THE ACTION OF ALKALIES ON PEPTIDES AND ON KETOPIPERAZINES

PubMed Central

Levene, P. A.; Pfaltz, M. H.

1925-01-01

1. The tripeptide glycyl-levo-alanyl-glycine in solution of either one or ten equivalents of alkali does not undergo racemization on standing. 2. The dipeptide levo-alanyl-glycine under the conditions given in (1) does not undergo racemization. 3. In ketopiperazines, levo-alanyl-glycine anhydride and in levo-prolyl-glycine anhydride under the influence of dilute alkalies, racemization takes place. 4. Racemization in the present experiments was never complete. The degree of racemization seems to depend, on the one hand, on the stability of the ketopiperazine ring; on the other, on the concentration of the alkali. 5. The significance of these observations will depend on the outcome of the work on a larger number of polypeptides and ketopiperazines. The work is now in progress in this laboratory. PMID:19872187

Formation of the racemic compound of ephedrine base from a physical mixture of its enantiomers in the solid, liquid, solution, or vapor state.

PubMed

Duddu, S P; Grant, D J

1992-08-01

Physical mixtures (conglomerates) of the two enantiomers of ephedrine base, each containing 0.5% (w/w) of water, were observed to be converted to the 1:1 racemic compound in the solid, liquid, solution, or vapor state. From a geometrically mixed racemic conglomerate of particle size 250-300 microns (50-60 mesh), the formation of the racemic compound follows second-order kinetics (first order with respect to each enantiomer), with a rate constant of 392 mol-1 hr-1 at 22 degrees C. The reaction appears to proceed via the vapor phase as indicated by the growth of the crystals of the racemic compound between diametrically separated crystals of the two enantiomers in a glass petri dish. The observed kinetics of conversion in the solid state are explained by a homogeneous reaction model via the vapor and/or liquid states. Formation of the racemic compound from the crystals of ephedrine enantiomers in the solution state may explain why Schmidt et al. (Pharm. Res. 5:391-395, 1988) observed a consistently lower aqueous solubility of the mixture than of the pure enantiomers. The solid phase in equilibrium with the solution at the end of the experiment was found to be the racemic compound, whose melting point and heat of fusion are higher than those of the enantiomers. An association reaction, of measurable rate, between the opposite enantiomers in a binary mixture in the solid, liquid, solution, or vapor state to form the racemic compound may be more common than is generally realized.

Alpha lipoic acid selectively inhibits proliferation and adhesion to fibronectin of v-H-ras-transformed 3Y1 cells.

PubMed

Yamasaki, Masao; Iwase, Masahiro; Kawano, Kazuo; Sakakibara, Yoichi; Suiko, Masahito; Nishiyama, Kazuo

2012-05-01

Here, we focused on the effects of racemic α-lipoic acid on proliferation and adhesion properties of 3Y1 rat fibroblasts and the v-H-ras-transformed derivative, HR-3Y1-2 cells. Racemic α-lipoic acid inhibited proliferation of HR-3Y1-2 but not 3Y1 cells at 0.3 and 1.0 mM. R-(+)-α-lipoic acid also inhibited proliferation of HR-3Y1-2 cells equivalent to that of racemic α-lipoic acid. In addition, racemic α-lipoic acid decreased intracellular reactive oxygen species levels in HR-3Y1 cells but not 3Y1 cells. Next, we evaluated the effects of racemic α-lipoic acid on cell adhesion to fibronectin. The results indicated that racemic α-lipoic acid decreased adhesive ability of HR-3Y1-2 cells to fibronectin-coated plates. As blocking antibody experiment revealed that β1-integrin plays a key role in cell adhesion in this experimental system, the effects of racemic α-lipoic acid on the expression of β1-integrin were examined. The results indicated that racemic α-lipoic acid selectively downregulated the expression of cell surface β1-integrin expression in HR-3Y1-2 cells. Intriguingly, exogenous hydrogen peroxide upregulated cell surface β1-integrin expression in 3Y1 cells. Taken together, these data suggest that reduction of intracellular reactive oxygen species levels by α-lipoic acid could be an effective means of ameliorating abnormal growth and adhesive properties in v-H-ras transformed cells.

Racemic crystallography of synthetic protein enantiomers used to determine the X-ray structure of plectasin by direct methods

PubMed Central

Mandal, Kalyaneswar; Pentelute, Brad L; Tereshko, Valentina; Thammavongsa, Vilasak; Schneewind, Olaf; Kossiakoff, Anthony A; Kent, Stephen B H

2009-01-01

We describe the use of racemic crystallography to determine the X-ray structure of the natural product plectasin, a potent antimicrobial protein recently isolated from fungus. The protein enantiomers l-plectasin and d-plectasin were prepared by total chemical synthesis; interestingly, l-plectasin showed the expected antimicrobial activity, while d-plectasin was devoid of such activity. The mirror image proteins were then used for racemic crystallization. Synchrotron X-ray diffraction data were collected to atomic resolution from a racemic plectasin crystal; the racemate crystallized in the achiral centrosymmetric space group with one l-plectasin molecule and one d-plectasin molecule forming the unit cell. Dimer-like intermolecular interactions between the protein enantiomers were observed, which may account for the observed extremely low solvent content (13%–15%) and more highly ordered nature of the racemic crystals. The structure of the plectasin molecule was well defined for all 40 amino acids and was generally similar to the previously determined NMR structure, suggesting minimal impact of the crystal packing on the plectasin conformation. PMID:19472324

Comparison of Levalbuterol and Racemic Albuterol Based on Cardiac Adverse Effects in Children

PubMed Central

Bio, Laura L.; Willey, Vincent J.; Poon, Cathy Y.

2011-01-01

OBJECTIVE To compare the cardiac effects of levalbuterol with those of racemic albuterol based on changes in heart rate (HR) in pediatric patients. METHODS The medical records of hospitalized children ages 1 month to 12 years, who received either levalbuterol or racemic albuterol via nebulizer for 3 consecutive doses between January 2006 and December 2008 were reviewed. The documented HR was collected prior to and after each administered dose of bronchodilator. The primary outcome was the largest percentage of change in HR between groups. Secondary outcomes of comparisons of the number of patients who had more than a 10% change in HR and incidence of tachycardia were included. RESULTS A total of 50 patients, 25 in each group, was included in the study. All patients in the racemic albuterol group received 2.5 mg per dose, while most of the patients in the levalbuterol group received 0.63 mg per dose (19 patients, 76%). Only 6 levalbuterol patients received a dose of 1.25 mg. Nineteen of 25 patients (76%) in the levalbuterol group were tachycardic prior to the first recorded dose compared to 15 patients (60%) in the racemic albuterol group (p = 0.36). The median of the largest percentage of change in HR was 4.1% (interquartile range [IQR], 1.8–8.7) in the levalbuterol group compared to 5% (IQR, 1.9–7.8) in the racemic albuterol group (p = 0.763). Four patients in the levalbuterol group experienced an HR increase of more than 10% compared to 5 patients in the racemic albuterol group (p = 1.0). CONCLUSION Levalbuterol and racemic albuterol bronchodilator therapies produced similar effects on HR. No clinically significant differences were detected in HR changes between the two treatment groups, despite administration of a larger equipotent albuterol dose in the racemic albuterol group than in the levalbuterol group. PMID:22479161

Competitive stereocomplexation, homocrystallization, and polymorphic crystalline transition in poly(L-lactic acid)/poly(D-lactic acid) racemic blends: molecular weight effects.

PubMed

Pan, Pengju; Han, Lili; Bao, Jianna; Xie, Qing; Shan, Guorong; Bao, Yongzhong

2015-05-28

Competitive crystallization kinetics, polymorphic crystalline structure, and transition of poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemic blends with a wide range of molecular weights (MWs) were symmetrically investigated. Stereocomplex (sc) crystallites are exclusively formed in the low-MW racemic blends. However, stereocomplexation is remarkably depressed, and homocrystallization becomes prevailing with increasing MWs of PLLA and PDLA. Suppressed stereocomplexation in high-MW (HMW) racemic blends is proposed to be due to the low chain diffusion ability and restricted intermolecular crystal nucleation/growth. Equilibrium melting point of sc crystallites first increases and then decreases as MW increases. Crystallinity and relative fraction of sc crystallites in racemic blends enhance with crystallization temperature (Tc), and the sc crystallites are merely formed at Tc > 170 °C because of their higher thermodynamic stability. In situ wide-angle X-ray diffraction (WAXD) analysis reveals that the stereocomplexation and homocrystallization are successive rather than completely simultaneous, and the stereocomplexation is preceding homocrystallization in isothermal crystallization of HMW racemic blends. Both initial crystalline structure of homocrystallites (hc) and MW influence the heating-induced hc-to-sc transition of HMW racemic blend drastically; the hc-to-sc transition becomes easier with decreasing Tc and MW. After crystallization at the same temperature, sc crystallites show smaller long period than their hc counterparts.

Separation and enrichment of enantiopure from racemic compounds using magnetic levitation.

PubMed

Yang, Xiaochuan; Wong, Shin Yee; Bwambok, David K; Atkinson, Manza B J; Zhang, Xi; Whitesides, George M; Myerson, Allan S

2014-07-18

Crystallization of a solution with high enantiomeric excess can generate a mixture of crystals of the desired enantiomer and the racemic compound. Using a mixture of S-/RS-ibuprofen crystals as a model, we demonstrated that magnetic levitation (MagLev) is a useful technique for analysis, separation and enantioenrichment of chiral/racemic products.

X-ray Structure of Native Scorpion Toxin BmBKTx1 by Racemic Protein Crystallography Using Direct Methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandal, Kalyaneswar; Pentelute, Brad L.; Tereshko, Valentina

2009-04-08

Racemic protein crystallography, enabled by total chemical synthesis, has allowed us to determine the X-ray structure of native scorpion toxin BmBKTx1; direct methods were used for phase determination. This is the first example of a protein racemate that crystallized in space group I41/a.

Recent advances in chirally pure proton pump inhibitors.

PubMed

Pai, Vikas; Pai, Nitin

2007-08-01

Chirality is a ubiquitous natural phenomenon resulting because of a differential spatial orientation of molecules around its chiral centre. This leads to the existence of two or more spatially dissimilar forms, known as stereoisomers or enantiomers, which are non-superimposable images of each other and may significantly differ from each other with respect to pharmacokinetic and pharmacodynamic properties and molecular interaction. Thus one isomer may offer significant pharmacokinetic and therapeutic advantages as compared to the other isomer or the racemic mixture (mixture containing both enantiomers). Proton pump inhibitors are a class of drugs which have been very effective in the management of acid-related disorders. The proton pumps currently available in the market including omeprazole, pantoprazole, rabeprazole and lansoprazole are racemic mixtures of the S and R isomers. Chirally pure forms of proton pump inhibitors show a superior metabolic and pharmacokinetic profile as compared to their racemates. The therapeutic efficacy is also superior to the parent racemate. This has been clearly demonstrated with the development of esomeprazole- the S-isomer of omeprazole. S-pantoprazole and dexrabeprazole also offer therapeutic advantages as compared to racemic pantoprazole and racemic rabeprazole respectively. This article reviews the chiral developments in the proton pump inhibitors and their clinical applications.

Racemization in Reverse: Evidence that D-Amino Acid Toxicity on Earth Is Controlled by Bacteria with Racemases

PubMed Central

Zhang, Gaosen; Sun, Henry J.

2014-01-01

D-amino acids are toxic for life on Earth. Yet, they form constantly due to geochemical racemization and bacterial growth (the cell walls of which contain D-amino acids), raising the fundamental question of how they ultimately are recycled. This study provides evidence that bacteria use D-amino acids as a source of nitrogen by running enzymatic racemization in reverse. Consequently, when soils are inundated with racemic amino acids, resident bacteria consume D- as well as L-enantiomers, either simultaneously or sequentially depending on the level of their racemase activity. Bacteria thus protect life on Earth by keeping environments D-amino acid free. PMID:24647559

Racemization in reverse: evidence that D-amino acid toxicity on Earth is controlled by bacteria with racemases.

PubMed

Zhang, Gaosen; Sun, Henry J

2014-01-01

D-amino acids are toxic for life on Earth. Yet, they form constantly due to geochemical racemization and bacterial growth (the cell walls of which contain D-amino acids), raising the fundamental question of how they ultimately are recycled. This study provides evidence that bacteria use D-amino acids as a source of nitrogen by running enzymatic racemization in reverse. Consequently, when soils are inundated with racemic amino acids, resident bacteria consume D- as well as L-enantiomers, either simultaneously or sequentially depending on the level of their racemase activity. Bacteria thus protect life on Earth by keeping environments D-amino acid free.

Concordance of Collagen-Based Radiocarbon and Aspartic-Acid Racemization Ages

PubMed Central

Bada, Jeffrey L.; Schroeder, Roy A.; Protsch, Reiner; Berger, Rainer

1974-01-01

By determining the extent of racemization of aspartic acid in a well-dated bone, it is possible to calculate the in situ first-order rate constant for the interconversion of the L and D enantiomers of aspartic acid. Collagen-based radiocarbon-dated bones are shown to be suitable samples for use in “calibrating” the racemization reaction. Once the aspartic-acid racemization reaction has been “calibrated” for a site, the reaction can be used to date other bones from the deposit. Ages deduced by this method are in good agreement with radiocarbon ages. These results provide evidence that the aspartic-acid racemization reaction is an important chronological tool for dating bones either too old or too small for radiocarbon dating. As an example of the potential application of the technique for dating fossil man, a piece of Rhodesian Man from Broken Hill, Zambia, was analyzed and tentatively assigned an age of about 110,000 years. PMID:4522802

Physical aspects of dexibuprofen and racemic ibuprofen.

PubMed

Leising, G; Resel, R; Stelzer, F; Tasch, S; Lanziner, A; Hantich, G

1996-12-01

This article presents a comparative study of ibuprofen materials in their solid state. Ibuprofen crystallizes into two different structures for the S(+) enantiomer (dexibuprofen) and racemic ibuprofen. The crystal structure of ibuprofen, its optical absorption and photoluminescence, and the thermodynamic results (melting point and heat of fusion) are discussed. From these physicochemical properties, the authors conclude that dexibuprofen, which is the most active species pharmaceutically, and racemic ibuprofen are inherently different solid-state materials.

Enantioconvergent Cross-Couplings of Racemic Alkylmetal Reagents with Unactivated Secondary Alkyl Electrophiles: Catalytic Asymmetric Negishi α-Alkylations of N-Boc-pyrrolidine

PubMed Central

Cordier, Christopher J.; Lundgren, Rylan J.; Fu, Gregory C.

2013-01-01

Although enantioconvergent alkyl-alkyl couplings of racemic electrophiles have been developed, there have been no reports of the corresponding reactions of racemic nucleophiles. Herein, we describe Negishi cross-couplings of racemic α-zincated N-Boc-pyrrolidine with unactivated secondary halides, thus providing a one-pot, catalytic asymmetric method for the synthesis of a range of 2-alkylpyrrolidines (an important family of target molecules) from N-Boc-pyrrolidine, a commercially available precursor. Preliminary mechanistic studies indicate that two of the most straightforward mechanisms for enantioconvergence (a dynamic kinetic resolution of the organometallic coupling partner and a simple β-hydride elimination/β-migratory insertion pathway) are unlikely to be operative. PMID:23869442

Racemization of (S)-profen thioesters by strong neutral bases in nonpolar organic solvents: implication for ion-pair kinetic basicity.

PubMed

Chen, Chia-Yin; Chang, Yu-Shang; Lin, Shun-An; Wen, Hui-I; Cheng, Yu-Chi; Tsai, Shau-Wei

2002-05-17

The racemization of (S)-profen 2,2,2-trifluoroethyl thioesters in isooctane with trioctylamine as base was carried out, in which the Hammett equation log(k(int)) = 3.584sigma - 3.745 was successfully applied to describe the electron-withdrawing effect of the substituents to the alpha-phenyl moiety of the thioesters. A combination of neutral strong organic bases with different nonpolar solvents was employed to determine the second-order interconversion constants for the racemization of (S)-naproxen 2,2,2-trifluoroethyl thioester, in which solvent hydrophobicity was found to have less effect on the racemization. Implication for ion-pair kinetic basicity scale for the neutral strong bases in isooctane was further discussed.

Stereoselective Effects of Abused “Bath Salt” Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation

PubMed Central

Gannon, Brenda M.; Williamson, Adrian; Suzuki, Masaki; Rice, Kenner C.

2016-01-01

3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit “bath salts” products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(+)-MDPV, and R(−)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(+)-MDPV, and R(−)-MDPV under a warm (28°C) or cool (20°C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(+)-MDPV was most potent, racemic MDPV was less potent than the S(+) enantiomer, and R(−)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(+)-MDPV and racemic MDPV, but R(−)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(−)-MDPV is less potent than S(+)-MDPV and racemic MDPV. Taken together, these data suggest that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse. PMID:26769917

Racemization of aspartic acid in root dentin as a tool for age estimation in a Kuwaiti population.

PubMed

Elfawal, Mohamed Amin; Alqattan, Sahib Issa; Ghallab, Noha Ayman

2015-01-01

Estimation of age is one of the most significant tasks in forensic practice. Amino acid racemization is considered one of the most reliable and accurate methods of age estimation and aspartic acid shows a high racemization reaction rate. The present study has investigated the application of aspartic acid racemization in age estimation in a Kuwaiti population using root dentin from a total of 89 upper first premolar teeth. The D/L ratio of aspartic acid was obtained by HPLC technique in a test group of 50 subjects and a linear regression line was established between aspartic acid racemization and age. The correlation coefficient (r) was 0.97, and the standard error of estimation was ±1.26 years. The racemization age "t" of each subject was calculated by applying the following formula: ln [(1 + D/L)/(1 - D/L)] = 0.003181 t + (-0.01591). When the proposed formula "estimated age t = ln [(1 + D/L)/(1 - D/L)] + 0.01591/0.003181" was applied to a validation group of 39 subjects, the range of error was less than one year in 82.1% of the cases and the standard error of estimation was ±1.12. The current work has established a reasonably significant correlation of the D-/L-aspartic acid ratio with age, and proposed an apparently reliable formula for calculating the age in Kuwaiti populations through aspartic acid racemization. Further research is required to find out whether similar findings are applicable to other ethnic populations. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Age estimation in forensic sciences: application of combined aspartic acid racemization and radiocarbon analysis.

PubMed

Alkass, Kanar; Buchholz, Bruce A; Ohtani, Susumu; Yamamoto, Toshiharu; Druid, Henrik; Spalding, Kirsty L

2010-05-01

Age determination of unknown human bodies is important in the setting of a crime investigation or a mass disaster because the age at death, birth date, and year of death as well as gender can guide investigators to the correct identity among a large number of possible matches. Traditional morphological methods used by anthropologists to determine age are often imprecise, whereas chemical analysis of tooth dentin, such as aspartic acid racemization, has shown reproducible and more precise results. In this study, we analyzed teeth from Swedish individuals using both aspartic acid racemization and radiocarbon methodologies. The rationale behind using radiocarbon analysis is that aboveground testing of nuclear weapons during the cold war (1955-1963) caused an extreme increase in global levels of carbon-14 ((14)C), which has been carefully recorded over time. Forty-four teeth from 41 individuals were analyzed using aspartic acid racemization analysis of tooth crown dentin or radiocarbon analysis of enamel, and 10 of these were split and subjected to both radiocarbon and racemization analysis. Combined analysis showed that the two methods correlated well (R(2) = 0.66, p < 0.05). Radiocarbon analysis showed an excellent precision with an overall absolute error of 1.0 +/- 0.6 years. Aspartic acid racemization also showed a good precision with an overall absolute error of 5.4 +/- 4.2 years. Whereas radiocarbon analysis gives an estimated year of birth, racemization analysis indicates the chronological age of the individual at the time of death. We show how these methods in combination can also assist in the estimation of date of death of an unidentified victim. This strategy can be of significant assistance in forensic casework involving dead victim identification.

Stereoselective Effects of Abused "Bath Salt" Constituent 3,4-Methylenedioxypyrovalerone in Mice: Drug Discrimination, Locomotor Activity, and Thermoregulation.

PubMed

Gannon, Brenda M; Williamson, Adrian; Suzuki, Masaki; Rice, Kenner C; Fantegrossi, William E

2016-03-01

3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit "bath salts" products. MDPV is a chiral molecule, but the contribution of each enantiomer to in vivo effects in mice has not been determined. To address this, mice were trained to discriminate 10 mg/kg cocaine from saline, and substitutions with racemic MDPV, S(+)-MDPV, and R(-)-MDPV were performed. Other mice were implanted with telemetry probes to monitor core temperature and locomotor responses elicited by racemic MDPV, S(+)-MDPV, and R(-)-MDPV under a warm (28°C) or cool (20°C) ambient temperature. Mice reliably discriminated the cocaine training dose from saline, and each form of MDPV fully substituted for cocaine, although marked potency differences were observed such that S(+)-MDPV was most potent, racemic MDPV was less potent than the S(+) enantiomer, and R(-)-MDPV was least potent. At both ambient temperatures, locomotor stimulant effects were observed after doses of S(+)-MDPV and racemic MDPV, but R(-)-MDPV did not elicit locomotor stimulant effects at any tested dose. Interestingly, significant increases in maximum core body temperature were only observed after administration of racemic MDPV in the warm ambient environment; neither MDPV enantiomer altered core temperature at any dose tested, at either ambient temperature. These studies suggest that all three forms of MDPV induce biologic effects, but R(-)-MDPV is less potent than S(+)-MDPV and racemic MDPV. Taken together, these data suggest that the S(+)-MDPV enantiomer is likely responsible for the majority of the biologic effects of the racemate and should be targeted in therapeutic efforts against MDPV overdose and abuse. U.S. Government work not protected by U.S. copyright.

Age estimation in forensic sciences: Application of combined aspartic acid racemization and radiocarbon analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alkass, K; Buchholz, B A; Ohtani, S

Age determination of unknown human bodies is important in the setting of a crime investigation or a mass disaster, since the age at death, birth date and year of death, as well as gender, can guide investigators to the correct identity among a large number of possible matches. Traditional morphological methods used by anthropologists to determine age are often imprecise, whereas chemical analysis of tooth dentin, such as aspartic acid racemization has shown reproducible and more precise results. In this paper we analyze teeth from Swedish individuals using both aspartic acid racemization and radiocarbon methodologies. The rationale behind using radiocarbonmore » analysis is that above-ground testing of nuclear weapons during the cold war (1955-1963) caused an extreme increase in global levels of carbon-14 ({sup 14}C) which have been carefully recorded over time. Forty-four teeth from 41 individuals were analyzed using aspartic acid racemization analysis of tooth crown dentin or radiocarbon analysis of enamel and ten of these were split and subjected to both radiocarbon and racemization analysis. Combined analysis showed that the two methods correlated well (R2=0.66, p < 0.05). Radiocarbon analysis showed an excellent precision with an overall absolute error of 0.6 {+-} 04 years. Aspartic acid racemization also showed a good precision with an overall absolute error of 5.4 {+-} 4.2 years. Whereas radiocarbon analysis gives an estimated year of birth, racemization analysis indicates the chronological age of the individual at the time of death. We show how these methods in combination can also assist in the estimation of date of death of an unidentified victim. This strategy can be of significant assistance in forensic casework involving dead victim identification.« less

Synthesis, Properties, and Two-Dimensional Adsorption Characteristics of [6]Hexahelicene-7-carboxylic acid.

PubMed

van der Meijden, Maarten W; Balandina, Tatyana; Ivasenko, Oleksandr; De Feyter, Steven; Wurst, Klaus; Kellogg, Richard M

2016-10-04

A convergent synthesis of racemic [6]hexahelicene-7-carboxylic acid by cross-coupling of a bicyclic and a tricyclic component is described. A metal-catalyzed ring-closure is also a fundamental component of the synthetic approach. Scanning tunneling microscopy (STM) measurements of the racemate self-assembled on Au(111) at liquid-solid interface revealed the formation of ordered racemic 2D crystals. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Racemic versus l-epinephrine aerosol in the treatment of postextubation laryngeal edema: results from a prospective, randomized, double-blind study.

PubMed

Nutman, J; Brooks, L J; Deakins, K M; Baldesare, K K; Witte, M K; Reed, M D

1994-10-01

To determine whether any advantage exists using racemic epinephrine instead of the more potent and less expensive levo(1)-epinephrine in the treatment of postextubation laryngeal edema. Prospective, double-blind, randomized study. Pediatric intensive care unit in a university teaching hospital. Twenty-eight patients with stridor during the immediate postextubation period. After extubation, patients demonstrating clinically important stridor were randomized in a double-blind fashion to receive an aerosol containing either 2.25% racemic or 1% l-epinephrine. Heart rate, respiratory rate, blood pressure, and stridor score were determined at 20, 40, and 60 mins and 4 and 8 hrs after the initial aerosol administration. Patients in both groups demonstrated significant (p < .01) reductions in stridor score after aerosol administration. No significant differences were observed between treatment groups in improvement in stridor score or the number of subsequent aerosols required. Respiratory rate decreased significantly 40 and 60 mins after l-epinephrine but not after racemic epinephrine. No significant change in heart rate or blood pressure occurred after aerosol administration in either group. These data suggest that aerosolized l-epinephrine is as effective as aerosolized racemic epinephrine in the treatment of postextubation laryngeal edema without additional adverse side effects. When dosed appropriately, l-epinephrine is a less expensive and more widely available alternative to racemic epinephrine for the treatment of postextubation laryngeal edema.

Resveratrol, 4' Acetoxy Resveratrol, R-equol, Racemic Equol or S-equol as Cosmeceuticals to Improve Dermal Health.

PubMed

Lephart, Edwin D

2017-06-03

Phytochemicals are botanical compounds used in dermatology applications as cosmeceuticals to improve skin health. Resveratrol and equol are two of the best-known polyphenolic or phytoestrogens having similar chemical structures and some overlapping biological functions to 17β-estradiol. Human skin gene expression was reviewed for 28 different biomarkers when resveratrol, 4' acetoxy resveratrol (4AR), R -equol, racemic equol or S -equol were tested. Sirtuin 1 activator (SIRT 1) was stimulated by resveratrol and 4AR only. Resveratrol, R -equol and racemic equol were effective on the aging biomarkers proliferating cell nuclear factor (PCNA), nerve growth factor (NGF), 5α-reductase and the calcium binding proteins S100 A8 and A9. Racemic equol and 4AR displayed among the highest levels for the collagens, elastin and tissue inhibitor of the matrix metalloproteinase 1 (TIMP 1). S -equol displayed the lowest level of effectiveness compared to the other compounds. The 4AR analog was more effective compared to resveratrol by 1.6-fold. R -equol and racemic equol were almost equal in potency displaying greater inhibition vs. resveratrol or its 4' analog for the matrix metalloproteinases (MMPs), but among the inflammatory biomarkers, resveratrol, 4AR, R -equol and racemic equol displayed high inhibition. Thus, these cosmeceuticals display promise to improve dermal health; however, further study is warranted to understand how phytochemicals protect/enhance the skin.

Fe(III)-EDDHA and -EDDHMA sorption on Ca-montmorillonite, ferrihydrite, and peat.

PubMed

Hernández-Apaolaza, L; Lucena, J J

2001-11-01

The effectiveness of Fe chelates as Fe sources and carriers in soil can be severely limited by the adsorption of Fe chelates or chelating agents in the solid phase. To study this phenomenon, well-characterized peat, Ca-montmorillonite, and ferrihydrite were used as model compounds, and the adsorption of Fe-EDDHA and Fe-EDDHMA chelates were studied. Sorption isotherms for the meso and racemic isomers of these chelates on the soil materials are described. The variability of sorption with pH in peat and ferrihydrite was also determined because both have variable surface charge at different pH values. In montmorillonite, at low concentrations, the retention of Fe from the Fe-EDDHMA chelate is greater than the one of the Fe-EDDHA chelate. As well as the concentration increased, the inverse situation occurs. The behavior of both meso and racemic isomers of chelates in contact with Ca-montmorillonite is similar. The Fe-meso-EDDHA isomer was highly adsorbed on ferrihydrite, but the racemic isomer is not significantly retained by this oxide. For Fe-EDDHMA isomers, the racemic isomer was more retained by the oxide, but a small sorption of the racemic isomer was also observed. Results suggest that Fe-EDDHA chelates were more retained in peat than Fe-EDDHMA chelates. The most retained isomer of Fe-EDDHA was the meso isomer. For Fe-EDDHMA, the adsorption was very low for both racemic and meso isomers.

Cysteine Racemization on IgG Heavy and Light Chains

PubMed Central

Zhang, Qingchun; Flynn, Gregory C.

2013-01-01

Under basic pH conditions, the heavy chain 220-light chain 214 (H220-L214) disulfide bond, found in the flexible hinge region of an IgG1, can convert to a thioether. Similar conditions also result in racemization of the H220 cysteine. Here, we report that racemization occurs on both H220 and L214 on an IgG1 with a λ light chain (IgG1λ) but almost entirely on H220 of an IgGl with a κ light chain (IgG1κ) under similar conditions. Likewise, racemization was detected at significant levels on H220 and L214 on endogenous human IgG1λ but only at the H220 position on IgG1κ. Low but measurable levels of d-cysteines were found on IgG2 cysteines in the hinge region, both with monoclonal antibodies incubated under basic pH conditions and on antibodies isolated from human serum. A simplified reaction mechanism involving reversible β-elimination on the cysteine is presented that accounts for both base-catalyzed racemization and thioether formation at the hinge disulfide. PMID:24142697

Expeditious access to unprotected racemic pyroglutamic acids.

PubMed

Isaacson, Jerry; Gilley, Cynthia B; Kobayashi, Yoshihisa

2007-05-11

A series of biologically intriguing pyroglutamic acids were synthesized in racemic form by employing indole-isonitrile and ammonium acetate in the Ugi 4-center-3-component reaction of gamma-ketoacids.

Amino Acid Racemization and the Preservation of Ancient DNA

NASA Technical Reports Server (NTRS)

Poinar, Hendrik N.; Hoss, Matthias

1996-01-01

The extent of racemization of aspartic acid, alanine, and leucine provides criteria for assessing whether ancient tissue samples contain endogenous DNA. In samples in which the D/L ratio of aspartic acid exceeds 0.08, ancient DNA sequences could not be retrieved. Paleontological finds from which DNA sequences purportedly millions of years old have been reported show extensive racemization, and the amino acids present are mainly contaminates. An exception is the amino acids in some insects preserved in amber.

Amino acid racemization dating of fossil bones, I. inter-laboratory comparison of racemization measurements

USGS Publications Warehouse

Bada, J.L.; Hoopes, E.; Darling, D.; Dungworth, G.; Kessels, H.J.; Kvenvolden, K.A.; Blunt, D.J.

1979-01-01

Enantiomeric measurements for aspartic acid, glutamic acid, and alanine in twenty-one different fossil bone samples have been carried out by three different laboratories using different analytical methods. These inter-laboratory comparisons demonstrate that D/L aspartic acid measurements are highly reproducible, whereas the enantiomeric measurements for the other amino acids show a wide variation between the three laboratories. At present, aspartic acid measurements are the most suitable for racemization dating of bone because of their superior analytical precision. ?? 1979.

Development and optimization of a new synthetic process for lorcaserin.

PubMed

Cluzeau, Jérôme; Stavber, Gaj

2018-02-15

A two-step process to synthesize racemic lorcaserin was developed from 2-(4-chlorophenyl)ethanol via formation of bromide or tosylate derivatives. These derivatives were reacted with allylamine in neat conditions to provide pure N-(4-chlorophenethyl)allylammonium chloride. This compound was cyclized in neat conditions using aluminum or zinc chloride to give racemic lorcaserin. After resolution of enantiomers, the wrong enantiomer was racemized and recycled to give new R-lorcaserin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oxidative kinetic resolution of racemic alcohols catalyzed by chiral ferrocenyloxazolinylphosphine-ruthenium complexes.

PubMed

Nishibayashi, Yoshiaki; Yamauchi, Akiyoshi; Onodera, Gen; Uemura, Sakae

2003-07-25

Oxidative kinetic resolution of racemic secondary alcohols by using acetone as a hydrogen acceptor in the presence of a catalytic amount of [RuCl(2)(PPh(3))(ferrocenyloxazolinylphosphine)] (2) proceeds effectively to recover the corresponding alcohols in high yields with an excellent enantioselectivity. When 1-indanol is employed as a racemic alcohol, the oxidation proceeds quite smoothly even in the presence of 0.0025 mol % of the catalyst 2 to give an optically active 1-indanol in good yield with high enantioselectivity (up to 94% ee), where turnover frequency (TOF) exceeds 80,000 h(-1). From a practical viewpoint, the kinetic resolution is investigated in a large scale, optically pure (S)-1-indanol (75 g, 56% yield, >99% ee) being obtained from racemic 1-indanol (134 g) by employing this kinetic resolution method twice.

Resveratrol, 4′ Acetoxy Resveratrol, R-equol, Racemic Equol or S-equol as Cosmeceuticals to Improve Dermal Health

PubMed Central

Lephart, Edwin D.

2017-01-01

Phytochemicals are botanical compounds used in dermatology applications as cosmeceuticals to improve skin health. Resveratrol and equol are two of the best-known polyphenolic or phytoestrogens having similar chemical structures and some overlapping biological functions to 17β-estradiol. Human skin gene expression was reviewed for 28 different biomarkers when resveratrol, 4′ acetoxy resveratrol (4AR), R-equol, racemic equol or S-equol were tested. Sirtuin 1 activator (SIRT 1) was stimulated by resveratrol and 4AR only. Resveratrol, R-equol and racemic equol were effective on the aging biomarkers proliferating cell nuclear factor (PCNA), nerve growth factor (NGF), 5α-reductase and the calcium binding proteins S100 A8 and A9. Racemic equol and 4AR displayed among the highest levels for the collagens, elastin and tissue inhibitor of the matrix metalloproteinase 1 (TIMP 1). S-equol displayed the lowest level of effectiveness compared to the other compounds. The 4AR analog was more effective compared to resveratrol by 1.6-fold. R-equol and racemic equol were almost equal in potency displaying greater inhibition vs. resveratrol or its 4′ analog for the matrix metalloproteinases (MMPs), but among the inflammatory biomarkers, resveratrol, 4AR, R-equol and racemic equol displayed high inhibition. Thus, these cosmeceuticals display promise to improve dermal health; however, further study is warranted to understand how phytochemicals protect/enhance the skin. PMID:28587197

Amino acids in modern and fossil woods

NASA Technical Reports Server (NTRS)

Lee, C.; Bada, J. L.; Peterson, E.

1976-01-01

The amino acid composition and the extent of racemization in several modern and fossil woods are reported. The method of analysis is described, and data are presented on the total amino acid concentration, the amino acid ratios, and the enantiomeric ratios in each sample. It is found that the amino acid concentration per gram of dry wood decreases with age of the sample, that the extent of racemization increases with increasing age, and that the amounts of aspartic acid, threonine, and serine decrease relative to valine with increasing age. The relative racemization rates of amino acids in wood, bone, and aqueous solution are compared, and it is shown that racemization in wood is much slower than in bone or aqueous solution. Racemization results for woods from the Kalambo Falls area of Zambia are used to calculate a minimum age of 110,000 years for the transition between the Sangoan and Acheulian industries at that site. This result is shown to be consistent with numerous radiometric dates for older Acheulian sites in Africa and to compare well with geologically inferred dates for the beginning of the Eemian and the end of the Acheulian industry in southern Africa.

Pharmacokinetics of ketamine and norketamine enantiomers after racemic or S-ketamine IV bolus administration in dogs during sevoflurane anaesthesia.

PubMed

Romagnoli, Noemi; Bektas, Rima N; Kutter, Annette P; Barbarossa, Andrea; Roncada, Paola; Hartnack, Sonja; Bettschart-Wolfensberger, Regula

2017-06-01

The aims of this study were to measure plasma levels of R- and S-ketamine and their major metabolites R- and S-norketamine following single intravenous bolus administration of racemic or S-ketamine in sevoflurane anaesthetised dogs and to calculate the relevant pharmacokinetic profiles. Six adult healthy beagle dogs were used in the study. An intravenous bolus of 4mg/kg racemic ketamine (RS-KET) or 2mg/kg S-ketamine (S-KET) was administered, with a three-weeks washout period between treatments. Venous blood samples were collected at fixed times until 900min and R- and S-ketamine as well as R- and S-norketamine plasma levels determined by liquid chromatography coupled with tandem mass spectrometry. Cardiovascular parameters were recorded during the anaesthesia until 240min. All dogs recovered well from anaesthesia. No statistical differences between groups were detected in any cardiovascular parameter. The pharmacokinetics of S-ketamine did not differ when injected intravenously alone or as part of the racemic mixture in dogs anaesthetised with sevoflurane. Following racemic ketamine, the area under the curve of R-norketamine was statistically higher than the one of S-norketamine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age estimation of living Indian individuals based on aspartic acid racemization from tooth biopsy specimen

PubMed Central

Rastogi, Manu; Logani, Ajay; Shah, Naseem; Kumar, Abhishek; Arora, Saurabh

2017-01-01

Background: Age estimation in living individuals is imperative to amicably settle civil and criminal disputes. A biochemical method based on amino acid racemization was evaluated for age estimation of living Indian individuals. Design: Caries-free maxillary/mandibular premolar teeth (n = 90) were collected from participants with age proof documents and divided into predefined nine age groups. Materials and Methods: Dentine biopsy from the labial aspect of the tooth crown was taken with an indigenously developed microtrephine. The samples were processed and subjected to gas chromatography. Dextrorotatory:levorotatory ratios were calculated, and a regression equation was formulated. Results: Across all age groups, an error of 0 ± 4 years between protein racemization age and chronological age was observed. Conclusion: Aspartic acid racemization from dentine biopsy samples could be a viable and accurate technique for age estimation of living individuals who have attained a state of skeletal maturity. PMID:29263613

Age estimation by amino acid racemization in human teeth.

PubMed

Ohtani, Susumu; Yamamoto, Toshiharu

2010-11-01

When an unidentified body is found, it is essential to establish the personal identity of the body in addition to investigating the cause of death. Identification is one of the most important functions of forensic dentistry. Fingerprint, dental, and DNA analysis can be used to accurately identify a body. However, if no information is available for identification, age estimation can contribute to the resolution of a case. The authors have been using aspartic acid racemization rates in dentin (D-aspartic acid/L-aspartic acid: D/L Asp) as an index for age estimation and have obtained satisfactory results. We report five cases of age estimation using the racemization method. In all five cases, estimated ages were accurate within a range ±3 years. We conclude that the racemization method is a reliable and practical method for estimating age. © 2010 American Academy of Forensic Sciences.

Phosphine-Catalyzed Doubly Stereoconvergent γ-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected α,α-Disubstituted α-Amino Acid Derivatives.

PubMed

Kalek, Marcin; Fu, Gregory C

2015-07-29

Methods have recently been developed for the phosphine-catalyzed asymmetric γ-addition of nucleophiles to readily available allenoates and alkynoates to generate useful α,β-unsaturated carbonyl compounds that bear a stereogenic center in either the γ or the δ position (but not both) with high stereoselectivity. The utility of this approach would be enhanced considerably if the stereochemistry at both termini of the new bond could be controlled effectively. In this report, we describe the achievement of this objective, specifically, that a chiral phosphepine can catalyze the stereoconvergent γ-addition of a racemic nucleophile to a racemic electrophile; through the choice of an appropriate heterocycle as the nucleophilic partner, this new method enables the synthesis of protected α,α-disubstituted α-amino acid derivatives in good yield, diastereoselectivity, and enantioselectivity.

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

PubMed Central

Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

2010-01-01

Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted. PMID:21118921

Effect of raceme-localized supplemental light on soybean reproductive abscission

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myers, R.L.; Brun, W.A.; Brenner, M.L.

The percentage of soybean (Glycine max (L.) Merr.) reproductive structures that abscise is a potentially important yield factor. To better understand the involvement of light in the abscission of reproductive structures, a series of in vitro raceme-culture and growth-chamber experiments were conducted. In the in vitro raceme-culture experiments, racemes with four to six flowers at or past anthesis were excised from the soybean plant (genotype IX93-100), embedded in a complete nutrient, solid agar medium, and subjected to various light treatments. A series of three experiments indicated that the racemes contain a photoreceptor, possibly phytochrome, capable of regulating sucrose accumulation. Inmore » each of the growth chamber studies, supplemental light was supplied directly to individual soybean flowers via fiber optic light guides. The light source increased the photon flux to the flowers by 10-fold. The first growth chamber experiment showed that flowers receiving supplemental light were more intense sinks for /sup 14/C-sucrose than were controls (intensity value of 1.0 vs 0.4 x 10/sup -7/, intensity = (dps of flower/dps of raceme)/(kg dry wt of flower)). In a second study, 42% of flowers treated with supplemental light set pods, while only 26% of control flowers set pods. A third experiment showed that red supplemental light produced 55% fruit set, compared to 41% set for far-red light, and 35% for controls. These experiments indicate that both photoassimilate accumulation and abscission in young soybean reproductive structures may be regulated by light quality.« less

Fenoterol enantiomers do not possess beneficial therapeutic properties of their racemic mixture in the rat model of post myocardial infarction dilated cardiomyopathy.

PubMed

Ahmet, Ismayil; Turner, Tia; Lakatta, Edward G; Talan, Mark I

2012-04-01

A salutary effect of β(2) adrenergic receptor (AR) agonist, fenoterol has been demonstrated in a rat model of post-myocardial infarction (MI) dilated cardiomyopathy (DCM). Recent reports on single cardiomyocyte experiments suggested that out of two enantiomers, RR and SS, that constitute a racemic mixture of fenoterol, only RR-enantiomer is an active component that might be a promising new drug for treatment of chronic heart failure. The objective of this study was to compare the efficacy of the RR enantiomer of fenoterol with efficacy of racemic fenoterol, and SS, an inactive enantiomer, in whole animal experimental models of DCM. Two weeks after induction of MI by permanent ligation of the anterior descending coronary artery early cardiac remodeling and MI size were assessed via echocardiography and rats were divided into treatment groups. Treatment (placebo, racemic fenoterol, RR- or SS-enantiomers of fenoterol) continued for 6 months while progression of DCM was followed by serial echocardiography. Compared with untreated rats, rats treated with racemic fenoterol demonstrated previously described attenuation of LV remodeling, functional decline and the arrest of the MI expansion during the first 2 months of treatment. On the contrary, the treatment with either RR-, or with SS-enantiomers of fenoterol was completely ineffective. The conclusion drawn on the basis of previous experiments with single cardiomyocytes that RR-enantiomer of fenoterol represents an active component of racemic fenoterol and can be further investigated as a new drug for treatment of chronic heart failure was not confirmed in the whole animal model of DCM.

Racemization of aspartic acid and phenylalanine in the sweetener aspartame at 100 degrees C.

PubMed Central

Boehm, M F; Bada, J L

1984-01-01

The racemization half-lives (i.e., the time required to reach a D/L = 0.33) at pH 6.8 for aspartic acid and phenylalanine in the sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester) were determined to be 13 and 23 hours, respectively, at 100 degrees C. Racemization at this pH does not occur in aspartame but rather in its diketopiperazine decomposition product. Our results indicate that the use of aspartame to sweeten neutral pH foods and beverages that are then heated at elevated temperature could generate D-aspartic acid and D-phenylalanine. The nutritive consequences of these D-amino acids in the human diet are not well established, and thus aspartame should probably not be used as a sweetener when the exposure of neutral pH foods and beverages to elevated temperatures is required. At pH 4, a typical pH of most foods and beverages that might be sweetened with aspartame, the half-lives are 47 hours for aspartic acid and 1200 hours for phenylalanine at 100 degrees C. Racemization at pH 4 takes place in aspartame itself. Although the racemization rates at pH 4 are slow and no appreciable racemization of aspartic acid and phenylalanine should occur during the normal use of aspartame, some food and beverage components could conceivably act as catalysts. Additional studies are required to evaluate whether the use of aspartame as a sugar substitute might not in turn result in an increased human consumption of D-aspartic acid and D-phenylalanine. PMID:6591191

Enantiomer fractions of chlordane components in sediment from U.S. Geological Survey sites in lakes and rivers

USGS Publications Warehouse

Ulrich, E.M.; Foreman, W.T.; Van Metre, P.C.; Wilson, J.T.; Rounds, S.A.

2009-01-01

Spatial, temporal, and sediment-type trends in enantiomer signatures were evaluated for cis- and trans-chlordane (CC, TC) in archived core, suspended, and surficial-sediment samples from six lake, reservoir, and river sites across the United States. The enantiomer fractions (EFs) measured in these samples are in good agreement with those reported for sediment, soil, and air samples in previous studies. The chlordane EFs were generally close to the racemic value of 0.5, with CC values ranging from 0.493 to 0.527 (usually >0.5) and TC values from 0.463 to 0.53 (usually <0.5). EF changes with core depth were detected for TC and CC in some cores, with the most non-racemic values near the top of the core. Surficial and suspended sediments generally have EF values similar to the top core layers but are often more non-racemic, indicating that enantioselective degradation is occurring before soils are eroded and deposited into bottom sediments. We hypothesize that rapid losses (desorption or degradation) from suspended sediments of the more bioavailable chlordane fraction during transport and initial deposition could explain the apparent shift to more racemic EF values in surficial and top core sediments. Near racemic CC and TC in the core profiles suggest minimal alteration of chlordane from biotic degradation, unless it is via non-enantioselective processes. EF values for the heptachlor degradate, heptachlor epoxide (HEPX), determined in surficial sediments from one location only were always non-racemic (EF ??? 0.66), were indicative of substantial biotic processing, and followed reported EF trends.

An integrated experimental and computational approach for characterizing the kinetics and mechanism of triadimefon racemization.

