under nutrient‐limiting conditions. The same polyester was produced when 5‐phenyl‐2,4‐pentadienoic acid was the only carbon source, and a mixture of two different polymers was produced when this bacterium was grown on a mixture of 5‐phenyl‐2,4‐pentadienoic acid and nonanoic acid. The polymer blend obtained was separated by fractional crystallization to yield poly(3‐hydroxy‐5‐phenylpentanoate) and the copolymer which is normally produced with nonanoic acid alone.
Improvement of the enantiorecognition ability of tyrosine‐derived chiral stationary phases: Direct resolution of 1,2‐amino‐alcohols (β‐blockers)
Authors: Tambute A. , Siret L. , Begos A. , Caude M. 
Published: January 2005

AbstractA novel chiral stationary phase (CSP) derived from tyrosine is evaluated with regard to the first generation commercially available (S)‐ChyRoSine‐A CSP, under normalphase or reversed‐phase liquid chromatographic (NPLC or RPLC) and subcritical fluid chromatographic (SubFC) conditions. The complete scope of application of these CSPs is reviewed. The novel CSP, which bears a bulkier functional group, displays a higher enantiorecognition ability than previously described (S)‐ChyRoSine‐A toward about 15 families of racemates, whatever the mobile phase conditions.The direct enantiomeric separation of 1,2‐amino‐alcohols (β‐blockers) is carried out on both CSPs. Facile separations are achieved within short analysis times using SubFC mode, whereas very poor separations are obtained using NPLC mode. These results disagree with previous theories (interchangeability between NPLC and SubFC modes).
The influence of aging on the stereoselective pharmacokinetics of propranolol in the rat
Authors: Vermeulen An M. , Belpaire Frans M. , Moerman Emmanuel , Smet Frits De , Bogaert Marc G. 
Published: January 2005

AbstractThe influence of aging on the pharmacokinetics and the tissue distribution of (R)‐ and of (S)‐propranolol was studied in 3‐, 12‐, and 24‐month‐old rats. After both iv and oral administration of rac‐propranolol, the plasma concentrations were higher for the (R)‐ than for the (S)‐enantiomer. For the tissue concentrations, the reverse was true. The free fraction of (S)‐propranolol in plasma was about 4 times larger than that of (R)‐propranolol, and this is the main factor responsible for the differences in kinetics between the two enantiomers. There was a suggestion for a difference in tissue binding between the two enantiomers. With aging, the plasma and tissue concentrations of both enantiomers increase, probably due to a decrease in blood clearance. Tissue binding did not change much with aging. Notwithstanding the marked differences between the kinetics of the propranolol enantiomers, the changes which occur with aging affect both enantiomers to the same degree.
Enantioselectivity of lipase‐catalyzed hydrolysis of some 2‐chloroethyl 2‐arylpropanoates studied by chiral reversed‐phase liquid chromatography
Authors: Allenmark Stig , Ohlsson Ann 
Published: January 2005

AbstractA technique based exclusively on chiral reversed‐phase liquid chromatography has been shown to greatly facilitate studies of enantioselectivity in lipase‐catalyzed hydrolysis of chiral organic esters. Only two sets of experimental data are needed to calculate the enantioselectivity (E) of a kinetically controlled enantiomer‐differentiating reaction of this kind, viz. the enantiomeric excess of the product (eep) or substrate (ees), and the degree of substrate conversion (c). The product enantiomers are well separated on a BSA‐based column, giving eep directly. In addition, separation of the (unresolved) ester substrate from the enantiomeric products gives c by integration. Via an optimization of the mobile phase used in the chiral chromatographic system, both these parameters can often be determined in a single run. Highly precise and detailed kinetic studies of the enzymatic reaction can thus be performed. In this way, E‐values have been determined for a series of 2‐chloroethyl 2‐arylpropanoates hydrolyzed in the presence of a Candida cylindracea lipase at pH 6.0 and 7.1. Effects on the E‐values from a partial purification and further processing of the lipase have also been studied.
Plasma determination of the enantiomers of SL 84.0418, a new antihyperglycaemic drug, by HPLC on a chiral α1‐agp column
Authors: Guinebault Paul , McAnena‐Morice Deirdre , Colafranceschi Colette , Rouchouse Alain 
Published: January 2005