EPA Science Inventory

Enantiomers of chiral molecules commonly exhibit differing pharmacokinetics and toxicities, which can introduce significant uncertainty when evaluating biological and environmental fates and potential risks to humans and the environment. However, racemization (the irreversible tr...

Additive free preparative chiral SFC separations of 2,2-dimethyl-3-aryl-propanoic acids.

PubMed

Wu, Dauh-Rurng; Yip, Shiuhang Henry; Li, Peng; Sun, Dawn; Kempson, James; Mathur, Arvind

2016-11-30

A series of racemic 2,2-dimethyl-3-aryl-propanoic acids were resolved by chiral supercritical fluid chromatography (SFC) without the use of an acidic additive, trifluoroacetic acid (TFA). The use of additive-free protic methanol as co-solvent in CO 2 was expanded to successfully resolve other series of carboxylic acid containing racemates. Large-scale SFC of racemic acid 4, 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanoic acid, in methanol without TFA as additive on both Chiralpak AD-H and Chiralcel OJ-H will be discussed, along with impact on throughput and solvent consumption. Investigation of co-solvent effect on peak sharpening of acid racemate 20, 2-(2-chloro-9-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanoic acid, without TFA further indicated that methanol in CO 2 provided improved peak shape compared with isopropanol (IPA) and acetonitrile. Finally, we discuss the resolution of basic aromatic chiral amines without the addition of basic additives such as diethylamine (DEA) and application of this protocol for the large-scale SFC separation of weakly basic indazole-containing racemate 14, methyl 3-(1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanoate, in methanol without DEA. Copyright © 2016 Elsevier B.V. All rights reserved.

Fenoterol Enantiomers do not Possess Beneficial Therapeutic Properties of Their Racemic Mixture in the Rat Model of Post Myocardial Infarction Dilated Cardiomyopathy

PubMed Central

Ahmet, Ismayil; Turner, Tia; Lakatta, Edward G.; Talan, Mark I.

2015-01-01

Purpose A salutary effect of β2 adrenergic receptor (AR) agonist, fenoterol has been demonstrated in a rat model of post-myocardial infarction (MI) dilated cardiomyopathy (DCM). Recent reports on single cardiomyocyte experiments suggested that out of two enantiomers, RR and SS, that constitute a racemic mixture of fenoterol, only RR-enantiomer is an active component that might be a promising new drug for treatment of chronic heart failure. The objective of this study was to compare the efficacy of the RR enantiomer of fenoterol with efficacy of racemic fenoterol, and SS, an inactive enantiomer, in whole animal experimental models of DCM. Methods Two weeks after induction of MI by permanent ligation of the anterior descending coronary artery early cardiac remodeling and MI size were assessed via echocardiography and rats were divided into treatment groups. Treatment (placebo, racemic fenoterol, RR- or SS-enantiomers of fenoterol) continued for 6 months while progression of DCM was followed by serial echocardiography. Results Compared with untreated rats, rats treated with racemic fenoterol demonstrated previously described attenuation of LV remodeling, functional decline and the arrest of the MI expansion during the first two months of treatment. On the contrary, the treatment with either RR-, or with SS-enantiomers of fenoterol was completely ineffective. Conclusion The conclusion drawn on the basis of previous experiments with single cardiomyocytes that RR-enantiomer of fenoterol represents an active component of racemic fenoterol and can be further investigated as a new drug for treatment of chronic heart failure was not confirmed in the whole animal model of DCM. PMID:22328006

Age Estimation in Forensic Sciences

PubMed Central

Alkass, Kanar; Buchholz, Bruce A.; Ohtani, Susumu; Yamamoto, Toshiharu; Druid, Henrik; Spalding, Kirsty L.

2010-01-01

Age determination of unknown human bodies is important in the setting of a crime investigation or a mass disaster because the age at death, birth date, and year of death as well as gender can guide investigators to the correct identity among a large number of possible matches. Traditional morphological methods used by anthropologists to determine age are often imprecise, whereas chemical analysis of tooth dentin, such as aspartic acid racemization, has shown reproducible and more precise results. In this study, we analyzed teeth from Swedish individuals using both aspartic acid racemization and radiocarbon methodologies. The rationale behind using radiocarbon analysis is that aboveground testing of nuclear weapons during the cold war (1955–1963) caused an extreme increase in global levels of carbon-14 (14C), which has been carefully recorded over time. Forty-four teeth from 41 individuals were analyzed using aspartic acid racemization analysis of tooth crown dentin or radiocarbon analysis of enamel, and 10 of these were split and subjected to both radiocarbon and racemization analysis. Combined analysis showed that the two methods correlated well (R2 = 0.66, p < 0.05). Radiocarbon analysis showed an excellent precision with an overall absolute error of 1.0 ± 0.6 years. Aspartic acid racemization also showed a good precision with an overall absolute error of 5.4 ± 4.2 years. Whereas radiocarbon analysis gives an estimated year of birth, racemization analysis indicates the chronological age of the individual at the time of death. We show how these methods in combination can also assist in the estimation of date of death of an unidentified victim. This strategy can be of significant assistance in forensic casework involving dead victim identification. PMID:19965905

Toxicity of Triadimefon Racemate and Enantiomers to Black Fly Larvae

EPA Science Inventory

Triadimefon is a conazole fungicide commonly used for commercial and agricultural fungal control on trees, ornamentals and fruits. It is a chiral compound, existing as R-(-) and S-(+) enantiomers and used as the racemate. This is of interest since the triadimefon enantiomers ca...

Determination of the X-ray structure of the snake venom protein omwaprin by total chemical synthesis and racemic protein crystallography.

PubMed

Banigan, James R; Mandal, Kalyaneswar; Sawaya, Michael R; Thammavongsa, Vilasak; Hendrickx, Antoni P A; Schneewind, Olaf; Yeates, Todd O; Kent, Stephen B H

2010-10-01

The 50-residue snake venom protein L-omwaprin and its enantiomer D-omwaprin were prepared by total chemical synthesis. Radial diffusion assays were performed against Bacillus megaterium and Bacillus anthracis; both L- and D-omwaprin showed antibacterial activity against B. megaterium. The native protein enantiomer, made of L-amino acids, failed to crystallize readily. However, when a racemic mixture containing equal amounts of L- and D-omwaprin was used, diffraction quality crystals were obtained. The racemic protein sample crystallized in the centrosymmetric space group P2(1)/c and its structure was determined at atomic resolution (1.33 A) by a combination of Patterson and direct methods based on the strong scattering from the sulfur atoms in the eight cysteine residues per protein. Racemic crystallography once again proved to be a valuable method for obtaining crystals of recalcitrant proteins and for determining high-resolution X-ray structures by direct methods.

Enantioselective hydrolysis of racemic styrene oxide and its substituted derivatives using newly-isolated Sphingopyxis sp. exhibiting a novel epoxide hydrolase activity.

PubMed

Woo, Jung-Hee; Lee, Eun Yeol

2014-02-01

(S)-Styrene oxide, (S)-2-chlorostyrene oxide (CSO), (S)-3-CSO and (S)-4-CSO with 99.9 %ee were obtained with a yield of 20.6, 39.3, 28.7 and 26.8 % from 4 mM corresponding racemic substrates using 10 mg cells of a newly-isolated Sphingopyxis sp. at pH 8.0 and 25 °C in 1 ml 100 mM Tris/HCl buffer after 420, 100, 120 and 55 min, respectively. For racemic 2CSO, well-known for one of the racemates that is difficult to obtained in enantiomerically pure form, (S)-2-CSO with 99.9 %ee, 39.3 % yield (theoretical yield 50 %) and enantiomeric ratio of 42.1 was obtained. The newly-isolated strain can thus be used as whole-cell biocatalyst in the production of various (S)-CSO with a chlorine group at different positions.

Chirality-dependent friction of bulk molecular solids.

PubMed

Yang, Dian; Cohen, Adam E

2014-08-26

We show that the solid-solid friction between bulk chiral molecular solids can depend on the relative chirality of the two materials. In menthol and 1-phenyl-1-butanol, heterochiral friction is smaller than homochiral friction, while in ibuprofen, heterochiral friction is larger. Chiral asymmetries in the coefficient of sliding friction vary with temperature and can be as large as 30%. In the three compounds tested, the sign of the difference between heterochiral and homochiral friction correlated with the sign of the difference in melting point between racemate (compound or conglomerate) and pure enantiomer. Menthol and ibuprofen each form a stable racemic compound, while 1-phenyl-1-butanol forms a racemic conglomerate. Thus, a difference between heterochiral and homochiral friction does not require the formation of a stable interfacial racemic compound. Measurements of chirality-dependent friction provide a unique means to distinguish the role of short-range intermolecular forces from all other sources of dissipation in the friction of bulk molecular solids.

Improvement of age estimation using amino acid racemization in a case of pink teeth.

PubMed

Ohtani, S; Yamada, Y; Yamamoto, I

1998-03-01

Age was estimated from pink teeth using racemization of dentinal aspartic acid. Materials for identification were two lower second premolars. The body was determined to be that of a 40-year-old man; however, the age of the decedent had been estimated to be 29 and 30 years by the conventional method and 30 years from findings in the oral cavity. To clarify the cause of this difference, the powdered teeth were further washed in 0.01 mol/L hydrochloric acid. The racemization ratio (D/L ratio) of ordinary white teeth from persons of known age was slightly lower than that before washing, whereas that of the teeth used for identification was higher than before washing. The calculated age of the decedent using the racemization ratio of his teeth was between 36 and 37 years. These results suggest that age estimated from pink teeth is probably underestimated, but a more accurate age estimate can be obtained after adequate washing.

Effectiveness of Iron Ethylenediamine-N,N'-bis(hydroxyphenylacetic) Acid (o,o-EDDHA/Fe3+) Formulations with Different Ratios of Meso and d,l-Racemic Isomers as Iron Fertilizers.

PubMed

Alcañiz, Sara; Jordá, Juana D; Cerdán, Mar

2017-01-18

Two o,o-EDDHA/Fe 3+ formulations (meso, 93.5% w/w of meso isomer; and d,l-racemic, 91.3% w/w of d,l-racemic mixture) were prepared, and their efficacy to avoid or to relieve iron deficiency in Fe-sufficient and Fe-deficient tomato plants grown on hydroponic solution was compared with that of the current o,o-EDDHA/Fe 3+ formulations (50% of meso and d,l-racemic isomers). The effectiveness of the three o,o-EDDHA/Fe 3+ formulations was different depending on the iron nutritional status of plants. The three o,o-EDDHA/Fe 3+ formulations tested were effective in preventing iron chlorosis in healthy plants. However, the higher the meso concentration in the formulations, the higher the effectiveness in the recovery of iron chlorotic plants from iron deficiency. Accordingly, o,o-EDDHA/Fe 3+ formulations rich in meso isomer are recommended in hydroponic systems.

Implications of Chirality of Drugs and Excipients in Physical Pharmacy.

NASA Astrophysics Data System (ADS)

Duddu, Sarma P.

1993-01-01

The interactions of enantiomers of a chiral drug with other chemical entities, which may lead to changes and stereoselective differences in the physicochemical properties of the drug, were investigated. The various interactions described below employed ephedrine, pseudoephedrine and some of their salts, and to a minor extent, propranolol hydrochloride. The interaction of ephedrinium or pseudoephedrinium with the achiral anion, salicylate, yielded crystalline salts with the notable exception of homochiral ephedrine. Racemic ephedrinium salicylate exists as a centrosymmetric crystal (P2_1/n) whereas racemic pseudoephedrinium salicylate is a mixture of homochiral crystals (P2 _1). The inability of ephedrinium to exist as a homochiral salicylate salt is attributed to a high energy conformation of the ephedrinium cation, following conformational analysis. Arising from conformationally favorable interactions, the crystallization of racemic ephedrinium salicylate from aqueous solutions was utilized to improve the enantiomeric purity of a partially resolved mixture of ephedrine from 60% to 82% in one crystallization step. Interaction of the opposite enantiomers of ephedrine and pseudoephedrine in the solid, liquid, solution and vapor state produced the respective racemic compounds. The formation of racemic ephedrine in the solid state as predominantly second order (k = 392 mol^{-1} hr^{-1}), probably mediated by the vapor phase. The formation of racemic pseudoephedrine was predominantly diffusion-controlled in the solid state via an intermediate non-crystalline phase. The interaction with traces of the opposite enantiomer during crystallization of (RS)-(-)-ephedrinium 2-naphthalenesulfonate and (SS)-(+)-pseudoephedrinium salicylate changed pharmaceutically important solid state properties, including dissolution rate. Uptake of the enantiomeric impurity was measured by a new, sensitive HPLC method. The enantiomeric impurity, at mole fractions <= 0.0027 greatly increased the lattice disorder, i.e. entropy, measured calorimetrically. The release of propranolol hydrochloride from a sustained-release matrix containing HPMC and racemic propranolol hydrochloride was stereoselective, though variable, suggesting a differential interaction of the two enantiomers with the hydrated chiral matrix. Thus, the interaction of a chiral drug with other chemical entities leads to significant, interpretable changes in the physicochemical properties of the drug, which may have important implications in the design and development of reliable and effective solid dosage forms.

Synthesis, Properties, and Two-Dimensional Adsorption Characteristics of 5-Amino[6]hexahelicene.

PubMed

van der Meijden, Maarten W; Gelens, Edith; Quirós, Natalia Murillo; Fuhr, Javier D; Gayone, J Esteban; Ascolani, Hugo; Wurst, Klaus; Lingenfelder, Magalí; Kellogg, Richard M

2016-01-22

A convergent synthesis of racemic 5-amino[6]hexahelicene is described. Cross-coupling reactions are used to assemble a pentacyclic framework, and a metal-catalyzed ring-closure comprises the final step. The enantiomers were separated by means of chromatography and the absolute configurations were assigned by comparison of the CD spectra with hexahelicene. The t1/2  value for racemization at 210 °C was approximately 1 hour. Scanning tunneling microscopy (STM) measurements were carried out on enantiopure and racemic samples of aminohelicene on Au(111) under ultrahigh vacuum (UHV) conditions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asymmetric synthesis of 5-arylcyclohexenones by rhodium(I)-catalyzed conjugate arylation of racemic 5-(trimethylsilyl)cyclohexenone with arylboronic acids.

PubMed

Chen, Qian; Kuriyama, Masami; Soeta, Takahiro; Hao, Xinyu; Yamada, Ken-ichi; Tomioka, Kiyoshi

2005-09-29

[reaction: see text] A catalytic asymmetric conjugate arylation of racemic 5-(trimethylsilyl)cyclohex-2-enone with arylboronic acids was catalyzed by 3 mol % chiral amidophosphane- or BINAP-Rh(I) in dioxane-water (10:1) to afford trans- and cis-3-aryl-5-(trimethylsilyl)cyclohexanones in high enantioselectivity. Dehydrosilylation of the product mixture with cupric chloride in DMF gave 5-arylcyclohex-2-enones with up to 93% ee in good yield. Enantiofacial selectivity with chiral phosphane-Rh(I) exceeds the trans-diastereoselectivity that is maintained in the achiral or racemic phosphane-Rh(I)-catalyzed conjugate arylation of 5-(trimethylsilyl)cyclohexenone.

Iridium-Catalyzed Kinetic Asymmetric Transformations of Racemic Allylic Benzoates

PubMed Central

Stanley, Levi M.; Bai, Chen; Ueda, Mitsuhiro; Hartwig, John F.

2010-01-01

Versatile methods for iridium-catalyzed, kinetic asymmetric substitution of racemic, branched allylic esters are reported. These reactions occur with a variety of aliphatic, aryl, and heteroaryl allylic benzoates to form the corresponding allylic substitution products in high yields (74–96%) with good to excellent enantioselectivity (84–98% ee) with a scope that encompasses a range of anionic carbon and heteroatom nucleophiles. These kinetic asymmetric processes occur with distinct stereochemical courses for racemic aliphatic and aromatic allylic benzoates, and the high reactivity of branched allylic benzoates enables enantioselective allylic substitutions that are slow or poorly selective with linear allylic electrophiles. PMID:20552969

Achiral-to-chiral transition in benzil solidification: analogies with racemic conglomerates systems showing deracemization.

PubMed

El-Hachemi, Zoubir; Arteaga, Oriol; Canillas, Adolf; Crusats, Joaquim; Sorrenti, Alessandro; Veintemillas-Verdaguer, Sabino; Ribo, Josep M

2013-07-01

Experimental results show that benzil (1,2-diphenyl-1,2-ethanedione), an achiral compound that crystallizes as a racemic conglomerate, yields by solidification polycrystalline scalemic mixtures of high enantiomeric excesses. These results are related to those previously reported in this type of compounds on deracemizations of racemic mixtures of crystal enantiomorphs obtained by wet grinding. However, the present results strongly suggest that these experiments cannot be explained without taking into account chiral recognition interactions at the level of precritical clusters. The conditions that would define a general thermodynamic scenario for such deracemizations are discussed. © 2013 Wiley Periodicals, Inc.

The Formation of Racemic Amino Acids by UV Photolysis of Interstellar Ice Analogs

NASA Technical Reports Server (NTRS)

Bernstein, Max P.; Dworkin, Jason P.; Sandford, Scott A.; Cooper, George; Allamandola, Louis J.; DeVincenzi, Donald (Technical Monitor)

2001-01-01

Small biologically relevant organic molecules including the amino acids glycine, alanine, and marine were formed in the laboratory by the UV (Ultraviolet) photolysis of realistic interstellar ice analogs, composed primarily of H2O, and including CH3OH, NH3, and HCN, under interstellar conditions. N-formyl glycine, cycloserine (4-amino-3-isoxazolidinone), and glycerol were detected before hydrolysis, and glycine, racemic alanine, racemic marine, glycerol, ethanolamine, and glyceric acid were found after hydrolysis. This suggests that some meteoritic amino acids (and other molecules) may be the direct result of interstellar ice photochemistry, expanding the current paradigm that they formed by reactions in liquid water on meteorite parent bodies.

Racemization of amino acids in fossil bones and teeth from the Olduvai Gorge region, Tanzania, East Africa

NASA Astrophysics Data System (ADS)

Bada, Jeffrey L.

1981-10-01

Investigation of amino acid racemization in fossil bones and teeth from the Olduvai Gorge region, Tanzania, indicates that aspartic acid racemization can be used to date samples which are less than ˜80,000-100,000 years old in this area. In older samples, significant secondary aspartic acid is apparently present and thus these samples have lower than expectedD/L aspartic acid ratios. Isoleucine in older samples, however, is apparently syngenetic with the samples, so the epimerization of isoleucine to alloisoleucine can be used with certain limitations to date fossil bones and teeth from the older stratigraphic sections in the Olduvai region.

The even-handed approach: strategies for the deployment of racemic chiral catalysts.

PubMed

Evans, Louise A; Hodnett, Neil S; Lloyd-Jones, Guy C

2012-02-13

Asymmetric catalysis is predominantly associated with the use of enantiomerically pure chiral ligands and catalysts. Although racemic chiral catalysts have been employed quite extensively in polymerization, their utility in mainstream organic synthesis and catalyst development has arguably been rather overlooked. This Minireview collates various themes for the strategic application of racemic ligands and catalysts, ranging from the estimation of selectivity and determination of enantiomeric excess, through to control of regio- and stereochemical outcomes, and mechanistic studies. What emerges is a clear picture that, in isolation or in concert with enantiopure catalysts, the "even-handed" approach has much to offer. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biosynthesis of (R)-phenyl-1,2-ethanediol from racemic styrene oxide by using bacterial and marine fish epoxide hydrolases.

PubMed

Kim, Hee Sook; Lee, Ok Kyung; Hwang, Seungha; Kim, Beum Jun; Lee, Eun Yeol

2008-01-01

Enantio-convergent hydrolysis of racemic styrene oxides was achieved to prepare enantiopure (R)-phenyl-1,2-ethanediol by using two recombinant epoxide hydrolases (EHs) of a bacterium, Caulobacter crescentus, and a marine fish, Mugil cephalus. The recombinant C. crescentus EH primarily attacked the benzylic carbon of (S)-styrene oxide, while the M. cephalus EH preferentially attacked the terminal carbon of (R)-styrene oxide, thus leading to the formation of (R)-phenyl-1,2-ethanediol as the main product. (R)-Phenyl-1,2-ethanediol was obtained with 90% enantiomeric excess and yield as high as 94% from 50 mM racemic styrene oxides in a one-pot process.

Amino acid racemization in amber-entombed insects: implications for DNA preservation

NASA Technical Reports Server (NTRS)

Bada, J. L.; Wang, X. S.; Poinar, H. N.; Paabo, S.; Poinar, G. O.

1994-01-01

DNA depurination and amino acid racemization take place at similar rates in aqueous solution at neutral pH. This relationship suggests that amino acid racemization may be useful in accessing the extent of DNA chain breakage in ancient biological remains. To test this suggestion, we have investigated the amino acids in insects entombed in fossilized tree resins ranging in age from <100 years to 130 million years. The amino acids present in 40 to 130 million year old amber-entombed insects resemble those in a modern fly and are probably the most ancient, unaltered amino acids found so far on Earth. In comparison to other geochemical environments on the surface of the Earth, the amino acid racemization rate in amber insect inclusions is retarded by a factor of >10(4). These results suggest that in amber insect inclusions DNA depurination rates would also likely be retarded in comparison to aqueous solution measurements, and thus DNA fragments containing many hundreds of base pairs should be preserved. This conclusion is consistent with the reported successful retrieval of DNA sequences from amber-entombed organisms.

Concentration variations of amino acids in mammalian fossils: effects of diagenesis and the implications for amino acid racemization analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blackwell, B.; Rutter, N.W.

Detailed amino acid analysis of bones, teeth, and antler from several mammal species have shown that concentrations of several amino acids can be related to three factors: type of material analyzed, diagenetic alteration of the material, and relative age of the fossil. Concentrations of several amino acids are significantly different in enamel compared to those of dentine or cement. This can be used to check that no contamination of one material by another has occurred, which is critical for using the data for amino acid dating, since all three materials have different racemization rates for some acids. With increased inmore » growth of secondary minerals, generally reduced amino acid concentrations are observed. Interacid ratios and concentrations vary significantly the norms expected for the type of material with increasing degrees of alteration. These effects can be linked to abnormal racemization ratios observed in the same samples. Therefore, abnormal concentrations and/or interacid ratios can be used to detect samples in which the D/L amino acid ratios otherwise appear normal, thereby insuring better accuracy of amino acid racemization analysis. For unaltered fossils, with increasing sample age regardless the type of material, some amino acids steadily degrade, while others actually increase in concentration initially due to their generation as by-products of decay. Preliminary studies indicate that this progressive alteration can used to complement racemization data for determining relative stratigraphic sequences.« less

Racemization of the Succinimide Intermediate Formed in Proteins and Peptides: A Computational Study of the Mechanism Catalyzed by Dihydrogen Phosphate Ion.

PubMed

Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi

2016-10-10

In proteins and peptides, d-aspartic acid (d-Asp) and d-β-Asp residues can be spontaneously formed via racemization of the succinimide intermediate formed from l-Asp and l-asparagine (l-Asn) residues. These biologically uncommon amino acid residues are known to have relevance to aging and pathologies. Although nonenzymatic, the succinimide racemization will not occur without a catalyst at room or biological temperature. In the present study, we computationally investigated the mechanism of succinimide racemization catalyzed by dihydrogen phosphate ion, H₂PO₄ - , by B3LYP/6-31+G(d,p) density functional theory calculations, using a model compound in which an aminosuccinyl (Asu) residue is capped with acetyl (Ace) and NCH₃ (Nme) groups on the N- and C-termini, respectively (Ace-Asu-Nme). It was shown that an H₂PO₄ - ion can catalyze the enolization of the H α -C α -C=O portion of the Asu residue by acting as a proton-transfer mediator. The resulting complex between the enol form and H₂PO₄ - corresponds to a very flat intermediate region on the potential energy surface lying between the initial reactant complex and its mirror-image geometry. The calculated activation barrier (18.8 kcal·mol -1 after corrections for the zero-point energy and the Gibbs energy of hydration) for the enolization was consistent with the experimental activation energies of Asp racemization.

Positionally isomeric organic gelators: structure-gelation study, racemic versus enantiomeric gelators, and solvation effects.

PubMed

Caplar, Vesna; Frkanec, Leo; Sijaković Vujicić, Natasa; Zinić, Mladen

2010-03-08

Low molecular weight gelator molecules consisting of aliphatic acid, amino acid (phenylglycine), and omega-aminoaliphatic acid units have been designed. By varying the number of methylene units in the aliphatic and omega-aminoaliphatic acid chains, as defined by descriptors m and n, respectively, a series of positionally isomeric gelators having different positions of the peptidic hydrogen-bonding unit within the gelator molecule has been obtained. The gelation properties of the positional isomers have been determined in relation to a defined set of twenty solvents of different structure and polarity and analyzed in terms of gelator versatility (G(ver)) and effectiveness (G(eff)). The results of gelation tests have shown that simple synthetic optimizations of a "lead gelator molecule" by variation of m and n, end-group polarity (carboxylic acid versus sodium carboxylate), and stereochemistry (racemate versus optically pure form) allowed the identification of gelators with tremendously improved versatility (G(ver)) and effectiveness (G(eff)). Dramatic differences in G(eff) values of up to 70 times could be observed between pure racemate/enantiomer pairs of some gelators, which were manifested even in the gelation of very similar solvents such as isomeric xylenes. The combined results of spectroscopic ((1)H NMR, FTIR), electron microscopy (TEM), and X-ray diffraction studies suggest similar organization of the positionally isomeric gelators at the molecular level, comprising parallel beta-sheet hydrogen-bonded primary assemblies that form inversed bilayers at a higher organizational level. Differential scanning calorimetry (DSC) studies of selected enantiomer/racemate gelator pairs and their o- and p-xylene gels revealed the simultaneous presence of different polymorphs in the racemate gels. The increased gelation effectiveness of the racemate compared to that of the single enantiomer is most likely a consequence of its spontaneous resolution into enantiomeric bilayers and their subsequent organization into polymorphic aggregates of different energy. The latter determine the gel fiber thickness and solvent immobilization capacity of the formed gel network.

Amino Acid Enantiomeric Ratios in Biogeochemistry: Complications and Opportunities

NASA Astrophysics Data System (ADS)

McDonald, G. D.; Sun, H. J.; Tsapin, A. I.

2003-12-01

Amino acid enantiomeric ratios have been used for many years as an indicator of the process of racemization, and thus as a method to determine the age of biological samples such as bones, shells, and teeth. Dating biological samples by this method relies on an accurate knowledge of the environmental temperatures the sample has experienced, and the racemization kinetic parameters in the sample matrix. In some environments, where an independent dating method such as radiocarbon is available, the observed amino acid D/L ratios are found to be either higher or lower than those expected due to racemization alone. The observed D/L ratios in these cases can be clues to biogeochemical processes operating in addition to, or in place of, chemical racemization. In Siberian permafrost (Brinton et al. 2002, Astrobiology 2, 77) we have found D/L ratios lower than expected, which we have interpreted as evidence for low-level D-amino acid metabolism and recycling in microorganisms previously thought to be metabolically dormant. In microbially-colonized Antarctic Dry Valley sandstones (McDonald and Sun 2002, Eos Trans. AGU 83, Fall Meet. Suppl., Abstract B11A-0720) we have found D/L ratios higher than can be accounted for by racemization alone, most likely due to the accumulation of D-amino-acid-containing peptidoglycan material from multiple bacterial generations. D/L profiles in polar ices and in ice-covered lakes (Tsapin et al. 2002, Astrobiology 2, 632) can be used to indicate the sources and histories of water or ice samples. Multiple biological and biogeochemical processes may complicate the interpretation of amino acid enantiomeric excesses in both terrestrial and extraterrestrial samples; however, amino acid racemization remains a useful tool in biogeochemistry and astrobiology. With a good knowledge of the environmental history of samples, amino acid D/L profiles can be used as a window into processes such as molecular repair and biomass turnover that are difficult to detect by other means, particularly over geological time scales.

Racemization of Isobornyl Chloride via Carbocations: A Nonclassical Look at a Classic Mechanism

ERIC Educational Resources Information Center

Rzepa, Henry S.; Allan, Charlotte S. M.

2010-01-01

Our understanding of carbonium ions as intermediates in chemical reaction mechanisms derives from the early work of Julius Stieglitz and the more famous Hans Meerwein, the latter studying the racemization of isobornyl chloride when treated with Lewis acids. This review analyzes how key mechanistic concepts for this reaction evolved and gives the…

High-yield conversion of (R)-2-octanol from the corresponding racemate by stereoinversion using Candida rugosa.

PubMed

Nie, Yao; Xu, Yan; Qing Mu, Xiao; Tang, Yan; Jiang, Juan; Hao Sun, Zhi

2005-01-01

Whole cells of Candida rugosa catalyzed the conversion of (R)-2-octanol from the corresponding racemate with the optical purity of 97% e.e. and yield of 92% in 10 h. The product was formed through a stereoinversion involving enantioselective oxidation and asymmetric reduction with 2-octanone as the intermediate.

Cocrystallization out of the blue: DL-mandelic acid/ethyl-DL-mandelate cocrystal

NASA Astrophysics Data System (ADS)

Tumanova, Natalia; Payen, Ricky; Springuel, Géraldine; Norberg, Bernadette; Robeyns, Koen; Le Duff, Cécile; Wouters, Johan; Leyssens, Tom

2017-01-01

This work focuses on a peculiar behavior of racemic mandelic acid in ethanol solution. Dissolution of racemic mandelic acid in ethanol followed by evaporation to dryness results in a DL-mandelic acid/ethyl-DL-mandelate cocrystal. This behavior indicates that racemic mandelic acid tends not only to transform into an ester in ethanol, but also to cocrystallize with untransformed acid molecules. Cocrystal formation for mandelic acid in ethanol was found to be reproducible under various conditions. DL-tropic acid and DL-phenyllactic acid that contain similar functional groups and that were tested as well, on the other hand, showed no cocrystal formation: DL-phenyllactic acid partly converted into an ester, whereas DL-tropic acid mostly recrystallized.

Enantioselective oxidation of racemic lactic acid to D-lactic acid and pyruvic acid by Pseudomonas stutzeri SDM.

PubMed

Gao, Chao; Qiu, Jianhua; Li, Jingchen; Ma, Cuiqing; Tang, Hongzhi; Xu, Ping

2009-03-01

D-lactic acid and pyruvic acid are two important building block intermediates. Production of D-lactic acid and pyruvic acid from racemic lactic acid by biotransformation is economically interesting. Biocatalyst prepared from 9 g dry cell wt l(-1) of Pseudomonas stutzeri SDM could catalyze 45.00 g l(-1)DL-lactic acid into 25.23 g l(-1)D-lactic acid and 19.70 g l(-1) pyruvic acid in 10h. Using a simple ion exchange process, D-lactic acid and pyruvic acid were effectively separated from the biotransformation system. Co-production of d-lactic acid and pyruvic acid by enantioselective oxidation of racemic lactic acid is technically feasible.

Racemic resolution of some DL-amino acids using Aspergillus fumigatus L-amino acid oxidase.

PubMed

Singh, Susmita; Gogoi, Binod K; Bezbaruah, Rajib L

2011-07-01

The ability of Aspergillus fumigatus L-amino acid oxidase (L-aao) to cause the resolution of racemic mixtures of DL-amino acids was investigated with DL-alanine, DL-phenylalanine, DL-tyrosine, and DL-aspartic acid. A chiral column, Crownpak CR+ was used for the analysis of the amino acids. The enzyme was able to cause the resolution of the three DL-amino acids resulting in the production of optically pure D-alanine (100% resolution), D-phenylalanine (80.2%), and D-tyrosine (84.1%), respectively. The optically pure D-amino acids have many uses and thus can be exploited industrially. This is the first report of the use of A. fumigatus L: -amino acid oxidase for racemic resolution of DL-amino acids.

Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs

PubMed Central

Jacques, Vincent; Czarnik, Anthony W.; Judge, Thomas M.; Van der Ploeg, Lex H. T.; DeWitt, Sheila H.

2015-01-01

Therapeutics developed and sold as racemates can exhibit a limited therapeutic index because of side effects resulting from the undesired enantiomer (distomer) and/or its metabolites, which at times, forces researchers to abandon valuable scaffolds. Therefore, most chiral drugs are developed as single enantiomers. Unfortunately, the development of some chirally pure drug molecules is hampered by rapid in vivo racemization. The class of compounds known as immunomodulatory drugs derived from thalidomide is developed and sold as racemates because of racemization at the chiral center of the 3-aminoglutarimide moiety. Herein, we show that replacement of the exchangeable hydrogen at the chiral center with deuterium allows the stabilization and testing of individual enantiomers for two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors. Using “deuterium-enabled chiral switching” (DECS), in vitro antiinflammatory differences of up to 20-fold are observed between the deuterium-stabilized enantiomers. In vivo, the exposure is dramatically increased for each enantiomer while they retain similar pharmacokinetics. Furthermore, the single deuterated enantiomers related to CC-122 exhibit profoundly different in vivo responses in an NCI-H929 myeloma xenograft model. The (−)-deuterated enantiomer is antitumorigenic, whereas the (+)-deuterated enantiomer has little to no effect on tumor growth. The ability to stabilize and differentiate enantiomers by DECS opens up a vast window of opportunity to characterize the class effects of thalidomide analogs and improve on the therapeutic promise of other racemic compounds, including the development of safer therapeutics and the discovery of new mechanisms and clinical applications for existing therapeutics. PMID:25775521

Racemic crystals of trolox derivatives compared to their chiral counterparts: Structural studies using solid-state NMR, DFT calculations and X-ray diffraction

NASA Astrophysics Data System (ADS)

Wałejko, P.; Paradowska, K.; Szeleszczuk, Ł.; Wojtulewski, S.; Baj, A.

2018-03-01

Trolox C (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) is a water-soluble vitamin E analogue that is available in enantiomeric forms R or S. Enantiomerically pure Trolox 1, its derivatives 2, 3 (R and S enantiomers) and racemic forms 1-3 were studied using solid-state 13C cross-polarisation (CP) magic angle spinning (MAS) NMR (13C CPMAS NMR). Gauge-including projector-augmented wave density functional theory (GIPAW DFT) calculations of the shielding constants supported the assignment of 13C resonances in the solid-state NMR spectra. For the 13C CPMAS NMR spectra of 1, resonances of pure enantiomers were significantly broader than those of the racemic R/S form. In order to explain these effects, five of the available crystal structures were analysed (1R/S, 3R/S, 2S and the newly measured 2R/S and 3S). Cyclic dimers with one R and one S enantiomer linked by two OHsbnd Odbnd C2b hydrogen bonds were formed in 1R/S. Similar hydrogen-bonded dimers were present in 3S but not in 3R/S, in which interactions are water-mediated. A comparison of X-ray diffraction, CPMAS NMR data and the DFT GIPAW calculations of racemic forms and pure enantiomers was conducted for the first time. Our results, particularly the solid-state NMR data, were discussed in relation to Wallach's rule, that the racemic crystal appears as more ordered than its chiral counterpart.

Chiral Polymers.

DTIC Science & Technology

1984-10-01

regardless of the method of polymerization. The styrene-bead copolymers were packed in HPLC columns, but none were especiall, effective in separating...enantiomers in a racemic mixture. The chiral butyrolactone polymer was coated on silica, but this material did not effect resolution of racemic mixtures in an...been effected utilizing chiral oxazolines3 prompted the initial efforts to synthesize various chiral 2-vinyl- oxazoline monomers for incorporation

Chemical synthesis of perfectly isotactic and high melting bacterial poly(3-hydroxybutyrate) from bio-sourced racemic cyclic diolide.

PubMed

Tang, Xiaoyan; Chen, Eugene Y-X

2018-06-11

Bacterial poly(3-hydroxybutyrate) (P3HB) is a perfectly isotactic, crystalline material possessing properties suitable for substituting petroleum plastics, but high costs and low volumes of its production are impractical for commodity applications. The chemical synthesis of P3HB via ring-opening polymerization (ROP) of racemic β-butyrolactone has attracted intensive efforts since the 1960s, but not yet produced P3HB with high isotacticity and molecular weight. Here, we report a route utilizing racemic cyclic diolide (rac-DL) derived from bio-sourced succinate. With stereoselective racemic catalysts, the ROP of rac-DL under ambient conditions produces rapidly P3HB with perfect isotacticity ([mm] > 99%), high melting temperature (T m  = 171 °C), and high molecular weight (M n  = 1.54 × 10 5  g mol -1 , Đ = 1.01). With enantiomeric catalysts, kinetic resolution polymerizations of rac-DL automatically stops at 50% conversion and yields enantiopure (R,R)-DL and (S,S)-DL with >99% e.e. and the corresponding poly[(S)-3HB] and poly[(R)-3HB] with high T m  = 175 °C.

Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

PubMed Central

Uchida, Ryota; Okamoto, Hinako; Ikuta, Naoko; Terao, Keiji; Hirota, Takashi

2015-01-01

α-Lipoic acid (LA) is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA) mixed at the ratio of 50:50) to rats, RLA showed higher plasma concentration than SLA, and its area under the plasma concentration-time curve from time zero to the last (AUC) was significantly about 1.26 times higher than that of SLA. However, after intravenous administration of the racemic mixture, the pharmacokinetic profiles, initial concentration (C0), AUC, and half-life (T1/2) of the enantiomers were not significantly different. After oral and intraduodenal administration of the racemic mixture to pyrolus-ligated rats, the AUCs of RLA were significantly about 1.24 and 1.32 times higher than that of SLA, respectively. In addition, after intraportal administration the AUC of RLA was significantly 1.16 times higher than that of SLA. In conclusion, the enantioselective pharmacokinetics of LA in rats arose from the fraction absorbed multiplied by gastrointestinal availability (FaFg) and hepatic availability (Fh), and not from the total clearance. PMID:26402669

Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats.

PubMed

Uchida, Ryota; Okamoto, Hinako; Ikuta, Naoko; Terao, Keiji; Hirota, Takashi

2015-09-21

α-Lipoic acid (LA) is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA) mixed at the ratio of 50:50) to rats, RLA showed higher plasma concentration than SLA, and its area under the plasma concentration-time curve from time zero to the last (AUC) was significantly about 1.26 times higher than that of SLA. However, after intravenous administration of the racemic mixture, the pharmacokinetic profiles, initial concentration (C₀), AUC, and half-life (T1/2) of the enantiomers were not significantly different. After oral and intraduodenal administration of the racemic mixture to pyrolus-ligated rats, the AUCs of RLA were significantly about 1.24 and 1.32 times higher than that of SLA, respectively. In addition, after intraportal administration the AUC of RLA was significantly 1.16 times higher than that of SLA. In conclusion, the enantioselective pharmacokinetics of LA in rats arose from the fraction absorbed multiplied by gastrointestinal availability (FaFg) and hepatic availability (Fh), and not from the total clearance.

Synthesis, characterization and crystal structure of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid

NASA Astrophysics Data System (ADS)

Muche, Simon; Müller, Matthias; Hołyńska, Małgorzata

2018-03-01

The condensation reaction of ortho-vanillin and L-cysteine leads to formation of a racemic mixture of (2RS,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid and not, as reported in the available literature, to a Schiff base. The racemic mixture was fully characterized by 1D and 2D NMR techniques, ESI-MS and X-ray diffraction. Addition of ZnCl2 led to formation of crystals in form of colorless needles, suitable for X-ray diffraction studies. The measured crystals were identified as the diastereomer (2R,4R)-2-(2-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid 1. The bulk material is racemic. Thiazolidine exists as zwitterion in solid state, as indicated by the crystal structure.

Dynamic Kinetic Resolution of Allylic Sulfoxides by Rh-Catalyzed Hydrogenation: A Combined Theoretical and Experimental Mechanistic Study

PubMed Central

Dornan, Peter K.; Kou, Kevin G. M.; Houk, K. N.; Dong, Vy M.

2014-01-01

A dynamic kinetic resolution (DKR) of allylic sulfoxides has been demonstrated by combining the Mislow [2,3]-sigmatropic rearrangement with catalytic asymmetric hydrogenation. The efficiency of our DKR was optimized by using low pressures of hydrogen gas to decrease the rate of hydrogenation relative to the rate of sigmatropic rearrangement. Kinetic studies reveal that the rhodium complex acts as a dual-role catalyst and accelerates the substrate racemization while catalyzing olefin hydrogenation. Scrambling experiments and theoretical modeling support a novel mode of sulfoxide racemization which occurs via a rhodium π-allyl intermediate in polar solvents. In non-polar solvents, however, the substrate racemization is primarily uncatalyzed. Computational studies suggest that the sulfoxide binds to rhodium via O–coordination throughout the catalytic cycle for hydrogenation. PMID:24350903

Total chemical synthesis and X-ray structure of kaliotoxin by racemic protein crystallography.

PubMed

Pentelute, Brad L; Mandal, Kalyaneswar; Gates, Zachary P; Sawaya, Michael R; Yeates, Todd O; Kent, Stephen B H

2010-11-21

Here we report the total synthesis of kaliotoxin by 'one pot' native chemical ligation of three synthetic peptides. A racemic mixture of D- and L-kaliotoxin synthetic protein molecules gave crystals in the centrosymmetric space group P1 that diffracted to atomic-resolution (0.95 Å), enabling the X-ray structure of kaliotoxin to be determined by direct methods.

Calibration of amino acid racemization (AAR) kinetics in United States mid-Atlantic Coastal Plain Quaternary mollusks using 87Sr/ 86Sr analyses: Evaluation of kinetic models and estimation of regional Late Pleistocene temperature history

USGS Publications Warehouse

Wehmiller, J.F.; Harris, W.B.; Boutin, B.S.; Farrell, K.M.

2012-01-01

The use of amino acid racemization (AAR) for estimating ages of Quaternary fossils usually requires a combination of kinetic and effective temperature modeling or independent age calibration of analyzed samples. Because of limited availability of calibration samples, age estimates are often based on model extrapolations from single calibration points over wide ranges of D/L values. Here we present paired AAR and 87Sr/ 86Sr results for Pleistocene mollusks from the North Carolina Coastal Plain, USA. 87Sr/ 86Sr age estimates, derived from the lookup table of McArthur et al. [McArthur, J.M., Howarth, R.J., Bailey, T.R., 2001. Strontium isotopic stratigraphy: LOWESS version 3: best fit to the marine Sr-isotopic curve for 0-509 Ma and accompanying Look-up table for deriving numerical age. Journal of Geology 109, 155-169], provide independent age calibration over the full range of amino acid D/L values, thereby allowing comparisons of alternative kinetic models for seven amino acids. The often-used parabolic kinetic model is found to be insufficient to explain the pattern of racemization, although the kinetic pathways for valine racemization and isoleucine epimerization can be closely approximated with this function. Logarithmic and power law regressions more accurately represent the racemization pathways for all amino acids. The reliability of a non-linear model for leucine racemization, developed and refined over the past 20 years, is confirmed by the 87Sr/ 86Sr age results. This age model indicates that the subsurface record (up to 80m thick) of the North Carolina Coastal Plain spans the entire Quaternary, back to ???2.5Ma. The calibrated kinetics derived from this age model yield an estimate of the effective temperature for the study region of 11??2??C., from which we estimate full glacial (Last Glacial Maximum - LGM) temperatures for the region on the order of 7-10??C cooler than present. These temperatures compare favorably with independent paleoclimate information for the region. ?? 2011 Elsevier B.V.

Stereochemistry and neuropharmacology of a 'bath salt' cathinone: S-enantiomer of mephedrone reduces cocaine-induced reward and withdrawal in invertebrates.

PubMed

Vouga, Alexandre; Gregg, Ryan A; Haidery, Maryah; Ramnath, Anita; Al-Hassani, Hassan K; Tallarida, Christopher S; Grizzanti, David; Raffa, Robert B; Smith, Garry R; Reitz, Allen B; Rawls, Scott M

2015-04-01

Knowledge about the neuropharmacology of mephedrone (MEPH) applies primarily to the racemate, or street form of the drug, but not to its individual enantiomers. Here, through chemical isolation of MEPH enantiomers and subsequent behavioral characterization in established invertebrate (planarian) assays, we began separating adverse effects of MEPH from potential therapeutic actions. We first compared stereotypical and environmental place conditioning (EPC) effects of racemic MEPH, S-MEPH, and R-MEPH. Stereotypy was enhanced by acute treatment (100-1000 μM) with each compound; however, S-MEPH was less potent and efficacious than racemate and R-MEPH. Both R-MEPH (10, 100, 250 μM) and racemate (100 μM) produced EPC, but S-MEPH was ineffective at all concentrations (10-100 μM). After showing that S-MEPH lacked rewarding efficacy, we investigated its ability to alter three of cocaine's behavioral effects (EPC, withdrawal, and stereotypy). Cocaine (1 μM) produced EPC that was abolished when S-MEPH (100 μM) was administered after cocaine conditioning. Spontaneous withdrawal from chronic cocaine exposure caused a reduction in motility that was not evident during acute or continuous cocaine treatment but was attenuated by S-MEPH (100 μM) treatment during the cocaine abstinence interval. Acute stereotypy produced by 1 mM cocaine, nicotine or racemic MEPH was not affected by S-MEPH (10-250 μM). The present results obtained using planarian assays suggest that the R-enantiomer of MEPH is predominantly responsible for its stimulant and rewarding effects and the S-enantiomer is capable of antagonizing cocaine's addictive-like behaviors without producing rewarding effects of its own. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oligopeptides and copeptides of homochiral sequence, via beta-sheets, from mixtures of racemic alpha-amino acids, in a one-pot reaction in water; relevance to biochirogenesis.

PubMed

Illos, Roni A; Bisogno, Fabricio R; Clodic, Gilles; Bolbach, Gerard; Weissbuch, Isabelle; Lahav, Meir

2008-07-09

As part of our studies on the biochirogenesis of peptides of homochiral sequence during early evolution, the formation of oligopeptides composed of 14-24 residues of the same handedness in the polymerization of dl-leucine (Leu), dl-phenylalanine (Phe), and dl-valine (Val) in aqueous solutions, by activation with N, N'-carbonyldiimidazole and then initiation with a primary amine, in a one-pot reaction, was demonstrated by MALDI-TOF MS using deuterium enantio-labeled alpha-amino acids. The formation of long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of l-Leu with l-isoleucine (Ile) or l-Phe with l- (1) N-Me-histidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of l- + d-alpha-amino acids, the long oligopeptides were composed mainly from oligo- l-Leu and oligo- d-Ile in the first system and oligo- d-Phe in the second. Furthermore, in the polymerization of mixtures of hydrophobic racemic alpha-amino acids dl-Leu, dl-Val, and dl-Phe and with added racemic dl-alanine and dl-tyrosine, copeptides of homochiral sequences are most dominantly represented. Possible routes for a spontaneous "mirror-symmetry breaking" process of the racemic mixtures of homochiral peptides are presented.

Fe uptake from meso and D,L-racemic Fe(o,o-EDDHA) isomers by strategy I and II plants.

PubMed

Cerdán, Mar; Alcañiz, Sara; Juárez, Margarita; Jordá, Juana D; Bermúdez, Dolores

2006-02-22

One of the most efficient fertilizers to correct Fe deficiency in calcareous soils and waters with high bicarbonate content is based on ferric ethylenediamine-N,N'-bis(o-hydroxyphenylacetic) acid [Fe(o,o-EDDHA)]. Fe(o,o-EDDHA) forms two groups of geometric isomers known as meso and D,L-racemic. To determine the Fe uptake from meso and D,L-racemic Fe(o,o-EDDHA), four iron-efficient plants, two plants representative of strategy I (tomato and pepper) and two plants representative of strategy II (wheat and oats), were grown in hydroponic culture. Results indicated that strategy II plants took up iron from both Fe(o,o-EDDHA) isomers equally. However, strategy I plants took mainly the iron associated with the meso form (the lowest stability isomer).

Silica-Immobilized Enzyme Reactors

DTIC Science & Technology

2007-08-01

relief from the symptoms of inflammation and pain Silica-IMERs 10 and is the mode of action of drugs such as aspirin and ibuprofen .[61] Serotonin...supports and using the enantiomeric selectivity of the enzyme to resolve racemic mixtures.[100] Immobilization onto supports with various pore sizes and...activity (~37%) and used as a packed- bed IMER to catalyze the racemic resolution of (S)-ketoprofen from its constituent enantiomers . The optically pure (S

Chemo-enzymatic Baeyer-Villiger oxidation of 4-methylcyclohexanone via kinetic resolution of racemic carboxylic acids: direct access to enantioenriched lactone.

PubMed

Drożdż, Agnieszka; Chrobok, Anna

2016-01-21

A new method for the asymmetric chemo-enzymatic Baeyer-Villiger oxidation of prochiral 4-methylcyclohexanone to (R)-4-methylcaprolactone in the presence of (±)-4-methyloctanoic acid, Candida Antarctica lipase B and 30% aq. H2O2 has been developed. A mechanism for the asymmetric induction based on kinetic resolution of racemic carboxylic acids is proposed.

Ipsenol, ipsdienol, ethanol, and á-pinene: trap lure blend for Cerambycidae and Buprestidae (Coleoptera) in pine forests of eastern North America

Treesearch

D. R. Miller; C. M. Crowe; K. J. Dodds; L. D. Galligan; P. de Groot; E. R. Hoebeke; A. E. Mayfield; T. M. Poland; K. F. Raffa; J. D. Sweeney

2015-01-01

In 2007-2008, we examined the flight responses of wood-boring beetles (Coleoptera: Cerambycidae and Buprestidae) to multiple-funnel traps baited with the pine volatiles, ethanol, and apinene [85% (–)], and the bark beetle pheromones, racemic ipsenol and racemic ipsdienol. Experiments were conducted in mature pine stands in Canada (Ontario and New Brunswick) and the...

Age estimation based on aspartic acid racemization in human sclera.

PubMed

Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie

2016-01-01

Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.

A resolution approach of racemic phenylalanine with aqueous two-phase systems of chiral tropine ionic liquids.

PubMed

Wu, Haoran; Yao, Shun; Qian, Guofei; Yao, Tian; Song, Hang

2015-10-30

Aqueous two-phase systems (ATPS) based on tropine type chiral ionic liquids and inorganic salt solution were designed and prepared for the enantiomeric separation of racemic phenylalanine. The phase behavior of IL-based ATPS was comprehensive investigated, and phase equilibrium data were correlated by Merchuk equation. Various factors were also systematically investigated for their influence on separation efficiency. Under the appropriate conditions (0.13g/g [C8Tropine]pro, 35mg/g Cu(Ac)2, 20mg/g d,l-phenylalanine, 0.51g/g H2O and 0.30g/g K2HPO4), the enantiomeric excess value of phenylalanine in solid phase (mainly containing l-enantiomer) was 65%. Finally, the interaction mechanism was studied via 1D and 2D NMR. The results indicate that d-enantiomer of phenylalanine interacts more strongly with chiral ILs and Cu(2+) based on the chiral ion-pairs space coordination mechanism, which makes it tend to remain in the top IL-rich phase. By contrast, l-enantiomer is transferred into the solid phase. Above chiral ionic liquids aqueous two-phase systems have demonstrated obvious resolution to racemic phenylalanine and could be promising alterative resolution approach for racemic amino acids in aqueous circumstance. Copyright © 2015. Published by Elsevier B.V.

Enantio-alteration of gene transcription associated with bioconcentration in adult zebrafish (Danio rerio) exposed to chiral PCB149

NASA Astrophysics Data System (ADS)

Chai, Tingting; Cui, Feng; Mu, Pengqian; Yang, Yang; Xu, Nana; Yin, Zhiqiang; Jia, Qi; Yang, Shuming; Qiu, Jing; Wang, Chengju

2016-01-01

Enantioselective enrichment of chiral PCB149 (2,2’,3,4’,5’,6-hexachlorobiphenyl) was analysed in adult zebrafish (Danio rerio) exposed to the racemate, (-)-PCB149, and (+)-PCB149. Greater enrichment of (-)-PCB149 compared to (+) PCB149 was observed following 0.5 ng/L exposure; however, as the exposure time and concentration increased, racemic enrichment was observed in adult fish exposed to the racemate. No biotransformation between the two isomers was observed in fish exposed to single enantiomers. When zebrafish were exposed to different forms of chiral PCB149, enantioselective expression of genes associated with polychlorinated biphenyls (PCBs) was observed in brain and liver tissues and enantioselective correlations between bioconcentration and target gene expression levels were observed in brain and liver tissues. The strong positive correlations between expression levels of target genes (alox5a and alox12) and PCB149 bioconcentration suggest that prolonged exposure to the racemate of chiral PCB149 may result in inflammation-associated diseases. Prolonged exposure to (-)-PCB149 may also affect metabolic pathways such as dehydrogenation and methylation in the brain tissues of adult zebrafish. Hepatic expression levels of genes related to the antioxidant system were significantly negatively correlated with bioconcentration following exposure to (+)-PCB149.

Characterization and quantification of racemic and meso-ethylenediamine-N,N'-bis(2-hydroxy-5-sulfophenylacetic) acid/iron (III) by ion-pair ultra-high performance liquid chromatography coupled with diode array detector and electrospray tandem mass spectrometry.

PubMed

Biasone, Alessandro; Cianci, Giusto; Di Tommaso, Donata; Piaggesi, Alberto; Tagliavini, Emilio; Galletti, Paola; Moretti, Fabio

2013-03-22

EDDHSA/Fe is a promising substitute of EDDHA/Fe to fight iron chlorosis. o,o-EDDHSA structure contains two chiral carbons giving the racemic and meso couples of stereoisomers. Ion-pair HPLC and UHPLC-UV/Vis-ESI-MS/MS methods were developed for the determination of racemic and meso-o,o-EDDHSA/Fe in commercial samples of chelates. The lack of a commercial EDDHSA standard was overcome by sulfonation of a commercial available o,o-EDDHA standard and subsequent quantification by (1)H-NMR. Assignment of configurations was carried out starting from racemic and meso-o,o-EDDHA/Fe by direct sulfonation to give the corresponding o,o-EDDHSA/Fe isomers. The performances of these methods were assessed in terms of intra and inter-day precision, linearity and selectivity. The high selectivity and lower detection limit (nanomolar) of the UHPLC-ESI-MS/MS method could allow to deepen the knowledge relative to meso and rac-o,o-EDDHSA/Fe interactions with plants, its fate in different soil conditions, its mobility and other environmental aspects. Copyright © 2013 Elsevier B.V. All rights reserved.

Responses of Cerambycidae and other insects to traps baited with ethanol, 2,3-hexanediol, and 3,2-hydroxyketone lures in north-central Georgia

Treesearch

Dan Miller; Christopher Crowe; P. D. Mayo; P. J. Silk; J. D. Sweeney

2015-01-01

In north-central Georgia, 13 species of woodboring beetles (Coleoptera: Cerambycidae: Cerambycinae) were attracted to multiple-funnel traps baited with ethanol and one of the following pheromones: (1) racemic 3-hydroxyhexan-2-one; (2) racemic 3-hydroxyoctan-2-one; and (3) syn-2,3-hexanediol. The following species were attracted to traps baited with ethanol and 3-...

Green chiral HPLC enantiomeric separations using high temperature liquid chromatography and subcritical water on Chiralcel OD and Chiralpak AD.

PubMed

Droux, Serge; Félix, Guy

2011-01-01

We report here the application of subcritical water in chiral separations on two popular polysaccharide chiral stationary phases (CSPs): Chiralpak AD and Chiralcel OD. The behavior of these two CSPs was studied under reversed phase conditions at room temperature to discover the maximum percentage of water in the mobile phase, which provided the separation of enantiomers of flavanone and benzoin, respectively, in a reasonable time (i.e., less than 1 h). Then, the stability of Chiralpak AD and Chiralcel OD versus temperature was investigated and discussed. Chiralcel OD separation of flavanone racemate was obtained at 120 °C with water and 2-propanol (80/20) as the mobile phase, while benzoin racemate was separated in pure water at 160 °C. Separations of several racemates were also presented, and advantages and limitations of the technique were discussed. Copyright © 2011 Wiley Periodicals, Inc.

Aminostratigraphy and faunal correlations of late Quaternary marine terraces, Pacific Coast, USA

USGS Publications Warehouse

Kennedy, G.L.; Lajoie, K.R.; Wehmiller, J.F.

1982-01-01

Recent studies using the extent of racemization of amino acids to date fossil mollusc shells in the Arctic1, the British Isles2 and on the Atlantic3,4 and Pacific5-13 coasts of North America have relied mainly on theoretical kinetic models of racemization. Ages generated in this fashion are highly model dependent and require estimates of integrated long-term diagenetic temperatures. We present here an alternative, empirical approach to aminostratigraphy in which we plot amino acid enantiomeric ratios versus latitude (for localities along the Pacific coast of the United States), and generate isochronal correlations by connecting data points of geographically proximal localities that have similar D:L ratios and zoogeographic aspect. Isochrons are calibrated at a few localities by independent radiometric dates. The diagenetic temperature effect on racemization is reflected in the slope of the isochrons, but the need to quantify temperature is eliminated. ?? 1982 Nature Publishing Group.

A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bunker, Richard D.; Mandal, Kalyaneswar; Bashiri, Ghader

Racemic protein crystallography was used to determine the X-ray structure of the predicted Mycobacterium tuberculosis protein Rv1738, which had been completely recalcitrant to crystallization in its natural L-form. Native chemical ligation was used to synthesize both L-protein and D-protein enantiomers of Rv1738. Crystallization of the racemic {D-protein + L-protein} mixture was immediately successful. The resulting crystals diffracted to high resolution and also enabled facile structure determination because of the quantized phases of the data from centrosymmetric crystals. The X-ray structure of Rv1738 revealed striking similarity with bacterial hibernation factors, despite minimal sequence similarity. As a result, we predict that Rv1738,more » which is highly up-regulated in conditions that mimic the onset of persistence, helps trigger dormancy by association with the bacterial ribosome.« less

A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography

DOE PAGES

Bunker, Richard D.; Mandal, Kalyaneswar; Bashiri, Ghader; ...

2015-04-07

Racemic protein crystallography was used to determine the X-ray structure of the predicted Mycobacterium tuberculosis protein Rv1738, which had been completely recalcitrant to crystallization in its natural L-form. Native chemical ligation was used to synthesize both L-protein and D-protein enantiomers of Rv1738. Crystallization of the racemic {D-protein + L-protein} mixture was immediately successful. The resulting crystals diffracted to high resolution and also enabled facile structure determination because of the quantized phases of the data from centrosymmetric crystals. The X-ray structure of Rv1738 revealed striking similarity with bacterial hibernation factors, despite minimal sequence similarity. As a result, we predict that Rv1738,more » which is highly up-regulated in conditions that mimic the onset of persistence, helps trigger dormancy by association with the bacterial ribosome.« less

Molecular Modulation of Inhibitors of Apoptosis as a Novel Approach for Radiosensitization of Human Prostate Cancer

DTIC Science & Technology

2008-11-01

was purified from natural racemic gossypol. Briefly, racemic gossypol was reacted with L - phenylalanine methyl ester hydrochloride overnight at room...solution of the resolved (F)-gossypol- phenylalanine methyl ester Schiff’s base was hydrolyzed by a mixture of tetrahydro- furan, glacial acetic acid...suppression of NF-kappaB-regulated antiapoptotic and metastatic gene products. Mol Pharmacol 2007; 71: 209-19. [136]Wang L , Du F, Wang X. TNF- alpha induces

Enantioselective cyclization of racemic supramolecular polymers.

PubMed

ten Cate, A Tessa; Dankers, Patricia Y W; Kooijman, Huub; Spek, Anthony L; Sijbesma, Rint P; Meijer, E W

2003-06-11

Homochiral hydrogen-bonded cyclic assemblies are formed in dilute solutions of racemic supramolecular polymers based on the quadruple hydrogen bonding 2-ureido-4[1H]-pyrimidinone unit, as observed by 1H NMR and SEC experiments. Preorganization of the monomers and the combined binding strength of the eight hydrogen bonds result in a very high stability of the cyclic aggregates with pronounced selectivity between homochiral and heterochiral cyclic species, usually only observed in crystalline or liquid crystalline phases.

Less common applications of simulated moving bed chromatography in the pharmaceutical industry.

PubMed

Huthmann, E; Juza, M

2005-10-21

Simulated moving bed (SMB) chromatography is often perceived in the pharmaceutical industry as chromatographic method for separating binary mixtures, like racemates. However, SMB can also be used for unbalanced separations, i.e. binary mixtures of varying compositions and multi-component mixtures. These less common application modes of isocratic SMB chromatography are exemplified for four different compounds (racemates and diastereomers) and discussed in view of the so-called 'triangle theory' from an industrial perspective.

Separation of the stereoisomers of the main metabolite of a non-steroidal anti-inflammatory drug, flobufen, by chiral high-performance liquid chromatography.

PubMed

Wsól, V; Fell, A F; Kvasnicková, E; Hais, I M

1997-02-07

The major metabolite of a novel non-steroidal anti-inflammatory drug, DL-4-(2',4'-difluorobiphenyl-4-yl)-2-oxo-2-methylbutanoic acid (flobufen, I), namely 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-gamma-butyrolactone (4-dihydroflobufen lactone, III), has four stereoisomers consisting of two racemic pairs of enantiomers. Of three chiral stationary phases tested, Cyclobond I beta-RSP (Astec) (beta-cylodextrin derivatized with R,S-hydroxypropyl) was best able to separate the (+2)(--) racemate, with a liquid phase containing acetonitrile as modifier and triethylamine acetate as buffer. Using the Box-Wilson Central Composite Design for three factors, an optimum combination of pH and concentrations of the modifier and buffer was eventually obtained. A chromatographic response function based on a combination of the Kaiser peak separation function, Pi, and retention time of the second eluting enantiomer, tRL, served as a response criterion for the process of optimization. The optimum conditions developed for the (+2)(--) racemate were also found to be suitable for separating the (+-)(-+) racemate, for which earlier studies had shown the separation to be more facile. Separation of the four stereoisomers of III, for which the chiral chromatographic system optimized in this study is proposed as the second stage, is targeted at a biochemical study of the stereoisomeric metabolism of I.

Trimeprazine is enantioselectively degraded by an activated sludge in ready biodegradability test conditions.

PubMed

Escuder-Gilabert, Laura; Martín-Biosca, Yolanda; Perez-Baeza, Mireia; Sagrado, Salvador; Medina-Hernández, María José

2018-05-09

A great number of available pharmaceuticals are chiral compounds. Although they are usually manufactured as racemic mixtures, they can be enantioselectively biodegraded as a result of microbial processes. In this paper, a biodegradability assay in similar conditions to those recommended in OECD tests of enantiomers of trimeprazine (a phenothiazine employed as a racemate) is carried out. Experiments were performed in batch mode using a minimal salts medium inoculated with an activated sludge (collected from a Valencian Waste Water Treatment Plant, WWTP) and supplemented with the racemate. The concentration of the enantiomers of trimeprazine were monitored by means of a chiral HPLC method using a cellulose-based chiral stationary phase and 0.5 M NaClO 4 /acetonitrile (60:40, v/v) mobile phases. Experiments were performed at three concentration levels of the racemate. In parallel, the optical density at 600 nm (OD600) was measured to control the biomass growth and to connect it with enantioselectivity. The calculated enantiomeric fractions (EF) offer the first evidence of enantioselective biodegradation of trimeprazine. A simplified Monod equation was used as a curve fitting approach for concentration (S), biodegradation (BD), and for the first time, EF experimental data in order to expand the usefulness of the results. Precision studies on S (repeatability conditions) and, for the first time, EF (intermediate precision conditions) were also performed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Buyid Silk and the Tale of Bibi Shahrbanu: Identification of Biomarkers of Artificial Aging (Forgery) of Silk.

PubMed

Moini, Mehdi; Rollman, Christopher M

2017-10-03

Buyid silk forgery is one of the most famous silk forgeries in the world. In 1924-1925, excavation of the Bibi Shahrbanu site in Iran unearthed several silk textiles. The silks were thought to be of the Buyid period (934-1062 BCE) of the Persian Empire and have since been known as the "Buyid silks". In the 1930s, more silk appeared and was reported as being from the Buyid period as well. Controversy over the authenticity of these silks escalated after the purchase of the silks by museums throughout the world. Extensive investigations of several of these silks have been conducted over the years with respect to iconography, weaving patterns, dyes/mordant, style, and even radiocarbon dating. It was found that most of the silks are not from Buyid period. To test the authenticity of these silk fabrics, the recently developed silk dating technique using amino acid racemization (AAR) in conjunction with capillary electrophoresis mass spectrometry was applied to 13 Buyid silk specimens from the Textile Museum collections. Among these silk specimens, the AAR ratios of only one specimen were consistent with authentic silk fabrics collected from various museums. In addition, the aspartic acid racemization ratio of this specimen was also consistent with its 14 C dating. The other "Buyid silks" showed excessive levels of amino acid racemization not only for aspartic acid, but also for phenylalanine and tyrosine, inconsistent with racemization rates of these amino acids in authentic historical silk fabrics. Treatment of modern silk with a base at different pH and temperature reproduced the AAR pattern of the Buyid silks, implying that chemical treatment with a base at relatively high temperatures was perhaps the method used to artificially age these fabrics. The results imply that the racemization ratios of aspartic acid, phenylalanine, and tyrosine can be used as biomarkers for identification of naturally versus artificially aged silk.

Binding of long-lasting local anesthetics to lipid emulsions.

PubMed

Mazoit, Jean-Xavier; Le Guen, Régine; Beloeil, Hélène; Benhamou, Dan

2009-02-01

Rapid infusion of lipid emulsion has been proposed to treat local anesthetic toxicity. The authors wanted to test the buffering properties of two commercially available emulsions made of long- and of long- and medium-chain triglycerides. Using the shake-flask method, the authors measured the solubility and binding of racemic bupivacaine, levobupivacaine, and ropivacaine to diluted Intralipid (Fresenius Kabi, Paris, France) and Medialipide (B-Braun, Boulogne, France). The apparent distribution coefficient expressed as the ratio of mole fraction was 823 +/- 198 and 320 +/- 65 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, at 500 mg in the Medialipide/buffer emulsion; and 1,870 +/- 92 and 1,240 +/- 14 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, in the Intralipid/buffer emulsion. Decreasing the pH from 7.40 to 7.00 of the Medialipide/buffer emulsion led to a decrease in ratio of molar concentration from 121 +/- 3.8 to 46 +/- 2.8 for bupivacaine, and to a lesser extent from 51 +/- 4.0 to 31 +/- 1.6 for ropivacaine. The capacity of the 1% emulsions was 871 and 2,200 microM for the 1% Medialipide and Intralipid emulsions, respectively. The dissociation constant was 818 and 2,120 microM for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively. Increasing the temperature from 20 to 37 degrees C led to a greater increase in affinity for ropivacaine (55%) than for bupivacaine (27%). When the pH of the buffer was decreased from 7.40 to 7.00, the affinity was decreased by a factor of 1.68, similar for both anesthetics. The solubility of long-acting local anesthetics in lipid emulsions and the high capacity of binding of these emulsions most probably explain their clinical efficacy in case of toxicity. The long-chain triglyceride emulsion Intralipid appears to be about 2.5 times more efficacious than the 50/50 medium-chain/long-chain Medialipide emulsion. Also, because of their higher hydrophobicity, racemic bupivacaine and levobupivacaine seem to clear more rapidly than ropivacaine.

D:L-AMINO Acids and the Turnover of Microbial Biomass

NASA Astrophysics Data System (ADS)

Lomstein, B. A.; Braun, S.; Mhatre, S. S.; Jørgensen, B. B.

2015-12-01

Decades of ocean drilling have demonstrated wide spread microbial life in deep sub-seafloor sediment, and surprisingly high microbial cell numbers. Despite the ubiquity of life in the deep biosphere, the large community sizes and the low energy fluxes in the vast buried ecosystem are still poorly understood. It is not know whether organisms of the deep biosphere are specifically adapted to extremely low energy fluxes or whether most of the observed cells are in a maintenance state. Recently we developed and applied a new culture independent approach - the D:L-amino acid model - to quantify the turnover times of living microbial biomass, microbial necromass and mean metabolic rates. This approach is based on the built-in molecular clock in amino acids that very slowly undergo chemical racemization until they reach an even mixture of L- and D- forms, unless microorganisms spend energy to keep them in the L-form that dominates in living organisms. The approach combines sensitive analyses of amino acids, the unique bacterial endospore marker (dipicolinic acid) with racemization dynamics of stereo-isomeric amino acids. Based on a heating experiment, we recently reported kinetic parameters for racemization of aspartic acid, glutamic acid, serine and alanine in bulk sediment from Aarhus Bay, Denmark. The obtained racemization rate constants were faster than the racemization rate constants of free amino acids, which we have previously applied in Holocene sediment from Aarhus Bay and in up to 10 mio yr old sediment from ODP Leg 201. Another important input parameter for the D:L-amino acid model is the cellular carbon content. It has recently been suggested that the cellular carbon content most likely is lower than previously thought. In recognition of these new findings, previously published data based on the D:L-amino acid model were recalculated and will be presented together with new data from an Arctic Holocene setting with constant sub-zero temperatures.

Aspartic acid racemization in dentin of the third molar for age estimation of the Chaoshan population in South China.

PubMed

Chen, Shisheng; Lv, Yanyi; Wang, Dian; Yu, Xiaojun

2016-09-01

Aspartic acid racemization in teeth has been increasingly used to estimate chronological age with a considerably high accuracy in forensic practice. The Chaoshan population in South China is relatively isolated in geography, and has specific lifestyle and dietary inhibits. It is still unknown whether this method is suitable for this population. The aim of this study was to analyze the relationship between chronological age and the d/l aspartic acid ratio in dentin in the third molar tooth of the Chaoshan population. Fifty-eight non-carious third molar teeth (31 mandibles and 27 maxillae), from 58 living individuals of known age (24 males and 34 females), were retrieved. Dentin was extracted from these teeth. The d- and l-aspartic acids in dentins were separated and detected by high performance liquid chromatography (HPLC). Linear regression was performed between the d/l aspartic acid ratio of dentins and chronological age. Results showed that the correlation coefficient (r) was 0.969, and the mean absolute error (MAE) was 2.19 years, its standard deviation (SD) was ±1.53 years, indicating excellent correlation. There was no significant difference in racemization rates of dentin between sexes (P=0.113, F=2.6), or between mandibles and maxillae (P=0.964, F=0.000). Results indicate that the ratio of the d and l forms of aspartic acid of dentins, in the third molar, is closely correlated with chronological age, special lifestyle do no obviously affect the accuracy of the age estimations by aspartic acid racemization of the dentin in the third molar and that aspartic acid racemization in the third molar dentin can be used as an accurate method to estimate chronological age in the Chaoshan population in South China. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Assessment of the use of racemic ketamine and its S(+) isomer, associated or not with low doses of fentanyl, in balneotherapy for major burn patients].

PubMed

Cantinho, Fernando Antônio de Freitas; Silva, Antonio Carlos Pereira da

2009-01-01

The care of the wounds of major burn patients triggers severe painful stimuli. The objective of this study was to assess the safety and efficacy of different drug combinations in anesthesia for balneotherapy. After approval by the Ethics Commission, 200 procedures of balneotherapy in 87 major burn adult patients were evaluated. Midazolam was used in all cases. The vials of ketamine were numbered and, therefore, at the time of the use, one did not know whether racemic or S(+)ketamine was being used. Each morning it was decided by drawing lots whether fentanyl would be used or not in the procedures of that day. Patients were included in one of four groups: ISO/sf (S(+) isomer without fentanyl), ISO/cf (S(+) isomer with fentanyl), RAC/sf (racemic ketamine without fentanyl), and RAC/cf (racemic ketamine with fentanyl). The initial doses proposed were as follows: midazolam, 0.06 mg.kg-1; ketamine, 1.0 to 1.1 mg.kg-1; and fentanyl, 0.8 (1/4)g.kg1-1; additional doses were administered as needed. Only one patient recalled the pain of balneotherapy. In the group that received S(+)ketamine, the use of fentanyl did not bring additional advantages; however, when associated with racemic ketamine, fentanyl reduced the total dose and the number of ketamine boluses. The extension of body surface burned was the main determinant of the severity of post-procedure pain. Reduced pain severity was the main factor considered by patients when grading their satisfaction with the anesthesia. The four different drug combinations proved to be safe and guaranteed the absence of pain during balneotherapy. Characteristics not directly related to the anesthetics proved to be more important in the incidence of post-procedure pain, which was the main factor considered by major burn patient to define their satisfaction with the anesthesia used.

[Study of selegiline and related compounds with x-ray diffraction].

PubMed

Simon, K; Böcskei, Z; Török, Z

1992-09-01

Selegiline and its parent compounds were studied by X-ray diffraction. It was established that the racemates of primary and secondary amines (p-fluoro-amphetamine, methamphetamine, p-fluoro-methamphetamine) hydrochloride do not form racemic compounds but crystalline as conglomerates, at the same time tertiary amines like selegiline and p-fluoro-selegiline hydrochlorides do. The crystalline structure of five enantiomeric hydrochlorides were determined, the CPhe-C-C-N torsion angle is anti-periplanar in all cases but in p-fluoro-amphetamine where it is gauche.

Absolute configuration and crystal packing for three chiral drugs prone to spontaneous resolution: Guaifenesin, methocarbamol and mephenesin

NASA Astrophysics Data System (ADS)

Bredikhin, Alexander A.; Gubaidullin, Aidar T.; Bredikhina, Zemfira A.; Krivolapov, Dmitry B.; Pashagin, Alexander V.; Litvinov, Igor A.

2009-02-01

Popular chiral drugs, guaifenesin, methocarbamol, and mephenesin were investigated by single-crystal X-ray analysis both for enantiopure and racemic samples. The absolute configurations for all substances were established through Flack parameter method. The conglomerate-forming nature for the compounds was confirmed by equivalence of crystal characteristics of enantiopure and racemic samples. The molecular structures and crystal packing details were evaluated and compared with one another for all three investigated substances.

Dynamic Kinetic Asymmetric Transformations of β-Stereogenic-α-Keto Esters via Direct Aldolization

PubMed Central

Corbett, Michael T.; Johnson, Jeffrey S.

2014-01-01

Dynamic kinetic asymmetric transformations (DyKAT) of racemic β-bromo-α-keto esters via direct aldolization of nitromethane and acetone provide access to fully substituted α-glycolic acid derivatives bearing a β-stereocenter. The aldol adducts are obtained in excellent yield with high relative and absolute stereocontrol under mild reaction conditions. Mechanistic studies determined that the reactions proceed through a facile catalyst-mediated racemization of the β-bromo-α-keto esters under a DyKAT Type I manifold. PMID:24222195

Concise Redox Deracemization of Secondary and Tertiary Amines with a Tetrahydroisoquinoline Core via a Nonenzymatic Process.

PubMed

Ji, Yue; Shi, Lei; Chen, Mu-Wang; Feng, Guang-Shou; Zhou, Yong-Gui

2015-08-26

A concise deracemization of racemic secondary and tertiary amines with a tetrahydroisoquinoline core has been successfully realized by orchestrating a redox process consisted of N-bromosuccinimide oxidation and iridum-catalyzed asymmetric hydrogenation. This compatible redox combination enables one-pot, single-operation deracemization to generate chiral 1-substituted 1,2,3,4-tetrahydroisoquinolines with up to 98% ee in 93% yield, offering a simple and scalable synthetic technique for chiral amines directly from racemic starting materials.

Interactions between ethanol, syn-2,3-hexanediol, 3-hydroxyhexan-2-one, and 3-hydroxyoctan-2-one lures on trap catches of hardwood longhorn beetles in southeastern united states

Treesearch

D R Miller; C M Crowe; P D Mayo; L S Reid; P J Silk; J D Sweeney

2017-01-01

The effectiveness of a four-component “super lure” consisting of ethanol (E) and the cerambycid pheromones syn-2,3-hexanediol (D6), racemic 3-hydroxyhexan-2-one (K6), and racemic 3-hydroxyoctan-2-one (K8) on trap catches of Cerambycidae (Coleoptera) was determined in southeast United States with seven trapping experiments in 2011–2013. We captured...

Stereoselective oxidation of racemic 1-arylethanols by basil cultured cells of Ocimum basilicum cv. Purpurascens.

PubMed

Itoh, Ken-ichi; Nakamura, Kaoru; Utsukihara, Takamitsu; Sakamaki, Hiroshi; Horiuchi, C Akira

2008-05-01

The biotransformation of racemic 1-phenylethanol (30 mg) with plant cultured cells of basil (Ocimum basilicum cv. Purpurascens, 5 g wet wt) by shaking 120 rpm at 25 degrees C for 7 days in the dark gave (R)-(+)-1-phenylethanol and acetophenone in 34 and 24% yields, respectively. The biotransformation can be applied to other 1-arylethanols and basil cells oxidized the (S)-alcohols to the corresponding ketones remaining the (R)-alcohols in excellent ee.

Molecular docking and panicolytic effect of 8-prenylnaringenin in the elevated T-maze.

PubMed

Bagatin, Mariane Cristovão; Tozatti, Camila Santos Suniga; Abiko, Layara Akemi; Yamazaki, Diego Alberto dos Santos; Silva, Priscila Rebeca Alves; Perego, Leonardo Martins; Audi, Elisabeth Aparecida; Seixas, Flavio Augusto Vicente; Basso, Ernani Abicht; Gauze, Gisele de Freitas

2014-01-01

The purpose of this study was to investigate the effects of the chronic administration of a racemic mixture of 8-prenylnaringenin (8-PN) on rats submitted to the elevated T-maze (ETM) model of generalized anxiety and panic disorders. The selective serotonin (SERT) reuptake inhibitor fluoxetine was used as a positive control. Rat locomotion was assessed in a circular arena following each drug treatment. The administration of racemic 8-PN for 21 d in rats increased one-way escape latencies from the ETM open arm, indicating a panicolytic effect. To evaluate the interactions of 8-PN with monoamine transporters, a docking study was performed for both the R and S configurations of 8-PN towards SERT, norepinephrine (NET) and dopamine transporters (DAT). The application of the docking protocol showed that (R)-8-PN provides greater affinity to all transporters than does the S enantiomer. This result suggests that enantiomer (R)-8-PN is the active form in the in vivo test of the racemic mixture.

Separation of non-racemic mixtures of enantiomers: an essential part of optical resolution.

PubMed

Faigl, Ferenc; Fogassy, Elemér; Nógrádi, Mihály; Pálovics, Emese; Schindler, József

2010-03-07

Non-racemic enantiomeric mixtures form homochiral and heterochiral aggregates in melt or suspension, during adsorption or recrystallization, and these diastereomeric associations determine the distribution of the enantiomers between the solid and other (liquid or vapour) phases. That distribution depends on the stability order of the homo- and heterochiral aggregates (conglomerate or racemate formation). Therefore, there is a correlation between the binary melting point phase diagrams and the experimental ee(I)vs. ee(0) curves (ee(I) refers to the crystallized enantiomeric mixtures, ee(0) is the composition of the starting ones). Accordingly, distribution of the enantiomeric mixtures between two phases is characteristic and usually significant enrichment can be achieved. There are two exceptions: no enrichment could be observed under thermodynamically controlled conditions when the starting enantiomer composition corresponded to the eutectic composition, or when the method used was unsuitable for separation. In several cases, when kinetic control governed the crystallization, the character of the ee(0)-ee(I) curve did not correlate with the melting point binary phase diagram.

Characterization of Crystal Chirality in Amino Acids Using Low-Frequency Raman Spectroscopy.

PubMed

Aviv, Hagit; Nemtsov, Irena; Mastai, Yitzhak; Tischler, Yaakov R

2017-10-19

We present a new method for differentiating racemic crystals from enantiopure crystals. Recently, developments in optical filters have enabled the facile use of Raman spectroscopy to detect low-frequency vibrational (LFV) modes. Here, for the first time, we use Raman spectroscopy to characterize the LFV modes for crystalline organic materials composed of chiral molecules. The LF-Raman spectra of racemic and enantiopure crystals exhibit a significant variation, which we attribute to different hydrogen-bond networks in the chiral crystal structures. Across a representative set of amino acids, we observed that when comparing racemic versus enantiopure crystals, the available LFV modes and their relative scattering intensity are strong functions of side chain polarity. Thus, LF-Raman can be used as a method that is complementary to the currently used methods for characterizing crystal chirality due to simpler, faster, and more sensitive measurements, along with the small sample size required, which is limited by the laser-beam diameter in the focus.

Rhodium-catalysed asymmetric allylic arylation of racemic halides with arylboronic acids

NASA Astrophysics Data System (ADS)

Sidera, Mireia; Fletcher, Stephen P.

2015-11-01

Csp2-Csp2 cross-coupling reactions between arylboronic acid and aryl halides are widely used in both academia and industry and are strategically important in the development of new agrochemicals and pharmaceuticals. Csp2-Csp3 cross-coupling reactions have been developed, but enantioselective variations are rare and simply retaining the stereochemistry is a problem. Here we report a highly enantioselective Csp2-Csp3 bond-forming method that couples arylboronic acids to racemic allyl chlorides. Both enantiomers of a cyclic chloride are converted into a single enantiomer of product via a dynamic kinetic asymmetric transformation. This Rh-catalysed method uses readily available and inexpensive building blocks and is mild and broadly applicable. For electron-deficient, electron-rich or ortho-substituted boronic acids better results are obtained with racemic allyl bromides. Oxygen substitution in the allyl halide is tolerated and the products can be functionalized to provide diverse building blocks. The approach fills a significant gap in the methods for catalytic asymmetric synthesis.

Determination of the Molecular Structures of Ferric Enterobactin and Ferric Enantioenterobactin Using Racemic Crystallography.

PubMed

Johnstone, Timothy C; Nolan, Elizabeth M

2017-10-25

Enterobactin is a secondary metabolite produced by Enterobacteriaceae for acquiring iron, an essential metal nutrient. The biosynthesis and utilization of enterobactin permits many Gram-negative bacteria to thrive in environments where low soluble iron concentrations would otherwise preclude survival. Despite extensive work carried out on this celebrated molecule since its discovery over 40 years ago, the ferric enterobactin complex has eluded crystallographic structural characterization. We report the successful growth of single crystals containing ferric enterobactin using racemic crystallization, a method that involves cocrystallization of a chiral molecule with its mirror image. The structures of ferric enterobactin and ferric enantioenterobactin obtained in this work provide a definitive assignment of the stereochemistry at the metal center and reveal secondary coordination sphere interactions. The structures were employed in computational investigations of the interactions of these complexes with two enterobactin-binding proteins, which illuminate the influence of metal-centered chirality on these interactions. This work highlights the utility of small-molecule racemic crystallography for obtaining elusive structures of coordination complexes.

Racemization and the origin of optically active organic compounds in living organisms

NASA Technical Reports Server (NTRS)

Bada, J. L.; Miller, S. L.

1987-01-01

The organic compounds synthesized in prebiotic experiments are racemic mixtures. A number of proposals have been offered to explain how asymmetric organic compounds formed on the Earth before life arose, with the influence of chiral weak nuclear interactions being the most frequent proposal. This and other proposed asymmetric syntheses give only sight enantiomeric excess and any slight excess will be degraded by racemization. This applies particularly to amino acids where half-lives of 10(5)-10(6) years are to be expected at temperatures characteristic of the Earth's surface. Since the generation of chiral molecules could not have been a significant process under geological conditions, the origins of this asymmetry must have occurred at the time of the origin of life or shortly thereafter. It is possible that the compounds in the first living organisms were prochiral rather than chiral; this is unlikely for amino acids, but it is possible for the monomers of RNA-like molecules.

Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography.

PubMed

Mandal, Kalyaneswar; Uppalapati, Maruti; Ault-Riché, Dana; Kenney, John; Lowitz, Joshua; Sidhu, Sachdev S; Kent, Stephen B H

2012-09-11

Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically synthesized D- and L- forms of the protein ligand showed reciprocal chiral specificity in surface plasmon resonance binding experiments: The L-protein ligand bound only to D-VEGF-A, whereas the D-protein ligand bound only to L-VEGF-A. The D-protein ligand, but not the L-protein ligand, inhibited the binding of natural VEGF(165) to the VEGFR1 receptor. Racemic protein crystallography was used to determine the high resolution X-ray structure of the heterochiral complex consisting of {D-protein antagonist + L-protein form of VEGF-A}. Crystallization of a racemic mixture of these synthetic proteins in appropriate stoichiometry gave a racemic protein complex of more than 73 kDa containing six synthetic protein molecules. The structure of the complex was determined to a resolution of 1.6 Å. Detailed analysis of the interaction between the D-protein antagonist and the VEGF-A protein molecule showed that the binding interface comprised a contact surface area of approximately 800 Å(2) in accord with our design objectives, and that the D-protein antagonist binds to the same region of VEGF-A that interacts with VEGFR1-domain 2.

Chiral separation of 3,4-methylenedioxymethamphetamine (MDMA) enantiomers using batch chromatography with peak shaving recycling and its effects on oxidative stress status in rat liver.

PubMed

Lourenço, Tiago C; Bósio, Graziela C; Cassiano, Neila M; Cass, Quezia B; Moreau, Regina L M

2013-01-25

This work reports the multimiligram separation of 3,4-methylenedioxy-methamphetamine (MDMA) enantiomers using batch chromatography with peak shaving recycling. The effect of both enantiomers compared to the racemic mixture was examined on the oxidative stress status of rat liver. The enantiomeric purification was performed using a based cyclodextrin chiral selector and methanol:ammonium acetate buffer (pH 6.0, 100mM) (30:70, v/v) as mobile phase. The average mass rate obtained was 40.0mg/day, providing 45.0mg of the (R)-(-)-MDMA (e.r. 99.0%) and 75.0mg (e.r. 96.0%) of (S)-(+)-MDMA. Racemic MDMA and both enantiomers were administered per orally to Wistar rats and oxidative stress status parameters, as liver total glutathione levels and malondialdehyde (MDA) production in liver were evaluated. There was a significant decrease in hepatic glutathione content in the racemic MDMA and the (R)-(-)-MDMA-treated rats when compared to the control and to (S)-(+)-MDMA. These results demonstrate that the R-enantiomer is the enantiomer that contributes to the depletion of hepatic glutathione induced by the racemic mixture. The high reactivity of the R-enantiomer of MDMA in the liver can also be observed in animals treated with (R)-(-)-MDMA. The production of malondialdehyde (MDA) by (R)-(-)-MDMA was significantly higher when compared to the other treated groups and control. Copyright © 2012 Elsevier B.V. All rights reserved.

Adsorption and Structure of Chiral Epoxides on Pd(111): Propylene Oxide and Glycidol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahapatra, Mausumi; Tysoe, Wilfred T.

Here, the adsorption of enantiopure versus racemic propylene oxide (PO) on Pd(111) is studied by temperature-programmed desorption (TPD) to explore possible differences in their saturation coverage. It is found that that the saturation coverage of enantiopure PO on Pd(111) is identical to that of racemic PO, in contrast to results on Pt(111) where significant coverage differences were found. The surface structures of enantiopure PO on Pd(111) were characterized by scanning tunneling microscopy (STM), which shows the formation of linear chains and hexagonal structures proposed to be due to freely rotating PO, in contrast to the relatively disordered PO overlayers foundmore » on Pt(111). STM experiments were carried out for enantiopure glycidol, which contains the same epoxy ring as PO, but where the methyl group of propylene oxide is replaced by a -CH 2OH group to provide a hydrogen-bonding sites. Glycidol STM images show the formation of completely different surface structures; at low coverages, glycidol forms pseudohexagonal structures which assemble from glycidol dimers, while at high coverages the surface shows extensive hydrogen-bonded networks. Density functional theory (DFT) calculations were carried out to model the enantiopure PO linear chain and the glycidol dimers that are observed by STM. Similar calculations were carried out for racemic PO and glycidol structures. The calculated interaction energies for the enantiopure and the racemic pairs reveal that there is no difference for homochiral versus heterochiral structures for both PO and glycidol on Pd(111).« less

Adsorption and Structure of Chiral Epoxides on Pd(111): Propylene Oxide and Glycidol

DOE PAGES

Mahapatra, Mausumi; Tysoe, Wilfred T.

2018-01-03

Here, the adsorption of enantiopure versus racemic propylene oxide (PO) on Pd(111) is studied by temperature-programmed desorption (TPD) to explore possible differences in their saturation coverage. It is found that that the saturation coverage of enantiopure PO on Pd(111) is identical to that of racemic PO, in contrast to results on Pt(111) where significant coverage differences were found. The surface structures of enantiopure PO on Pd(111) were characterized by scanning tunneling microscopy (STM), which shows the formation of linear chains and hexagonal structures proposed to be due to freely rotating PO, in contrast to the relatively disordered PO overlayers foundmore » on Pt(111). STM experiments were carried out for enantiopure glycidol, which contains the same epoxy ring as PO, but where the methyl group of propylene oxide is replaced by a -CH 2OH group to provide a hydrogen-bonding sites. Glycidol STM images show the formation of completely different surface structures; at low coverages, glycidol forms pseudohexagonal structures which assemble from glycidol dimers, while at high coverages the surface shows extensive hydrogen-bonded networks. Density functional theory (DFT) calculations were carried out to model the enantiopure PO linear chain and the glycidol dimers that are observed by STM. Similar calculations were carried out for racemic PO and glycidol structures. The calculated interaction energies for the enantiopure and the racemic pairs reveal that there is no difference for homochiral versus heterochiral structures for both PO and glycidol on Pd(111).« less

An examination of the thermodynamics of fusion, vaporization, and sublimation of ibuprofen and naproxen by correlation gas chromatography.

PubMed

Maxwell, Rachel; Chickos, James

2012-02-01

The vaporization enthalpies of (S)-ibuprofen and (S)-naproxen measured by correlation gas chromatography at T = 298.15 K are reported and compared with literature values. Adjustment of the fusion enthalpies of (RS)- and (S)-ibuprofen and (S)-naproxen to T = 298.15 K and combined with the vaporization enthalpy of the (S)-enantiomer of both ibuprofen and naproxen also at T = 298.15 K resulted in the sublimation enthalpies of both (S)-enantiomers. On the assumption that the vaporization enthalpy of the racemic form of ibuprofen is within the experimental uncertainty of the chiral form, the sublimation enthalpy of racemic ibuprofen was also evaluated. The vaporization and sublimation enthalpies compare favorably to the most of the literature values for the racemic form of ibuprofen but differ from the value reported for chiral ibuprofen. The literature values of (S)-naproxen are somewhat smaller than the values measured in this work. The following vaporization enthalpies were measured for (S)-ibuprofen and (S)-naproxen, respectively: ΔH(vap) (298.15 K), 106.0 ± 5.5, 132.2 ± 5.0 kJ·mol(-1) . Sublimation enthalpies of 122.7 ± 5.6 and 155.2 ± 7.1 kJ·mol(-1) were calculated for the (S)-enantiomers of ibuprofen and naproxen and a value of 128.9 ± 5.8 kJ·mol(-1) was estimated for the racemic form of ibuprofen. Copyright © 2011 Wiley Periodicals, Inc.

New estimates of asymmetric decomposition of racemic mixtures by natural beta-radiation sources

NASA Technical Reports Server (NTRS)

Hegstrom, R. A.; Rich, A.; Van House, J.