AbstractSL 84.0418 is a new antihyperglycaemic drug. It is an orally active and selective α2‐adrenoceptor antagonist. This molecule, a pyrroloindole derivative, contains an asymmetric center yielding two enantiomers. In order to evaluate the pharmacokinetic profile of both enantiomers following oral administration of the racemate we have developed an HPLC method for their separation and quantification. The liquid—liquid extraction involved three steps with two salting‐out procedures at pH 11.5 before and after a back‐extraction with 0.005 M H2SO4. The enantiomers were separated by HPLC on a stainless‐steel column (100 x 4.0 mm) packed with a chiral α1 ‐acid. The UV response was linear from 1 to 250 ng/ml for both enantiomers. The relative standard deviation (RSD) for reproducibility was below 10.7%. Using quality control samples, precision was found below 7.8% and accuracy was 108%. Extraction recoveries were ca. 60% for both enantiomers and 94% for the internal standard. Column life was brought up to 2 months, which corresponds to about 1,000 injections of biological extract. No guard column was used, but a daily back‐flush was carried out. This method is suitable for routine analysis and 30 to 40 plasma samples a day can be processed. This method allows the definition of the pharmacokinetic profile of both enantiomers of SL 84.0418 in human plasma after single oral administration of doses as low as 20 mg of the racemic drug.
The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide
Authors: Butler Brent T. , Silvey Gary , Michael Houston D. , Borcherding David R. , Vaughn Valerie L. , McPhail Andrew T. , Radzik Donna M. , Wynberg Hans , Ten Hoeve W. , Van Echten E. , Ahmed Nahed K. , Linnik Matthew D. 
Published: January 2005

AbstractRac‐ML‐1035 (MDL 201,035: 4‐amino‐5‐chloro‐2‐[2‐(methylsulfinyl)ethoxy]— N‐[2‐(diethylamino)ethyl] benzamide hydrochloride) is a racemic gastroprokinetic with serotonergic (5‐hydroxytryptamine, 5‐HT) activity and a novel chiral sulfoxide substituent. Chromatographic and chemical methods have been developed to resolve the enantiomers of rac‐ML‐1035, and the absolute configuration of the (R)‐enantiomer has been determined. We also report pharmacological characterization of rac‐ML‐1035 and its respective isomers. Radioligand binding to rat cortical membranes revealed that (R)‐ML‐1035 (MDL 201,226) and (S)‐ML‐1035 (MDL 201,227) had equivalent activity at the 5‐HT3 receptor. However, in isolated tissue studies including field‐stimulated guinea pig ileum, field‐stimulated rat fundic strip, and nonstimulated guinea pig ileum, (S)‐ML‐1035 was equally potent yet had greater maximal activity than (R)‐ML‐1035 in eliciting or facilitating cholinergic contractions. Thus, enantiomers of rac‐ML‐1035 can be resolved, and the relative configuration of these isomers influences their pharmacological activity. © 1992 Wiley‐Liss, Inc.
Chiroptical detection during liquid chromatography: Applications to stereoanalysis and stereodynamics
Authors: Mannschreck Albrecht 
Published: January 2005

AbstractQualitative and quantitative use of polarimetry at one wavelength for detection during liquid chromatography is briefly reviewed. Acquisition of circular dichroism spectra by stopped‐flow and nonstop measurements has been further developed. Reasons are given why the angle of rotation, i.e., the polarimeter, is preferred for monochromatic use and differential absorbance, i.e., the dichrograph, for polychromatic requirements. Both methods are demonstrated by novel applications, mainly to enantiomers which interconvert thermally via intramolecular processes. © 1992 Wiley‐Liss, Inc.
Chromatographic resolution of the chiral isomers of several β‐blockers over cellulose tris(3,5‐dimethylphenylcarbamate) chiral stationary phase
Authors: Ching C.B. , Lim B.G. , Lee E.J.D. , Ng S.C. 
Published: January 2005