1985-01-01

Some recent calculations that appeared to invalidate the Vester-Ulbricht hypothesis, which suggests that the chirality of biological molecules originates from the beta-radiolysis of prebiotic racemic mixtures, are reexamined. These calculations apparently showed that the radiolysis-induced chiral polarization can never exceed the chiral polarization produced by statistical fluctuations. It is here shown that several overly restrictive conditions were imposed on these calculations which, when relaxed, allow the radiolysis-induced polarization to exceed that produced by statistical fluctuations, in accordance with the Vester-Ulbricht hypothesis.

Controlled synthesis of racemic indenyl rare-earth metal complexes via the cooperation between the intramolecular coordination of donor atoms and a bridge.

PubMed

Zhou, Shuangliu; Wu, Zhangshuan; Zhou, Lingmin; Wang, Shaowu; Zhang, Lijun; Zhu, Xiancui; Wei, Yun; Zhai, Jinhua; Wu, Jie

2013-06-03

The reactions of Me2Si(C9H6CH2CH2-DG)2 (DG = NMe2 (1), CH2NMe2 (2), OMe (3), and N(CH2CH2)2O (4)) with [(Me3Si)2N]3RE(μ-Cl)Li(THF)3 in toluene afforded a series of racemic divalent rare-earth metal complexes: {η(5):η(1):η(5):η(1)-Me2Si(C9H5CH2CH2-DG)2}RE (DG = NMe2, RE = Yb (6) and Eu (7); DG = CH2NMe2, RE = Yb (8), Eu (9), and Sm (10); DG = OMe, RE = Yb (11) and Eu (12); DG = N(CH2CH2)2O, RE = Yb (13) and Eu (14)). Similarly, the racemic divalent rare-earth metal complexes {η(5):η(1):η(5):η(1)-Me2Si(C9H5CH2CH2CH2NMe2)(C9H5CH2CH2OMe)}RE (RE = Yb (15) and Eu (16)) were also obtained. The reaction of Me2Si(C9H5CH2CH2OMe)2Li2 with NdCl3 gave a racemic dimeric neodymium chloride {η(5):η(1):η(5)-Me2Si(C9H5CH2CH2OMe)2NdCl}2 (17), whereas the reaction of Me2Si(C9H5CH2CH2NMe2)2Li2 with SmCl3 afforded a racemic dinuclear samarium chloride bridged by lithium chloride {η(5):η(1):η(5):η(1)-Me2Si(C9H5CH2CH2NMe2)2SmCl}2(μ-LiCl) (18). Further reaction of complex 18 with LiCH2SiMe3 provided an unexpected rare-earth metal alkyl complex {η(5):η(1):η(5):η(1):σ-Me2Si(C9H5CH2CH2NMe2)[(C9H5CH2CH2N(CH2)Me]}Sm (19) through the activation of an sp(3) C-H bond α-adjacent to the nitrogen atom. Complexes 19 and {η(5):η(1):η(5):η(1):σ-Me2Si(C9H5CH2CH2NMe2)[(C9H5CH2CH2N(CH2)Me]}Y (20) were also obtained by one-pot reactions of Me2Si(C9H5CH2CH2NMe2)2Li2 with RECl3 followed by treatment with LiCH2SiMe3. All compounds were fully characterized by spectroscopic methods and elemental analysis. Complexes 6-10 and 14-20 were further characterized by single-crystal X-ray diffraction analysis. All of the prepared rare-earth metal complexes were racemic, suggesting that racemic organo rare-earth metal complexes could be controllably synthesized by the cooperation between a bridge and the intramolecular coordination of donor atoms.

Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus vascular endothelial growth factor} protein complex by racemic crystallography

PubMed Central

Mandal, Kalyaneswar; Uppalapati, Maruti; Ault-Riché, Dana; Kenney, John; Lowitz, Joshua; Sidhu, Sachdev S.; Kent, Stephen B.H.

2012-01-01

Total chemical synthesis was used to prepare the mirror image (D-protein) form of the angiogenic protein vascular endothelial growth factor (VEGF-A). Phage display against D-VEGF-A was used to screen designed libraries based on a unique small protein scaffold in order to identify a high affinity ligand. Chemically synthesized D- and L- forms of the protein ligand showed reciprocal chiral specificity in surface plasmon resonance binding experiments: The L-protein ligand bound only to D-VEGF-A, whereas the D-protein ligand bound only to L-VEGF-A. The D-protein ligand, but not the L-protein ligand, inhibited the binding of natural VEGF165 to the VEGFR1 receptor. Racemic protein crystallography was used to determine the high resolution X-ray structure of the heterochiral complex consisting of {D-protein antagonist + L-protein form ofVEGF-A}. Crystallization of a racemic mixture of these synthetic proteins in appropriate stoichiometry gave a racemic protein complex of more than 73 kDa containing six synthetic protein molecules. The structure of the complex was determined to a resolution of 1.6 Å. Detailed analysis of the interaction between the D-protein antagonist and the VEGF-A protein molecule showed that the binding interface comprised a contact surface area of approximately 800 Å2 in accord with our design objectives, and that the D-protein antagonist binds to the same region of VEGF-A that interacts with VEGFR1-domain 2. PMID:22927390

Field response of Dendroctonus frontalis (Coleoptera: Scolytinae) to synthetic semiochemicals in Chiapas, Mexico.

PubMed

Moreno, Benjamín; Macías, Jorge; Sullivan, Brian T; Clarke, Stephen R

2008-12-01

Dendroctonus frontalis Zimmermann (Coleoptera: Scolytinae) is the most serious pest of pines (Pinus spp.) in Mexico. Conspecifics are attracted to trees undergoing colonization by the aggregation pheromone frontalin, which is synergized by odors of pine oleoresin released from beetle-damaged host tissue. Synthetic racemic frontalin combined with turpentine has been the operational bait used in traps for monitoring populations of D. frontalis in Mexico as well as the United States. Recently, racemic endo-brevicomin has been reported to be a synergist of the frontalin/turpentine bait and as an important component of the aggregation pheromone for D. frontalis populations in the United States. To determine whether racemic endo-brevicomin also might function as an aggregation synergist for the geographically isolated D. frontalis populations of Central America and Mexico, we performed a field trapping trial in Lagunas de Montebello National Park, Chiapas, Mexico, during July and August 2007. The combination of endo-brevicomin (placed either directly on the trap or 4 m away) plus racemic frontalin and turpentine caught at least 5 times more D. frontalis of both sexes than did turpentine either alone or in combination with either frontalin or endo-brevicomin. The addition of endo-brevicomin to the frontalin/turpentine bait also increased the proportion of females trapped. We conclude that the addition of endo-brevicomin might substantially improve the efficiency of the frontalin/turpentine bait for monitoring of D. frontalis in Central America and Mexico. We discuss factors that reconcile our results with previous studies that reported endo-brevicomin to be an attractant antagonist for populations of D. frontalis in Mexico and Honduras.

Stereoselectivity of the arene epoxide pathway of mephenytoin hydroxylation in man.

PubMed

Küpfer, A; Lawson, J; Branch, R A

1984-02-01

Stereoselective metabolism of mephenytoin has been investigated in four normal subjects by comparing urinary recoveries of hydroxylated metabolites after administration of racemic RS-mephenytoin (1.4 mmol/day) and R-mephenytoin (0.7 mmol/day) on separate occasions. Gas chromatography-mass spectrometry was employed to measure the urinary recovery of 3-methyl-5-(4-hydroxyphenyl)-5-ethylhydantoin (4-OH-M) and mephenytoin catechol, methylcatechol, and dihydrodiol metabolites. Following a single oral dose of racemic mephenytoin, 4-OH-M, mephenytoin catechol, and methylcatechol metabolites were identified in urine mainly as conjugates, whereas the dihydrodiol metabolite was recovered mainly in its unconjugated form. Urinary elimination of each metabolite was similar on days 1 and 10 of chronic racemic mephenytoin administration. Following R-mephenytoin administration, urinary recoveries of hydroxylated metabolites were five to 10 times smaller than after administration of the racemic drug. This implies substrate-stereoselective hydroxylation of the S-enantiomer of mephenytoin. In one subject with a genetic deficiency of aromatic mephenytoin hydroxylation deficiency, the excretion of each hydroxylated mephenytoin metabolite after RS-mephenytoin administration was decreased to 5-15% of the values found in the four extensively hydroxylating study volunteers. The impaired formation of hydroxylated mephenytoin metabolites in genetic hydroxylation deficiency, in conjunction with stereoselective hydroxylation of S-mephenytoin via an extensive NIH shift in normal man, is consistent with the hypothesis that the formation of the S-mephenytoin arene oxide is under genetic control and represents the initial enzymatic reaction of stereoselective aromatic mephenytoin hydroxylation. The formation of this potentially reactive metabolite of S-mephenytoin may have implications in mephenytoin-induced toxicity.

[11C]metaraminol, a false neurotransmitter: preparation, metabolite studies and positron emission tomography examination in monkey.

PubMed

Någren, K; Halldin, C; Swahn, C G; Suhara, T; Farde, L

1996-04-01

No-carrier-added racemic [11C]metaraminol was prepared by a selective condensation of [11C]nitroethane with 3-hydroxy-benzaldehyde using tetrabutylammonium fluoride in tetrahydrofuran (THF) as a catalyst, followed by a reduction with Raney nickel in formic acid. [11C]Metaraminol was produced in 30 to 45% decay-corrected yield from [11C]nitroethane (13 to 20% decay corrected from [11C]CO2) within 45 to 55 min total synthesis time. Reversed phase high-performance liquid chromatography (HPLC) was used for the separation of the racemic erythro- and threo-forms of [11C]metaraminol. The radiochemical purity was higher than 98%, and the specific radioactivity at the end of synthesis was 500 to 800 Ci/mmol (18 to 30 GBq/mumol). Positron emission tomography (PET) examination of racemic erythro-[11C]metaraminol in a Cynomolgus monkey showed a high uptake of radioactivity in the heart. Following pretreatment with the selective norepinephrine reuptake inhibitor desipramine, the radioactivity uptake in the myocardium was markedly reduced (80%), demonstrating the specificity of erythro-[11C]metaraminol for the norepinephrine reuptake system of the heart. Pretreatment with desipramine had no effect on radioactivity in lung. The metabolism was rapid for [11C]metaraminol. The amounts of the total radioactivity representing [11C]metaraminol in plasma, determined by HPLC, were 14% at 6 min and 8% at 34 min. The high specific uptake of racemic erythro-[11C]metaraminol indicates that enantiomerically pure (R,S)-[11C]metaraminol has potential for detailed mapping of the sympathetic innervation of the human myocardium.

Molecular and chiral analyses of some protein amino acid derivatives in the Murchison and Murray meteorite

NASA Astrophysics Data System (ADS)

Pizzarello, Sandra; Cooper, George W.

2001-07-01

The varied organic suite extracted from the Murchison meteorite contains several amino acids that are common to the biosphere. Some of these have been found to be non-racemic, but the indigenous nature of their L-enantiomeric excesses has been subject to debate in view of possible terrestrial contamination. We have investigated two amino acids of common terrestrial and meteoritic occurrence, alanine and glutamic acid, and assessed their indigenous enantiomeric ratios in the Murchison and Murray meteorites through the ratios of some of their derivatives. Analyzed were: N-acetyl alanine, ??imino propioacetic acid, N-acetyl glutamic acid and pyroglutamic acid. Both alanine derivatives were found to be racemic, while those of glutamic acid showed L-enantiomeric excesses varying from 16% to 47.2% for pyroglutamic acid, and from 8.6% to 41% for N-acetyl glutamic acid. The ?13C was determined for the two enantiomers of Murchison pyroglutamic acid both before and after acid hydrolysis of the lactam to glutamic acid. The values of +27.7 (D-pyro), +10.0 (L-pyro), +32.2 (D-glu) and +14.6 (L-glu) were obtained. The racemic nature of alanine derivatives strongly suggests that alanine itself, as indigenous to the meteorite, is racemic. The explanation of the L-enantiomeric excesses found for glutamic acid derivatives is less direct; however, the variability of the enantiomeric ratios for these compounds and the distinctly lower ?13C values determined for pyroglutamic L-enantiomer point to a terrestrial contamination, possibly dating to the time of fall.

Chirality Emergence in Thin Solid Films of Amino Acids by Polarized Light from Synchrotron Radiation and Free Electron Laser

PubMed Central

Takahashi, Jun-ichi; Shinojima, Hiroyuki; Seyama, Michiko; Ueno, Yuko; Kaneko, Takeo; Kobayashi, Kensei; Mita, Hajime; Adachi, Mashahiro; Hosaka, Masahito; Katoh, Masahiro

2009-01-01

One of the most attractive hypothesis for the origin of homochirality in terrestrial bioorganic compounds is that a kind of “chiral impulse” as an asymmetric excitation source induced asymmetric reactions on the surfaces of such materials such as meteorites or interstellar dusts prior to the existence of terrestrial life (Cosmic Scenario). To experimentally introduce chiral structure into racemic films of amino acids (alanine, phenylalanine, isovaline, etc.), we irradiated them with linearly polarized light (LPL) from synchrotron radiation and circularly polarized light (CPL) from a free electron laser. After the irradiation, we evaluated optical anisotropy by measuring the circular dichroism (CD) spectra and verified that new Cotton peaks appeared at almost the same peak position as those of the corresponding non-racemic amino acid films. With LPL irradiation, two-dimensional anisotropic structure expressed as linear dichroism and/or linear birefringence was introduced into the racemic films. With CPL irradiation, the signs of the Cotton peaks exhibit symmetrical structure corresponding to the direction of CPL rotation. This indicates that some kinds of chiral structure were introduced into the racemic film. The CD spectra after CPL irradiation suggest the chiral structure should be derived from not only preferential photolysis but also from photolysis-induced molecular structural change. These results suggest that circularly polarized light sources in space could be associated with the origin of terrestrial homochirality; that is, they would be effective asymmetric exciting sources introducing chiral structures into bio-organic molecules or complex organic compounds. PMID:19742124

Necessary conditions for the emergence of homochirality via autocatalytic self-replication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stich, Michael; Ribó, Josep M.; Blackmond, Donna G., E-mail: blackmond@scripps.edu

We analyze a recent proposal for spontaneous mirror symmetry breaking based on the coupling of first-order enantioselective autocatalysis and direct production of the enantiomers that invokes a critical role for intrinsic reaction noise. For isolated systems, the racemic state is the unique stable outcome for both stochastic and deterministic dynamics when the system is in compliance with the constraints dictated by the thermodynamics of chemical reaction processes. In open systems, the racemic outcome also results for both stochastic and deterministic dynamics when driving the autocatalysis unidirectionally by external reagents. Nonracemic states can result in the latter only if the reversemore » reactions are strictly zero: these are kinetically controlled outcomes for small populations and volumes, and can be simulated by stochastic dynamics. However, the stability of the thermodynamic limit proves that the racemic outcome is the unique stable state for strictly irreversible externally driven autocatalysis. These findings contradict the suggestion that the inhibition requirement of the Frank autocatalytic model for the emergence of homochirality may be relaxed in a noise-induced mechanism.« less

Organocatalytic aza-Michael/retro-aza-Michael reaction: pronounced chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction.

PubMed

Cai, Yong-Feng; Li, Li; Luo, Meng-Xian; Yang, Ke-Fang; Lai, Guo-Qiao; Jiang, Jian-Xiong; Xu, Li-Wen

2011-05-01

A detailed experimental investigation of an aza-Michael reaction of aniline and chalcone is presented. A series of Cinchona alkaloid-derived organocatalysts with different functional groups were prepared and used in the aza-Michael and retro-aza-Michael reaction. There was an interesting finding that a complete reversal of stereoselectivity when a benzoyl group was introduced to the cinchonine and cinchonidine. The chirality amplification vs. time proceeds in the quinine-derived organocatalyst containing silicon-based bulky group, QN-TBS, -catalyzed aza-Michael reaction under solvent-free conditions. In addition, we have demonstrated for the first time that racemization was occurred in suitable solvents under mild conditions due to retro-aza-Michael reaction of the Michael adduct of aniline with chalcone. These indicate the equilibrium of retro-aza-Michael reaction and aza-Michael reaction produce the happening of chirality amplification in aza-Michael reaction and racemization via retro-aza-Michael reaction under different conditions, which would be beneficial to the development of novel chiral catalysts for the aza-Michael reactions. Copyright © 2011 Wiley-Liss, Inc.

Behavioral bioassays of termite trail pheromones : Recruitment and orientation effects of cembrene-A inNasutitermes costalis (Isoptera: Termitidae) and discussion of factors affecting termite response in experimental contexts.

PubMed

Hall, P; Traniello, J F

1985-11-01

The monocyclic 14-membered ring diterpene, cembrene-A, previously identified as a nasutitermitine trail pheromone, was tested for its effectiveness as a trail pheromone inNasutitermes costalis. Artificial trails prepared from serial dilutions of racemic cembrene-A over a concentration range of 10(-1)-10(-6) mg/ml were ineffective in recruiting termites. Serial dilutions of racemic cembrene-A ranging in concentration from 10(-1) to 10(-5) mg/ml produced an orientation effect. Chiral cembrene-A produced recruitment in soldiers at 10(-1) and 10(-3) mg/ml and was less ineffective in recruiting workers. Soldiers always showed a lower and more variable recruitment response to chiral cembrene-A than to sternal gland extracts. The behavioral response to both chiral and racemic cembrene-A was different in quantity and quality from that observed for sternal gland extract. Based on the results of these behavioral tests, cembrene-A appears to be a generalized nasute orientation pheromone which may show recruitment properties at unnaturally high concentrations.

Gender differences in D-aspartic acid content in skull bone.

PubMed

Torikoshi-Hatano, Aiko; Namera, Akira; Shiraishi, Hiroaki; Arima, Yousuke; Toubou, Hirokazu; Ezaki, Jiro; Morikawa, Masami; Nagao, Masataka

2012-12-01

In forensic medicine, the personal identification of cadavers is one of the most important tasks. One method of estimating age at death relies on the high correlation between racemization rates in teeth and actual age, and this method has been applied successfully in forensic odontology for several years. In this study, we attempt to facilitate the analysis of racemized amino acids and examine the determination of age at death on the basis of the extent of aspartic acid (Asp) racemization in skull bones. The specimens were obtained from 61 human skull bones (19 females and 42 males) that underwent judicial autopsy from October 2010 to May 2012. The amount of D-Asp and L-Asp, total protein, osteocalcin, and collagen I in the skull bones was measured. Logistic regression analysis was performed for age, sex, and each measured protein. The amount of D-Asp in the female skull bones was significantly different from that in the male skull bones (p = 0.021), whereas the amount of L-Asp was similar. Thus, our study indicates that the amount of D-Asp in skull bones is different between the sexes.

Pharmacological evaluation of a novel cyclic phosphatidic acid derivative 3-S-cyclic phosphatidic acid (3-S-cPA).

PubMed

Nozaki, Emi; Gotoh, Mari; Tanaka, Ryo; Kato, Masaru; Suzuki, Takahiro; Nakazaki, Atsuo; Hotta, Harumi; Kobayashi, Susumu; Murakami-Murofushi, Kimiko

2012-05-15

Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator possessing cyclic phosphate ring, which is necessary for its specific biological activities. To stabilize cyclic phosphate ring of cPA, we synthesized a series of cPA derivatives. We have shown that racemic 3-S-cPA, with a phosphate oxygen atom replaced with a sulfur atom at the sn-3, was a more effective autotaxin (ATX) inhibitor than cPA. In this study, we showed that racemic 3-S-cPA also had potent biological activities such as inhibition of cancer cell migration, suppression of the nociceptive reflex, and attenuation of ischemia-induced delayed neuronal cell death in the hippocampal CA1. Moreover, we synthesized both enantiomers of palmitoleoyl derivative of 3-S-cPA, and found that the chirality of 3-S-cPA is not involved in ATX inhibition. Based on these findings, racemic 3-S-cPA is suggested as an effective therapeutic compound like cPA. Copyright © 2012 Elsevier Ltd. All rights reserved.

Flow chemistry and polymer-supported pseudoenantiomeric acylating agents enable parallel kinetic resolution of chiral saturated N-heterocycles

NASA Astrophysics Data System (ADS)

Kreituss, Imants; Bode, Jeffrey W.

2017-05-01

Kinetic resolution is a common method to obtain enantioenriched material from a racemic mixture. This process will deliver enantiopure unreacted material when the selectivity factor of the process, s, is greater than 1; however, the scalemic reaction product is often discarded. Parallel kinetic resolution, on the other hand, provides access to two enantioenriched products from a single racemic starting material, but suffers from a variety of practical challenges regarding experimental design that limit its applications. Here, we describe the development of a flow-based system that enables practical parallel kinetic resolution of saturated N-heterocycles. This process provides access to both enantiomers of the starting material in good yield and high enantiopurity; similar results with classical kinetic resolution would require selectivity factors in the range of s = 100. To achieve this, two immobilized quasienantiomeric acylating agents were designed for the asymmetric acylation of racemic saturated N-heterocycles. Using the flow-based system we could efficiently separate, recover and reuse the polymer-supported reagents. The amide products could be readily separated and hydrolysed to the corresponding amines without detectable epimerization.

Laser spectroscopy and dynamics of crystal lattices of chirally pure and racemic phases of amino acids

NASA Astrophysics Data System (ADS)

Belyanchikov, M. A.; Gorelik, V. S.; Gorshunov, B. P.; Pyatyshev, A. Yu.

2017-03-01

Strong sharp lines due to the librational modes characterized by a pseudoscalar symmetry type have been found in the low-frequency Raman spectra of the lattices of glycine and tyrosine amino acids. The intensities of these lines exceed those for Raman scattering in the region of intramolecular vibrations. The spectra of chirally pure and racemic phases of amino acids differ significantly. The results obtained can be used to observe stimulated Raman scattering from the librational modes of crystalline amino acids and monitor the chiral purity of bioactive preparations containing amino acids.

Tandem rhodium catalysis:Exploiting sulfoxides for asymmetric transition-metal catalysis

PubMed Central

Kou, K. G. M.

2015-01-01

Sulfoxides are uncommon substrates for transition-metal catalysis due to their propensity to inhibit catalyst turnover. In a collaborative effort with Ken Houk, we developed the first dynamic kinetic resolution (DKR) of allylic sulfoxides using asymmetric rhodium-catalyzed hydrogenation. Detailed mechanistic analysis of this transformation using both experimental and theoretical methods revealed rhodium to be a tandem catalyst that promoted both hydrogenation of the alkene and racemization of the allylic sulfoxide. Using a combination of deuterium labelling and DFT studies, a novel mode of allylic sulfoxide racemization via a Rh(III)-π-allyl intermediate was identified. PMID:25940066

Synthesis of racemic β-chamigrene, a spiro[5.5]undecane sequiterpene.

PubMed

Antonsen, Simen; Skattebøl, Lars; Stenstrøm, Yngve

2014-12-10

The present paper describes a total synthesis of racemic β-chamigrene, a sesquiterpene with a spiro[5.5]undecane carbon framework. Compared with previously reported β-chamigrene syntheses, we were able to reduce the total number of reaction steps, which also resulted in a significant improvement of the overall yield. The commercially available ketone 6-methylhept-5-en-2-one was transformed by known simple procedures into 3,3-dimethyl-2-methylenecyclohexanone. This reacted with isoprene by a Diels-Alder reaction to give a spiro ketone. An olefination reaction on this compound gave the target molecule.

Enantiodivergent Hydroboration Reactions of a Racemic Allenylsilane with Diisopinocampheylborane and Curtin-Hammett Controlled Double Asymmetric Crotylboration Reactions of (S)-E-α-phenyldimethylsilyl(ddiisopinocampheyl)-crotylborane

PubMed Central

Chen, Ming; Roush, William R.

2013-01-01

The enantiodivergent hydroboration reactions of racemic allenylsilane (±)-4 with (dIpc)2BH and subsequent crotylboration of achiral aldehydes with the product crotylborane (S)-E-5 at −78 °C provide (E)-δ-silyl-anti-homoallylic alcohols 6 in 71–89% yield and with 93–96% ee. Intriguingly, mismatched double asymmetric crotylboration reactions of enantioenriched chiral aldehydes 20 with (S)-E-5 proceed under Curtin-Hammett control to give anti-3-hydroxylcrotylsilanes 24 as the only products. PMID:24039304

Enantiodivergent hydroboration reactions of a racemic allenylsilane with diisopinocampheylborane and Curtin–Hammett controlled double asymmetric crotylboration reactions of (S)-E-αphenyldimethylsilyl(ddiisopinocampheyl)-crotylborane

PubMed Central

Chen, Ming; Roush, William R.

2013-01-01

The enantiodivergent hydroboration reactions of racemic allenylsilane (±)-4 with (dIpc)2BH and subsequent crotylboration of achiral aldehydes with the product crotylborane (S)-E-5 at −78 °C provide (E)-δ-silyl-anti-homoallylic alcohols 6 in 71–89% yield and with 93–96% ee. Intriguingly, mismatched double asymmetric crotylboration reactions of enantioenriched chiral aldehydes 20 with (S)-E-5 proceed under Curtin–Hammett control to give anti-β-hydroxylcrotylsilanes 24 as the only products. PMID:24068848

Tandem rhodium catalysis: exploiting sulfoxides for asymmetric transition-metal catalysis.

PubMed

Kou, K G M; Dong, V M

2015-06-07

Sulfoxides are uncommon substrates for transition-metal catalysis due to their propensity to inhibit catalyst turnover. In a collaborative effort with Ken Houk, we developed the first dynamic kinetic resolution (DKR) of allylic sulfoxides using asymmetric rhodium-catalyzed hydrogenation. A detailed mechanistic analysis of this transformation using both experimental and theoretical methods revealed rhodium to be a tandem catalyst that promoted both hydrogenation of the alkene and racemization of the allylic sulfoxide. Using a combination of deuterium labelling and DFT studies, a novel mode of allylic sulfoxide racemization via a Rh(III)-π-allyl intermediate was identified.

Sources and Fate of Chiral Organochlorine Pesticides in Western U.S. National Park Ecosystems

PubMed Central

Genualdi, Susan A.; Hageman, Kimberly J.; Ackerman, Luke K.; Usenko, Sascha; Simonich, Staci L. Massey

2011-01-01

The enantiomer fractions (EFs) of alpha-hexachlorocyclohexane (α-HCH), cis-, trans-, and oxychlordane, and heptachlor epoxide were measured in 73 snow, fish, and sediment samples collected from remote lake catchments, over a wide range of latitudes, in seven western U.S. National Parks/Preserves in order to investigate their sources, fate, accumulation and biotransformation in these ecosystems. The present study is novel because these lakes had no inflow or outflow and the measurement of chiral organochlorine pesticides (OCPs) EFs in snowpack from these lake catchments provided a better understanding of the OCP sources in the Western U.S., while their measurement in fish and sediment provided a better understanding of their biotic transformations within the lake catchments. Non-racemic α-HCH was measured in seasonal snowpack collected from continental U.S. National Parks, while racemic α-HCH was measured in seasonal snowpack collected from the Alaskan parks, suggesting the influence of regional sources to the continental U.S. parks and long-range sources to the Alaskan parks. The α-HCH EFs measured in trout collected from the lake catchments were similar to the α-HCH EFs measured in seasonal snowpack collected from the same lake catchments, suggesting that these fish did not biotransform α-HCH enantioselectively. Racemic cis-chlordane was measured in seasonal snowpack and sediment collected from Sequoia, indicating that it had not undergone significant enantioselective biotransformation in urban soils since its use as a termiticide in the surrounding urban areas. However, non-racemic cis-chlordane was measured in seasonal snowpack and sediments from Rocky Mountain, suggesting cis-chlordane does undergo enantioselective biotransformation in agricultural soils. The trout from these lakes showed preferential biotransformation of the (+)-enantiomer of cis-chlordane and the (−)-enantiomer of trans-chlordane. PMID:21462235

Racemization of Valine by Impact-Induced Heating

NASA Astrophysics Data System (ADS)

Furukawa, Yoshihiro; Takase, Atsushi; Sekine, Toshimori; Kakegawa, Takeshi; Kobayashi, Takamichi

2018-03-01

Homochirality plays an important role in all living organisms but its origin remains unclear. It also remains unclear whether such chiral molecules survived terrestrial heavy impact events. Impacts of extraterrestrial objects on early oceans were frequent and could have affected the chirality of oceanic amino acids when such amino acids accumulated during impacts. This study investigated the effects of shock-induced heating on enantiomeric change of valine with minerals such as olivine ([Mg0.9, Fe0.1]2SiO4), hematite (Fe2O3), and calcite (CaCO3). With a shock wave generated by an impact at 0.8 km/s, both d- and l-enriched valine were significantly decomposed and partially racemized under all experimental conditions. Different minerals had different shock impedances; therefore, they provided different P-T conditions for identical impacts. Furthermore, the high pH of calcite promoted the racemization of valine. The results indicate that in natural hypervelocity impacts, amino acids in shocked oceanic water would have decomposed completely, since impact velocity and the duration of shock compression and heating are typically greater in hypervelocity impact events than those in experiments. Even with the shock wave by the impact of small and decelerated projectiles in which amino acids survive, the shock heating may generate sufficient heat for significant racemization in shocked oceanic water. However, the duration of shock induced heating by small projectiles is limited and the population of such decelerated projectiles would be limited. Therefore, even though impacts of asteroids and meteorites were frequent on the prebiotic Earth, impact events would not have significantly changed the ee of proteinogenic amino acids accumulated in the entire ocean.

Effect of Seed Position on Parental Plant on Proportion of Seeds Produced with Nondeep and Intermediate Physiological Dormancy

PubMed Central

Lu, Juan J.; Tan, Dun Y.; Baskin, Carol C.; Baskin, Jerry M.

2017-01-01

The position in which seeds develop on the parental plant can have an effect on dormancy-break and germination. We tested the hypothesis that the proportion of seeds with intermediate physiological dormancy (PD) produced in the proximal position on a raceme of Isatis violascens plants is higher than that produced in the distal position, and further that this difference is related to temperature during seed development. Plants were watered at 3-day intervals, and silicles and seeds from the proximal (early) and distal (late) positions of racemes on the same plants were collected separately and tested for germination. After 0 and 6 months dry storage at room temperature (afterripening), silicles and seeds were cold stratified for 0–16 weeks and tested for germination. Mean daily maximum and minimum temperatures during development/maturation of the two groups of seeds did not differ. A higher proportion of seeds with the intermediate level than with the nondeep level of PD was produced by silicles in the proximal position than by those in the distal position, while the proportion of seeds with nondeep PD was higher in the distal than in the proximal position of the raceme. The differences were not due only to seed mass. Since temperature and soil moisture conditions were the same during development of the seeds in the raceme, differences in proportion of seeds with intermediate and nondeep PD are attributed to position on parental plant. The ecological consequence of this phenomenon is that it ensures diversity in dormancy-breaking and germination characteristics within a seed cohort, a probable bet-hedging strategy. This is the first demonstration of position effects on level of PD in the offspring. PMID:28232842

Does Aspartic Acid Racemization Constrain the Depth Limit of the Subsurface Biosphere?

NASA Technical Reports Server (NTRS)

Onstott, T C.; Magnabosco, C.; Aubrey, A. D.; Burton, A. S.; Dworkin, J. P.; Elsila, J. E.; Grunsfeld, S.; Cao, B. H.; Hein, J. E.; Glavin, D. P.;

Methadone: A Substrate and Mechanism-Based Inhibitor of CYP19 (Aromatase)

PubMed Central

Bies, Robert; Kamden, Landry K.; Desta, Zeruesenay; Flockhart, David A.

2010-01-01

The peripheral conversion of testosterone to estradiol by aromatase is the primary source of endogenous estrogen in postmenopausal women. Studies indicating that placental aromatase is able to metabolize methadone to its primary metabolite, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidin (EDDP), led us to test the hypothesis that methadone is able to act as an inhibitor of aromatase. Using recombinant human CYP19, we examined the ability of methadone to bring about either reversible or mechanism-based inhibition of the conversion of testosterone to estradiol. To test for reversible inhibition, racemic methadone or its metabolite EDDP or 2-ethyl-5-methyl-3, 3-diphenylpyrroline (EMDP) was incubated for 30 min with testosterone at the Km (4 μM). To test for mechanism-based inhibition, microsomal preincubations were performed for up to 30 min using racemic methadone (1–1000 μM), R- or S-methadone (0.5–500 μM), or EDDP or EMDP (10 and 100 μM) followed by incubation with testosterone at a Vmax concentration (50 μM). Racemic methadone, EDDP, and EMDP did not act as competitive inhibitors of CYP19. Preincubation of methadone, EDDP, or EMDP with CYP19 resulted in time- and concentration-dependent inhibition, indicating a mechanism-based reaction that destroys CYP19 activity. The KI and kinact values for racemic methadone were calculated to be 40.6 ± 2.8 μM and 0.061 ± 0.001 min−1, respectively. No stereoselectivity was observed. Methadone is metabolized by CYP19 and may act as a potent inhibitor of CYP19 in vivo. These findings may contribute to variability in methadone clearance, to drug-drug interactions, and to side effects observed in individual patients. PMID:20410453

Does aspartic acid racemization constrain the depth limit of the subsurface biosphere?

PubMed

Onstott, T C; Magnabosco, C; Aubrey, A D; Burton, A S; Dworkin, J P; Elsila, J E; Grunsfeld, S; Cao, B H; Hein, J E; Glavin, D P; Kieft, T L; Silver, B J; Phelps, T J; van Heerden, E; Opperman, D J; Bada, J L

2014-01-01

Previous studies of the subsurface biosphere have deduced average cellular doubling times of hundreds to thousands of years based upon geochemical models. We have directly constrained the in situ average cellular protein turnover or doubling times for metabolically active micro-organisms based on cellular amino acid abundances, D/L values of cellular aspartic acid, and the in vivo aspartic acid racemization rate. Application of this method to planktonic microbial communities collected from deep fractures in South Africa yielded maximum cellular amino acid turnover times of ~89 years for 1 km depth and 27 °C and 1-2 years for 3 km depth and 54 °C. The latter turnover times are much shorter than previously estimated cellular turnover times based upon geochemical arguments. The aspartic acid racemization rate at higher temperatures yields cellular protein doubling times that are consistent with the survival times of hyperthermophilic strains and predicts that at temperatures of 85 °C, cells must replace proteins every couple of days to maintain enzymatic activity. Such a high maintenance requirement may be the principal limit on the abundance of living micro-organisms in the deep, hot subsurface biosphere, as well as a potential limit on their activity. The measurement of the D/L of aspartic acid in biological samples is a potentially powerful tool for deep, fractured continental and oceanic crustal settings where geochemical models of carbon turnover times are poorly constrained. Experimental observations on the racemization rates of aspartic acid in living thermophiles and hyperthermophiles could test this hypothesis. The development of corrections for cell wall peptides and spores will be required, however, to improve the accuracy of these estimates for environmental samples. © 2013 John Wiley & Sons Ltd.

Alpha B- and βA3-crystallins containing d-aspartic acids exist in a monomeric state.

PubMed

Sakaue, Hiroaki; Takata, Takumi; Fujii, Norihiko; Sasaki, Hiroshi; Fujii, Noriko

2015-01-01

Crystallin stability and subunit-subunit interaction are essential for eye lens transparency. There are three types of crystallins in lens, designated as α-, β-, and γ-crystallins. Alpha-crystallin is a hetero-polymer of about 800kDa, consisting of 35-40 subunits of two different αA- and αB-subunits, each of 20kDa. The β/γ-crystallin superfamily comprises oligomeric β-crystallin (2-6 subunits) and monomeric γ-crystallin. Since lens proteins have very long half-lives, they undergo numerous post-translational modifications including racemization, isomerization, deamidation, oxidation, glycation, and truncation, which may decrease crystallin solubility and ultimately cause cataract formation. Racemization and isomerization of aspartyl (Asp) residues have been detected only in polymeric α- and oligomeric β-crystallin, while the situation in monomeric γ-crystallin has not been studied. Here, we investigated the racemization and isomerization of Asp in the γ-crystallin fraction of elderly donors. The results show that Asp residues of γS-, γD- and γC-crystallins were not racemized and isomerized. However, strikingly, we found that a portion of αB-crystallin and βA3-crystallin moved to the lower molecular weight fraction which is the same size of γ-crystallin. In those fractions, Asp-96 of αB-crystallin and Asp-37 of βA3-crystallin were highly inverted, which do not occur in the native lens higher molecular weight fraction. Our results indicate the possibility that the inversion of Asp residues may induce dissociation of αB- and βA3-crystallins from the polymeric and oligomeric states. This is the first report that stereoinversion of amino acids disturbs lens protein assembly in aged human lens. Copyright © 2014 Elsevier B.V. All rights reserved.

Collagen turnover in normal and degenerate human intervertebral discs as determined by the racemization of aspartic acid.

PubMed

Sivan, Sarit-Sara; Wachtel, Ellen; Tsitron, Eve; Sakkee, Nico; van der Ham, Frits; Degroot, Jeroen; Roberts, Sally; Maroudas, Alice

2008-04-04

Knowledge of rates of protein turnover is important for a quantitative understanding of tissue synthesis and catabolism. In this work, we have used the racemization of aspartic acid as a marker for the turnover of collagen obtained from healthy and pathological human intervertebral disc matrices. We measured the ratio of the d- and l-isomers in collagen extracted from these tissues as a function of age between 16 and 77 years. For collagen taken from healthy discs, the fractional increase of d-Asp was found to be 6.74 x 10(-4)/year; for degenerate discs, the corresponding rate was 5.18 x 10(-4)/year. Using the racemization rate found previously for the stable population of collagen molecules in dentin, we found that the rate of collagen turnover (k(T)) in discs is not constant but rather a decreasing function of age. The average turnover rate in normal disc between the ages of 20 and 40 is 0.00728 +/- 0.00275/year, and that between the ages of 50 and 80 is 0.00323 +/- 0.000947/year, which correspond to average half-lives of 95 and 215 years, respectively. Turnover of collagen from degenerate discs may be more rapid than that found for normal discs; however, statistical analysis leaves this point uncertain. The finding of a similar correlation between the accumulation of d-Asp and that of pentosidine for three normal collagenous tissues further supports the idea that the accumulation of pentosidine in a particular tissue can, along with the racemization of aspartic acid, be used as a reliable measure of protein turnover.

Mechanistic and kinetic insights into the thermally induced rearrangement of alpha-pinene.

PubMed

Stolle, Achim; Ondruschka, Bernd; Findeisen, Matthias

2008-11-07

The thermal rearrangement of alpha-pinene (1) is interesting from mechanistic as well as kinetic point of view. Carrier gas pyrolyses with 1 and its acyclic isomers ocimene (2) and alloocimene (3) were performed to investigate the thermal network of these hydrocarbons. Kinetic analysis of the major reaction steps allows for a deeper insight in the reaction mechanism. Thus it was possible to explain the racemization of 1, the formation of racemic limonene (4), and the absence of the primary pyrolysis product 2 in the reaction mixture resulting from thermal rearrangement of 1. Results supported the conclusion that the reactions starting with 1 involve biradical transition states.

The gas chromatographic resolution of DL-isovaline

NASA Technical Reports Server (NTRS)

Flores, J. J.; Bonner, W. A.; Van Dort, M. A.

1977-01-01

Isovaline is of cosmological interest because it is one of the 12 non-protein amino acids which have been isolated from the Murchison meteorite, and unlike the other chiral amino acids in this meteorite, it has no alpha-hydrogen at its asymmetric center and hence cannot racemize by the customary alpha-hydrogen-dependent mechanisms which engender racemization in ordinary amino acids. Experiments were conducted in which a .01 M solution of N-TFA-DL-isovalyl-L-leucine isopropyl ester in nitromethane was injected into the capillary column of a gas chromatograph coupled to a digital electronic integrator-recorder. Efflux times and integrated peak area percents are shown next to each diastereometer peak.

Molecular Bases of Enantioselectivity of Haloalkane Dehalogenase DbjA

NASA Astrophysics Data System (ADS)

Sato, Yukari; Natsume, Ryo; Prokop, Zbynek; Brezovsky, Jan; Chaloupkova, Radka; Damborsky, Jiri; Nagata, Yuji; Senda, Toshiya

Enzymes are widely used for the synthesis of pharmaceuticals, agrochemicals, and food additives because they can catalyze high enantioselective transformations. In order to construct selective enzymes by protein engineering, it is important to understand the molecular basis of enzyme-substrate interactions that contribute to enantioselectivity. The haloalkane dehalogenase DbjA showed high enantioselectivity for two racemic mixtures: α-bromoesters and β-bromoalkanes. Thermodynamic analysis, protein crystallography, and computer simulations indicated that DbjA carries two bases for the enantiodiscrimination of each racemic mixture. This study helps us understand the molecular basis of the enantioselectivity and opens up new possibilities for constructing enantiospecific biocatalysts through protein engineering.

Effect of the chiral discrimination on the vibrational properties of (R)-, (S)- and (R, S)-ibuprofen/methyl-β-cyclodextrin inclusion complexes

NASA Astrophysics Data System (ADS)

Crupi, V.; Guella, G.; Majolino, D.; Mancini, I.; Paciaroni, A.; Rossi, B.; Venuti, V.; Verrocchio, P.; Viliani, G.

2011-05-01

The effects of chiral discrimination of ibuprofen (IBP) on the complexation process with methyl-β-cyclodextrin (Me-β-CD) were investigated in the solid phase by FTIR-ATR spectroscopy and numerical simulation. The inclusion mechanism was deduced from the temperature-dependent analysis of the vibrational spectra, in the C=O stretching region, of complexes formed by Me-β-CD with the two enantiomeric and the racemic forms of IBP. The mechanism turned out to be enthalpy-driven, with IBP enantiomers giving rise to more stable inclusion complexes with respect to the racemate.

2-Methyltetrahydrofuran and cyclopentyl methyl ether for green solid-phase peptide synthesis.

PubMed

Jad, Yahya E; Acosta, Gerardo A; Khattab, Sherine N; de la Torre, Beatriz G; Govender, Thavendran; Kruger, Hendrik G; El-Faham, Ayman; Albericio, Fernando

2016-02-01

2-MeTHF and CPME were evaluated as greener alternatives for the most employed solvents in peptide synthesis. The ability of these solvents to dissolve amino acid derivatives and a range of coupling reagents were evaluated as well as the swelling of polystyrene and polyethylene glycol resins. In addition, racemization and coupling efficiencies were also determined. We concluded that the use of 2-MeTHF with combination of DIC/OxymaPure gave the lowest racemization level during stepwise synthesis of Z-Phg-Pro-NH2 and the highest purity during SPPS of Aib-enkephalin pentapeptide (H-Tyr-Aib-Aib-Phe-Leu-NH2).

Chiral J-aggregates of atropo-enantiomeric perylene bisimides and their self-sorting behavior.

PubMed

Xie, Zengqi; Stepanenko, Vladimir; Radacki, Krzysztof; Würthner, Frank

2012-06-04

Herein we report on structural, morphological, and optical properties of homochiral and heterochiral J-aggregates that were created by nucleation-elongation assembly of atropo-enantiomerically pure and racemic perylene bisimides (PBIs), respectively. Our detailed studies with conformationally stable biphenoxy-bridged chiral PBIs by UV/Vis absorption, circular dichroism (CD) spectroscopy, and atomic force microscopy (AFM) revealed structurally as well as spectroscopically quite different kinds of J-aggregates for enantiomerically pure and racemic PBIs. AFM investigations showed that enantiopure PBIs form helical nanowires of unique diameter and large length-to-width ratio by self-recognition, while racemic PBIs provide irregular-sized particles by self-discrimination of the enantiomers at the stage of nucleation. Steady-state fluorescence spectroscopy studies revealed that the photoluminescence efficiency of homochiral J-aggregated nanowires (47±3%) is significantly higher than that of heterochiral J-aggregated particle-like aggregates (12±3%), which is explained in terms of highly ordered molecular stacking in one-dimensional nanowires of homochiral J-aggregates. Our present results demonstrate the high impact of homochirality on the construction of well-defined nanostructures with unique optical properties. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of a new drug of abuse: cathinone derivative 1-(3,4-dimethoxyphenyl)-2-(ethylamino)pentan-1-one.

PubMed

Weiß, Jennifer A; Taschwer, Magdalena; Kunert, Olaf; Schmid, Martin G

2015-03-01

Recently, novel psychoactive drugs for human abuse such as amphetamines, phenethylamines, benzofuries, and tryptamines, cathinones have gained high popularity. These designer drugs are mainly sold via online stores as "bath salts" and are labeled "not for human consumption." Due to the novelty of the compounds, only a little information about pharmacology, toxicology, and the long-term damage they may cause is available. Moreover, there are only few analytical methods for their identification and analysis. Among new cathinone derivatives, 1-(3,4-dimethoxyphenyl)-2-(ethylamino)pentan-1-one (DL-4662), became available via an internet shop. A sample of this compound was purchased and investigated. The first aim of our study was an identity check by NMR spectroscopy and gas chromatography with mass spectrometry. As many of the recreational drugs are chiral and are mainly sold as racemates, a further goal of our research was enantioseparation by gas chromatography with mass spectrometry and high-performance liquid chromatography with UV detection, to prove whether DL-4662 was traded enantiomerically pure or as racemic mixture. Both chiral separation methods showed the presence of a racemate. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-assembling Structures and Sol-Gel Transition of Optically Active and Racemic 12-Hydroxystearic Acids in Organic Solvents

NASA Astrophysics Data System (ADS)

Takeno, Hiroyuki; Mochizuki, Tomomitsu; Yoshiba, Kazuto; Kondo, Shingo; Dobashi, Toshiaki

Self-assembling structures and sol-gel transition in solution of optically active and racemic 12-Hydroxystearic acids (HSA) have been investigated by means of small-angle X-ray scattering (SAXS), differential scanning calorimetry and rheological measurements. Apparently two kinds of gel, transparent gel and turbid gel were obtained in different solvents or by changing concentrations in the same solvent. The melting temperature of the turbid gel is higher than that of the transparent gel. The difference can be qualitatively explained by the dissolution of the crystals (melting point depression) in non-ideal solutions. The SAXS profiles of the transparent gel composed of fibrillar structures have a similar shape at different concentrations, although the intensity is larger for the gels with higher concentrations of 12-HSA. The SAXS analysis reveals that the cross-section of fibrils have square or circular shape (no anisotropic shape) with the radius of gyration 83 Å. On the other hand, for the turbid gel structural inhomnogeneity becomes significant with concentration. The gelation properties and the structures are found to be similar in the racemic HSA gel and the optically active (D-HSA) gel.

Enantioseparation of Mandelic Acid Enantiomers With Magnetic Nano-Sorbent Modified by a Chiral Selector.

PubMed

Tarhan, Tuba; Tural, Bilsen; Tural, Servet; Topal, Giray

2015-11-01

In this study, R(+)-α-methylbenzylamine-modified magnetic chiral sorbent was synthesized and assessed as a new enantioselective solid phase sorbent for separation of mandelic acid enantiomers from aqueous solutions. The chemical structures and magnetic properties of the new sorbent were characterized by vibrating sample magnetometry, transmission electron microscopy, Fourier transform infrared spectroscopy, and dynamic light scattering. The effects of different variables such as the initial concentration of racemic mandelic acid, dosage of sorbent, and contact time upon sorption characteristics of mandelic acid enantiomers on magnetic chiral sorbent were investigated. The sorption of mandelic acid enantiomers followed a pseudo-second-order reaction and equilibrium experiments were well fitted to a Langmuir isotherm model. The maximum adsorption capacity of racemic mandelic acid on to the magnetic chiral sorbent was found to be 405 mg g(-1). The magnetic chiral sorbent has a greater affinity for (S)-(+)-mandelic acid compared to (R)-(-)-mandelic acid. The optimum resolution was achieved with 10 mL 30 mM of racemic mandelic acid and 110 mg of magnetic chiral sorbent. The best percent enantiomeric excess values (up to 64%) were obtained by use of a chiralpak AD-H column. © 2015 Wiley Periodicals, Inc.

Origins of hydration differences in homochiral and racemic crystals of aspartic acid.

PubMed

Juliano, Thomas R; Korter, Timothy M

2015-02-26

The propensity for crystalline hydrates of organic molecules to form is related to the strength of the interactions between molecules, including the chiral composition of the molecular solids. Specifically, homochiral versus racemic crystalline samples can exhibit distinct differences in their ability to form energetically stable hydrates. The focus of the current study is a comparison of the crystal structures and intermolecular forces found in solid-state L-aspartic acid, DL-aspartic acid, and L-aspartic acid monohydrate. The absence of experimental evidence for the DL-aspartic acid monohydrate is considered here in terms of the enhanced thermodynamic stability of the DL-aspartic acid anhydrate crystal as compared to the L-aspartic acid anhydrate as revealed through solid-state density functional theory calculations and terahertz spectroscopic measurements. The results indicate that anhydrous DL-aspartic acid is the more stable solid, not due to intermolecular forces alone but also due to the improved conformations of the molecules within the racemic solid. Hemihydrated and monohydrated forms of DL-aspartic acid have been computationally evaluated, and in each case, the hydrates produce destabilized aspartic acid conformations that prevent DL-aspartic acid hydrate formation from occurring.

Synthesis and Utilization of Trialkylammonium-Substituted Cyclodextrins as Water-Soluble Chiral NMR Solvating Agents for Anionic Compounds.

PubMed

Dowey, Alison E; Puentes, Cira Mollings; Carey-Hatch, Mira; Sandridge, Keyana L; Krishna, Nikhil B; Wenzel, Thomas J

2016-04-01

Cationic trialkylammonium-substituted α-, β-, and γ-cyclodextrins containing trimethyl-, triethyl-, and tri-n-propylammonium substituent groups were synthesized and analyzed for utility as water-soluble chiral nuclear magnetic resonance (NMR) solvating agents. Racemic and enantiomerically pure (3-chloro-2-hydroxypropyl)trimethyl-, triethyl-, and tri-n-propyl ammonium chloride were synthesized from the corresponding trialkyl amine hydrochloride and either racemic or enantiomerically pure epichlorohydrin. The ammonium salts were then reacted with α-, β-, and γ-cyclodextrins at basic pH to provide the corresponding randomly substituted cationic cyclodextrins. The (1) H NMR spectra of a range of anionic, aromatic compounds was recorded with the cationic cyclodextrins. Cyclodextrins with a single stereochemistry at the hydroxy group on the (2-hydroxypropyl)trialkylammonium chloride substituent were often but not always more effective than the corresponding cyclodextrin in which the C-2 position was racemic. In several cases, the larger triethyl or tri-n-propyl derivatives were more effective than the corresponding trimethyl derivative at causing enantiomeric differentiation. None of the cyclodextrin derivatives were consistently the most effective for all of the anionic compounds studied. © 2016 Wiley Periodicals, Inc.

Identification of osteocalcin as a permanent aging constituent of the bone matrix: basis for an accurate age at death determination.

PubMed

Ritz, S; Turzynski, A; Schütz, H W; Hollmann, A; Rochholz, G

1996-01-12

Age at death determination based on aspartic acid racemization in dentin has been applied successfully in forensic odontology for several years now. An age-dependent accumulation of D-aspartic acid has also recently been demonstrated in bone osteocalcin, one of the most abundant noncollagenous proteins of the organic bone matrix. Evaluation of these initial data on in vivo racemization of aspartic acid in bone osteocalcin was taken a step further. After purification of osteocalcin from 53 skull bone specimens, the extent of aspartic acid racemization in this peptide was determined. The D-aspartic acid content of purified bone osteocalcin exhibited a very close relationship to age at death. This confirmed identification of bone osteocalcin as a permanent, 'aging' peptide of the organic bone matrix. Its D-aspartic acid content may be used as a measure of its age and hence that of the entire organism. The new biochemical approach to determination of age at death by analyzing bone is complex and demanding from a methodologic point of view, but appears to be superior in precision and reproducibility to most other methods applicable to bone.

Mineral induced formation of sugar phosphates

NASA Technical Reports Server (NTRS)

Pitsch, S.; Eschenmoser, A.; Gedulin, B.; Hui, S.; Arrhenius, G.

1995-01-01

Glycolaldehyde phosphate, sorbed from highly dilute, weakly alkaline solution into the interlayer of common expanding sheet structure metal hydroxide minerals, condenses extensively to racemic aldotetrose-2, 4-diphophates, and aldohexose-2, 4, 6-triphosphates. The reaction proceeds mainly through racemic erythrose-2, 4-phosphate, and terminates with a large fraction of racemic altrose-2, 4, 6-phosphate. In the absence of an inductive mineral phase, no detectable homogeneous reaction takes place in the concentration- and pH range used. The reactant glycolaldehyde phosphate is practically completely sorbed within an hour from solutions with concentrations as low as 50 micron; the half-time for conversion to hexose phosphates is of the order of two days at room temperature and pH 9.5. Total production of sugar phosphates in the mineral interlayer is largely independent of the glycolaldehyde phosphate concentration in the external solution, but is determined by the total amount of GAP offered for sorption up to the capacity of the mineral. In the presence of equimolar amounts of rac-glyceraldehyde-2-phosphate, but under otherwise similar conditions, aldopentose-2, 4, -diphosphates also form, but only as a small fraction of the hexose-2, 4, 6-phosphates.

Probes for Narcotic Receptor Mediated Phenomena. 37.1 Synthesis and Opioid Binding Affinity of the Final Pair of Oxide-Bridged Phenylmorphans, the ortho- and para-b Isomers and Their N-Phenethyl Analogues, and the Synthesis of the N-Phenethyl Analogues of the ortho- and para-d Isomers

PubMed Central

Kurimura, Muneaki; Liu, Hehua; Sulima, Agnieszka; Hashimoto, Akihiro; Przybyl, Anna K.; Ohshima, Etsuo; Kodato, Shinichi; Deschamps, Jeffrey R.; Dersch, Christina M.; Rothman, Richard B.; Lee, Yong Sok; Jacobson, Arthur E.; Rice, Kenner C.

2008-01-01

In the isomeric series of 12 racemic topologically rigid N-methyl analogues of oxide-bridged phenylmorphans, all but two of the racemates, the ortho- and para-b-oxide-bridged phenylmorphansa 20 and 12, have remained to be synthesized. The b-isomers were very difficult to synthesize because of the highly strained 5,6-trans-fused ring junction that had to be formed. Our successful strategy required functionalization of the position para (or ortho) to a fluorine atom on the aromatic ring using an electron-withdrawing nitro group to activate that fluorine. The racemic N-phenethyl analogues 24 and 16 were moderately potent κ-receptor antagonists in the [35S]GTPγS assay. We synthesized the N-phenethyl-substituted oxide-bridged phenylmorphans in the ortho- and para-d oxide-bridged phenylmorphana series (51 and 52) which had not been previously evaluated using contemporary receptor binding assays to see whether they also have higher affinity for opioid receptors than their N-methyl relatives 46 and 47. PMID:19053757

Chiral magnetic microspheres purified by centrifugal field flow fractionation and microspheres magnetic chiral chromatography for benzoin racemate separation

PubMed Central

Tian, Ailin; Qi, Jing; Liu, Yating; Wang, Fengkang; Ito, Yoichiro; Wei, Yun

2013-01-01

Separation of enantiomers still remains a challenge due to their identical physical and chemical properties in a chiral environment, and the research on specific chiral selector along with separation techniques continues to be conducted to resolve individual enantiomers. In our laboratory the promising magnetic chiral microspheres Fe3O4@SiO2@cellulose-2, 3-bis (3, 5-dimethylphenylcarbamate) have been developed to facilitate the resolution using both its magnetic property and chiral recognition ability. In our present studies this magnetic chiral selector was first purified by centrifuge field flow fractionation, and then used to separate benzoin racemate by a chromatographic method. Uniform-sized and masking-impurity-removed magnetic chiral selector was first obtained by field flow fractionation with ethanol through a spiral column mounted on the type-J planetary centrifuge, and using the purified magnetic chiral selector, the final chromatographic separation of benzoin racemate was successfully performed by eluting with ethanol through a coiled tube (wound around the cylindrical magnet to retain the magnetic chiral selector as a stationary phase) submerged in dry ice. In addition, an external magnetic field facilitates the recycling of the magnetic chiral selector. PMID:23891368

MDMA (N-methyl-3,4-methylenedioxyamphetamine) and its stereoisomers: Similarities and differences in behavioral effects in an automated activity apparatus in mice.

PubMed

Young, Richard; Glennon, Richard A

2008-01-01

Racemic MDMA (0.3-30 mg/kg), S(+)-MDMA (0.3-30 mg/kg), R(-)-MDMA (0.3-50 mg/kg) and saline vehicle (10 ml/kg) were comprehensively evaluated in fully automated and computer-integrated activity chambers, which were designed for mice, and provided a detailed analysis of the frequency, location, and/or duration of 18 different activities. The results indicated that MDMA and its isomers produced stimulation of motor actions, with S(+)-MDMA and (+/-)-MDMA usually being more potent than R(-)-MDMA in measures such as movement (time, distance, velocity), margin distance, rotation (clockwise and counterclockwise), and retraced activities. Interestingly, racemic MDMA appeared to exert a greater than expected potency and/or an enhanced effect on measures such as movement episodes, center actions (entries and distance), clockwise rotations, and jumps; actions that might be explained by additive or synergistic (i.e. potentiation) effects of the stereoisomers. In other measures, the enantiomers displayed different effects: S(+)-MDMA produced a preference to induce counterclockwise (versus clockwise) rotations, and each isomer exerted a different profile of effect on vertical activities and jumps. Furthermore, each isomer of MDMA appeared to attenuate the effect of its opposite enantiomer on some behaviors; antagonism effects that were surmised from a lack of expected activities by racemic MDMA. S(+)-MDMA (but not R(-)-MDMA), for example, produced an increase in vertical entries (rearing) and a preference to increase counterclockwise (versus clockwise) rotations; (+/-)-MDMA also should have induced such effects but did not. Apparently, R(-)-MDMA, when combined with S(+)-MDMA to form (+/-)-MDMA, prevented the appearance of those increases (from control) in activities. Similarly, R(-)-MDMA (but not S(+)-MDMA) produced increases in episodes (i.e. jumps) and vertical distance that racemic MDMA also should have, but were not, exhibited. Evidently, the presence of S(+)-MDMA in the racemic mixture inhibited the appearance of those increases (from control) in behavior. Taken together, the various and complex effects of MDMA and its stereoisomers are noted and a strategy is suggested for future studies that stresses the importance of steric effects and interplay, probable interaction(s) with various neurotransmitters, and interaction(s) with the particular behavioral or biological event (or action) being measured.

MDMA (N-methyl-3,4-methylenedioxyamphetamine) and its Stereoisomers: Similarities and Differences in Behavioral Effects in an Automated Activity Apparatus in Mice

PubMed Central

Young, Richard; Glennon, Richard A.

2010-01-01

Racemic MDMA (0.3 – 30 mg/kg), S(+)-MDMA (0.3 – 30 mg/kg), R(-)-MDMA (0.3 – 50 mg/kg) and saline vehicle (10 ml/kg) were comprehensively evaluated in fully automated and computer-integrated activity chambers, which were designed for mice, and provided a detailed analysis of the frequency, location, and/or duration of 18 different activities. The results indicated that MDMA and its isomers produced stimulation of motor actions, with S(+)-MDMA and (±)-MDMA usually being more potent than R(-)-MDMA in measures such as movement (time, distance, velocity), margin distance, rotation (clockwise and counterclockwise), and retraced activities. Interestingly, racemic MDMA appeared to exert a greater than expected potency and/or an enhanced effect on measures such as movement episodes, center actions (entries and distance), clockwise rotations, and jumps; actions that might be explained by additive or synergistic (i.e. potentiation) effects of the stereoisomers. In other measures, the enantiomers displayed different effects: S(+)-MDMA produced a preference to induce counterclockwise (versus clockwise) rotations, and each isomer exerted a different profile of effect on vertical activities and jumps. Furthermore, each isomer of MDMA appeared to attenuate the effect of its opposite enantiomer on some behaviors; antagonism effects that were surmised from a lack of expected activities by racemic MDMA. S(+)-MDMA (but not R(-)-MDMA), for example, produced an increase in vertical entries (rearing) and a preference to increase counterclockwise (versus clockwise) rotations; (±)-MDMA also should have induced such effects but did not. Apparently, R(-)-MDMA, when combined with S(+)-MDMA to form (±)-MDMA, prevented the appearance of those increases (from control) in activities. Similarly, R(-)-MDMA (but not S(+)-MDMA) produced increases in episodes (i.e. jumps) and vertical distance that racemic MDMA also should have, but were not, exhibited. Evidently, the presence of S(+)-MDMA in the racemic mixture inhibited the appearance of those increases (from control) in behavior. Taken together, the various and complex effects of MDMA and its stereoisomers are noted and a strategy is suggested for future studies that stresses the importance of steric effects and interplay, probable interaction(s) with various neurotransmitters, and interaction(s) with the particular behavioral or biological event (or action) being measured. PMID:17904622

Semi-Microscale Williamson Ether Synthesis and Simultaneous Isolation of an Expectorant from Cough Tablets

NASA Astrophysics Data System (ADS)

Stabile, Ryan G.; Dicks, Andrew P.

2003-03-01

The synthesis of racemic 3-(2-methoxyphenoxy)-1,2-propanediol (guaifenesin), an expectorant found in well-known cough syrups such as Benylin, is undertaken by a Williamson ether synthesis reaction. The same compound is simultaneously isolated and characterized from commercially available Guai-Aid cough tablets. The experiment is well-suited towards the introductory part of an advanced organic laboratory course and complements typical lecture topics in a stimulating manner. Consideration is given towards reaction mechanisms, stereochemistry, optical activity, pharmaceutical synthesis, and spectroscopic analysis. Discussion of the merits or disadvantages of marketing a drug as a racemic mixture, with reference to the notorious thalidomide case study, and the concept of enantioselective synthesis is possible.

Saponification of esters of chiral alpha-amino acids anchored through their amine function on solid support.

PubMed

Cantel, Sonia; Desgranges, Stéphane; Martinez, Jean; Fehrentz, Jean-Alain

2004-06-01

Anchoring an alpha-amino acid residue by its amine function onto a solid support is an alternative to develop chemistry on its carboxylic function. This strategy can involve the use of amino-acid esters as precursors of the carboxylic function. A complete study on the Wang-resin was performed to determine the non racemizing saponification conditions of anchored alpha-amino esters. The use of LiOH, NaOH, NaOSi(Me)3, various solvents and temperatures were tested for this reaction. After saponification and cleavage from the support, samples were examined through their Marfey's derivatives by reversed phase HPLC to evaluate the percentage of racemization.

Enantiomeric Excesses of Acid Labile Amino Acid Precursors of the Murchison Meteorite

NASA Astrophysics Data System (ADS)

Pizzarello, Sandra

1998-10-01

Amino acids present in carbonaceous chondrite are extracted in water in part as free compounds and in approximately equal part as acid labile precursors. On the assumption that they would be free of contamination, the precursors of two Murchison amino acids that have terrestrial occurrence, alanine and glutamic acid, have been targeted for analysis of their enantiomeric ratios. Pyroglutamic acid, the precursor of glutamic acid, was found with an L-enantiomeric excess comparable to that of the free acid, while alanine's precursor, N-acetyl alanine, appears approximately racemic. Also alpha-imino propioacetic acid, a proposed end product of alanine synthesis in the meteorite, was analyzed and found racemic.

Enantiomeric Excesses of Acid Labile Amino Acid Precursors of the Murchison Meteorite

NASA Technical Reports Server (NTRS)

Pizzarello, Sandra

1998-01-01

Amino acids present in carbonaceous chondrite are extracted in water in part as free compounds and in approximately equal part as acid labile precursors. On the assumption that they would be free of contamination, the precursors of two Murchison amino acids that have terrestrial occurrence, alanine and glutamic acid, have been targeted for analysis of their enantiomeric ratios. Pyroglutamic acid, the precursor of glutamic acid, was found with an L-enantiomeric excess comparable to that of the free acid, while alanine's precursor, N-acetyl alanine, appears approximately racemic. Also alpha-imino propioacetic acid, a proposed end product of alanine synthesis in the meteorite, was analyzed and found racemic.

Mechanism of the Enantioselective Oxidation of Racemic Secondary Alcohols Catalyzed by Chiral Mn(III)–Salen Complexes

PubMed Central

Brown, M. Kevin; Blewett, Megan M.; Colombe, James R.; Corey, E. J.

2010-01-01

The experiments described here clarify the mechanism and origin of the enantioselectivity of the oxidation of racemic secondary alcohols catalyzed by chiral Mn(III)–salen complexes using HOBr, Br2/H2O/KOAc or PhI(OAc)2/H2O/KBr as a stoichiometric oxidant. Key points of the proposed pathway include (1) the formation of a Mn(V)–salen dibromide, (2) its subsequent reaction with the alcohol to give an alkoxy-Mn(V) species, and (3) carbonyl-forming elimination to produce the ketone via a highly organized transition state with intramolecular transfer of hydrogen from carbon to an oxygen of the salen ligand. PMID:20666410

Racemic synthesis and solid phase peptide synthesis application of the chimeric valine/leucine derivative 2-amino-3,3,4-trimethyl-pentanoic acid.

PubMed

Pelà, M; Del Zoppo, L; Allegri, L; Marzola, E; Ruzza, C; Calo, G; Perissutti, E; Frecentese, F; Salvadori, S; Guerrini, R

2014-07-01

The synthesis of non natural amino acid 2-amino-3,3,4-trimethyl-pentanoic acid (Ipv) ready for solid phase peptide synthesis has been developed. Copper (I) chloride Michael addition, followed by a Curtius rearrangement are the key steps for the lpv synthesis. The racemic valine/leucine chimeric amino acid was then successfully inserted in position 5 of neuropeptide S (NPS) and the diastereomeric mixture separated by reverse phase HPLC. The two diastereomeric NPS derivatives were tested for intracellular calcium mobilization using HEK293 cells stably expressing the mouse NPS receptor where they behaved as partial agonist and pure antagonist.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Li; Zhang, Yun; Wei, Zhehao

We report in this work detailed measurements on the chiral and achiral sum-frequency vibrational spectra in the C-H stretching vibration region (2800-3050cm-1) of the air/liquid interfaces of R-limonene and S-limonene, using the recently developed high-resolution broadband sum-frequency generation vibrational spectroscopy (HR-BB-SFG-VS). The achiral SFG spectra of R-limonene and S-limonene, as well as the equal amount (50/50) racemic mixture show that the enantiomers are with the same interfacial orientations. The interference chiral SFG spectra of the limonene enantiomers exhibit spectral signature from chiral response of the Cα-H stretching mode, and spectral signature from prochiral response of the CH2 asymmetric stretching mode,more » respectively. The chiral spectral feature of the Cα-H stretching mode changes sign from R-limonene to S-limonene, and disappears for the 50/50 racemic mixture. While the prochiral spectral feature of the CH2 asymmetric stretching mode is the same for R-limonene and S-limonene, and also surprisingly remains the same for the 50/50 racemic mixture. These results provided detail information in understanding the structure and chirality of molecular interfaces, and demonstrated the sensitivity and potential of SFG-VS as unique spectroscopic tool for chirality characterization and chiral recognition at the molecular interface.« less

GABA-B Agonist Baclofen Normalizes Auditory-Evoked Neural Oscillations and Behavioral Deficits in the Fmr1 Knockout Mouse Model of Fragile X Syndrome

PubMed Central

Featherstone, R.; Naschek, M.; Nam, J.; Du, A.; Wright, S.; Weger, R.; Akuzawa, S.

2017-01-01

Abstract Fragile X syndrome is a genetic condition resulting from FMR1 gene mutation that leads to intellectual disability, autism-like symptoms, and sensory hypersensitivity. Arbaclofen, a GABA-B agonist, has shown efficacy in some individuals with FXS but has become unavailable after unsuccessful clinical trials, prompting interest in publicly available, racemic baclofen. The present study investigated whether racemic baclofen can remediate abnormalities of neural circuit function, sensory processing, and behavior in Fmr1 knockout mice, a rodent model of fragile X syndrome. Fmr1 knockout mice showed increased baseline and auditory-evoked high-frequency gamma (30–80 Hz) power relative to C57BL/6 controls, as measured by electroencephalography. These deficits were accompanied by decreased T maze spontaneous alternation, decreased social interactions, and increased open field center time, suggestive of diminished working memory, sociability, and anxiety-like behavior, respectively. Abnormal auditory-evoked gamma oscillations, working memory, and anxiety-related behavior were normalized by treatment with baclofen, but impaired sociability was not. Improvements in working memory were evident predominantly in mice whose auditory-evoked gamma oscillations were dampened by baclofen. These findings suggest that racemic baclofen may be useful for targeting sensory and cognitive disturbances in fragile X syndrome. PMID:28451631

Optically active polyurethane@indium tin oxide nanocomposite: Preparation, characterization and study of infrared emissivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Yong; Zhou, Yuming, E-mail: ymzhou@seu.edu.cn; Ge, Jianhua

Highlights: ► Silane coupling agent of KH550 was used to connect the ITO and polyurethanes. ► Infrared emissivity values of the hybrids were compared and analyzed. ► Interfacial synergistic action and orderly secondary structure were the key factors. -- Abstract: Optically active polyurethane@indium tin oxide and racemic polyurethane@indium tin oxide nanocomposites (LPU@ITO and RPU@ITO) were prepared by grafting the organics onto the surfaces of modified ITO nanoparticles. LPU@ITO and RPU@ITO composites based on the chiral and racemic tyrosine were characterized by FT-IR, UV–vis spectroscopy, X-ray diffraction (XRD), SEM, TEM, and thermogravimetric analysis (TGA), and the infrared emissivity values (8–14 μm)more » were investigated in addition. The results indicated that the polyurethanes had been successfully grafted onto the surfaces of ITO without destroying the crystalline structure. Both composites possessed the lower infrared emissivity values than the bare ITO nanoparticles, which indicated that the interfacial interaction had great effect on the infrared emissivity. Furthermore, LPU@ITO based on the optically active polyurethane had the virtue of regular secondary structure and more interfacial synergistic actions between organics and inorganics, thus it exhibited lower infrared emissivity value than RPU@ITO based on the racemic polyurethane.« less

Chiral magnetic microspheres purified by centrifugal field flow fractionation and microspheres magnetic chiral chromatography for benzoin racemate separation.

PubMed

Tian, Ailin; Qi, Jing; Liu, Yating; Wang, Fengkang; Ito, Yoichiro; Wei, Yun

2013-08-30

Separation of enantiomers still remains a challenge due to their identical physical and chemical properties in a chiral environment, and the research on specific chiral selector along with separation techniques continues to be conducted to resolve individual enantiomers. In our laboratory the promising magnetic chiral microspheres Fe3O4@SiO2@cellulose-2, 3-bis (3,5-dimethylphenylcarbamate) have been developed to facilitate the resolution using both its magnetic property and chiral recognition ability. In our present studies this magnetic chiral selector was first purified by centrifuge field flow fractionation, and then used to separate benzoin racemate by a chromatographic method. Uniform-sized and masking-impurity-removed magnetic chiral selector was first obtained by field flow fractionation with ethanol through a spiral column mounted on the type-J planetary centrifuge, and using the purified magnetic chiral selector, the final chromatographic separation of benzoin racemate was successfully performed by eluting with ethanol through a coiled tube (wound around the cylindrical magnet to retain the magnetic chiral selector as a stationary phase) submerged in dry ice. In addition, an external magnetic field facilitates the recycling of the magnetic chiral selector. Copyright © 2013 Elsevier B.V. All rights reserved.

Synthesis of monodentate ferrocenylphosphines and their application to the palladium-catalyzed Suzuki reaction of aryl chlorides.

PubMed

Pickett, Tom E; Roca, Francesc X; Richards, Christopher J

2003-04-04

Racemic and enantiopure ((p)()S)-1-bromo-2-methylferrocene 6 were synthesized in 4 steps from 2-(4,4-dimethyloxazolinyl)ferrocene and (S)-2-(4-methylethyloxazolinyl)ferrocene, respectively (46 and 81% overall yield). Bromolithium exchange and addition of ClPR(2) gave the corresponding racemic or enantiopure 2-methylferrocenyl phosphine ligands 2-MeFcPR(2) 11 (R = Ph), 12 (R = Cy), and 13 (R = (t)Bu) in 28-93% yield. Use of PCl(3) gave the C(3)-symmetric phosphine (2-MeFc)(3)P 5 from ((p)()S)-6(72% yield) but racemic 6 did not lead to the formation of triferrocenyl phosphines. Combination of 5 and Pd(2)(dba)(3) gave an active catalyst for the Suzuki reaction of aryl chlorides, for example, 4-chlorotoluene and phenylboronic acid reacted at only 60 degrees C in dioxane (86% yield). Other examples are reported together with the use of 12 in this same protocol. From the X-ray crystal structure of 5 the cone angle was determined as 211 degrees. With this, and the electronic character of 11, 12, and other phosphines (derived from nu(CO) of trans-[(R(3)P)(2)Rh(CO)Cl]), an analysis is made of the steric and electronic influences on ligand activity in the Suzuki reaction.

Preparation of optically active (2RS,3SR)-2-amino-3-hydroxy-3-phenylpropanoic acid (threo-beta-phenylserine) via optical resolutions by replacing and preferential crystallization.

PubMed

Shiraiwa, Tadashi; Kawashima, Yuka; Ikaritani, Atsushi; Suganuma, Yumiko; Saijoh, Reiichi

2006-08-01

To obtain optically active threo-2-amino-3-hydroxy-3-phenylpropanoic acid (1) via optical resolutions by replacing and preferential crystallization, the racemic structure of (2RS,3SR)-1 hydrochloride [(2RS,3SR)-1.HCl] was examined based on the melting point, solubility, and infrared spectrum. (2RS,3SR)-1.HCl was indicated to exist as a conglomerate at room temperature, although it forms a racemic compound at the melting point. When, in optical resolution by replacing crystallization, L-phenylalanine methyl ester hydrochloride (L-2) was used as the optically active co-solute, (2R,3S)-1.HCl was preferentially crystallized from the supersaturated racemic solution; the use of D-2 as the co-solute afforded (2S,3R)-1.HCl with an optical purity of 95%. In addition, optical resolution by preferential crystallization was successfully achieved to give successively (2R,3S)- and (2S,3R)-1.HCl with optical purities of 90-92%. The (2R,3S)- and (2S,3R)-1.HCl purified by recrystallization from 1-propanol were treated with triethylamine in methanol to give optically pure (2R,3S)- and (2S,3R)-1.

Kinetic disposition of lorazepam with focus on the glucuronidation capacity, transplacental transfer in parturients and racemization in biological samples.

PubMed

Papini, Olga; da Cunha, Sergio Pereira; da Silva Mathes, Angelo do Carmo; Bertucci, Carlo; Moisés, Elaine Christine Dantas; de Barros Duarte, Luciana; de Carvalho Cavalli, Ricardo; Lanchote, Vera Lucia

2006-02-13

The present study investigates the kinetic disposition with focus on the racemization, glucuronidation capacity and the transplacental transfer of lorazepam in term parturients during labor. The study was conducted on 10 healthy parturients aged 18-37 years with a gestational age of 36-40.1 weeks, treated with a single oral dose of 2 mg racemic lorazepam 2-9 h before delivery. Maternal venous blood and urine samples were obtained over a 0-48 h interval and the umbilical cord sample was obtained immediately after clamping. Lorazepam enantiomers were determined in plasma and urine samples by LC-MS/MS using a Chiralcel OD-R column. In vitro racemization of lorazepam required the calculation of the pharmacokinetic parameters as isomeric mixtures. The data were fitted to two-compartment model and the pharmacokinetic parameters are reported as means (95% CI): t(1/2a) 3.2h (2.6-3.7 h), K(a) 0.23 h(-1) (0.19-0.28 h(-1)), t(1/2) 10.4h (9.4-11.3h), beta 0.068 h(-1) (0.061-0.075h(-1)), AUC(0-infinity) 175.3(ngh)/ml (145.7-204.8(ngh)/ml), Cl/F 2.6 ml/(minkg) (2.3-2.9 ml/(minkg)), Vd/F178.8l (146.5-211.1l), Fel 0.3% (0.1-0.5%), and Cl(R) 0.010 ml/(minkg) (0.005-0.015 ml/(minkg)). Placental transfer of lorazepam evaluated as the ratio of vein umbilical/maternal vein plasma concentrations, obtained as an isomeric mixture, was 0.73 (0.52-0.94). Pregnancy changes the pharmacokinetics of lorazepam, with an increase in the apparent distribution volume, an increase in apparent oral clearance, and a reduction of elimination half-life. The increase in oral clearance may indicate an increase in glucuronidation capacity, with a possible reduction in the plasma concentrations of drugs depending on glucuronidation capacity as the major metabolic pathway.

Synthesis of Enantiopure Alicyclic Ethers and Their Activity on the Chemosensory Organ of the Ectoparasite of Honey Bees, Varroa destructor.

PubMed

Pinnelli, Govardhana R; Singh, Nitin K; Soroker, Victoria; Plettner, Erika

2016-11-16

The preparation of enantiopure conformationally restricted alicyclic ethers and their inhibitory activities on the chemosensory organ of the Varroa destructor, a parasite of honey bees, are reported in this article. We tested the effect of enantiopure ethers of cis-5-(2'-hydroxyethyl)cyclopent-2-en-1-ol on the Varroa chemosensory organ by electrophysiology, for their ability to inhibit the responses to two honey bee-produced odors that are important for the mite to locate its host: nurse bee head space odor and (E)-β-ocimene, a honey bee brood pheromone. Previous work with the racemic compounds showed that they suppress the mite's olfactory response to its bee host, which led to incorrect host choice. Based on a structure-activity relationship, we predicted that the two most active compounds-cis-1-butoxy-5-(2'-methoxyethyl)cyclopent-2-ene, cy{4,1}, and (cis-1-ethoxy-5-(2'ethoxyethyl)cyclopent-2-ene, cy{2,2}-could have opposite active enantiomers. Here we studied the enantiomers of both ethers, whose preparation involved enzymatic resolution of racemic diol cis-5-(2'-hydroxyethyl)cyclopent-2-en-1-ol using Lipase AK with vinyl acetate. The racemic diol was prepared from commercially available 2,5-norbornadiene. We observed that the responses of the chemosensory organ to honey bee head space volatiles were significantly decreased by both enantiomers of cy{4,1} and cy{2,2}, but that responses to (E)-β-ocimene were decreased significantly only by (+)-cy{4,1} (1R,5S) and (-)-cy{2,2} (1S,5R) and not by their respective enantiomers. The importance of this result is that the racemates could be used to inhibit olfactory detection of bee odors by mites, without a loss in activity relative to the more expensive enantiopure compounds.

Phase behavior and crystal structure of 3-(1-naphthyloxy)- and 3-(4-indolyloxy)-propane-1,2-diol, synthetic precursors of chiral drugs propranolol and pindolol

NASA Astrophysics Data System (ADS)

Bredikhin, Alexander A.; Gubaidullin, Aidar T.; Bredikhina, Zemfira A.; Fayzullin, Robert R.; Samigullina, Aida I.; Zakharychev, Dmitry V.

2013-08-01

Valuable precursors of popular chiral drugs propranolol and pindolol, 3-(1-naphthyloxy)-propane-1,2-diol 3 and 3-(4-indolyloxy)-propane-1,2-diol 4 were investigated by IR spectroscopy, DSC, and X-ray diffraction methods. Both compounds, crystallizing from enantiopure feed material, form "guaifenesin-like" crystal packing in which the classic H-bonded bilayers, framed in both sides by hydrophobic fragments of the molecules, acts as the basic crystal-forming motif. Diol 4 prone to spontaneous resolution and conserves its packing pattern crystallizing from racemate. Under the same conditions, diol 3 forms weakly stable solid racemic compound. Some reasons for such a behavior are identified and discussed.

S-Amlodipine: An Isomer with Difference—Time to Shift from Racemic Amlodipine

PubMed Central

Mohan, J. C.; Iyengar, S. S.; Hiremath, Jagdish; Sathyamurthy, Immaneni; Bansal, Sandeep; Kahali, Dhiman; Dasbiswas, Arup

2018-01-01

Calcium channel blockers are among the first-line drugs for treatment of hypertension (HTN). S-amlodipine (S-AM), an S-enantiomer of amlodipine, is available in India and in other countries like China, Korea, Russia, Ukraine, and Nepal. Being clinically researched for nearly two decades, we performed in-depth review of S-AM. This review discusses clinical evidence from total 42 studies (26 randomized controlled trials, 14 observational studies, and 2 meta-analyses) corroborating over 7400 patients treated with S-AM. Efficacy and safety of S-AM in HTN in comparison to racemic amlodipine, used as monotherapy and in combination with other antihypertensives, efficacy in angina, and pleiotropic benefits with S-AM, are discussed in this review. PMID:29887996

Conformational arm-wrestling: battles for stereochemical control in benzamides bearing matched and mismatched chiral 2- and 6-substituents.

PubMed

Clayden, Jonathan; Foricher, Yann J Y; Helliwell, Madeleine; Johnson, Paul; Mitjans, David; Vinader, Victoria

2006-02-07

The orientation of a tertiary amide group adjacent to an aromatic ring may be governed by the stereochemistry of an adjacent chiral substituent. With a chiral substituent in both ortho positions, matched/mismatched pairs of isomers result. Evidence for matched stereochemistry is provided by the clean NMR spectra of single conformers, while mismatching gives poor or unexpected selectivities in the formation of chiral substituents, or mixtures of amide conformers. Attempts to use the match-mismatch effect to select for racemic pairs of enantiomeric substituents, and hence develop a "racemate-sequestering" reagent, are described, along with the use of "matching" to scavenge a single enantiomer of a diamine from material of incomplete enantiomeric purity.

Enantiomeric-Enriched Ferrocenes: Synthesis, Chiral Resolution, and Mathematic Evaluation of CD-chiral Selector Energies with Ferrocene-Conjugates.

PubMed

Snegur, Lubov V; Borisov, Yurii A; Kuzmenko, Yuliya V; Davankov, Vadim A; Ilyin, Mikhail M; Ilyin, Mikhail M; Arhipov, Dmitry E; Korlyukov, Alexander A; Kiselev, Sergey S; Simenel, Alexander A

2017-08-25

Enantiomeric-enriched ferrocene-modified pyrazoles were synthesized via the reaction of the ferrocene alcohol, ( S )-FcCH(OH)CH₃ (Fc = ferrocenyl), with various pyrazoles in acidic conditions at room temperature within several minutes. X-ray structural data for racemic ( R , S )-1 N -(3,5-dimethyl pyrazolyl)ethyl ferrocene ( 1 ) and its ( S )-enantiomer ( S )- 1 were determined. A series of racemic pyrazolylalkyl ferrocenes was separated into enantiomers by analytical HPLC on β- and γ-cyclodextrins (CD) chiral stationary phases. The quantum chemical calculations of interaction energies of β-CD were carried out for both ( R )- and ( S )-enantiomers. A high correlation between experimental HPLC data and calculated interaction energies values was obtained.

Enantioselective analysis of citalopram and escitalopram in postmortem blood together with genotyping for CYP2D6 and CYP2C19.

PubMed

Carlsson, Björn; Holmgren, Anita; Ahlner, Johan; Bengtsson, Finn

2009-03-01

Citalopram is marketed as a racemate (50:50) mixture of the S(+)-enantiomer and R(-)-enantiomer and the active S(+)-enantiomer (escitalopram) that possess inhibitory effects. Citalopram was introduced in Sweden in 1992 and is the most frequently used antidepressant to date in Sweden. In 2002, escitalopram was introduced onto the Swedish market for treatment of depression and anxiety disorders. The main objective of this study was to investigate S(+)-citalopram [i.e., the racemic drug (citalopram) or the enantiomer (escitalopram)] present in forensic autopsy cases positive for the presence of citalopram in routine screening using a non-enantioselective bioanalytical method. Fifty out of the 270 samples found positive by gas chromatography-nitrogen-phosphorus detection were further analyzed using enantioselective high-performance liquid chromatography. The 50 cases were genotyped for CYP2D6 and CYP2C19, as these isoenzymes are implicated in the metabolism of citalopram and escitalopram. In samples positive for racemic citalopram using the screening method for forensic autopsy cases, up to 20% would have been misinterpreted in the absence of an enantioselective method. An enantioselective method is thus necessary for correct interpretation of autopsy cases, after the enantiomer has been introduced onto the market. The percentage of poor metabolizers was 6% for CYP2D6 and 8% for CYP2C19.

Enantioselectivity and Thermostability of a Novel Hyperhermotolerant Lipase from Geobacillus Thermodenitrificans nr68 (Lip.nr-68) on Secondary Racemic Alcohols Acetylation

NASA Astrophysics Data System (ADS)

Nik Him, N. R.; Ibrahim, D.

2018-05-01

In our previous work, a new lipase enzyme has been purified from a species identified as a Gram negative Geobacillus thermodenitrificans nr68, isolated from a hot spring in Malaysia with growth temperature of 48°C. This new lipase, called Lip.nr-68 has been characterized as a hyperthermotolerant protein with high stability at 65°C and has been showing excellent characteristics that are very much comparable yet better than some of those of well-known industrially-used lipases. It shows high activity against long-chain triglycerides with molecular weight of the purified enzyme estimated to be 33.5 kDa using SDS-PAGE analysis. This paper is focusing on hyperthermotolerant Lip.nr-68 performance in promoting for enantioselectivity activities towards three secondary racemic alcohols namely 1-phenylethanol, 1-cyclohexilethanol and 1-(naft-2-il) ethanol by acetylation with vinyl acetate. Lip.nr-68 has been confirmed to show high and usual enantioselectivitiy according to the Kazlauskas Rule towards all secondary racemic alcohols and has significantly approved as an enantiomer selective biocatalyst towards 1-phenylethanol and 1-cyclohexylethanol at 65°C. Lip.nr-68 has showed a reduction of (R) and (S) enantiomers as well as the production of 68-98% ee and almost 94% yield of 3-4 mg/ml for 1-cyclohexilethanol.

Enantioselective analysis of etodolac in human plasma by LC-MS/MS: Application to clinical pharmacokinetics.

PubMed

de Miranda Silva, Carolina; Rocha, Adriana; Tozatto, Eduardo; da Silva, Lucienir Maria; Donadi, Eduardo Antônio; Lanchote, Vera Lucia

2016-02-20

Etodolac is a non-steroidal anti-inflammatory drug with preferential inhibition of cyclooxigenase-2 and is widely used in the management of pain in patients with inflammatory arthritis. Etodolac is available as a racemic mixture of (-)-(R)-Etodolac and (+)-(S)-Etodolac; cyclooxigenases inhibition is attributed to (+)-(S)-Etodolac. According to our knowledge, this is the first method for determination of etodolac enantiomers in plasma using LC-MS/MS. Plasma extraction were performed with 25μL of plasma and 1mL of n-hexane:ethyl acetate (95:5); racemic ibuprofen was used as internal standard. Resolution of enantiomers were performed in a Chiralcel(®)OD-H column; deprotonated [M-H](-) and their respective ion products were monitored at transitions of 286>242 for etodolac enantiomers and 205>161 for ibuprofen. The quantitation limit was 3.2ng/mL for both enantiomers in plasma. The method was applied to study the pharmacokinetics of etodolac enantiomers after the administration of a 300 and 400mg dose of racemic drug to a healthy volunteer. Analysis of plasma samples showed higher plasma concentration of (-)-(R)-Etodolacfor both doses (300mg dose: AUC(0-∞)49.80 versus 4.55ugh/mL;400mg dose: AUC(0-∞) 63.90 versus 6.00ugh/mL) with an (R)-(+)/(S)-(-) ratio of approximately 11. Copyright © 2015 Elsevier B.V. All rights reserved.

Chiral signatures of chlordanes indicate changing sources to the atmosphere over the past 30 years

NASA Astrophysics Data System (ADS)

Bidleman, Terry F.; Wong, Fiona; Backe, Cecilia; Södergren, Anders; Brorström-Lundén, Eva; Helm, Paul A.; Stern, Gary A.

2004-11-01

Chlordane was used as an insecticide for half a century until its withdrawal from the world market in 1997. Trans- and cis-chlordane (TC, CC) are racemic in the technical product, but undergo enantioselective degradation in soil to leave nonracemic residues. In most cases, the (+) enantiomer of TC and the (-) enantiomer of CC are depleted, leading to enantiomer fractions, EF = (+) / [ (+) + (-) ], that are < 0.500 for TC and > 0.500 for CC. Nonracemic EFs of TC and CC, showing the same degradation preference as soils, were found in 1998-2001 air samples from stations in Arctic Canada and Finland, and on the west coast of Sweden. Environmental samples representing different time periods of chlordane history were also examined in: (a) archived atmospheric deposition samples collected in Sweden, Slovakia and Iceland in 1971-1973, (b) soils from southern Sweden sampled in 2001 and (c) a laminated lake sediment core from the Canadian Arctic representing ∼50 years of accumulation. TC and CC were racemic or nearly so in the historical atmospheric deposition samples and nonracemic in the Swedish soils. The EF of TC in the dated lake sediment core decreased from nearly racemic in the past to nonracemic in recent times. These observations suggest that sources of chlordane to the atmosphere have changed over time and are now influenced to a greater extent by emission from soils.

Immobilized chiral tropine ionic liquid on silica gel as adsorbent for separation of metal ions and racemic amino acids.

PubMed

Qian, Guofei; Song, Hang; Yao, Shun

2016-01-15

Tropine-type chiral ionic liquid with proline anion was immobilized on silica gel by chemical modification method for the first time, which was proved by elemental, infrared spectrum and thermogravimetric analysis. Secondly, the performance of this kind of ionic liquid-modified silica gel was investigated in the adsorption of some metal ions, which included Cu(2+), Fe(3+), Mn(2+) and Ni(2+). Then the effects of time, initial concentration and temperature on adsorption for Cu(2+) ions were studied in detail, which was followed by the further research of adsorption kinetics and thermodynamics. The adsorption could be better described by pseudo-second-order kinetics model and that the process was spontaneous, exothermic and entropy decreasing. In the mode of 'reuse after adsorption', the ionic liquid-modified silica gel with saturated adsorption of Cu(2+) was finally used in resolution of racemic amino acids for the first time. The static experiment showed that adsorption rate of two enantiomers was obviously different. Inspired by this, the complex was packed in chromatographic column for the separation of racemic amino acids and d-enantiomers were firstly eluted by water or ethanol. Steric hindrance was found as one of key influencing factors for its effect on the stability of the complex. Copyright © 2015 Elsevier B.V. All rights reserved.

Analytical and semipreparative chiral separation of cis-itraconazole on cellulose stationary phases by high-performance liquid chromatography.