AbstractThe optical resolution of seven β‐blockers which have in common the N‐isopropyl‐3‐aryloxy‐2‐hydroxypropylamine moiety was carried out by HPLC using the cellulose tris(3,5‐dimethylphenylcarbamate) chiral stationary phase to quantitatively characterize the enantioselectivity of these compounds. The capacity factors and separation factors at different column temperature were determined with some qualitative trends derived. A compensation effect was observed for these compounds where there exists an approximately linear relationship between the enantiomeric differences in enthalpic and entropic energies. © 1992 Wiley‐Liss, Inc.
Optical stability of gossypol
Authors: Jaroszewski Jerzy W. , Strøm‐Hansen Thorbjørn , Hansen Lars Lindgaard 
Published: January 2005

AbstractThe optical stability of gossypol [1,1',6,6',7,7'‐hexahydroxy‐3,3'‐dimetyl‐5,5'‐bis(1‐methylethyl)‐2,2'‐binaphthalene‐8,8'‐dicarboxaldehyde], a natural product exhibiting profoundly enantiospecific antitumor and male antifertility action, was investigated by means of computational methods and thermal racemization experiments. The calculations on gossypol and several derivatives and model compounds were carried out using the MM2 force field; energies and geometries of minimum energy conformations, as well as structures along various inversion pathways, were calculated. According to the calculations, gossypol (the dialdehyde form) and its simple analogues are not thermally racemizable (energy barriers for rotational inversion above 50 kcal/mol). By contrast, the calculations suggest that the acetal tautomer of gossypol and its dehydration product (anhydrogossypol) are thermally racemizable, although the energy barriers are still relatively high (35–40 kcal/mol). Optically pure (+)‐anhydrogossypol was prepared and characterized; its racemization became rapid only at high temperatures (180–200°C). When dehydration of gossypol was hindered (in aqueous solution), no racemization of gossypol was observed after prolonged heating at 90°C. © 1992 Wiley‐Liss, Inc.
Computer‐Aided models for optimization of eluent parameters in chiral liquid chromatography
Authors: Tucker R.P. , Fell A.F. , Berridge J.C. , Coleman M.W. 
Published: January 2005

AbstractThe application of a central composite design to the enantiomeric separation of the antifungal drug tioconazole is investigated. The design involves application of a mathematical model to the data to model the response in regions of the factor space not investigated in the experimental design. The significance of the variable terms in the model is assessed statistically and those terms declared not significant are removed from the model. The statistical adequacy of these reduced models is discussed, together with an examination of the prediction errors of the models. Three‐dimensional predicted response surfaces for the complete models are presented and the predictive performance assessed. © 1992 Wiley‐Liss, Inc.
Formation of glycine conjugate and (–)‐(R)‐enantiomer from (+)‐(S)‐2‐phenylpropionic acid suggesting the formation of the coa thioester intermediate of (+)‐(S)‐enantiomer in dogs
Authors: Tanaka Y. , Shimomura Y. , Hirota T. , Nozaki A. , Ebata M. , Takasaki W. , Shigehara E. , Hayashi R. , Caldwell J. 
Published: January 2005

AbstractIt has been proposed that the chiral inversion of the 2‐arylpropionic acids is due to the stereospecific formation of the (–)‐R‐profenyl‐CoA thioesters which are putative intermediates in the inversion. Accordingly, amino acid conjugation, for which the CoA thioesters are obligate intermediates, should be restricted to those optical forms which give rise to the (–)‐R‐profenyl‐CoA, i.e., the racemates and the (–)‐(R)‐isomers. We have examined this problem in dogs with respect to 2‐phenylpropionic acid(2‐PPA). Regardless of the optical configuration of 2‐phenylpropionic acid administered, the glycine conjugate was the major urinary metabolite and this was shown to be exclusively the (+)‐(S)‐enantiomer by chiral HPLC. Both (–)‐(R)‐ and (+)‐(S)‐2‐phenylpropionic acid were present in plasma after the administration of either antipode, and further evidence of the chiral inversion of both enantiomers was provided by the presence of some 25% of the opposite enantiomer in the free 2‐phenylpropionic acid and its glucuronide excreted in urine after administration of (–)‐(R)‐ and (+)‐(S)‐2‐phenylpropionic acid. The (+)‐(S)‐enantiomer underwent chiral inversion to the (–)‐(R)‐antipode when incubated with dog hepatocytes. These data suggests that both enantiomers of 2‐phenylpropionic acid are substrates for canine hepatic acyl CoA ligase(s) and thus undergo chiral inversion, but that the CoA thioester of only (+)‐(S)‐2‐phenylpropionic acid is a substrate for the glycine N‐acyl transferase. These studies are presently being extended to the structure and species specificity of the reverse inversion and amino acid conjugation of profen NSAIDs. © 1992 Wiley‐Liss, Inc.
Optical isomers of a leukotriene b4 antagonist have differential effects on granulocyte diapedesis in the guinea pig dermis
Authors: Fretland Donald J. , Widomski Deborah L. , Anglin Charles P. , Yu Stella , Djuric Stevan W. 
Published: January 2005