PubMed

Kurka, Ondřej; Kučera, Lukáš; Bednář, Petr

2016-07-01

cis-Itraconazole is a chiral antifungal drug administered as a racemate. The knowledge of properties of individual cis-itraconazole stereoisomers is vital information for medicine and biosciences as different stereoisomers of cis-itraconazole may possess different affinity to certain biological pathways in the human body. For this purpose, either chiral synthesis of enantiomers or chiral separation of racemate can be used. This paper presents a two-step high-performance liquid chromatography approach for the semipreparative isolation of four stereoisomers (two enantiomeric pairs) of itraconazole using polysaccharide stationary phases and volatile organic mobile phases without additives in isocratic mode. The approach used involves the separation of the racemate into three fractions (i.e. two pure stereoisomers and one mixed fraction containing the remaining two stereoisomers) in the first run and consequent separation of the collected mixed fraction in the second one. For this purpose, combination of cellulose tris-(4-methylbenzoate) and cellulose tris-(3,5-dimehylphenylcarbamate) columns with complementary selectivity for cis-itraconazole provided full separation of all four stereoisomers (with purity of each isomer > 97%). The stereoisomers were collected, their optical rotation determined and their identity confirmed based on the results of a previously published study. Pure separated stereoisomers are subjected to further biological studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

On the reported optical activity of amino acids in the Murchison meteorite

USGS Publications Warehouse

Bada, J.L.; Cronin, J.R.; Ho, M.-S.; Kvenvolden, K.A.; Lawless, J.G.; Miller, S.L.; Oro, John; Steinberg, S.

1983-01-01

In analyses of extracts from the Murchison meteorite (a carbonaceous chondrite), Engel and Nagy1 reported an excess of L-enantiomers for several protein amino acids but found that the non-protein amino acids were racemic. They suggested that the excess of L-isomers might have resulted from an asymmetric synthesis or decomposition. Their results disagree with those obtained previously2-4 and they claim this is due to improved methodology. In fact, their extraction method and analytical procedure (gas chromatography-mass spectrometry, GC-MS) was similar to those used in the original report2 of amino acids in the Murchison meteorite except that they used specific ion monitoring in the GC-MS measurements. We found the results of Engel and Nagy odd in that likely contaminants (the protein amino acids ala, leu, glu, asp and pro) were nonracemic while unlikely contaminants (isovaline and ??-amino-n-butyric acid) were racemic. For example, Engel and Nagy report that the leucine is ???90% L-enantiomer in the water-extracted sample whereas isovaline (??-methyl-??-aminobutyric acid) is racemic. It would be most unusual for an abiotic stereoselective decomposition or synthesis of amino acids to occur with protein amino acids but not with non-protein amino acids. We now show here that the explanation of terrestrial contamination is consistent with their results and is much more probable. ?? 1983 Nature Publishing Group.

Enigmatic Isovaline: Investigating the Stability, Racemization, and Formation of a Non-biological Meteoritic Amino Acid

NASA Technical Reports Server (NTRS)

Hudson, Reggie; Moore, Marla; Lewis, Ariel; Dworkin, Jason

2008-01-01

Among the Murchison meteoritic amino acids, isovaline stands out as being both nonbiological (non-protein) and having a relatively high abundance. While approximately equal amounts of D- and L-isovaline have been reported in Murchison and other CM meteorites, the molecule's structure appears to prohibit its racemization in aqueous solutions. We recently have investigated the low-temperature solid-phase chemistry of both isovaline and valine with an eye toward each molecule's formation, stability, and possible interconversions of D and L enantiomers. Ion-irradiated isovaline- and valinecontaining ices were examined by IR spectroscopy and highly-sensitive liquid chromatography/time-of-flight mass spectral methods to assess both amino acid destruction and racemization. Samples were studied in the presence and in the absence of water-ice, and the destruction of both isovaline and valine was measured as a function of radiation dose. In addition, we have undertaken experiments to synthesize isovaline, valine, and their amino acid isomers by solid-phase radiation-chemical pathways other than the oft-invoked Strecker process. This presentation will review and summarize some of our recent findings. -- Our work has been supported by a grant to the Goddard Center for Astrobiology through the NASA Astrobiology Institute. Experiments were performed in the Cosmic Ice Laboratory (RLH, MHM, AL) and the Astrobiology Analytical Laboratory (JPD, DPG) at the NASA Goddard Space Flight Center.

A dual-catalysis approach to enantioselective [2 + 2] photocycloadditions using visible light.

PubMed

Du, Juana; Skubi, Kazimer L; Schultz, Danielle M; Yoon, Tehshik P

2014-04-25

In contrast to the wealth of catalytic systems that are available to control the stereochemistry of thermally promoted cycloadditions, few similarly effective methods exist for the stereocontrol of photochemical cycloadditions. A major unsolved challenge in the design of enantioselective catalytic photocycloaddition reactions has been the difficulty of controlling racemic background reactions that occur by direct photoexcitation of substrates while unbound to catalyst. Here, we describe a strategy for eliminating the racemic background reaction in asymmetric [2 + 2] photocycloadditions of α,β-unsaturated ketones to the corresponding cyclobutanes by using a dual-catalyst system consisting of a visible light-absorbing transition-metal photocatalyst and a stereocontrolling Lewis acid cocatalyst. The independence of these two catalysts enables broader scope, greater stereochemical flexibility, and better efficiency than previously reported methods for enantioselective photochemical cycloadditions.

Synthetic strategy for preparing chiral double-semicrystalline polyether block copolymers

DOE PAGES

McGrath, Alaina J.; Shi, Weichao; Rodriguez, Christina G.; ...

2014-12-11

Here, we report an effective strategy for the synthesis of semi-crystalline block copolyethers with well-defined architecture and stereochemistry. As an exemplary system, triblock copolymers containing either atactic (racemic) or isotactic ( R or S) poly(propylene oxide) end blocks with a central poly(ethylene oxide) mid-block were prepared by anionic ring-opening procedures. Stereochemical control was achieved by an initial hydrolytic kinetic resolution of racemic terminal epoxides followed by anionic ring-opening polymerization of the enantiopure monomer feedstock. The resultant triblock copolymers were highly isotactic (meso triads [ mm]% ~ 90%) with optical microscopy, differential scanning calorimetry, wide angle x-ray scattering and small anglemore » x-ray scattering being used to probe the impact of the isotacticity on the resultant polymer and hydrogel properties.« less

Experiments on the abiotic amplification of optical activity

NASA Technical Reports Server (NTRS)

Bonner, W. A.; Blair, N. E.; Dirbas, F. M.

1981-01-01

Experiments concerning the physical mechanisms for the abiotic generation and chemical mechanisms for the amplification of optical activity in biological compounds are reviewed. Attention is given to experiments involving the determination of the differential adsorption of racemic amino acids on d- and l-quartz, the asymmetric photolysis of racemic amino acids by circularly polarized light, and the asymmetric radiolysis of solid amino acids by longitudinally polarized electrons, and the enantiomeric enrichments thus obtained are noted. Further experiments on the amplification of the chirality in the polymerization of D, L-amino acid mixtures and the hydrolysis of D-, L-, and D, L-polypeptides are discussed. It is suggested that a repetitive cycle of partial polymerization-hydrolyses may account for the abiotic genesis of optically enriched polypeptides on the primitive earth.

Micelle Enhanced Fluorimetric and Thin Layer Chromatography Densitometric Methods for the Determination of (±) Citalopram and its S – Enantiomer Escitalopram

PubMed Central

Taha, Elham A.; Salama, Nahla N.; Wang, Shudong

2009-01-01

Two sensitive and validated methods were developed for determination of a racemic mixture citalopram and its enantiomer S-(+) escitalopram. The first method was based on direct measurement of the intrinsic fluorescence of escitalopram using sodium dodecyl sulfate as micelle enhancer. This was further applied to determine escitalopram in spiked human plasma, as well as in the presence of common and co-administerated drugs. The second method was TLC densitometric based on various chiral selectors was investigated. The optimum TLC conditions were found to be sensitive and selective for identification and quantitative determination of enantiomeric purity of escitalopram in drug substance and drug products. The method can be useful to investigate adulteration of pure isomer with the cheap racemic form. PMID:19652757

Micelle enhanced fluorimetric and thin layer chromatography densitometric methods for the determination of (+/-) citalopram and its S-enantiomer escitalopram.

PubMed

Taha, Elham A; Salama, Nahla N; Wang, Shudong

2009-04-07

Two sensitive and validated methods were developed for determination of a racemic mixture citalopram and its enantiomer S-(+) escitalopram. The first method was based on direct measurement of the intrinsic fluorescence of escitalopram using sodium dodecyl sulfate as micelle enhancer. This was further applied to determine escitalopram in spiked human plasma, as well as in the presence of common and co-administrated drugs. The second method was TLC densitometric based on various chiral selectors was investigated. The optimum TLC conditions were found to be sensitive and selective for identification and quantitative determination of enantiomeric purity of escitalopram in drug substance and drug products. The method can be useful to investigate adulteration of pure isomer with the cheap racemic form.

Preparation of tritium-labeled optical isomers of amino acids by ligand exchange chromatography on polyacrylamide sorbent containing L-phenylalanine groupings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zolotarev, Yu.A.; Penkina, V.I.; Dostavalov, I.N.

Tritium-labeled optically active amino acids are obtained by resolving racemates of the corresponding amino acids by chromatography on a chiral polyacrylamide sorbent, filled with copper ions. The chiral sorbent is obtained by the action of formaldehyde and L-phenylalanine on a Biogel P-4 polyacrylamide gel in an alkaline medium. Data are given on the ligand exchange chromatography of amino acids on this sorbent, depending on the degree of filling of the sorbent by copper ions and the concentration of the eluent. Conditions were selected for the quantitative resolution of racemates of amino acids and examples are given of a preparative obtainingmore » of tritium labeled optical isomers of amino acids.« less

Use Of Amino Acid Racemization To Investigate The Metabolic Activity Of ?Dormant? Microorganisms In Siberian Permafrost

NASA Astrophysics Data System (ADS)

Tsapin, A.; McDonald, G.

2002-12-01

Permafrost occupies a significant part of North America and Eurasia, and accounts for around 20% of Earth?s land surface. Permafrost represents a temperature-stable environment that allows the prolonged survival of microbial lineages at subzero temperatures. Microorganisms from ancient permafrost have been revived and isolated in pure cultures. Permafrost is a unique environment serving as a "natural gene bank", with many species frozen in time (i.e. preserved in an unchanging evolutionary state). Permafrost presents a golden niche for future biotechnology, and is also a unique environment for studying longevity and survivability microorganisms (pro- and eukaryotes). Permafrost, alone among cold environments, offers a sedimentary column in which, in one borehole made in the thick permafrost, we can observe in the preserved genetic material the history of biological evolution during the last several hundred thousand or maybe even a few million years. A thorough study of the phylogenetic relationships of organisms at each depth, as well as comparisons between different depths of permafrost, using molecular evolution techniques, will give us a unique window into the process of evolution of microbial communities over geologic time. The longevity of (micro)organisms in cold environments is of great interest to astrobiology since cryospheres are common phenomena in the solar system, particularly on satellites, comets and asteroids, and on some of the planets. Recent data from the Mars Global Surveyor mission suggest the possibility of permafrost or perhaps even liquid water under the Martian surface. The probability of finding life on Mars, if it exists, is probably higher in such environments. In addition, the evaluation of the possibility of transfer of living organisms between planets via impact ejecta needs the information on the maximum time over which microorganisms in cold environments can remain dormant and subsequently revive and reproduce. Our strategy for the search for extraterrestrial life or its remnants is based on studying the most probable environments in which life (extant or extinct) may be found, and determining the maximum period of time over which such life could be preserved. The terrestrial permafrost, inhabited by cold adapted microbes, can be considered as an extraterrestrial analog environment. The cells and their metabolic end-products in Earth's permafrost can be used in the search for possible ecosystems and potential inhabitants on extraterrestrial cryogenic bodies. The study of microorganisms (or their remnants) that were buried for a few million years in permafrost provides us with a unique opportunity to determine the long-term viability of (micro)organisms. We have analyzed the degree of racemization of aspartic acid in permafrost samples from Northern Siberia (Brinton et al. 2002, Astrobiology 2, 77), an area from which microorganisms of apparent ages up to a few million years have previously been isolated and cultured. We find that the extent of aspartic acid racemization in permafrost cores increases very slowly up to an age of approximately 25,000 years (around 5 m depth). The apparent temperature of racemization over the age range 0-25,000 years, determined using measured aspartic acid racemization rate constants, is ?19 C. This apparent racemization temperature is significantly lower than the measured environmental temperature (?11 to ?13 C), and suggests active recycling of D-aspartic acid in Siberian permafrost up to an age of around 25,000 years. This indicates that permafrost organisms are capable of repairing some molecular damage incurred while they are in a ?dormant? state over geologic time.

21 CFR 184.1890 - α-Tocopherols.

Code of Federal Regulations, 2014 CFR

2014-04-01

... concentrate and is a red, nearly odorless, viscous oil. It is obtained by vacuum steam distillation of edible... condensing racemic isophytol with trimethyl hydroquinone. It is a pale yellow viscous oil at room temperature...

21 CFR 184.1890 - α-Tocopherols.

Code of Federal Regulations, 2013 CFR

2013-04-01

... commercially as a concentrate and is a red, nearly odorless, viscous oil. It is obtained by vacuum steam... by condensing racemic isophytol with trimethyl hydroquinone. It is a pale yellow viscous oil at room...

21 CFR 184.1890 - α-Tocopherols.

Code of Federal Regulations, 2012 CFR

2012-04-01

... commercially as a concentrate and is a red, nearly odorless, viscous oil. It is obtained by vacuum steam... by condensing racemic isophytol with trimethyl hydroquinone. It is a pale yellow viscous oil at room...

Interim Policy for Evaluation of Stereoisomeric Pesticides

EPA Pesticide Factsheets

An interim approach for determining data requirements for non-racemic mixtures of stereoisomeric pesticides. These data are needed in order to assess the risk posed to ecosystems and drinking water sources by these mixtures.

Fluorescent high-performance liquid chromatographic analysis of vigabatrin enantiomers after derivatizing with naproxen acyl chloride.

PubMed

Hsieh, Chun-Yu; Wang, Shing-Yaw; Kwan, Aij-Lie; Wu, Hsin-Lung

2008-01-18

Vigabatrin is widely used as an anticonvulsant in the treatment of seizures. Vigabatrin is usually supplied as racemate in formulation, but only the (S)-(+)-enantiomer of vigabatrin is pharmacologically active. A simple and sensitive liquid chromatographic method is described for the separation and quantification of vigabatrin enantiomers. The method is based on derivatizing racemic vigabatrin with a fluorescent chiral reagent (naproxen acyl chloride). The resulting diastereomeric derivatives are highly responsive to a fluorimetric detector (lambda(ex)=230 nm, lambda(em)=350 nm). The lower quantitation limit of the method is attainable at 25 nM for (S)-(+)-vigabatrin or (R)-(-)-vigabatrin with a detection limit of about 2.5 nM (S/N=3 with 10 microl injected). Application of the method to the analysis of vigabatrin in serum of dosed patients proved feasible.

A Dual-Catalysis Approach to Enantioselective [2+2] Photocycloadditions Using Visible Light

PubMed Central

Du, Juana; Skubi, Kazimer L.; Schultz, Danielle M.; Yoon, Tehshik P.

2015-01-01

In contrast to the wealth of catalytic systems that are available to control the stereochemistry of thermally promoted cycloadditions, few similarly effective methods exist for the stereocontrol of photochemical cycloadditions. A major unsolved challenge in the design of enantioselective catalytic photocycloaddition reactions has been the difficulty of controlling racemic background reactions that occur by direct photoexcitation of substrates while unbound to catalyst. Here we describe a strategy for eliminating the racemic background reaction in asymmetric [2+2] photocycloadditions of α,β-unsaturated ketones to the corresponding cyclobutanes by employing a dual-catalyst system consisting of a visible light-absorbing transition metal photocatalyst and a stereocontrolling Lewis acid co-catalyst. The independence of these two catalysts enables broader scope, greater stereochemical flexibility, and better efficiency than previously reported methods for enantioselective photochemical cycloadditions. PMID:24763585

Lipase-Catalyzed Kinetic Resolution of Novel Antifungal N-Substituted Benzimidazole Derivatives.

PubMed

Łukowska-Chojnacka, Edyta; Staniszewska, Monika; Bondaryk, Małgorzata; Maurin, Jan K; Bretner, Maria

2016-04-01

A series of new N-substituted benzimidazole derivatives was synthesized and their antifungal activity against Candida albicans was evaluated. The chemical step included synthesis of appropriate ketones containing benzimidazole ring, reduction of ketones to the racemic alcohols, and acetylation of alcohols to the esters. All benzimidazole derivatives were obtained with satisfactory yields and in relatively short times. All synthesized compounds exhibit significant antifungal activity against Candida albicans 900028 ATCC (% cell inhibition at 0.25 μg concentration > 98%). Additionally, racemic mixtures of alcohols were separated by lipase-catalyzed kinetic resolution. In the enzymatic step a transesterification reaction was applied and the influence of a lipase type and solvent on the enantioselectivity of the reaction was studied. The most selective enzymes were Novozyme SP 435 and lipase Amano AK from Pseudomonas fluorescens (E > 100). © 2016 Wiley Periodicals, Inc.

Primordial soup was edible: abiotically produced Miller-Urey mixture supports bacterial growth.

PubMed

Xie, Xueshu; Backman, Daniel; Lebedev, Albert T; Artaev, Viatcheslav B; Jiang, Liying; Ilag, Leopold L; Zubarev, Roman A

2015-09-28

Sixty years after the seminal Miller-Urey experiment that abiotically produced a mixture of racemized amino acids, we provide a definite proof that this primordial soup, when properly cooked, was edible for primitive organisms. Direct admixture of even small amounts of Miller-Urey mixture strongly inhibits E. coli bacteria growth due to the toxicity of abundant components, such as cyanides. However, these toxic compounds are both volatile and extremely reactive, while bacteria are highly capable of adaptation. Consequently, after bacterial adaptation to a mixture of the two most abundant abiotic amino acids, glycine and racemized alanine, dried and reconstituted MU soup was found to support bacterial growth and even accelerate it compared to a simple mixture of the two amino acids. Therefore, primordial Miller-Urey soup was perfectly suitable as a growth media for early life forms.

Chiral resolution of spin angular momentum in linearly polarized and unpolarized light

PubMed Central

Hernández, R. J.; Mazzulla, A.; Provenzano, C.; Pagliusi, P.; Cipparrone, G.

2015-01-01

Linearly polarized (LP) and unpolarized (UP) light are racemic entities since they can be described as superposition of opposite circularly polarized (CP) components of equal amplitude. As a consequence they do not carry spin angular momentum. Chiral resolution of a racemate, i.e. separation of their chiral components, is usually performed via asymmetric interaction with a chiral entity. In this paper we provide an experimental evidence of the chiral resolution of linearly polarized and unpolarized Gaussian beams through the transfer of spin angular momentum to chiral microparticles. Due to the interplay between linear and angular momentum exchange, basic manipulation tasks, as trapping, spinning or orbiting of micro-objects, can be performed by light with zero helicity. The results might broaden the perspectives for development of miniaturized and cost-effective devices. PMID:26585284

Design and Synthesis of Novel Arctigenin Analogues for the Amelioration of Metabolic Disorders

PubMed Central

2015-01-01

Analogues of the natural product (−)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (−)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure–activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes. PMID:25941553

Design and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders.

PubMed

Duan, Shudong; Huang, Suling; Gong, Jian; Shen, Yu; Zeng, Limin; Feng, Ying; Ren, Wenming; Leng, Ying; Hu, Youhong

2015-04-09

Analogues of the natural product (-)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (-)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure-activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes.

Effects of nano-SiO2 on the adsorption of chiral metalaxyl to agricultural soils.

PubMed

Huang, Junxing; Liang, Chuanzhou; Zhang, Xu

2017-06-01

The application of nanotechnology in agriculture, pesticide delivery and other related fields increases the occurrence of engineered nanoparticles (ENPs) in soil. Since ENPs have larger surface areas and normally a high adsorption capacity for organic pollutants, they are thought to influence the transport of pesticides in soils and thereafter influence the uptake and transformation of pesticides. The adsorption pattern of racemic-metalaxyl on agricultural soils including kinetics and isotherms changed in the presence of nano-SiO 2 . The adsorption of racemic-metalaxyl on agricultural soil was not enantioselective, in either the presence or the absence of SiO 2 . The adsorption of racemic-metalaxyl on SiO 2 decreased to some extent in soil-SiO 2 mixture, and the absolute decrease was dependent on soil properties. The decreased adsorption of metalaxyl on SiO 2 in soil-SiO 2 mixture arose from the competitive adsorption of soil-dissolved organic matter and the different dispersion and aggregation behaviors of SiO 2 in the presence of soil. Interactions between SiO 2 and soil particles also contributed to the decreased adsorption of metalaxyl on SiO 2 , and the interactions were analyzed by extended Derjaguin-Landau-Verwey-Overbeek theory. The results showed that the presence of nano-particles in soils could decrease the mobility of pesticides in soils and that this effect varied with different soil compositions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Homochiral drugs: a demanding tendency of the pharmaceutical industry.

PubMed

Núñez, María C; García-Rubiño, M Eugenia; Conejo-García, Ana; Cruz-López, Olga; Kimatrai, María; Gallo, Miguel A; Espinosa, Antonio; Campos, Joaquín M

2009-01-01

The issue of drug chirality is now a major theme in the design and development of new drugs, underpinned by a new understanding of the role of molecular recognition in many pharmacologically relevant events. In general, three methods are utilized for the production of a chiral drug: the chiral pool, separation of racemates, and asymmetric synthesis. Although the use of chiral drugs predates modern medicine, only since the 1980's has there been a significant increase in the development of chiral pharmaceutical drugs. An important commercial reason is that as patents on racemic drugs expire, pharmaceutical companies have the opportunity to extend patent coverage through development of the chiral switch enantiomers with desired bioactivity. Stimulated by the new policy statements issued by the regulatory agencies, the pharmaceutical industry has systematically begun to develop chiral drugs in enantiometrically enriched pure forms. This new trend has caused a tremendous change in the industrial small- and large-scale production to enantiomerically pure drugs, leading to the revisiting and updating of old technologies, and to the development of new methodologies of their large-scale preparation (as the use of stereoselective syntheses and biocatalyzed reactions). The final decision whether a given chiral drug will be marketed in an enantiomerically pure form, or as a racemic mixture of both enantiomers, will be made weighing all the medical, financial and social proficiencies of one or other form. The kinetic, pharmacological and toxicological properties of individual enantiomers need to be characterized, independently of a final decision.

The Structure and Function of a Microbial Allantoin Racemase Reveal the Origin and Conservation of a Catalytic Mechanism.

PubMed

Cendron, Laura; Ramazzina, Ileana; Puggioni, Vincenzo; Maccacaro, Eleonora; Liuzzi, Anastasia; Secchi, Andrea; Zanotti, Giuseppe; Percudani, Riccardo

2016-11-22

The S enantiomer of allantoin is an intermediate of purine degradation in several organisms and the final product of uricolysis in nonhominoid mammals. Bioinformatics indicated that proteins of the Asp/Glu racemase superfamily could be responsible for the allantoin racemase (AllR) activity originally described in Pseudomonas species. In these proteins, a cysteine of the catalytic dyad is substituted with glycine, yet the recombinant enzyme displayed racemization activity with a similar efficiency (k cat /K M ≈ 5 × 10 4 M -1 s -1 ) for the R and S enantiomers of allantoin. The protein crystal structure identified a glutamate residue located three residues downstream (E78) that can functionally replace the missing cysteine; the catalytic role of E78 was confirmed by site-directed mutagenesis. Allantoin can undergo racemization through formation of a bicyclic intermediate (faster) or proton exchange at the chiral center (slower). By monitoring the two alternative mechanisms by 13 C and 1 H nuclear magnetic resonance, we found that the velocity of the faster reaction is unaffected by the enzyme, whereas the velocity of the slower reaction is increased by 7 orders of magnitude. Protein phylogenies trace the origin of the racemization mechanism in enzymes acting on glutamate, a substrate for which proton exchange is the only viable reaction mechanism. This mechanism was inherited by allantoin racemase through divergent evolution and conserved in spite of the substitution of catalytic residues.

Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic alkylation

NASA Astrophysics Data System (ADS)

You, Hengzhi; Rideau, Emeline; Sidera, Mireia; Fletcher, Stephen P.

2015-01-01

The development of new reactions forming asymmetric carbon-carbon bonds has enabled chemists to synthesize a broad range of important carbon-containing molecules, including pharmaceutical agents, fragrances and polymers. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. An alternative strategy--dynamic kinetic asymmetric transformation--involves the transformation of a racemic starting material into a single enantiomer product, with greater than 50 per cent maximum yield. The use of stabilized nucleophiles (pKa < 25, where Ka is the acid dissociation constant) in palladium-catalysed asymmetric allylic alkylation reactions has proved to be extremely versatile in these processes. Conversely, the use of non-stabilized nucleophiles in such reactions is difficult and remains a key challenge. Here we report a copper-catalysed dynamic kinetic asymmetric transformation using racemic substrates and alkyl nucleophiles. These nucleophiles have a pKa of >=50, more than 25 orders of magnitude more basic than the nucleophiles that are typically used in such transformations. Organometallic reagents are generated in situ from alkenes by hydrometallation and give highly enantioenriched products under mild reaction conditions. The method is used to synthesize natural products that possess activity against tuberculosis and leprosy, and an inhibitor of para-aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction proceeds through a rapidly isomerizing intermediate. We anticipate that this approach will be a valuable complement to existing asymmetric catalytic methods.

Proline-catalysed asymmetric amination of alpha,alpha-disubstituted aldehydes: synthesis of configurationally stable enantioenriched alpha-aminoaldehydes.

PubMed

Vogt, Henning; Vanderheiden, Sylvia; Bräse, Stefan

2003-10-07

Proline-catalysed amination of alpha,alpha-disubstituted racemic aldehydes with azodicarboxylates proceeds smoothly to give configurationally stable scalemic aldehydes and oxazolidinones in up to 86% ee.

An obstacle in preparing alloisoleucine.

PubMed

Laird, W M; Matai, S; Synge, R L

1970-03-01

Alloisoleucine, prepared from a mixture of racemic isoleucine-alloisoleucine diastereoisomers, can be heavily contaminated with isoleucine if the recrystallization of acetyl-dl-alloisoleucine is controlled by melting point only. Two commercial specimens were found to be thus contaminated.

CHIRAL PESTICIDES: OCCURRENCE AND SIGNIFICANCE

EPA Science Inventory

Like amino acids, certain pesticides exist in "left-handed" and "right-handed" (chiral) forms. Commercially available chiral pesticides are produced as racemic mixtures in which the ratio of the two forms (or enantiomers) is 1:1. Enantiomers have the same ...

ENANTIOSELECTIVITY IN THE BIODEGRADATION OF PCB ATROPISOMERS

EPA Science Inventory

Microcosms inoculated with sediment from two locations in a contaminated reservoir, Lake Hartwell, SC, USA, degraded certain PCB atropisomers enantioselectively while other atropisomers were degraded in racemic proportions. The microcosms were spiked with either 234-236 PCB (PCB...

A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography.

PubMed

Bunker, Richard D; Mandal, Kalyaneswar; Bashiri, Ghader; Chaston, Jessica J; Pentelute, Bradley L; Lott, J Shaun; Kent, Stephen B H; Baker, Edward N

2015-04-07

Protein 3D structure can be a powerful predictor of function, but it often faces a critical roadblock at the crystallization step. Rv1738, a protein from Mycobacterium tuberculosis that is strongly implicated in the onset of nonreplicating persistence, and thereby latent tuberculosis, resisted extensive attempts at crystallization. Chemical synthesis of the L- and D-enantiomeric forms of Rv1738 enabled facile crystallization of the D/L-racemic mixture. The structure was solved by an ab initio approach that took advantage of the quantized phases characteristic of diffraction by centrosymmetric crystals. The structure, containing L- and D-dimers in a centrosymmetric space group, revealed unexpected homology with bacterial hibernation-promoting factors that bind to ribosomes and suppress translation. This suggests that the functional role of Rv1738 is to contribute to the shutdown of ribosomal protein synthesis during the onset of nonreplicating persistence of M. tuberculosis.

Engineering chiral porous metal-organic frameworks for enantioselective adsorption and separation

NASA Astrophysics Data System (ADS)

Peng, Yongwu; Gong, Tengfei; Zhang, Kang; Lin, Xiaochao; Liu, Yan; Jiang, Jianwen; Cui, Yong

2014-07-01

The separation of racemic molecules is of substantial significance not only for basic science but also for technical applications, such as fine chemicals and drug development. Here we report two isostructural chiral metal-organic frameworks decorated with chiral dihydroxy or -methoxy auxiliares from enantiopure tetracarboxylate-bridging ligands of 1,1‧-biphenol and a manganese carboxylate chain. The framework bearing dihydroxy groups functions as a solid-state host capable of adsorbing and separating mixtures of a range of chiral aromatic and aliphatic amines, with high enantioselectivity. The host material can be readily recycled and reused without any apparent loss of performance. The utility of the present adsorption separation is demonstrated in the large-scale resolution of racemic 1-phenylethylamine. Control experiments and molecular simulations suggest that the chiral recognition and separation are attributed to the different orientations and specific binding energies of the enantiomers in the microenvironment of the framework.

Comparison of amino acid racemization geochronometry with lithostratigraphy, biostratigraphy, uranium-series coral dating, and magnetostratigraphy in the Atlantic Coastal Plain of the southeastern United States

USGS Publications Warehouse

McCartan, L.; Owens, J.P.; Blackwelder, B. W.; Szabo, B. J.; Belknap, D.F.; Kriausakul, N.; Mitterer, R.M.; Wehmiller, J.F.

1982-01-01

The results of an integrated study comprising litho- and biostratigraphic investigations, uranium-series coral dating, amino acid racemization in molluscs, and paleomagnetic measurements are compared to ascertain relative and absolute ages of Pleistocene deposits of the Atlantic Coastal Plain in North and South Carolina. Four depositional events are inferred for South Carolina and two for North Carolina by all methods. The data suggest that there are four Pleistocene units containing corals that have been dated at about 100,000 yr, 200,000 yr, 450,000 yr, and over 1,000,000 yr. Some conflicts exist between the different methods regarding the correlation of the younger of these depositional events between Charleston and Myrtle Beach. Lack of good uranium-series dates for the younger material at Myrtle Beach makes the correlation with the deposits at Charleston more difficult. ?? 1982.

Green chiral HPLC study of the stability of Chiralcel OD under high temperature liquid chromatography and subcritical water conditions.

PubMed

Droux, S; Roy, M; Félix, G

2014-10-01

We report here the study of the stability under subcritical water conditions of one of the most popular polysaccharide chiral stationary phase (CSP): Chiralcel OD. This CSP was used under high temperature and reversed phase conditions with acetonitrile and 2-propanol as modifier, respectively. The evolution of selectivity and resolution was investigated both in normal and reversed mode conditions with five racemates after packing, heating at 150 °C and separations of some racemic compounds under different high temperatures and mobile phase conditions. The results show that after using at high temperature and subcritical water conditions the selectivity was only moderately affected while the resolution fell dramatically especially in reversed mode due to the creation of a void at the head of the columns which reflects the dissolution of the silica matrix. Copyright © 2014 Elsevier B.V. All rights reserved.

Distribution and enantiomeric composition of amino acids in the Murchison meteorite

NASA Technical Reports Server (NTRS)

Engel, M. H.; Nagy, B.

1982-01-01

Studies of the amino acid contents and enantiomeric compositions of a single stone from the Murchison meteorite are reported. Water-extracted and 6M HCl-extracted samples from the meteorite interior of meteorite fragments were analyzed by gas chromatography and combined gas chromatography-chemical ionization mass spectrometry. Examination of the D/L ratios of glutamic acid, aspartic acid, proline, leucine and alanine reveals those amino acids extractable by water to be partially racemized, whereas the acid-extracted amino acids were less racemized. The amino acid composition of the stone is similar to those previously reported, including the absence of serine, threonine, tyrosine phenylalanine and methionine and the presence of unusual amino acids including such as isovaline, alpha-aminoisobutyric acid and pseudoleucine. It is concluded that the most likely mechanism accounting for the occurrence of nonracemic amino acid mixtures in the Murchison meteorite is by extraterrestrial stereoselective synthesis or decomposition reactions.

Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites.

PubMed

Cooper, George; Rios, Andro C

2016-06-14

Biological polymers such as nucleic acids and proteins are constructed of only one-the d or l-of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System's earliest (∼4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life's carbohydrate-related biopolymers.

Intermixed adatom and surface-bound adsorbates in regular self-assembled monolayers of racemic 2-butanethiol on Au(111).

PubMed

Ouyang, Runhai; Yan, Jiawei; Jensen, Palle S; Ascic, Erhad; Gan, Shiyu; Tanner, David; Mao, Bingwei; Niu, Li; Zhang, Jingdong; Tang, Chunguang; Hush, Noel S; Reimers, Jeffrey R; Ulstrup, Jens

2015-04-07

In situ scanning tunneling microscopy combined with density functional theory molecular dynamics simulations reveal a complex structure for the self-assembled monolayer (SAM) of racemic 2-butanethiol on Au(111) in aqueous solution. Six adsorbate molecules occupy a (10×√3)R30° cell organized as two RSAuSR adatom-bound motifs plus two RS species bound directly to face-centered-cubic and hexagonally close-packed sites. This is the first time that these competing head-group arrangements have been observed in the same ordered SAM. Such unusual packing is favored as it facilitates SAMs with anomalously high coverage (30%), much larger than that for enantiomerically resolved 2-butanethiol or secondary-branched butanethiol (25%) and near that for linear-chain 1-butanethiol (33%). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A question about the potential cardiac toxicity of escitalopram.

PubMed

Howland, Robert H

2012-04-01

Previous reviews have focused on the potential cardiac toxicity of the racemic drug citalopram (Celexa(®)). Evaluating the safety of escitalopram (Lexapro(®)) is an important issue to consider, since it is the S-enantiomer of citalopram. Escitalopram has a small effect on the QTc interval. A prolonged QTc was seen in 2% to 14% of escitalopram overdose cases, without serious cardiac sequelae. The QTc prolongation effect of citalopram in beagle dogs has been attributed to the minor metabolite racemic didemethylcitalopram (DDCT). Whether the escitalopram minor metabolite S-DDCT has this effect is not known. Concentrations of S-DDCT are lower than DDCT, but for a broad range of doses of escitalopram and citalopram, the S-DDCT and DDCT concentrations are well below the QTc prolonging concentrations reported in dogs. There is no strong evidence from human and animal studies that the cardiac safety of escitalopram is significantly superior to that of citalopram. Copyright 2012, SLACK Incorporated.

A top-down approach to crystal engineering of a racemic Δ2-isoxazoline.

PubMed

Lombardo, Giuseppe M; Rescifina, Antonio; Chiacchio, Ugo; Bacchi, Alessia; Punzo, Francesco

2014-02-01

The crystal structure of racemic dimethyl (4RS,5RS)-3-(4-nitrophenyl)-4,5-dihydroisoxazole-4,5-dicarboxylate, C13H12N2O7, has been determined by single-crystal X-ray diffraction. By analysing the degree of growth of the morphologically important crystal faces, a ranking of the most relevant non-covalent interactions determining the crystal structure can be inferred. The morphological information is considered with an approach opposite to the conventional one: instead of searching inside the structure for the potential key interactions and using them to calculate the crystal habit, the observed crystal morphology is used to define the preferential lines of growth of the crystal, and then this information is interpreted by means of density functional theory (DFT) calculations. Comparison with the X-ray structure confirms the validity of the strategy, thus suggesting this top-down approach to be a useful tool for crystal engineering.

Efficient chemoenzymatic dynamic kinetic resolution of 1-heteroaryl ethanols.

PubMed

Vallin, Karl S A; Wensbo Posaric, David; Hamersak, Zdenko; Svensson, Mats A; Minidis, Alexander B E

2009-12-18

The scope and limitation of the combined ruthenium-lipase induced dynamic kinetic resolution (DKR) through O-acetylation of racemic heteroaromatic secondary alcohols, i.e., 1-heteroaryl substituted ethanols, was investigated. After initial screening of reaction conditions, Candida antarctica lipase B (Novozyme 435, N435) together with 4-chloro-phenylacetate as acetyl-donor for kinetic resolution (KR), in conjunction with the ruthenium-based Shvo catalyst for substrate racemization in toluene at 80 degrees C, enabled DKR with high yields and stereoselectivity of various 1-heteroaryl ethanols, such as oxadiazoles, isoxazoles, 1H-pyrazole, or 1H-imidazole. In addition, DFT calculations based on a simplified catalyst complex model for the catalytic (de)hydrogenation step are in agreement with the previously reported outer sphere mechanism. These results support the further understanding of the mechanistic aspects behind the difference in reactivity of 1-heteroaryl substituted ethanols in comparison to reference substrates, as often referred to in the literature.

Chirality-controlled crystallization via screw dislocations.

PubMed

Sung, Baeckkyoung; de la Cotte, Alexis; Grelet, Eric

2018-04-11

Chirality plays an important role in science from enantiomeric separation in chemistry to chiral plasmonics in nanotechnology. However, the understanding of chirality amplification from chiral building blocks to ordered helical superstructures remains a challenge. Here, we demonstrate that topological defects, such as screw dislocations, can drive the chirality transfer from particle to supramolecular structure level during the crystallization process. By using a model system of chiral particles, which enables direct imaging of single particle incorporation into growing crystals, we show that the crystallization kinetic pathway is the key parameter for monitoring, via the defects, the chirality amplification of the crystalline structures from racemic to predominantly homohelical. We provide an explanation based on the interplay between geometrical frustration, racemization induced by thermal fluctuations, and particle chirality. Our results demonstrate that screw dislocations not only promote the growth, but also control the chiral morphology and therefore the functionality of crystalline states.

Probes for narcotic receptor mediated phenomena. 42. Synthesis and in vitro pharmacological characterization of the N-methyl and N-phenethyl analogues of the racemic ortho-c and para-c oxide-bridged phenylmorphans

PubMed Central

Kim, Jin-Hee; Deschamps, Jeffrey R.; Rothman, Richard B.; Dersch, Christina M.; Folk, John E.; Cheng, Kejun; Jacobson, Arthur E.; Rice, Kenner C.

2011-01-01

A new synthesis of N-methyl and N-phenethyl substituted ortho-c and para-c oxide-bridged phenylmorphans, using N-benzyl- rather than N-methyl-substituted intermediates, was used and the pharmacological properties of these compounds were determined. The N-phenethyl substituted ortho-c oxide-bridged phenylmorphan (rac-(3R,6aS,11aS)-2-phenethyl-2,3,4,5,6,11a-hexahydro-1H-3,6a-methanobenzofuro[2,3-c]azocin-10-ol (12)) was found to have the highest μ-opioid receptor affinity (Ki = 1.1 nM) of all of the a- through f-oxide-bridged phenylmorphans. Functional data ([35S]GTP-γ-S) showed that the racemate 12 was more than three times more potent than naloxone as an μ-opioid antagonist. PMID:21570305

Fungal volatiles: Semiochemicals for stored-product beetles (Coleoptera: Cucujidae).

PubMed

Pierce, A M; Pierce, H D; Borden, J H; Oehlschlager, A C

1991-03-01

Responses by five species of cucujid grain beetles (mixed-sex adults) to various volatiles were assessed by means of a two-choice, pitfall olfactometer. The test volatiles were short-chain alcohols and ketones known to be produced by fungi. Both racemic and chiral 1-octen-3-ols were strong attractants forCryptolestes ferrugineus (Stephens), as had been found previously forOryzaephilus surinamensis (L.),O. mercator (Fauvel), andAhasverus advena (Waltl). 3-Methylbutanol was another good attractant for these four cucujids, and it was the only test compound to whichCathartus quadricollis (Guér.) responded positively. 1-Octen-3-one, racemic 3-octanol, and 3-octanone showed various degrees of attractiveness for the former four species of cucujids.O. surinamensis was the only species of test beetle to show much positive response to 2-phenylethanol and ethanol. ForO. mercator andO. surinamensis, 3-methylbutanol enhanced positive response to their respective cucujolide aggregation pheromones.

HPLC enantioseparation of racemic bupropion, baclofen and etodolac: modification of conventional ligand exchange approach by pre-column formation of chiral ligand exchange complexes.

PubMed

Singh, Manisha; Bhushan, Ravi

2016-11-01

Separation of racemic mixture of (RS)-bupropion, (RS)-baclofen and (RS)-etodolac, commonly marketed racemic drugs, has been achieved by modifying the conventional ligand exchange approach. The Cu(II) complexes were first prepared with a few l-amino acids, namely, l-proline, l-histidine, l-phenylalanine and l-tryptophan, and to these was introduced a mixture of the enantiomer pair of (RS)-bupropion, or (RS)-baclofen or (RS)-etodolac. As a result, formation of a pair of diastereomeric complexes occurred by 'chiral ligand exchange' via the competition between the chelating l-amino acid and each of the two enantiomers from a given pair. The diastereomeric mixture formed in the pre-column process was loaded onto HPLC column. Thus, both the phases during chromatographic separation process were achiral (i.e. neither the stationary phase had any chiral structural feature of its own nor did the mobile phase have any chiral additive). Separation of diastereomers was successful using a C 18 column and a binary mixture of MeCN and TEAP buffer of pH 4.0 (60:40, v/v) as mobile phase at a flow rate of 1 mL/min and UV detection at 230 nm for (RS)-Bup, 220 nm for (RS)-Bac and 223 nm for (RS)-Etd. Baseline separation of the two enantiomers was obtained with a resolution of 6.63 in <15 min. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Soybean fruit development and set at the node level under combined photoperiod and radiation conditions

PubMed Central

Nico, Magalí; Mantese, Anita I.; Miralles, Daniel J.; Kantolic, Adriana G.

2016-01-01

In soybean, long days during post-flowering increase seed number. This positive photoperiodic effect on seed number has been previously associated with increments in the amount of radiation accumulated during the crop cycle because long days extend the duration of the crop cycle. However, evidence of intra-nodal processes independent of the availability of assimilates suggests that photoperiodic effects at the node level might also contribute to pod set. This work aims to identify the main mechanisms responsible for the increase in pod number per node in response to long days; including the dynamics of flowering, pod development, growth and set at the node level. Long days increased pods per node on the main stems, by increasing pods on lateral racemes (usually dominated positions) at some main stem nodes. Long days lengthened the flowering period and thereby increased the number of opened flowers on lateral racemes. The flowering period was prolonged under long days because effective seed filling was delayed on primary racemes (dominant positions). Long days also delayed the development of flowers into pods with filling seeds, delaying the initiation of pod elongation without modifying pod elongation rate. The embryo development matched the external pod length irrespective of the pod’s chronological age. These results suggest that long days during post-flowering enhance pod number per node through a relief of the competition between pods of different hierarchy within the node. The photoperiodic effect on the development of dominant pods, delaying their elongation and therefore postponing their active growth, extends flowering and allows pod set at positions that are usually dominated. PMID:26512057

Functional Characterization of Alanine Racemase from Schizosaccharomyces pombe: a Eucaryotic Counterpart to Bacterial Alanine Racemase

PubMed Central

Uo, Takuma; Yoshimura, Tohru; Tanaka, Naotaka; Takegawa, Kaoru; Esaki, Nobuyoshi

2001-01-01

Schizosaccharomyces pombe has an open reading frame, which we named alr1+, encoding a putative protein similar to bacterial alanine racemase. We cloned the alr1+ gene in Escherichia coli and purified the gene product (Alr1p), with an Mr of 41,590, to homogeneity. Alr1p contains pyridoxal 5′-phosphate as a coenzyme and catalyzes the racemization of alanine with apparent Km and Vmax values as follows: for l-alanine, 5.0 mM and 670 μmol/min/mg, respectively, and for d-alanine, 2.4 mM and 350 μmol/min/mg, respectively. The enzyme is almost specific to alanine, but l-serine and l-2-aminobutyrate are racemized slowly at rates 3.7 and 0.37% of that of l-alanine, respectively. S. pombe uses d-alanine as a sole nitrogen source, but deletion of the alr1+ gene resulted in retarded growth on the same medium. This indicates that S. pombe has catabolic pathways for both enantiomers of alanine and that the pathway for l-alanine coupled with racemization plays a major role in the catabolism of d-alanine. Saccharomyces cerevisiae differs markedly from S. pombe: S. cerevisiae uses l-alanine but not d-alanine as a sole nitrogen source. Moreover, d-alanine is toxic to S. cerevisiae. However, heterologous expression of the alr1+ gene enabled S. cerevisiae to grow efficiently on d-alanine as a sole nitrogen source. The recombinant yeast was relieved from the toxicity of d-alanine. PMID:11244061

Determining D/L Ratios of Amino Acids Found in Ice Above Lake Vostok Using ESI/CIT Mass Spectroscopy

NASA Technical Reports Server (NTRS)

Tsapin, A.; Kanik, I.; Beegle, L. W.; Wu, L.; Cooks, R. G.

2003-01-01

Astrobiology is an area where longevity of (micro) organisms is of great interest. Cryospheres are common phenomena in the solar system, particularly on satellites, comets and asteroids, as well as at least some of the planets. Recent data from the Mars Global Surveyor mission suggest the possibility of permafrost or perhaps even liquid water under the Martian surface [2]. These environments may be the areas in which the probability of finding life is the highest. This issue is of concern due to the probable evolution of planetary environments such as that of Mars from more hospitable to less hospitable conditions over the history of the solar system. In addition, evaluation of the possible transfer of living organisms between planets via impact ejecta [3] is dependent on knowledge of the maximum time periods over which microorganisms can remain dormant and subsequently revive and reproduce.Amino acid racemization dating, or aminostratigraphy, has been used for many years to date biological systems, and has been examined as a possible biosignature detection technique for Mars. We have suggested using amino acid racemization as one of the most indicative biosignatures [4]. Only life systems produce preferential synthesis of L-amino acids versus D-amino acids. Almost all amino acids in terrestrial organisms can be found only in the L-enantiomeric form.We studied the level of amino acid racemization, specifically of aspartic acid, in permafrost samples from eastern Siberia. Also we analyzed samples of ice from borehole drilled to lake Vostok, Antarctica.

Chemical Principles Revisited: Archaeological Dating.

ERIC Educational Resources Information Center

Rowe, M. W.

1986-01-01

Discusses methods used to date archaeological artifacts and other remains. They include: (1) nuclear dating techniques (radiocarbon dating, accelerator radiocarbon dating, thermoluminescence, and others); (2) chemical dating techniques (amino acid racemization, obsidian hydration dating, elemental content changes, and thermal analysis dating); and…

Enantiomer Ratios of Meteoritic Sugar Derivatives

NASA Technical Reports Server (NTRS)

Cooper, George

2012-01-01

Carbonaceous meteorites contain a diverse suite of soluble organic compounds. Studies of these compounds reveal the Solar System's earliest organic chemistry. Among the classes of organic compounds found in meteorites are keto acids (pyruvic acid, etc.), hydroxy tricarboxylic acids (1), amino acids, amides, purines and pyrimidines. The Murchison and Murray meteorites are the most studied for soluble and insoluble organic compounds and organic carbon phases. The majority of (indigenous) meteoritic compounds are racemic, (i.e., their D/L enantiomer ratios are 50:50). However, some of the more unusual (non-protein) amino acids contain slightly more of one enantiomer (usually the L) than the other. This presentation focuses on the enantiomer analyses of three to six-carbon (3C to 6C) meteoritic sugar acids. The molecular and enantiomer analysis of corresponding sugar alcohols will also be discussed. Detailed analytical procedures for sugar-acid enantiomers have been described. Results of several meteorite analyses show that glyceric acid is consistently racemic (or nearly so) as expected of non-biological mechanisms of synthesis. Also racemic are 4-C deoxy sugar acids: 2-methyl glyceric acid; 2,4-dihydroxybutyric acid; 2,3-dihydroxybutyric acid (two diastereomers); and 3,4-dihydroxybutyric acid. However, a 4C acid, threonic acid, has never been observed as racemic, i.e., it possesses a large D excess. In several samples of Murchison and one of GRA 95229 (possibly the most pristine carbonaceous meteorite yet analyzed) threonic acid has nearly the same D enrichment. In Murchison, preliminary isotopic measurements of individual threonic acid enantiomers point towards extraterrestrial sources of the D enrichment. Enantiomer analyses of the 5C mono-sugar acids, ribonic, arabinonic, xylonic, and lyxonic also show large D excesses. It is worth noting that all four of these acids (all of the possible straight-chained 5C sugar acids) are present in meteorites, including the rare lyxonic acid, and their relative abundances are in equilibrium proportions. In addition (in contrast to the above D-only excesses), some of the above acids are found in biology as the L enantiomer. Whether rare are common, all of the 6C sugar acids that are present in sufficient amounts to allow enantiomer analysis (Mannonic, gluconic, altronic, talonic, idonic, gulonic, and galactonic) also, apparently, possess significant D excesses.

Hepatic and pulmonary apoptosis after hemorrhagic shock in swine can be reduced through modifications of conventional Ringer's solution.

PubMed

Ayuste, Eduardo C; Chen, Huazhen; Koustova, Elena; Rhee, Peter; Ahuja, Naresh; Chen, Zhang; Valeri, C Robert; Spaniolas, Konstantinos; Mehrani, Tina; Alam, Hasan B

2006-01-01

Cytotoxic properties of racemic (D-,L-isomers) lactated Ringer's solution detected in vitro and in small animal experiments, have not been confirmed in large animal models. Our hypothesis was that in a clinically relevant large animal model of hemorrhage, resuscitation with racemic lactated Ringer's solution would induce cellular apoptosis, which can be attenuated by elimination of d-lactate. Yorkshire swine (n = 49, weight 40-58 kg) were subjected to uncontrolled (iliac arterial and venous injuries) and controlled hemorrhage, totaling 40% of estimated blood volume. They were randomized (n = 7/group) to control groups, which consisted of (1) no hemorrhage (NH), (2) no resuscitation (NR), or resuscitation groups, which consisted of (3) 0.9% saline (NS), (4) racemic lactated Ringer's (DL-LR), (5) L-isomer lactated Ringer's (L-LR), (6) Ketone Ringer's (KR), (7) 6% hetastarch in 0.9% saline (Hespan). KR was identical to LR except for equimolar substitution of lactate with beta-hydroxybutyrate. Resuscitation was performed in three phases, simulating (1) prehospital, (2) operative, (3) postoperative/recovery periods. Arterial blood gasses, circulating cytokines (TNF-alpha, IL-1, -6, -10), and markers of organ injury were serially measured. Metabolic activity of brain, and liver, was measured with microdialysis. Four hours postinjury, organs were harvested for Western blotting, ELISA, TUNEL assay, and immunohistochemistry. All resuscitation strategies restored blood pressure, but clearance of lactic acidosis was impeded following DL-LR resuscitation. Metabolic activity decreased during shock and improved with resuscitation, without any significant inter-group differences. Levels of cytokines in circulation were similar, but tissue levels of TNF in liver and lung increased six- and threefolds (p < 0.05) in NR group. In liver, all resuscitation strategies significantly decreased TNF levels compared with the NR group, but in the lung resuscitation with lactated Ringer (DL and L isomers) failed to decrease tissue TNF levels. DL-LR resuscitation also increased apoptosis (p < 0.05) in liver and lung, which was not seen after resuscitation with other solutions. In this large animal model of hemorrhagic shock, resuscitation with conventional (racemic) LR solution increased apoptotic cell death in liver and lung. This effect can be prevented by simple elimination of D-lactate from the Ringer's solution.

Lattice modes of the chirally pure and racemic phases of tyrosine crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belyanchikov, M. A.; Gorelik, V. S., E-mail: gorelik@sci.lebedev.ru; Gorshunov, B. P.

High-Q librational modes have been found to be present in the infrared absorption and Raman spectra of chirally pure L-tyrosine. Such modes can serve as terahertz radiation detectors and generators in chirally pure biostructures.

An Integrated Experimental and Computational Approach for Characterizing the Kinetics and Mechanism of Triadimefon Racemization

EPA Science Inventory

Enantiomers of chiral molecules commonly exhibit different environmental fates, pharmacokinetics, and toxicities. Ignoring these differences can introduce significant uncertainty when modeling the physiological and environmental fate of chlral chemicals and evaluating their risk ...

Enantioselective Toxicity and Biotransformation of Fipronil in the Fathead Minnow (Pimephales promelas)

EPA Science Inventory

Fipronil is a relatively new chiral phenylpyrazole insecticide used to control both agricultural and household invertebrate pests. Fipronil is applied as a racemate, or equal mixture, of its two enantiomers. As regulations on older pesticides increase, production and applicatio...

Enantioselective pharmacokinetics of primaquine in healthy human volunteers

USDA-ARS?s Scientific Manuscript database

Primaquine (PQ), a racemic drug, is the only treatment available for radical cure of relapsing Plasmodium vivax malaria and blocking transmission of P. falciparum malaria. Recent studies have shown differential pharmacologic and toxicologic profiles of individual PQ enantiomers in rodent, dog, and p...

Protective effects of S+ ketamine and atropine against lethality and brain damage during soman-induced status epilepticus in guinea-pigs.

PubMed

Dorandeu, Frederic; Baille, Valerie; Mikler, John; Testylier, Guy; Lallement, Guy; Sawyer, Thomas; Carpentier, Pierre

2007-05-20

Soman poisoning is known to induce full-blown tonic-clonic seizures, status epilepticus (SE), seizure-related brain damage (SRBD) and lethality. Previous studies in guinea-pigs have shown that racemic ketamine (KET), with atropine sulfate (AS), is very effective in preventing death, stopping seizures and protecting sensitive brain areas when given up to 1h after a supra-lethal challenge of soman. The active ketamine isomer, S(+) ketamine (S-KET), is more potent than the racemic mixture and it also induces less side-effects. To confirm the efficacy of KET and to evaluate the potential of S-KET for delayed medical treatment of soman-induced SE, we studied different S-KET dose regimens using the same paradigm used with KET. Guinea-pigs received pyridostigmine (26 microg/kg, IM) 30min before soman (62 microg/kg, 2 LD(50), IM), followed by therapy consisting of atropine methyl nitrate (AMN) (4 mg/kg, IM) 1min following soman exposure. S-KET, with AS (10mg/kg), was then administered IM at different times after the onset of seizures, starting at 1h post-soman exposure. The protective efficacy of S-KET proved to be comparable to KET against lethality and SRBD, but at doses two to three times lower. As with KET, delaying treatment by 2h post-poisoning greatly reduced efficacy. Conditions that may have led to an increased S-KET brain concentration (increased doses or number of injections, adjunct treatment with the oxime HI-6) did not prove to be beneficial. In summary, these observations confirm that ketamine, either racemic or S-KET, in association with AS and possibly other drugs, could be highly effective in the delayed treatment of severe soman intoxication.

Effects of etravirine on the pharmacokinetics and pharmacodynamics of warfarin in rats

PubMed Central

John, J; John, M; Wu, L; Hsiao, C; Abobo, CV; Liang, D

2013-01-01

Background and Purpose Warfarin is often used with etravirine (ETV) to prevent HIV-related thromboembolic events. As both warfarin and ETV bind to plasma proteins and are metabolized by hepatic cytochrome P450s, they are likely to interact. Hence, we evaluated the effect of ETV on the pharmacokinetics and blood clotting time of racemic warfarin in rats. Experimental Approach Two groups of male Sprague-Dawley rats, in which the jugular vein had been cannulated, were studied. The control group (n = 10) received 1 mg·kg−1 racemic warfarin i.v., and the test group (n = 13) 1 mg·kg−1 of racemic warfarin followed by 25 mg·kg−1 ETV i.v. Serial blood samples were collected for up to 144 h and the blood clotting time (calculated as international normalized ratio [INR]) measured in blood plasma at each sample point. Plasma concentrations of R-warfarin, S-warfarin, R-7-hydroxywarfarin and S-7-hydroxywarfarin were measured by a LC/MS/MS method using a chiral lux cellulose-1 column. Pharmacokinetic parameters were analysed using non-compartmental methods. Key Results ETV significantly increased, by threefold, the systemic clearance and volume of distribution of S-warfarin, but not those of R-warfarin. ETV decreased the total AUC of warfarin, but had no effect on its elimination half-life. ETV also increased the systemic clearance of both R-7-hydroxywarfarin and S-7-hydroxywarfarin but only increased the volume of distribution of R-7-hydroxywarfarin. Interestingly, the effect of warfarin on blood clotting time (INR) was significantly increased in the presence of etravirine. Conclusion and Implications Our data suggest that etravirine may potentiate the anticoagulant effect of warfarin and this could have clinical significance. PMID:23215758

Perioperative epidural or intravenous ketamine does not improve the effectiveness of thoracic epidural analgesia for acute and chronic pain after thoracotomy.

PubMed

Tena, Beatriz; Gomar, Carmen; Rios, Jose

2014-06-01

Persistent postsurgical pain (PPP) after thoracotomy effect 50% to 80%. Nerve damage and central sensitization involving NDMDAr activation may play an important role. This study evaluates the efficacy of adding intravenous (IV) or epidural ketamine to thoracic epidural analgesia (TEA) after thoracotomy. Double-blind randomized study on patients undergoing thoracotomy allocated to one of the following: group Kiv (IV racemic ketamine 0.5 mg/kg preincisional +0.25 mg/kg/h for 48 h), group Kep (epidural racemic ketamine 0.5 mg/kg preincisional +0.25 mg/kg/h for 48 h), or group S (saline). Postoperative analgesia was ensured by TEA with ropivacaine and fentanyl. Pain visual analog scales (VAS), Neuropathic Pain Symptom Inventory, Catastrophizing Scale, and Quantitative Sensory Testing, measuring both the peri-incisional and distant hyperalgesia area, were conducted preoperatively and postoperatively until 6 months. Plasma ketamine levels and stability of the analgesic solutions were analyzed. A total of 104 patients were included. PPP incidence was 20% at 6 months. Pain scores on coughing were significantly lower in Kiv and Kep than in S at 24 and 72 hours, but there were no differences afterwards. There were no significant differences in pain at rest, Neuropathic Pain Symptom Inventory, and Catastrophizing Scale, or in the area of mechanical allodynia at any time. Adverse effects were mild. Plasma ketamine levels did not differ significantly between groups. Analgesic solutions were stable. Adding epidural or IV racemic ketamine to TEA after thoracotomy did not lead to any reduction in PPP or allodynia. Epidural administration produced similar plasma ketamine levels to the IV route.

Scalable Preparation and Differential Pharmacologic and Toxicologic Profiles of Primaquine Enantiomers

PubMed Central

Tekwani, Babu L.; Herath, H. M. T. Bandara; Sahu, Rajnish; Gettayacamin, Montip; Tungtaeng, Anchalee; van Gessel, Yvonne; Baresel, Paul; Wickham, Kristina S.; Bartlett, Marilyn S.; Fronczek, Frank R.; Melendez, Victor; Ohrt, Colin; Reichard, Gregory A.; McChesney, James D.; Rochford, Rosemary; Walker, Larry A.

2014-01-01

Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (−)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (−)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3 days, while (−)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human G6PD deficiency, it was also demonstrated that (−)-(R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (−)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (−)-(R)-PQ may have a better safety margin than the racemate in human. PMID:24913163

New Complexity-Building Reactions of Alpha-Keto Esters

NASA Astrophysics Data System (ADS)

Bartlett, Samuel L.

I. Introduction: Importance of Asymmetric Catalysis and the Reactivity Patterns of alpha-Keto Esters. II. Synthesis of Complex Tertiary Glycolates by Enantioconvergent Arylation of Stereochemically Labile alpha-Keto Esters. Enantioconvergent arylation reactions of boronic acids and racemic ?-stereogenic alpha-keto esters have been developed. The reactions are catalyzed by a chiral (diene)Rh(I) complex and provide a wide array of beta-stereogenic tertiary aryl glycolate derivatives with high levels of diastereo- and enantioselectivity. Racemization studies employing a series of sterically differentiated tertiary amines suggest that the steric nature of the amine base additive exerts a significant influence on the rate of substrate racemization. III. Palladium-Catalyzed beta-Arylation of alpha-Keto Esters . A catalyst system derived from commercially available Pd2(dba) 3 and PtBu3 has been applied to the coupling of alpha-keto ester enolates and aryl bromides. The reaction provides access to an array of beta-stereogenic alpha-keto ester derivatives. When the air stable ligand precursor PtBu 3˙HBF4 is employed, the reaction can be carried out without use of a glovebox. The derived products are of broad interest given the prevalence of the alpha-keto acid substructure in biologically important molecules. IV. Catalytic Enantioselective [3+2] Cycloaddition of alpha-Keto Ester Enolates and Nitrile Oxides. An enantioselective [3+2] cycloaddition reaction between nitrile oxides and transiently generated enolates of alpha-keto esters has been developed. The catalyst system was found to be compatible with in situ nitrile oxide generation conditions. A versatile array of nitrile oxides and alpha-keto esters could participate in the cycloaddition, providing novel 5-hydroxy-2-isoxazolines in high chemical yield with high levels of diastereo- and enantioselectivity. Notably, the optimal reaction conditions circumvented concurrent reaction via O-imidoylation and hetero-[3+2] pathways.

A chiral enantioseparation generic strategy for anti-Alzheimer and antifungal drugs by short end injection capillary electrophoresis using an experimental design approach.

PubMed

Abdel-Megied, Ahmed M; Hanafi, Rasha S; Aboul-Enein, Hassan Y

2018-02-01

The present study describes a generic strategy using capillary electrophoretic (CE) method for chiral enantioseparation of anti-Alzheimer drugs, namely, donepezil (DON), rivastigmine (RIV), and antifungal drugs, namely, ketoconazole (KET), Itraconazole (ITR), fluconazole (FLU), and sertaconazole (SRT) in which these drugs have different basic and acidic properties. Several modified cyclodextrins (CDs) were applied for enantioseparation of racemates such as highly sulfated α, γ CDs, hydroxyl propyl-β-CD, and Sulfobutyl ether-β-CD. The starting screening conditions consist of 50-mM phosphate-triethanolamine buffer at pH 2.5, an applied voltage of 15 kV, and a temperature of 25°C. The CE strategy implemented in the separation starts by screening prior to the optimization stage in which an experimental design is applied. The design of experiment (DOE) was based on a full factorial design of the crucial two factors (pH and %CD) at three levels, to make a total of nine (3 2 ) experiments with high, intermediate, and low values for both factors. Evaluation of the proposed strategy pointed out that best resolution was obtained at pH 2.5 for five racemates using low percentages of HS-γ-CD, while SBE-β-CD was the most successful chiral selector offering acceptable resolution for all the six racemates, with the best separation at low pH values and at higher %CD within 10-min runtime. Regression study showed that the linear model shows a significant lack of fit for all chiral selectors, anticipating that higher orders of the factors are most likely to be present in the equation with possible interactions. © 2017 Wiley Periodicals, Inc.

Rediscovering Chirality - Role of S-Metoprolol in Cardiovascular Disease Management.

PubMed

Mohan, Jagdish C; Shah, Siddharth N; Chinchansurkar, Sunny; Dey, Arindam; Jain, Rishi

2017-06-01

The process of drug discovery and development today encompass a myriad of paths for bringing a new therapeutic molecule that has minimal adverse effects and of optimal use to the patient. Chirality was proposed in the direction of providing a purer and safer form of drug [Ex- cetrizine and levocetrizine]. Decades have passed since the introduction of this concept and numerous chiral molecules are in existence in therapeutics, yet somehow this concept has been ignored. This review aims to rediscover the ignored facts about chirality, its benefits and clear some common myths considering the example of S-Metoprolol in the management of Hypertension and other cardiovascular diseases. Relevant articles from Pubmed, Embase, Medline and Google Scholar were searched using the terms "Chiral", "Chirality", "Enantiomers", "Isomers", "Isomerism", "Stereo-chemistry", and "S-Metoprolol". Out of 103 articles found 17 articles mentioning in general about the concept of chirality and articles on study of S-metoprolol in various cardiovascular diseases were then reviewed. Many articles mention about the importance of chirality yet the concept has not been highlighted much. Clear benefits with chiral molecules have been documented for various drug molecules few amongst them being anaesthetics, antihypertensives, antidepressants. Benefits of S-metoprolol over racemate are also clear in terms of responder rates, dose of administration and adverse effects profile in various cardiovascular diseases. Chirality is a good way forward in providing a new drug molecule which is safe with lesser pharmacokinetic and pharmacodynamics variability, lesser side effects and more potent action. S-metoprolol is chirally pure form of racemate metoprolol and has lesser side effects, is safer in patients of COPD and Diabetes who also have hypertension and comparable responder rates at half the doses when compared to racemate.

Headspace gas chromatography-mass spectrometry analysis of isoflurane enantiomers in blood samples after anesthesia with the racemic mixture.

PubMed

Schmidt, R; Wahl, H G; Häberle, H; Dieterich, H J; Schurig, V

1999-01-01

Several in vivo and in vitro studies on the stereoselective potency of isoflurane enantiomers suggest beneficial effects of the (+)-(S)-enantiomer. In order to detect possible differences in the pharmacokinetics of isoflurane enantiomers, a clinical study of 41 patients undergoing general anesthesia maintained with racemic isoflurane was performed. The isoflurane enantiomers were analyzed in blood samples drawn before induction, at cessation (day 0), and up to eight days after isoflurane anesthesia (day 1-8). A multipurpose sampler (Gerstel MPS) was used for the headspace gas chromatography-mass spectrometry (GC/MS) analysis, and it was combined with a cold injection system (Gerstel CIS 3) for coldtrapping, enrichment, and focusing of the analyte. The enantiomer separation was achieved by using a capillary column coated with octakis(3-O-butanoyl-2,6-di-O-pentyl)-gamma-cyclodextrin (Lipodex E) dissolved in the polysiloxane PS 255. Detection was done in the selected ion monitoring mode with ions m/z 117 and m/z 149. An enrichment of (+)-(S)-isoflurane in all blood samples drawn after anesthesia was found. The highest enantiomer bias, up to 52-54% (+)-(S)-isoflurane as compared to 50% for the racemate, was observed on day 2 for most of the patients. Furthermore, quantification of isoflurane in blood samples of five patients was done by enantiomer labeling, employing enantiomerically pure (+)-(S)-isoflurane as internal standard. The isoflurane concentration decreased rapidly from 383 nmol/ml to 0.6 nmol/ml (mean values) eight days after anesthesia. The present study shows differences in the pharmacokinetics of isoflurane enantiomers in man. However, it is not possible to distinguish between enantioselective distribution and enantioselective metabolism, if any.

Enantioselective degradation of ofloxacin and levofloxacin by the bacterial strains Labrys portucalensis F11 and Rhodococcus sp. FP1.

PubMed

Maia, Alexandra S; Tiritan, Maria Elizabeth; Castro, Paula M L

2018-07-15

Fluoroquinolones are a class of antibiotics widely prescribed in both human and veterinary medicine of high environmental concern and characterized as environmental micropollutants due to their ecotoxicity and persistence and antibacterial resistance potential. Ofloxacin and levofloxacin are chiral fluoroquinolones commercialized as racemate and in enantiomerically pure form, respectively. Since the pharmacological properties and toxicity of the enantiomers may be very different, understanding the stereochemistry of these compounds should be a priority in environmental monitoring. This work presents the biodegradation of racemic ofloxacin and its (S)-enantiomer levofloxacin by the bacterial strains Labrys portucalensis F11 and Rhodococcus sp. FP1 at a laboratory-scale microcosm following the removal and the behavior of the enantiomers. Strain F11 could degrade both antibiotics almost completely when acetate was supplied regularly to the cultures. Enrichment of the (R)-enantiomer was observed in FP1 and F11 cultures supplied with ofloxacin. Racemization was observed in the biodegradation of the pure (S)-ofloxacin (levofloxacin) by strain F11, which was confirmed by liquid chromatography - exact mass spectrometry. Biodegradation of ofloxacin at 450 µg L -1 by both bacterial strains expressed good linear fits (R 2 > 0.98) according to the Rayleigh equation. The enantiomeric enrichment factors were comprised between - 22.5% to - 9.1%, and - 18.7% to - 9.0% in the biodegradation of ofloxacin by strains F11 and FP1, respectively, with no significant differences for the two bacteria under the same conditions. This is the first time that enantioselective biodegradation of ofloxacin and levofloxacin by single bacteria is reported. Copyright © 2018 Elsevier Inc. All rights reserved.

Soybean fruit development and set at the node level under combined photoperiod and radiation conditions.

PubMed

Nico, Magalí; Mantese, Anita I; Miralles, Daniel J; Kantolic, Adriana G

2016-01-01

In soybean, long days during post-flowering increase seed number. This positive photoperiodic effect on seed number has been previously associated with increments in the amount of radiation accumulated during the crop cycle because long days extend the duration of the crop cycle. However, evidence of intra-nodal processes independent of the availability of assimilates suggests that photoperiodic effects at the node level might also contribute to pod set. This work aims to identify the main mechanisms responsible for the increase in pod number per node in response to long days; including the dynamics of flowering, pod development, growth and set at the node level. Long days increased pods per node on the main stems, by increasing pods on lateral racemes (usually dominated positions) at some main stem nodes. Long days lengthened the flowering period and thereby increased the number of opened flowers on lateral racemes. The flowering period was prolonged under long days because effective seed filling was delayed on primary racemes (dominant positions). Long days also delayed the development of flowers into pods with filling seeds, delaying the initiation of pod elongation without modifying pod elongation rate. The embryo development matched the external pod length irrespective of the pod's chronological age. These results suggest that long days during post-flowering enhance pod number per node through a relief of the competition between pods of different hierarchy within the node. The photoperiodic effect on the development of dominant pods, delaying their elongation and therefore postponing their active growth, extends flowering and allows pod set at positions that are usually dominated. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Tandem Reactions for Streamlining Synthesis

PubMed Central

HUSSAIN, MAHMUD M.; WALSH, PATRICK J.

2009-01-01

CONSPECTUS In 1980 Sharpless and Katsuki introduced the asymmetric epoxidation of prochiral allylic alcohols (the Sharpless-Katsuki Asymmetric Epoxidation), which enabled the rapid synthesis of highly enantioenriched epoxy alcohols. This reaction was a milestone in the development of asymmetric catalysis because it was the first highly enantioselective oxidation reaction. Furthermore, it provided access to enantioenriched allylic alcohols that are now standard starting materials in natural product synthesis. In 1981 Sharpless and coworkers made another seminal contribution by describing the kinetic resolution (KR) of racemic allylic alcohols. This work demonstrated that small-molecule catalysts could compete with enzymatic catalysts in KRs. For these pioneering works, Sharpless was awarded the 2001 Nobel Prize with Knowles and Noyori. Despite these achievements, the Sharpless KR is not an efficient method to prepare epoxy alcohols with high enantiomeric excess (ee). First, the racemic allylic alcohol must be prepared and purified. KR of the racemic allylic alcohol must be stopped at low conversion, because the ee of the product epoxy alcohol decreases as the KR progresses. Thus, better methods to prepare epoxy alcohols containing stereogenic carbinol carbons are needed. This Account summarizes our efforts to develop one-pot methods for the synthesis of various epoxy alcohols and allylic epoxy alcohols with high enantio-, diastereo-, and chemoselectivity. Our laboratory developed titanium-based catalysts for use in the synthesis of epoxy alcohols with tertiary carbinols. The catalysts are involved in the first step, which is an asymmetric alkyl or allyl addition to enones. The resulting intermediates are then subjected to a titanium-directed diastereoselective epoxidation to provide tertiary epoxy alcohols. Similarly, the synthesis of acyclic epoxy alcohols begins with asymmetric additions to enals and subsequent epoxidation. The methods described here enable the synthesis of skeletally diverse epoxy alcohols. PMID:18710197

The "racemic approach" in the evaluation of the enantiomeric NorA efflux pump inhibition activity of 2-phenylquinoline derivatives.

PubMed

Carotti, Andrea; Ianni, Federica; Sabatini, Stefano; Di Michele, Alessandro; Sardella, Roccaldo; Kaatz, Glenn W; Lindner, Wolfgang; Cecchetti, Violetta; Natalini, Benedetto

2016-09-10

Among the mechanisms adopted by bacteria, efflux pumps (EPs) have been recognized as being significantly involved in contributing to resistance to commonly used antibacterial agents. However, little is known about their three-dimensional structures or the steric requirements for their inhibition. Lack of such knowledge includes NorA, one of the most studied Staphylococcus aureus EPs. In the present study, the use of two commercialized Cinchona alkaloid-based zwitterionic chiral stationary phases allowed the enantioseparation of four 2-((2-(4-propoxyphenyl)quinolin-4-yl)oxy)alkylamines 1-4 previously found to be potent S. aureus NorA efflux pump inhibitors when tested as racemates. In the identified optimal polar-ionic conditions (MeOH/THF/H2O-49/49/2 (v/v/v)+25mM formic acid, 12.5mM diethylamine), repeated consecutive injections of 1 allowed the isolation of sufficient amount of its enantiomers (2.6mg and 2.8mg, for (R)-1 and (S)-1, respectively) and then to evaluate their ability to inhibit the S. aureus NorA efflux pump. The biological evaluation highlighted the main contribution of the (R)-1 enantiomer to both the EtBr efflux inhibition and synergistic effect with against SA-1199B (norA+/A116E GrlA) respect to the racemate activity. The comparison between the experimental electronic circular dichroism and the time-dependent density functional theory calculations spectra of the two isolated enantiomeric fractions allowed for all compounds a clear and easy assignment of the enantiomeric elution order. Copyright © 2016 Elsevier B.V. All rights reserved.

A full evaluation for the enantiomeric impacts of lactofen and its metabolites on aquatic macrophyte Lemna minor.

PubMed

Wang, Fang; Liu, Donghui; Qu, Han; Chen, Li; Zhou, Zhiqiang; Wang, Peng

2016-09-15

Pesticide pollution of surface water represents a considerable danger for the aquatic plants which play very crucial roles in aquatic system such as oxygen production, nutrient cycling, water quality controlling and sediment stabilization. In this work, the toxic effects of the chiral herbicide lactofen and its three metabolites (desethyl lactofen, acifluorfene and amino acifluorfene) to the aquatic plant Lemna minor (L. minor) on enantiomeric level were evaluated. The influences on growth rate, fresh weight, content of photosynthetic pigment, protein and malondialdehyde (MDA) and the activities of antioxidant defense enzymes (catalase (CAT) and superoxide dismutase (SOD)) were measured after 7 days of exposure. L. minor growth was inhibited in the order of (S)-desethyl lactofen > racemic-desethyl lactofen > (R)-desethyl lactofen > racemic-lactofen > (S)-lactofen > (R)-lactofen > acifluorfene > amino acifluorfene, and the IC50 (7d) values showed desethyl lactofen was the most powerful compound which was about twice as toxic as lactofen. The contents of chlorophylls (Chl) and carotenoids (Car) were significantly reduced by the chemicals, while, the levels of protein, MDA and the activity of CAT and SOD enzymes increased in most cases. The obtained results revealed that lactofen and its metabolites had an undesirable effect on L. minor, in terms of physiological and biochemical aspects. Besides, enantioselective toxicity of lactofen and desethyl lactofen to L. minor was observed. The S-enantiomer of desethyl lactofen was more toxic than the corresponding R-enantiomer. Furthermore, racemic lactofen was more toxic than the individual enantiomers. The side effects of pesticide metabolites and the enantioselectivity should be considered in developing optically pure products and risk assessment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of racemic warfarin in healthy subjects

PubMed Central

Lilja, Jari J; Backman, Janne T; Neuvonen, Pertti J

2005-01-01

Aims Case reports suggest that gemfobrozil can increase the anticoagulant effect of warfarin. Because gemfibrozil inhibits CYP2C9 in vitro, we studied its effects on the pharmacokinetics and pharmacodynamics of racemic warfarin. Methods In a randomized cross-over study, 10 healthy subjects ingested 600 mg gemfibrozil or placebo twice daily for 8 days. On day 3, they were administered a single dose of 10 mg racemic R-S-warfarin orally. The concentrations of R- and S-warfarin in plasma and thromboplastin time were monitored up to 168 h. Results Gemfibrozil decreased the mean (±SD) area under the plasma concentration-time curve [AUC(0–∞)] of S-warfarin by 11%, from 19.9 ± 5.2 mg l−1 h to 17.6 ± 4.7 mg l−1 h (95% CI on the difference −3.7, −0.78; P < 0.01) and that of R-warfarin by 6% from 31.3 ± 7.5 mg l−1 h during the gemfibrozil phase to 29.5 ± 6.9 mg l−1 h during the placebo phase (95% CI −3.3, −0.33; P < 0.05). There were no significant differences in the elimination half-lives of S- or R-warfarin between the phases. Gemfibrozil did not alter the anticoagulant effect of warfarin. Conclusion Unexpectedly, gemfibrozil slightly decreased the plasma concentrations of R- and S-warfarin. Displacement of warfarin from plasma albumin by gemfibrozil or its interference with the absorption of warfarin could explain the present findings. Usual therapeutic doses of gemfibrozil seem to have limited effects on the pharmacokinetics and pharmacodynamics of single dose warfarin in healthy subjects. PMID:15801938

The effect of various doses of pheromone on mating disruption in gypsy moth population

Treesearch

Ksenia Tcheslavskaia; Alexei A. Sharov; Kevin W. Thorpe; Carlyle C. Brewster

2003-01-01

An experiment was conducted in June-August 2001 in the Cumberland and Appomattox- Buckingham State Forests, Virginia to evaluate the effects of various doses of synthetic pheromone (racemic disparlure) on mating disruption of the gypsy moth, Lymantria dispar (L.).

DISTRIBUTION OF PCB 84 ENANTIOMERS IN C57BL/6 MICE

EPA Science Inventory

Nineteen of the 209 possible PCB congeners exist as pairs of stable rotational isomers that are enantiomeric to each other. A racemic mixture of PCB atropisomers is present in technical PCB mixtures, thus raising concerns about enantioselective distribution, metabolism, and dispo...

TOXICITY OF FIPRONIL AND ITS ENANTIOMERS TO MARINE AND FRESHWATER NON-TARGETS

EPA Science Inventory

Fipronil is a phenylpyrazole insecticide used in agricultural and domestic settings for controlling various insect pests in crops, lawns, and residential structures. Fipronil is chiral; however, it is released into the environment as a racemic mixture of two enantiomers. In this ...

ENANTIOSELECTIVE CHRONIC TOXICITY OF FIPRONIL TO CERIODAPHNIA DUBIA

EPA Science Inventory

Fipronil is a phenylpyrazole pesticide that has greatly increased in popularity in recent years. As a chiral molecule, fipronil is released into the environment as a 1:1 mixture (called a racemate) of its two enantiomers. Previous toxicity work has indicated that the enantiomer...

(±)-Pestalachloride D, an antibacterial racemate of chlorinated benzophenone derivative from a soft coral-derived fungus Pestalotiopsis sp.

PubMed

Wei, Mei-Yan; Li, Dan; Shao, Chang-Lun; Deng, Dong-Sheng; Wang, Chang-Yun

2013-03-28

A new antibacterial chlorinated benzophenone derivative, (±)-pestalachloride D (1), along with a related analog, (±)-pestalachloride C (2), was recently isolated from the marine-derived fungus Pestalotiopsis sp. isolated from a soft coral Sarcophyton sp. collected from Yongxing Island in the South China Sea. Both chiral HPLC analysis and single-crystal X-ray data indicated that 1 is a racemic mixture. Interestingly, 1 did not exhibit any effect in the zebrafish embryo teratogenicity assay, while 2 led to abnormal growth. The potential impact on zebrafish embryo growth is discussed based on their crystal structures. The main difference of crystal structures between 1 and 2 is that the six-member non-aromatic ring (O4, C10, C9, C8, C2', and C3') in 1 exhibits a distorted chair conformation, while 2 shows a distorted boat conformation. Moreover, compounds 1 and 2 both exhibited moderate antibacterial activity.

A germination bioassay as a toxicological screening system for studying the effects of potential prodrugs of naproxen.

PubMed

Gonzalez-de la Parra, M; Ramos-Mundo, C; Jimenez-Estrada, M; Ponce-de Leon, C; Castillo, R; Tejeda, V; Cuevas, K G; Enriquez, R G

1998-01-01

A germination bioassay with radish (Raphanus sativus L.) seeds was developed as a toxicological screening system for assessing the effects of new potential prodrugs of naproxen, as an alternative to animals and animal cell toxicity screens. Both enantiomers of naproxen (6-methoxy-α-methyl-2-naphthaleneacetic acid) and naproxol (6-methoxy-β-2-naphthaleneethanol), and their racemic mixtures, inhibited the radicle growth of R. sativus at a concentration of 1mM, while only (R)-(+ )-naproxol and racemic naproxol inhibited the hypocotyl growth of R. sativus at the same concentration. Four novel combinatorial esters, naproxen naproxyl esters (6-methoxy-β-methyl-2-naphthaleneethyl 6-methoxy-α-methyl-2-naphthaleneacetate), resulting from the combinatorial chemistry of the esterification reaction between naproxen and naproxol, were synthesised and then tested in the germination bioassay, at a concentration of 0.5mM. It was found that they did not inhibit either the radicle or the hypocotyl growth of R. sativus. 1998 FRAME.

Enantiomerically enriched, polycrystalline molecular sieves

DOE PAGES

Brand, Stephen K.; Schmidt, Joel E.; Deem, Michael W.; ...

2017-05-01

Zeolite and zeolite-like molecular sieves are being used in a large number of applications such as adsorption and catalysis. Achievement of the long-standing goal of creating a chiral, polycrystalline molecular sieve with bulk enantioenrichment would enable these materials to perform enantioselective functions. Here, we report the synthesis of enantiomerically enriched samples of a molecular sieve. For this study, enantiopure organic structure directing agents are designed with the assistance of computational methods and used to synthesize enantioenriched, polycrystalline molecular sieve samples of either enantiomer. Computational results correctly predicted which enantiomer is obtained, and enantiomeric enrichment is proven by high-resolution transmission electronmore » microscopy. The enantioenriched and racemic samples of the molecular sieves are tested as adsorbents and heterogeneous catalysts. The enantioenriched molecular sieves show enantioselectivity for the ring opening reaction of epoxides and enantioselective adsorption of 2-butanol (the R enantiomer of the molecular sieve shows opposite and approximately equal enantioselectivity compared with the S enantiomer of the molecular sieve, whereas the racemic sample of the molecular sieve shows no enantioselectivity).« less

Solubility and some crystallization properties of conglomerate forming chiral drug guaifenesin in water.

PubMed

Fayzullin, Robert R; Lorenz, Heike; Bredikhina, Zemfira A; Bredikhin, Alexander A; Seidel-Morgenstern, Andreas

2014-10-01

The solubility of 3-(2-methoxyphenoxy)-propane-1,2-diol, the well-known chiral drug guaifenesin 1, in water has been investigated by means of polythermal and isothermal approaches. It was found that the solubilities of racemic and enantiomeric diols rac- and (R)-1 depend strongly on temperature. The ternary phase diagram of the guaifenesin enantiomers in water in the temperature range between 10°C and 40°C was constructed. Clear evidence was obtained that rac-1 crystallizes as a stable conglomerate. The Meyerhoffer coefficient for the guaifenesin-water system is more than two and strongly depends on temperature. Neither crystalline hydrates nor polymorphs were detected within the range of conditions covered. Metastable zone width data with regard to primary nucleation were also collected for rac-1 and (R)-1. On the basis of the knowledge acquired, the resolution of racemic guaifenesin by preferential crystallization from solution could be realized successfully. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Enantioseparation of racemic 4-aryl-3,4-dihydro-2(1H)-pyrimidones on chiral stationary phases based on 3,5-dimethylanilides of N-(4-alkylamino-3,5-dinitro)benzoyl L-alpha-amino acids.

PubMed

Kontrec, Darko; Vinković, Vladimir; Sunjić, Vitomir; Schuiki, Birgit; Fabian, Walter M F; Kappe, C Oliver

2003-06-01

Three novel chiral packing materials for high-performance liquid chromatography were prepared by covalently binding of (2S)-N-(3,5-dimethylphenyl)-2-[(4-chloro-3,5-dinitrophenyl)carbonylamino]propan-amide (7), (2S)-N-(3,5-dimethylphenyl)-2-[(4-chloro-3,5-dinitrophenyl)carbonylamino]-4-methylpentanamide (8), and (2S)-N-(3,5-dimethylphenyl)-2-[(4-chloro-3,5-dinitrophenyl)carbonyl-amino]-2-phenylacetamide (9) to aminopropyl silica. The resulting chiral stationary phases (CSPs 1-3) proved effective for the resolution of racemic 4-aryl-3,4-dihydro-2(1H)-pyrimidone derivatives (TR 1-14). The mechanism of their enantioselection, supported by the elution order of (S)-TR 13 and (R)-TR 13 and molecular modeling of the complex of the slower running (S)-TR 13 with CSP 1 is discussed. Copyright 2003 Wiley-Liss, Inc.

A comparative study on the crystal structure of bicycle analogues to the natural phytotoxin helminthosporins

NASA Astrophysics Data System (ADS)

Barbosa, Luiz Cláudio de Almeida; Teixeira, Robson Ricardo; Nogueira, Leonardo Brandão; Maltha, Celia Regina Alvares; Doriguetto, Antônio Carlos; Martins, Felipe Terra

2016-02-01

Herein we described structural insights of a series of analogues to helminthosporin phytotoxins. The key reaction used to prepare the compounds corresponded to the [3 + 4] cycloaddition between the oxyallyl cation generated from 2,4-dibromopentan-3-one and different furans. Their structures were confirmed upon IR, NMR and X-ray diffraction analyses. While bicycles 7, 8 and 9 crystallize in the centrosymmetric monoclinic space group P21/c, compound 10 was solved in the noncentrosymmetric orthorhombic space group P212121. The solid materials obtained were shown to be racemic crystals (7, 8, 9) or racemic conglomerate (10). In all compounds, there is formation of a bicycle featured by fused tetrahydropyranone and 2,5-dihydrofuran rings. They adopt chair and envelope conformations, respectively. Crystal packing of all compounds is stabilized through C-H•••O contacts. Conformational aspects as well as similarities and differences among the crystal structures of the synthesized analogues are discussed.

Clinical pharmacology review of escitalopram for the treatment of depression.

PubMed

Pastoor, Devin; Gobburu, Joga

2014-01-01

Depression is a serious and debilitating psychiatric condition with serious societal health and economic implications. Escitalopram , the S-enantiomer of racemic citalopram, is an effective treatment for major depressive disorder. This review covers the clinical pharmacology of escitalopram, with emphasis on regulatory approval. Its pharmacokinetics, pharmacodynamics and clinical efficacy for major depressive disorder are evaluated, along with data regarding safety and tolerability. Drug development of escitalopram was heavily guided by prior approval of citalopram. Select safety and efficacy studies for escitalopram in combination with supportive evidence from the results of prior citalopram studies allowed for regulatory approval for acute and maintenance claims in both adults and adolescents, while minimizing burden on the sponsor. Escitalopram has been shown to have better efficacy and safety profile than other selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor drugs, including racemic citalopram. The first generic escitalopram was approved in 2012, along with Abbreviated New Drug Applications. The associated cost savings have helped reduce the burden of weighing the benefits of escitalopram over less-expensive alternatives.

Self-Assembled Chiral Photonic Crystals from a Colloidal Helix Racemate.

PubMed

Lei, Qun-Li; Ni, Ran; Ma, Yu-Qiang

2018-06-20

Chiral crystals consisting of microhelices have many optical properties, while presently available fabrication processes limit their large-scale applications in photonic devices. Here, by using a simplified simulation method, we investigate a bottom-up self-assembly route to build up helical crystals from the smectic monolayer of a colloidal helix racemate. With increasing the density, the system undergoes an entropy-driven cocrystallization by forming crystals of various symmetries with different helical shapes. In particular, we identify two crystals of helices arranged in binary honeycomb and square lattices, which are essentially composed of two sets of opposite-handed chiral crystals. Photonic calculations show that these chiral structures can have large complete photonic band gaps. In addition, in the self-assembled chiral square crystal, we also find dual polarization band gaps that selectively forbid the propagation of circularly polarized light of a specific handedness along the helical axis direction. The self-assembly process in our proposed system is robust, suggesting possibilities of using chiral colloids to assemble photonic metamaterials.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borszeky, K.; Mallat, T.; Aeschiman, R.

The chemo- and enantioselective hydrogenation of pyruvic acid oxime have been studied on Pd/alumina, the latter in the presence of the 1,2-amino alcohol type alkaloids ephedrine, cinchonidine, and cinchonine. High yields of racemic alanine (90-98%) were obtained in the absence of alkaloids in polar solvents at 0-45{degrees}C and 10 bar. Enantioselection increased with higher temperature and alkalid: oxime molar ratio. A 1:1 ephedrine: oxime molar ratio afforded the best enantiomeric excess (26%). The presence of alkaloid resulted in a decrease of reaction rate by a factor of up to 140, compared to the racemic hydrogenation. Based on X-ray crystal structuremore » analysis of the alkaloid-pyruvic acid oxime adduct, a mechanism is proposed for the steric course of the reaction. Extended interactions by multiple H bonds between the adsorbed alkaloid-oxime salt units on the Pd surface is assumed to be at the origin of the moderate enantioselectivity and the very low enantioselective hydrogenation rate. 28 refs., 5 figs., 3 tabs.« less

Enantioselective chromatography in analysis of triacylglycerols common in edible fats and oils.

PubMed

Kalpio, Marika; Nylund, Matts; Linderborg, Kaisa M; Yang, Baoru; Kristinsson, Björn; Haraldsson, Gudmundur G; Kallio, Heikki

2015-04-01

Enantiomers of racemic triacylglycerol (TAG) mixtures were separated using two chiral HPLC columns with a sample recycling system and a UV detector. A closed system without sample derivatisation enabled separation and identification by using enantiopure reference compounds of eleven racemic TAGs with C12-C22 fatty acids with 0-2 double bonds. The prolonged separation time was compensated for by fewer pretreatment steps. Presence of one saturated and one unsaturated fatty acid in the asymmetric TAG favoured the separation. Enantiomeric resolution, at the same time with stronger retention of TAGs, increased with increasing fatty acid chain length in the sn-1(3) position. Triunsaturated TAGs containing oleic, linoleic or palmitoleic acids did not separate. The elution order of enantiomers was determined by chemoenzymatically synthesised enantiopure TAGs with a co-injection method. The method is applicable to many natural fats and oils of low unsaturation level assisting advanced investigation of lipid synthesis and metabolism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chirality- and sequence-selective successive self-sorting via specific homo- and complementary-duplex formations

PubMed Central

Makiguchi, Wataru; Tanabe, Junki; Yamada, Hidekazu; Iida, Hiroki; Taura, Daisuke; Ousaka, Naoki; Yashima, Eiji

2015-01-01

Self-recognition and self-discrimination within complex mixtures are of fundamental importance in biological systems, which entirely rely on the preprogrammed monomer sequences and homochirality of biological macromolecules. Here we report artificial chirality- and sequence-selective successive self-sorting of chiral dimeric strands bearing carboxylic acid or amidine groups joined by chiral amide linkers with different sequences through homo- and complementary-duplex formations. A mixture of carboxylic acid dimers linked by racemic-1,2-cyclohexane bis-amides with different amide sequences (NHCO or CONH) self-associate to form homoduplexes in a completely sequence-selective way, the structures of which are different from each other depending on the linker amide sequences. The further addition of an enantiopure amide-linked amidine dimer to a mixture of the racemic carboxylic acid dimers resulted in the formation of a single optically pure complementary duplex with a 100% diastereoselectivity and complete sequence specificity stabilized by the amidinium–carboxylate salt bridges, leading to the perfect chirality- and sequence-selective duplex formation. PMID:26051291

Enantioselective resolution of Rac-terbutaline and evaluation of optically pure R-terbutaline hydrochloride as an efficient anti-asthmatic drug.