AbstractLeukotriene B4 (LTB4) is a proinflammatory product of arachidonic acid metabolism that has been implicated in a number of inflammatory diseases. When injected intradermally into the guinea pig, LTB4 has been shown to elicit a dose‐dependent infiltration of granulocytes as assessed by the level of the neutrophil marker enzyme myeloperoxidase. SC‐41930 [7‐[3‐(4‐acetyl‐3‐methoxy‐2‐propylphenoxy)propoxy]‐3,4‐dihydro‐8‐propyl‐2H‐1‐benzopyran‐2‐carboxylic acid] is a potent LTB4 receptor antagonist. When compounds were coadministered along with LTB4 (35 ng) into the dermal site, racemic SC‐41930, (+)‐SC‐41930, and (–)‐SC‐41930 each inhibited granulocyte accumulation with ED50 values of 340 ± 30, 98 ± 5.7, and 1000 ± 142 ng, respectively; when given intravenously inhibited with ED50 values of 0.5 ± 0.06, 0.3 ± 0.04, and 1.4 ± 0.19 mg/kg, respectively; and when given intragastrically inhibited with ED50 values of 1.7 ± 0.20, 1.4 ± 0.23, and 3.0 ± 0.41 mg/kg, respectively. © 1992 Wiley‐Liss, Inc.
HPLC resolution of atropoisomeric compounds on a csp derived from (1R;2R)‐diaminocyclohexane: Thermodynamic data from variable temperature chromatography
Authors: Galli B. , Gasparrini F. , Misiti D. , Pierini M. , Villani C. , Bronzetti M. 
Published: January 2005

AbstractThe preparation and a preliminary chromatographic evaluation of a novel polymeric chiral stationary phase (CSP) derived from (1R;2R)‐diaminocyclohexane (DACH) are presented. A radical copolymerization process has been employed to generate a silica‐based chiral sorbent, showing considerable high chemical and thermal stability and stereoselectivity toward racemic compounds capable of H‐bonding (3‐hydroxy‐benzodiazepin‐2‐ones, chlorthalidone, atropoisomeric sulfur compounds, etc.); in the present paper we present the investigation on the resolution of racemic dihydroxy biarylic atropoisomers; the effects of eluent composition and of temperature on the separation ability of the CSP have been studied in order to elucidate the recognition mechanism operating in these chiral separations. © 1992 Wiley‐Liss, Inc.
Chromatographic optical resolution on trans‐1,2‐diaminocyclohexane derivatives: Theory and applications
Authors: Gasparrini F. , Misiti D. , Villani C. 
Published: January 2005

AbstractAn overall view on some new chiral stationary phases based on (trans)‐1,2‐diaminocyclohexane is illustrated. The selected chiral moiety, derivatized with different aroyl groups, has been linked to a silica matrix in order to give chiral stationary phases (CSPs) enabling them to be used efficiently in the normal and reverse phase, both for analytical and preparative purposes. In addition new polymeric CSPs have been prepared by using the same selector, suitably modified, as monomer. The new chiral stationary phases have been characterised by physicochemical methods and used for the resolution of various racemic compounds classes such as α‐aryloxyacetic acids, alcohols, sulfoxides, selenoxides, phosphinates, tertiaryphosphine oxides, benzodiazepines etc. without prederivatization or as amines, amino acids, amino alcohols, nonsteroidal antiinflammatory agents in a derivatized form. The separated solutes structural variety suggests that multiple interaction sites are involved in the recognition process: some thermodynamic data relative to the CSPs—selectands interactions are also illustrated. © 1992 Wiley‐Liss, Inc.
Use of cellulose‐based stationary phases for chiral separation in open tubular column chromatography
Authors: Juvancz Z. , Grolimund K. , Francotte E. 
Published: January 2005

AbstractApplication of cellulose‐based chiral stationary phases was extended to open tubular columns. These chiral materials were mixed with achiral matrix stationary phases. Compromises were found among the polarity and the ratio of achiral matrix polymers against the content of the chiral cellulose derivative in order to optimize the resolution of the investigated racemates. In GC, the high efficiency feature of open tubular columns allows fast analysis, however, compounds which express strong H‐bond interaction with cellulose derivatives elute with a bad peak shape. The application of these stationary phases for open tubular SFC was more successful, because the solvation power of the mobile phase can compensate the strong interaction between the solute and the cellulose derivative. Immobilization of the stationary phases were achieved for SFC purposes. © 1992 Wiley‐Liss, Inc.
Stereoselective features of (R)‐ and (S)‐atenolol: Clinical pharmacological, pharmacokinetic, and radioligand binding studies
Authors: Stoschitzky Kurt , Egginger Gabriele , Zernig Gerald , Klein Werner , Lindner Wolfgang 
Published: January 2005

AbstractIn a randomized, double‐blind, cross‐over study in 12 healthy volunteers, the effects of single oral doses of 100 mg rac‐atenolol were compared during exercise to those of equal amounts of the optically pure enantiomers, i.e., 50 mg (R)‐ and 50 mg (S)‐atenolol. The mean rate pressure product decreased with rac‐atenolol (−37%; P < 0.01) and half‐dosed (S)‐atenolol (−35%; P < 0.01) to the same extent, whereas (R)‐atenolol caused no effect. Radioligand binding studies in beta‐adrenergic receptors of the guinea pig heart yielded a eudismic ratio of 46 for (S)‐ to (R)‐atenolol. The mean AUCs, maximal plasma concentrations, and plasma half‐lives of the enantiomers were similar regardless of whether they were administered as optically pure enantiomers or as racemic mixture. On the other hand, the AUC of (R)‐atenolol was 1.08‐fold greater (P < 0.01) than that of the (S)‐enantiomer. The reason for this finding remains unclear. We conclude that only (S)‐atenolol, but not (R)‐atenolol, contributes to the beta‐blocking effect of currently used rac‐atenolol since the same effect can be elicited with the (S)‐enantiomer alone. © 1993 Wiley‐Liss, Inc.
Stereoselective hydrolysis of triglycerides by animal and microbial lipases
Authors: Rogalska Ewa , Cudrey Claire , Ferrato Francine , Verger Robert 
Published: January 2005

AbstractIn the present paper, a study on the stereoselectivity of 25 lipases of animal and microbial origin towards homogeneous prochiral triglycerides is presented. All the lipases tested catalyse the hydrolysis of the chemically alike but sterically nonequivalent ester groups in trioctanoin and triolein with different degrees of stereobias, depending on the fatty acyl chain length of the substrate (Rogalska et al., J. Biol. Chem. 256:20271–20276, 1990). Hydrolysis of the sn‐2 ester group is catalysed by very few lipases and only Candida antarctica A shows a clear preference for this position. Most of the lipases investigated (12 with trioctanoin and 16 with triolein) showed a preference for the sn‐1 position. Using trioctanoin as substrate we observed a total stereoselectivity for position sn‐1 with Pseudomonas sp. and Pseudomonas aeruginosa and for position sn‐3 with Candida antarctica B. This was not the case with triolein as substrate. Among the 23 lipases studied here and the other two lipases described previously (Rogalska et al., J. Biol. Chem. 256:20271–20276, 1990), 17 show a higher stereoselectivity with trioctanoin than with triolein. With guinea pig pancreatic lipase and with three mold lipases (Geotrichum candidum M, Geotrichum candidum A, and Candida antarctica B), the preference switches from sn‐3 to sn‐1 when the acyl chain length increases from eight to 18 carbon atoms. The main conclusion to emerge from the present study is that the specific stereopreference of each lipase for a given substrate under given lipolytic conditions can be said to be its fingerprint. © 1993 Wiley‐Liss, Inc.