PubMed

Beng, Huimin; Zhang, Hao; Jayachandra, R; Li, Junxiao; Wu, Jie; Tan, Wen

2018-06-01

Terbutaline is a β 2 -adrenoceptor agonist for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among the two isomers of terbutaline (TBT 2), R-isomer was found to be the potent enantiomer in generating therapeutic effect, while S-isomer has been reported to show side effects. In this study, R-terbutaline hydrochloride (R-TBH 6) was synthesized through chiral resolution from the racemic terbutaline sulfate (rac-TBS 1) with 99.9% enantiomeric excess (ee) in good overall yield (53.6%). Further, R-TBH 6 nebulized solution was prepared in half dosage of Bricanyl®, which is a marketed product of racemic terbutaline and evaluated in vitro aerosol performance and in vivo anti-asthmatic effect on guinea pigs via. pulmonary delivery. From the investigation, it is evident that R-TBH 6 nebulized solution of half dosage performed similar fine aerosol characteristics and anti-asthmatic effect with Bricanyl®. © 2018 Wiley Periodicals, Inc.

Efficient optical resolution of amino acid by alanine racemaze chiral analogue supported on mesoporous carbon

NASA Astrophysics Data System (ADS)

Jang, D.; Kim, K.; Park, D.; Kim, G.

2012-09-01

Optically pure D-amino acids are industrially important chiral building blocks for the synthesis of pharmaceuticals, food ingredients, and drug intermediates. Chemoenzymatic dynamic kinetic-resolution processes have recently been developed for deracemization of amino acids. S-ARCA would be a good candidate for the selective adsorption of D amino acid through the imine formation reaction. The organic phase containing S-ARCA adsorbent, TPPC or Ionic Liquid (as a phase transfer catalyst) in MC were coated on the surfaces of mesoporous carbon C-SBA-15(CMK). The aqueous solution of racemic D/L-amino acid and NaOH were added to the carbon support coated with ARCA. The D/L ratios on ARCA and in solution were determined with increasing reaction time. S-ARCA has a unique property for the selective adsorption of D- amino acid (up to 90% selcetivity) in the racemic mixture. The fixed bed reactor containing ARCA/carbon support was also adopted successfully for the selective separation of amino acid.

Enantioconvergent biohydrolysis of racemic styrene oxide to R-phenyl-1, 2-ethanediol by a newly isolated filamentous fungus Aspergillus tubingensis TF1.

PubMed

Duarah, Aparajita; Goswami, Amrit; Bora, Tarun C; Talukdar, Madhumita; Gogoi, Binod K

2013-08-01

An effort was made to isolate biocatalysts hydrolyzing epoxides from various ecological niches of northeast India, a biodiversity hot spot zone of the world and screened for epoxide hydrolase activity to convert different racemic epoxides to the corresponding 1, 2-vicinal diols. Screening of a total of 450 microorganisms isolated was carried out using NBP colorimetric assay. One of the strains TF1, after internal transcribed spacer sequence analysis, identified as Aspergillus tubingensis, showed promising enantioconvergent epoxide hydrolase activity. The hydrolysis of unsubstituted styrene oxide (1) occurred to give 97 % ee of R-(-)-1-phenylethane-1, 2-diol (6) with more than 99 % conversion within 45 min incubation. It is shown to be a cheap and practical biocatalyst for one step asymmetric synthesis of chiral R-diol. The other representative substrates (2-5), although underwent hydrolysis with more than 99 % conversion beyond 15 h, exhibited poor enantioselectivity.

Molecular Mobility of an Amorphous Chiral Pharmaceutical Compound: Impact of Chirality and Chemical Purity.

PubMed

Viel, Quentin; Delbreilh, Laurent; Coquerel, Gérard; Petit, Samuel; Dargent, Eric

2017-08-17

A dielectric relaxation spectroscopy (DRS) study was performed to investigate the molecular mobility of amorphous chiral diprophylline (DPL). For this purpose, both racemic DPL and a single enantiomer of DPL were considered. After fast cooling from the melt at very low temperature (-140 °C), progressive heating below and above the glass transition (T g ≈ 37 °C) induces two secondary relaxations (γ- and δ-) and primary relaxations (α-) for both enantiomeric compositions. After chemical purification of our samples by means of cooling recrystallization, no γ-process could be detected by DRS. Hence, it was highlighted that the molecular mobility in the glassy state is influenced by the presence of theophylline (TPH), the main impurity in DPL samples. We also proved that the dynamic behavior of a single enantiomer and the racemic mixture of the same purified compound are quasi-identical. This study demonstrates that the relative stability and the molecular mobility of chiral amorphous drugs are strongly sensitive to chemical purity.

Enantiomerically enriched, polycrystalline molecular sieves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brand, Stephen K.; Schmidt, Joel E.; Deem, Michael W.

Zeolite and zeolite-like molecular sieves are being used in a large number of applications such as adsorption and catalysis. Achievement of the long-standing goal of creating a chiral, polycrystalline molecular sieve with bulk enantioenrichment would enable these materials to perform enantioselective functions. Here, we report the synthesis of enantiomerically enriched samples of a molecular sieve. For this study, enantiopure organic structure directing agents are designed with the assistance of computational methods and used to synthesize enantioenriched, polycrystalline molecular sieve samples of either enantiomer. Computational results correctly predicted which enantiomer is obtained, and enantiomeric enrichment is proven by high-resolution transmission electronmore » microscopy. The enantioenriched and racemic samples of the molecular sieves are tested as adsorbents and heterogeneous catalysts. The enantioenriched molecular sieves show enantioselectivity for the ring opening reaction of epoxides and enantioselective adsorption of 2-butanol (the R enantiomer of the molecular sieve shows opposite and approximately equal enantioselectivity compared with the S enantiomer of the molecular sieve, whereas the racemic sample of the molecular sieve shows no enantioselectivity).« less

Enantioselective separation of racemic juvenile hormone III by normal-phase high-performance liquid chromatography and preparation of [(2)H(3)]juvenile hormone III as an internal standard for liquid chromatography-mass spectrometry quantification.

PubMed

Ichikawa, Akio; Ono, Hiroshi; Furuta, Kenjiro; Shiotsuki, Takahiro; Shinoda, Tetsuro

2007-08-17

Juvenile hormone III (JH III) racemate was prepared from methyl (2E,6E)-farnesoate via epoxidation with 3-chloroperbenzoic acid (mCPBA). Enantioselective separation of JH III was conducted using normal-phase high-performance liquid chromatography (HPLC) on a chiral stationary phase. [(2)H(3)]Methyl (2E,6E)-farnesoate was also prepared from (2E,6E)-farnesoic acid and [(2)H(4)]methanol (methanol-d(4)) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 4-dimethylaminopyridine (DMAP); the conjugated double bond underwent isomerization to some degree. Epoxidation of [(2)H(3)]methyl (2E,6E)-farnesoate with mCPBA gave a novel deuterium-substituted internal standard [(2)H(3)]JH III (JH III-d(3)). The standard curve was produced by linear regression using the peak area ratios of JH III and JH III-d(3) in liquid chromatography-mass spectrometry (LC-MS).

Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites

PubMed Central

Cooper, George; Rios, Andro C.

2016-01-01

Biological polymers such as nucleic acids and proteins are constructed of only one—the d or l—of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System’s earliest (∼4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life’s carbohydrate-related biopolymers. PMID:27247410

Effects of bay substituents on the racemization barriers of perylene bisimides: resolution of atropo-enantiomers.

PubMed

Osswald, Peter; Würthner, Frank

2007-11-21

The activation parameters for the interconversion of atropisomers (P- and M-enantiomer) of core-twisted perylene bisimides have been determined by dynamic NMR spectroscopy (DNMR) and time- and temperature-dependent CD spectroscopy. By comparing the activation parameters of a series of perylene bisimides containing halogen or aryloxy substituents in the bay area (1,6,7,12-positions), a clear structure-property relationship has been found that demonstrates that the kinetic and thermodynamic parameters for the inversion of enantiomers are dependent on the apparent overlap parameter Sigmar* of the bay substituents. This study reveals a high stability (DeltaG(368 K) = 118 kJ/mol) for the atropo-enantiomers of tetrabromo-substituted perylene bisimide in solution. Accordingly, the enantiomers of this derivative could be resolved by HPLC on a chiral column. These enantiomers do not racemize in solution at room temperature and, thus, represent the first examples of enantiomerically pure core-twisted perylene bisimides.

(±)-Pestalachloride D, an Antibacterial Racemate of Chlorinated Benzophenone Derivative from a Soft Coral-Derived Fungus Pestalotiopsis sp

PubMed Central

Wei, Mei-Yan; Li, Dan; Shao, Chang-Lun; Deng, Dong-Sheng; Wang, Chang-Yun

2013-01-01

A new antibacterial chlorinated benzophenone derivative, (±)-pestalachloride D (1), along with a related analog, (±)-pestalachloride C (2), was recently isolated from the marine-derived fungus Pestalotiopsis sp. isolated from a soft coral Sarcophyton sp. collected from Yongxing Island in the South China Sea. Both chiral HPLC analysis and single-crystal X-ray data indicated that 1 is a racemic mixture. Interestingly, 1 did not exhibit any effect in the zebrafish embryo teratogenicity assay, while 2 led to abnormal growth. The potential impact on zebrafish embryo growth is discussed based on their crystal structures. The main difference of crystal structures between 1 and 2 is that the six-member non-aromatic ring (O4, C10, C9, C8, C2′, and C3′) in 1 exhibits a distorted chair conformation, while 2 shows a distorted boat conformation. Moreover, compounds 1 and 2 both exhibited moderate antibacterial activity. PMID:23538869

Molecular parity violation via comets?

PubMed

Meierhenrich, U; Thiemann, W H; Rosenbauer, H

1999-01-01

Recent theoretical and experimental investigations referring to the origin of homochirality are reviewed and integrated into the hitherto known state of the art. Attention is directed to an extraterrestrial scenario, which describes the interaction of circularly polarized synchrotron radiation with interstellar organic matter. Following this Bonner-Rubenstein hypothesis, optically active molecules could be transferred to Earth via comets. We plan to identify any enantiomeric enhancement in organic molecules of the cometary matter in situ. The present preliminary experimental study intends to optimize gas-chromatographic conditions for the separation of racemates into their enantiomer constituents on the surface of the comet 46P/Wirtanen. Underivatized racemic pairs of alcohols, diols, and phenyl-substituted amines have been separated with the help of a stationary trifluoroacetyl-cyclodextrin phase. We are still developing a technique that will enable us to detect any enantiomeric enhancement of specific simple organic molecules both in cometary or Martian matter in situ and in meteorites found on Earth. Copyright 1999 Wiley-Liss, Inc.

Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites

NASA Astrophysics Data System (ADS)

Cooper, George; Rios, Andro C.

2016-06-01

Biological polymers such as nucleic acids and proteins are constructed of only one—the d or l—of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System’s earliest (˜4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life’s carbohydrate-related biopolymers.

Mass-transfer limitations for immobilized enzyme-catalyzed kinetic resolution of racemate in a fixed-bed reactor.

PubMed

Xiu, G H; Jiang, L; Li, P

2001-07-05

A mathematical model has been developed for immobilized enzyme-catalyzed kinetic resolution of racemate in a fixed-bed reactor in which the enzyme-catalyzed reaction (the irreversible uni-uni competitive Michaelis-Menten kinetics is chosen as an example) was coupled with intraparticle diffusion, external mass transfer, and axial dispersion. The effects of mass-transfer limitations, competitive inhibition of substrates, deactivation on the enzyme effective enantioselectivity, and the optical purity and yield of the desired product are examined quantitatively over a wide range of parameters using the orthogonal collocation method. For a first-order reaction, an analytical solution is derived from the mathematical model for slab-, cylindrical-, and spherical-enzyme supports. Based on the analytical solution for the steady-state resolution process, a new concise formulation is presented to predict quantitatively the mass-transfer limitations on enzyme effective enantioselectivity and optical purity and yield of the desired product for a continuous steady-state kinetic resolution process in a fixed-bed reactor. Copyright 2001 John Wiley & Sons, Inc.

Enantiomeric resolution of methylamphetamine and ephedrine: does this affect the δ13 C, δ15 N and δ2 H stable isotope ratios of the product?

PubMed

Grzechnik, Alexandra K; George, Adrian V; Mitchell, Linda; Collins, Michael; Salouros, Helen

2018-05-22

The use of stable isotope ratio mass spectrometry as a profiling tool for methylamphetamine has evolved over the last decade. Stable isotope ratios of carbon (δ 13 C), nitrogen (δ 15 N) and hydrogen (δ 2 H) of methylamphetamine are useful in determining the precursor used to manufacture methylamphetamine, and in many cases the synthetic origin of the methylamphetamine precursor. More recently samples of seized methylamphetamine show that a resolution step is being employed in the manufacturing process. We sought to determine whether the δ 13 C, δ 15 N and δ 2 H values were affected by either a resolution performed on racemic methylamphetamine or a resolution on racemic ephedrine, a commonly used precursor to methylamphetamine. We found that for the types of resolution studied, IRMS is still able to provide useful information on the provenance of a methylamphetamine sample. This article is protected by copyright. All rights reserved.

21 CFR 184.1212 - Calcium pantothenate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Calcium pantothenate. 184.1212 Section 184.1212... Listing of Specific Substances Affirmed as GRAS § 184.1212 Calcium pantothenate. (a) Calcium pantothenate... and the DL-racemic mixture of calcium pantothenate are used in food. Commercial calcium pantothenate...

ENANTIOMERIC OCCURRENCE AND DISTRIBUTION OF CHIRAL ORGANOCHLORINE COMPOUNDS IN U.S. RIVER SEDIMENT AND BIOTA

EPA Science Inventory

River sediment and biota (fish, bivalves) from throughout the continental U.S. were analyzed for chiral organochlorine compounds (o,p'-DDT and DDD, some chlordane compounds, PCB atropisomers) to assess spatial trends in environmental chirality. Chiral PCB enantiomers were racemic...

ACUTE AND CHRONIC EFFECTS OF FIPRONIL AND ITS ENANTIOMERS TO AQUATIC ORGANISMS

EPA Science Inventory

Fipronil is a phenylpyrazole insecticide used in agriculture and domestic settings for controlling various insect pests in crops, lawns and residential structures. Fipronil is chiral; however, it is released into the environment as a racemic mixture of two enantiomers. In this st...

DISTRIBUTION OF PCB 84 ENANTIOMERS IN C56BL/6 MICE

EPA Science Inventory

At room temperature, nineteen of the 209 possible PCB congeners exist as pairs of stable rotational isomers that are enantiomeric to each other. A racemic mixture of each of these PCB atropisomers is present in technical mixtures, thus raising concerns about enantioselective dis...

Chemistry for Kids: What Do Chemists Do? A Program for Grades 1-3.

ERIC Educational Resources Information Center

Umland, Jean B.

1985-01-01

Proposes a simple solution to the problem of expressing graphically absolute configuration, racemic character, and relative configuration in molecules. As demonstrated by several examples, the proposed convention brings added clarity and simplicity to structural drawings and renders graphic displays of chiral molecules as explicit and information…

Meeting in China: Differential Toxicity and Accumulation of Fipronil Enantiomers in the Fathead Minnow (Pimephales promelas)

EPA Science Inventory

Fipronil is a chiral insecticide applied as a racemate with two enantiomers. Because of its high log KOC, fipronil will be found primarily in sediments of aquatic environments. Although a number of studies have examined toxicity in aquatic invertebrates, data on enantioselective...

Differential Toxicity and Accumulation of Fipronil Enantiomers in the Fathead Minnow (Pimephales promelas)

EPA Science Inventory

Fipronil is a chiral insecticide applied as a racemate of two enantiomers. Because of its high log Koc, fipronil will be found primarily in sediments of aquatic environments. Although a number of studies have examined toxicity in aquatic invertebrates, data on enantioselective t...

Enantioselective Total Synthesis of Natural Isoflavans: Asymmetric Transfer Hydrogenation/Deoxygenation of Isoflavanones with Dynamic Kinetic Resolution.

PubMed

Keßberg, Anton; Lübken, Tilo; Metz, Peter

2018-05-02

A concise and highly enantioselective synthesis of structurally diverse isoflavans from a single chromone is described. The key transformation is a single-step conversion of racemic isoflavanones into virtually enantiopure isoflavans by domino asymmetric transfer hydrogenation/deoxygenation with dynamic kinetic resolution.

The formal total synthesis of (+/-)-strychnine via a cobalt-mediated [2 + 2 + 2]cycloaddition.

PubMed

Eichberg, M J; Dorta, R L; Lamottke, K; Vollhardt, K P

2000-08-10

A short, highly convergent total synthesis of racemic isostrychnine, and thus strychnine, has been completed. The route involves 14 steps in the longest linear sequence and is highlighted by a cobalt-mediated [2 + 2 + 2]cycloaddition of an alkynylindole nucleus to acetylene.

Three new norsesquiterpenoids from the seeds of Alpinia galanga.

PubMed

Bian, Meng-Qin; Kang, Jie; Wang, Hong-Qing; Zhang, Qing-Jian; Liu, Chao; Chen, Ruo-Yun

2014-01-01

From the seeds of Alpinia galanga Willd., three new norsesquiterpenoid racemic mixtures, galanols A-C (1-3) were isolated, along with three known sesquiterpenoids (4-6). Their structures were elucidated by means of UV, IR, HR-ESI-MS, 1D NMR and 2D NMR spectroscopic data.

Electrophysiological and olfactometer responses of two histerid predators to three pine bark beetle pheromones

Treesearch

William P. Shepherd; Brian T. Sullivan; Richard A. Goyer; Kier D. Klepzig

2005-01-01

We measured electrophysiological responses in the antennae of two predaceous hister beetles, Platysoma parallelum and Plegaderus transversus, exposes to racemic mixtures of primary aggregation pheromones of scolytid bark beetle prey, ipsenol, ipsdienol, and frontalin. No significant differences were found for either histerid...

Field response of Dendroctonus frontalis (Coleoptera: Scolytinae) to Synthetic Semiochemicals in Chiapas, Mexico.

Treesearch

Benjamin Moreno; Jorge Macias; Brian T. Sullivan; Stephen R. Clarke

2008-01-01

Dendroctonus frontalis Zimmermann (Coleoptera: Scolytinae) is the most serious pest of pines (Pinus spp.) in Mexico. Con specifics are attracted to trees undergoing colonization by the aggregation pheromone frontalin, which is synergized by odors of pine oleoresin released from beetle-damaged host tissue. Synthetic racemic frontalin...

Synthesis of racemic 9-methyl-10-hexadecenoic acid.

PubMed

Carballeira, N M; Sostre, A; Restituyo, J A

1999-02-01

The marine bacterial fatty acid 9-methyl-10-hexadecenoic acid was conveniently prepared in 6 steps and in a 22% overall yield, starting from commercially available methyl 10-hydroxydecanoate. The naturally occurring fatty acid has the E double bond configuration as confirmed by gas chromatographic co-elution experiments.

A Study on Amino Acids: Synthesis of Alpha-Aminophenylacetic Acid (Phenylglycine) and Determination of its Isoelectric Point.

ERIC Educational Resources Information Center

Barrelle, M.; And Others

1983-01-01

Background information and procedures are provided for an experimental study on aminophenylacetic acid (phenylglycine). These include physical chemistry (determination of isoelectric point by pH measurement) and organic chemistry (synthesis of an amino acid in racemic form) experiments. (JN)

Stereoselective disposition of proton pump inhibitors.

PubMed

Andersson, Tommy; Weidolf, Lars

2008-01-01

It is estimated that about half of all therapeutic agents are chiral, but most of these drugs are administered in the form of the racemic mixture, i.e. a 50/50 mixture of its enantiomers. However, chirality is one of the main features of biology, and many of the processes essential for life are stereoselective, implying that two enantiomers may work differently from each other in a physiological environment. Thus, receptors or metabolizing enzymes would recognize one of the ligand enantiomers in favour of the other. With one exception, all presently marketed proton pump inhibitors (PPIs)--omeprazole, lansoprazole, pantoprazole and rabeprazole--used for the treatment of gastric acid-related diseases are racemic mixtures. The exception is esomeprazole, the S-enantiomer of omeprazole, which is the only PPI developed as a single enantiomer drug. The development of esomeprazole (an alkaline salt thereof, e.g. magnesium or sodium) was based on unique metabolic properties that clearly differentiated esomeprazole from omeprazole, the racemate. At comparable doses, these properties led to several clinical advantages, for example higher bioavailability in the majority of patients, i.e. the extensive metabolizers (EMs; 97% in Caucasian and 80-85% in Asian populations), lower exposure in poor metabolizers (PMs; 3% in Caucasian and 15-20% in Asian populations) and lower interindividual variation. For the other, i.e. racemic, PPIs there are some data available on the characteristics of the individual enantiomers, and we have therefore undertaken to analyse the current literature with the purpose of evaluating the potential benefits of developing single enantiomer drugs from lansoprazole, pantoprazole and rabeprazole. For lansoprazole, the plasma concentrations of the S-enantiomer are lower than those of the R-enantiomer in both EMs and PMs, and, consequently, the variability in the population or between EMs and PMs is not likely to decrease with either of the lansoprazole enantiomers. Furthermore, plasma protein binding differs between the two lansoprazole enantiomers, in that the amount of the free S-enantiomer is two-fold higher than that of the R-enantiomer. This will counteract the difference seen in total plasma concentrations of the enantiomers. Also, studies using expressed human cytochrome P450 isoenzymes show that the metabolism of one enantiomer is significantly affected by the presence of the other, which is likely to result in different pharmacokinetics when administering a single enantiomer. For pantoprazole, there is a negligible difference in plasma concentrations between the two enantiomers in EMs, while the difference is substantial in PMs. The difference in AUC between PMs and EMs would decrease to some extent, but in the majority of the population the variability and efficacy would not be altered with a single enantiomer of pantoprazole. The metabolism of the enantiomers of rabeprazole displays stereoselectivity comparable to that of lansoprazole, i.e. the exposure of the R-enantiomer is higher than that of the S-enantiomer in EMs as well as in PMs, which, by analogy to lansoprazole, makes them less suitable for development of a single enantiomer drug. Furthermore, the chiral stability of the rabeprazole enantiomers may be an issue because of significant degradation of rabeprazole to its sulfide analogue, which is subject to non-stereoselective metabolic regeneration of a mixture of the two enantiomers. In conclusion, in contrast to esomeprazole, the S-enantiomer of omeprazole, minimal if any clinical advantages would be expected in developing any of the enantiomers of lansoprazole, pantoprazole, or rabeprazole as compared with their racemates.

Total Synthesis of (+)- and (±)-Hosieine A.

PubMed

Huang, Yu-Wen; Kong, Ke; Wood, John

2018-05-03

Described here is a concise total synthesis of the highly potent nicotinic acetylcholine receptor antagonist hosieine A in racemic ((±)-2) and enantioenriched ((+)-2) forms. The synthesis requires only 7-steps and features a telescoped reaction sequence initiated by a gold-catalyzed Rautenstrauch reaction. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microscale Synthesis of Chiral Alcohols via Asymmetric Catalytic Transfer Hydrogenation

ERIC Educational Resources Information Center

Peeters, Christine M.; Deliever, Rik; De Vos, Dirk

2009-01-01

Synthesis of pure enantiomers is a key issue in industry, especially in areas connected to life sciences. Catalytic asymmetric synthesis has emerged as a powerful and practical tool. Here we describe an experiment on racemic reduction and asymmetric reduction via a catalytic hydrogen transfer process. Acetophenone and substituted acetophenones are…

ENANTIOMER FRACTIONS OF CHLORDANE COMPOUNDS IN SEDIMENT SAMPLES FROM U.S. GEOLOGICAL SURVEY SITES IN LAKES, RIVERS AND RESERVOIRS

EPA Science Inventory

The environmental behavior of the enantiomers of cis- and trans-chlordane has been the topic of much research since the first chiral separations on cyclodextrin gas chromatography (GC) columns. When chlordane is manufactured, it is always a racemic mixture (equal portion of two e...

Biomimetic synthesis and antiproliferative properties of racemic natural(-) and unnnatural(+) glyceollin I

USDA-ARS?s Scientific Manuscript database

A 14-step biomimetic synthetic route to glyceollin I in ca. 1.5% overall yield has been developed. In addition to being useful for the elaboration of analogs that can contribute to SAR, this route provides practical access to analytical standards that may be used for quality control purposes when gl...

21 CFR 184.1212 - Calcium pantothenate.

Code of Federal Regulations, 2014 CFR

2014-04-01

...-isomer, 137-08-6) is a salt of pantothenic acid, one of the vitamins of the B complex. Only the D-isomer of pantothenic acid has vitamin activity, although both the D-isomer and the DL- racemic mixture of....archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. (c) In accordance with § 184...

21 CFR 184.1890 - α-Tocopherols.

Code of Federal Regulations, 2011 CFR

2011-04-01

... commercially as a concentrate and is a red, nearly odorless, viscous oil. It is obtained by vacuum steam distillation of edible vegetable oil products. (2) dl-α-Tocopherol (CAS Reg. No. 10191-41-0) is a mixture of... by condensing racemic isophytol with trimethyl hydroquinone. It is a pale yellow viscous oil at room...

21 CFR 184.1890 - α-Tocopherols.

Code of Federal Regulations, 2010 CFR

2010-04-01

... commercially as a concentrate and is a red, nearly odorless, viscous oil. It is obtained by vacuum steam distillation of edible vegetable oil products. (2) dl-α-Tocopherol (CAS Reg. No. 10191-41-0) is a mixture of... by condensing racemic isophytol with trimethyl hydroquinone. It is a pale yellow viscous oil at room...

Two new isobenzofuranone derivatives from the fruiting bodies of Hericium erinaceus.

PubMed

Li, Jing; Wang, Xu-Li; Li, Guang; Xu, Ping-Sheng; Xu, Kang-Ping; Tan, Gui-Shan

2017-11-01

Two new isobenzofuranone derivatives erinaceolactones G and H (1 and 2) were isolated from the ethanolic extract of fruiting bodies of Hericium erinaceus. Their structures were characterized on the basis of spectroscopic evidences. Compound 2 was suggested to be racemic by specific rotation, which was resolved by chiral HPLC into enantiomers.

The resolution of acyclic P-stereogenic phosphine oxides via the formation of diastereomeric complexes: A case study on ethyl-(2-methylphenyl)-phenylphosphine oxide.

PubMed

Bagi, Péter; Varga, Bence; Szilágyi, András; Karaghiosoff, Konstantin; Czugler, Mátyás; Fogassy, Elemér; Keglevich, György

2018-04-01

As an example of acyclic P-chiral phosphine oxides, the resolution of ethyl-(2-methylphenyl)-phenylphosphine oxide was elaborated with TADDOL derivatives, or with calcium salts of the tartaric acid derivatives. Besides the study on the resolving agents, several purification methods were developed in order to prepare enantiopure ethyl-(2-methylphenyl)-phenylphosphine oxide. It was found that the title phosphine oxide is a racemic crystal-forming compound, and the recrystallization of the enantiomeric mixtures could be used for the preparation of pure enantiomers. According to our best method, the (R)-ethyl-(2-methylphenyl)-phenylphosphine oxide could be obtained with an enantiomeric excess of 99% and in a yield of 47%. Complete racemization of the enantiomerically enriched phosphine oxide could be accomplished via the formation of a chlorophosphonium salt. Characterization of the crystal structures of the enantiopure phosphine oxide was complemented with that of the diastereomeric intermediate. X-ray analysis revealed the main nonbonding interactions responsible for enantiomeric recognition. © 2018 Wiley Periodicals, Inc.

Characterization of a novel deep-sea microbial esterase EstC10 and its use in the generation of ( R)-methyl2-chloropropionate

NASA Astrophysics Data System (ADS)

Gong, Yanhui; Ma, Sanmei; Wang, Yongfei; Xu, Yongkai; Sun, Aijun; Zhang, Yun; Hu, Yunfeng

2018-03-01

A novel esterase EstC10 from Bacillus sp. CX01 isolated from the deep sea of the Western Pacific Ocean and the functionalities of EstC10 was characterized. At present, the reports about the kinetic resolution of racemic methyl 2-chloropropionate were quite rare. So we developed deep-sea microbial esterase EstC10 as a novel biocatalyst in the kinetic resolution of racemic methyl 2-chloropropionate and generate ( R)-methyl 2-chloropropionate with high enantiomeric excess (>99%) after the optimization of process parameters such as pH, temperature, organic co-solvents, surfactants, substrate concentration and reaction time. Notably, the optimal substrate concentration (80 mmol/L) of esterase EstC10 was higher than the kinetic resolution of another esterase, Est12-7 (50 mmol/L). The novel microbial esterase EstC10 identified from the deep sea was a promising green biocatalyst in the generation of ( R)-methyl 2-chloropropionate as well of many other valuable chiral chemicals in industry.

Enantioselective determination of metconazole in multi matrices by high-performance liquid chromatography.

PubMed

He, Rujian; Fan, Jun; Tan, Qi; Lai, Yecai; Chen, Xiaodong; Wang, Tai; Jiang, Ying; Zhang, Yaomou; Zhang, Weiguang

2018-02-01

A reliable and effective HPLC analytical method has been developed to stereoselectively quantify metconazole in soil and flour matrices. Effects of polysaccharide chiral stationary phase, type and content of alcoholic modifier on separation of racemic metconazole have been discussed in detail. Resolution and quantitative determination of metconazole stereoisomers were performed by using an Enantiopak OD column, with the n-hexane-ethanol mixture (97:3, v/v) at the flow rate of 1.0mL/min. Then, extraction and cleanup procedures followed by the modified QuEChERS (quick, easy, cheap, effective, rugged and safe) method were used for metconazole racemate in soil and flour matrices. The residual analysis method was validated. Good linearity (R 2 ≥ 0.9997) and recoveries (94.98-104.89%, RSD ≤ 2.0%) for four metconazole stereoisomers were obtained. In brief, this proposed method showed good accuracy and precision, which might be applied in enantioselective determination, residual quantitative analysis, and degradation of metconazole in food and environmental matrices. Copyright © 2017 Elsevier B.V. All rights reserved.

Templated Native Silk Smectic Gels

NASA Technical Reports Server (NTRS)

Park, Jae-Hyung (Inventor); Valluzzi, Regina (Inventor); Jin, Hyoung-Joon (Inventor)

2013-01-01

One aspect of the present invention relates to a method of preparing a fibrous protein smectic hydrogel by way of a solvent templating process, comprising the steps of pouring an aqueous fibrous protein solution into a container comprising a solvent that is not miscible with water; sealing the container and allowing it to age at about room temperature; and collecting the resulting fibrous protein smectic hydrogel and allowing it to dry. Another aspect of the present invention relates to a method of obtaining predominantly one enantiomer from a racemic mixture, comprising the steps of pouring an aqueous fibrous protein solution into a container comprising a solvent that is not miscible with water; sealing the container and allowing it to age at about room temperature; allowing the enantiomers of racemic mixture to diffuse selectively into the smectic hydrogel in solution; removing the smectic hydrogel from the solution; rinsing predominantly one enantiomer from the surface of the smectic hydrogel; and extracting predominantly one enantiomer from the interior of the smectic hydrogel. The present invention also relates to a smectic hydrogel prepared according to an aforementioned method.

Templated Native Silk Smectic Gels

NASA Technical Reports Server (NTRS)

Park, Jae-Hyung (Inventor); Valluzzi, Regina (Inventor); Jin, Hyoung-Joon (Inventor)

2016-01-01

One aspect of the present invention relates to a method of preparing a fibrous protein smectic hydrogel by way of a solvent templating process, comprising the steps of pouring an aqueous fibrous protein solution into a container comprising a solvent that is not miscible with water; sealing the container and allowing it to age at about room temperature; and collecting the resulting fibrous protein smectic hydrogel and allowing it to dry. Another aspect of the present invention relates to a method of obtaining predominantly one enantiomer from a racemic mixture, comprising the steps of pouring an aqueous fibrous protein solution into a container comprising a solvent that is not miscible with water; sealing the container and allowing it to age at about room temperature; allowing the enantiomers of racemic mixture to diffuse selectively into the smectic hydrogel in solution; removing the smectic hydrogel from the solution; rinsing predominantly one enantiomer from the surface of the smectic hydrogel; and extracting predominantly one enantiomer from the interior of the smectic hydrogel. The present invention also relates to a smectic hydrogel prepared according to an aforementioned method.

Exploring the origins of selectivity in soluble epoxide hydrolase from Bacillus megaterium† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7ob01847a

PubMed Central

Serrano-Hervás, Eila

2017-01-01

Epoxide hydrolase (EH) enzymes catalyze the hydration of racemic epoxides to yield their corresponding vicinal diols. These enzymes present different enantio- and regioselectivity depending upon either the substrate structure or the substitution pattern of the epoxide ring. In this study, we computationally investigate the Bacillus megaterium epoxide hydrolase (BmEH)-mediated hydrolysis of racemic styrene oxide (rac-SO) and its para-nitro styrene oxide (rac-p-NSO) derivative using density functional theory (DFT) and an active site cluster model consisting of 195 and 197 atoms, respectively. Full reaction mechanisms for epoxide ring opening were evaluated considering the attack at both oxirane carbons and considering two possible orientations of the substrate at the BmEH active site. Our results indicate that for both SO and p-NSO substrates the BmEH enantio- and regioselectivity is opposite to the inherent (R)-BmEH selectivity, the attack at the benzylic position (C1) of the (S)-enantiomer being the most favoured chemical outcome. PMID:29026902

Enantiomeric and Diastereoisomeric Relationships: A Practical Approach

NASA Astrophysics Data System (ADS)

Durieu, V.; Martiat, G.; Vandergeten, M. Ch.; Pirsoul, F.; Toubeau, F.; van Camp, Agnès

2000-06-01

We describe an experiment in organic chemistry in which the students prepare, purify, and characterize optical isomers. The three optical isomers of the bisoxalamides obtained by the reaction of racemic 1-phenylethylamine with diethyloxalate are separable by flash chromatography into the racemic mixture of (R,R) + (S,S) oxalamides and the (R,S) meso compound. The purified diastereomers are characterized using UV and IR spectra and mp. The mixture may also be quantitatively analyzed by HPLC. The meso isomer and the enantiomers are formed in nearly identical quantities. This observation offers us a means to calculate the optical purity of the starting a-phenylethylamine: the incorporation of an R or S carbon into the oxalamide is assumed to be purely statistical. After resolution of the alpha-phenylethylamines by a previously described procedure and transformation of the enriched R(+) and S(-) amines into the corresponding bisoxalamides, the students determine the diastereomeric composition of their products by HPLC. The calculated ee's of the enriched R(+) and S(-)-amines are similar to those obtained through optical rotation measurements. The advantage of our method is that it requires a much smaller sample of resolved amine.

Biochemical transformation of lignin for deriving valued commodities from lignocellulose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gall, Daniel L.; Ralph, John; Donohue, Timothy J.

The biochemical properties of lignin present major obstacles to deriving societally beneficial entities from lignocellulosic biomass, an abundant and renewable feedstock. Similar to other biopolymers such as polysaccharides, polypeptides, and ribonucleic acids, lignin polymers are derived from multiple types of monomeric units. However, lignin’s renowned recalcitrance is largely attributable to its racemic nature and the variety of covalent inter-unit linkages through which its aromatic monomers are linked. Indeed, unlike other biopolymers whose monomers are consistently inter-linked by a single type of covalent bond, the monomeric units in lignin are linked via non-enzymatic, combinatorial radical coupling reactions that give rise tomore » a variety of inter-unit covalent bonds in mildly branched racemic polymers. Yet, despite the chemical complexity and stability of lignin, significant strides have been made in recent years to identify routes through which valued commodities can be derived from it. This paper discusses emerging biological and biochemical means through which degradation of lignin to aromatic monomers can lead to the derivation of commercially valuable products.« less

Biochemical transformation of lignin for deriving valued commodities from lignocellulose

DOE PAGES

Gall, Daniel L.; Ralph, John; Donohue, Timothy J.; ...

2017-03-24

The biochemical properties of lignin present major obstacles to deriving societally beneficial entities from lignocellulosic biomass, an abundant and renewable feedstock. Similar to other biopolymers such as polysaccharides, polypeptides, and ribonucleic acids, lignin polymers are derived from multiple types of monomeric units. However, lignin’s renowned recalcitrance is largely attributable to its racemic nature and the variety of covalent inter-unit linkages through which its aromatic monomers are linked. Indeed, unlike other biopolymers whose monomers are consistently inter-linked by a single type of covalent bond, the monomeric units in lignin are linked via non-enzymatic, combinatorial radical coupling reactions that give rise tomore » a variety of inter-unit covalent bonds in mildly branched racemic polymers. Yet, despite the chemical complexity and stability of lignin, significant strides have been made in recent years to identify routes through which valued commodities can be derived from it. This paper discusses emerging biological and biochemical means through which degradation of lignin to aromatic monomers can lead to the derivation of commercially valuable products.« less

Surface chirality of CuO thin films.

PubMed

Widmer, Roland; Haug, Franz-Josef; Ruffieux, Pascal; Gröning, Oliver; Bielmann, Michael; Gröning, Pierangelo; Fasel, Roman

2006-11-01

We present X-ray photoelectron spectroscopy (XPS) and X-ray photoelectron diffraction (XPD) investigations of CuO thin films electrochemically deposited on an Au(001) single-crystal surface from a solution containing chiral tartaric acid (TA). The presence of enantiopure TA in the deposition process results in a homochiral CuO surface, as revealed by XPD. On the other hand, XPD patterns of films deposited with racemic tartaric acid or the "achiral" meso-tartaric acid are completely symmetric. A detailed analysis of the experimental data using single scattering cluster calculations reveals that the films grown with l(+)-TA exhibit a CuO(1) orientation, whereas growth in the presence of d(-)-TA results in a CuO(11) surface orientation. A simple bulk-truncated model structure with two terminating oxygen layers reproduces the experimental XPD data. Deposition with alternating enantiomers of tartaric acid leads to CuO films of alternating chirality. Enantiospecifity of the chiral CuO surfaces is demonstrated by further deposition of CuO from a solution containing racemic tartaric acid. The pre-deposited homochiral films exhibit selectivity toward the same enantiomeric deposition pathway.

Involvement of abscisic acid in correlative control of flower abscission in soybean

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yarrow, G.L.

1985-01-01

Studies were carried out in three parts: (1) analysis of endogenous abscisic acid (ABA) in abscising and non-abscising flowers, (2) partitioning of radio-labelled ABA and photoassimilates within the soybean raceme, and (3) shading experiments, wherein endogenous levels, metabolism and partitioning of ABA were determined. Endogenous concentrations of ABA failed to show any consistent relationship to abscission of soybean flowers. Partitioning of radiolabelled ABA and photoassimilates displayed consistently higher sink strengths (% DPM) for both /sup 3/H-ABA and /sup 14/C-photoassimilates for non-abscising flowers than for abscising flowers within control racemes. Shading flowers with aluminum foil, 48 hrs prior to sampling, resultedmore » in lowered endogenous ABA concentrations at 12, 17 and 22 days after anthesis (DAA), but not at 0 or 4 DAA. No differences were found in the catabolism of /sup 3/H-ABA between shaded (abscising) and non-shaded (non-abscising) flowers. Reduced partitioning of ABA and photoassimilates to shaded flowers resulted when shades were applied at 0, 4, 12, and 17 DAA, but not at 22 DAA.« less

[Enantioselectivity in the excretion of glucuronides of carprofen in man, dogs and horses].

PubMed

Delatour, P; Garnier, F; Maire, R

1996-10-01

After administration of the racemic drug, the stereoselective quantification of the enantiomers of free and conjugated carprofen was performed in human plasma and in plasma, urine and bile of dogs and horses. In humans, the plasma profile of free carprofen and its glucuronides is not stereoselective and the glucuronides excreted in urine are close to a racemate. In dogs and horses on the contrary, the R(-) enantiomer of the free drug is predominant in plasma, while urine and/or bile concentrations of the glucuronides are high in comparison to plasma with a strong selectivity for the S(+) enantiomer. Because glucuronidation of carprofen, as a carboxylic compound, is known to be the major metabolic pathway in most species, interspecies discrepancies in the stereoselective disposition of carprofen seem to be mainly related to the stereoselectivity in the excretion of the glucuronides. Finally, the high plasma concentrations of carprofen glucuronides in human in comparison to other animal species suggest that the former could be specifically subjected to immunological side effects in the time course of treatments by this type of compounds.

A Combined Experimental and Theoretical Study on the Formation of Interstellar Propylene Oxide (CH3CHCH2O)—A Chiral Molecule

NASA Astrophysics Data System (ADS)

Bergantini, Alexandre; Abplanalp, Matthew J.; Pokhilko, Pavel; Krylov, Anna I.; Shingledecker, Christopher N.; Herbst, Eric; Kaiser, Ralf I.

2018-06-01

This work reveals via a combined experimental, computational, and astrochemical modeling study that racemic propylene oxide (c-C3H6O)—the first chiral molecule detected outside Earth toward the high-mass star-forming region Sagittarius B2(N)—can be synthesized by non-equilibrium reactions initiated by the effects of secondary electrons generated in the track of cosmic rays interacting with ice-coated interstellar grains through excited-state and spin-forbidden reaction pathways operating within low-temperature interstellar ices at 10 K. Our findings confront traditional hypotheses that thermal chemistries followed by processing of interstellar grains dictate the formation of complex organic molecules (COMs) in molecular clouds. Instead, we reveal a hitherto poorly quantified reaction class involving excited-state and spin-forbidden chemistry leading to racemic mixtures of COMs inside interstellar ices prior to their sublimation in star-forming regions. This fundamental production mechanism is of essential consequence in aiding our understanding of the origin and evolution of chiral molecules in the universe.

Distinctive effect on nerve growth factor-induced PC12 cell neurite outgrowth by two unique neolignan enantiomers from Illicium merrillianum

PubMed Central

Tian, Xinhui; Yue, Rongcai; Zeng, Huawu; Li, Honglin; Shan, Lei; He, Weiwei; Shen, Yunheng; Zhang, Weidong

2015-01-01

Merrillianoid (1), a racemic neolignan possessing the characteristic benzo-2,7-dioxabicyclo[3.2.1]octane moiety, was isolated from the branches and leaves of Illicium merrillianum. Chiral separation of 1 gave two enantiomers (+)−1 and (−)−1. The structure of 1 was established by comprehensive spectroscopic analysis and single crystal X-ray diffraction. The absolute configurations of enantiomers were determined by quantum mechanical calculation. Compound (+)−1 exhibited a better neurotrophic activity than racemate 1 by promoting nerve growth factor (NGF) induced PC12 cell neurite outgrowth, while (−)−1 showed a distinctive inhibitory effect. Furthermore, a mechanism study indicated that the two enantiomers influenced NGF-induced neurite outgrowth of PC12 cells possibly by interacting with the trkA receptor, and extracellular signal regulated kinases 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) in Ras/ERK signal cascade. But the phosphorylation level of serine/threonine kinase Akt1 and Akt2 in PI3K/Akt signal pathway showed no significant difference between (+)−1 and (−)−1. PMID:26585042

Thin Layer Chromatographic Resolution of Some β-adrenolytics and a β2-Agonist Using Bovine Serum Albumin as Chiral Additive in Stationary Phase.

PubMed

Malik, Poonam; Bhushan, Ravi

2018-01-01

Direct enantiomeric resolution of commonly used five racemic β-adrenolytics, namely, bisoprolol, atenolol, propranolol, salbutamol and carvedilol has been achieved by thin layer chromatography using bovine serum albumin (BSA) as chiral additive in stationary phase. Successful resolution of the enantiomers of all racemic β-adrenolytics was achieved by use of different composition of simple organic solvents having no buffer or inorganic ions. The effect of variation in pH, temperature, amount of BSA as the additive, and composition of mobile phase on resolution was systematically studied. Spots were visualized in iodine vapors. Native enantiomers for each of the five analytes were isolated and identified and their elution order was determined. The limit of detection was found to be 0.7, 1.2, 0.84, 1.6 and 0.9 μg (per spot) for each enantiomer of bisoprolol, atenolol, propranolol, salbutamol and carvedilol, respectively. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Racemization of alanine by the alanine racemases from Salmonella typhimurium and Bacillus stearothermophilus: energetic reaction profiles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faraci, W.S.; Walsh, C.T.

1988-05-03

Alanine racemases are bacterial pyridoxal 5'-phosphate (PLP) dependent enzymes providing D-alanine as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall. Two isozymic alanine racemases, encoded by the dadB gene and the alr gene, from the Gram-negative mesophilic Salmonella typhimurium and one from the Gram-positive thermophilic Bacillus stearothermophilus have been examined for the racemization mechanism. Substrate deuterium isotope effects and solvent deuterium isotope effects have been measured in both L ..-->.. D and D..-->.. L directions for all three enzymes to assess the degree to which abstraction of the ..cap alpha..-proton or protonation of substratemore » PLP carbanion is limiting in catalysis. Additionally, experiments measuring internal return of ..cap alpha..-/sup 3/H from substrate to product and solvent exchange/substrate conversion experiments in /sup 3/H/sub 2/O have been used with each enzyme to examine the partitioning of substrate PLP carbanion intermediates and to obtain the relative heights of kinetically significant energy barriers in alanine racemase catalysis.« less

Chirally directed formation of nanometer-scale proline clusters.

PubMed

Myung, Sunnie; Fioroni, Marco; Julian, Ryan R; Koeniger, Stormy L; Baik, Mu-Hyun; Clemmer, David E

2006-08-23

Ion mobility measurements, combined with molecular mechanics simulations, are used to study enantiopure and racemic proline clusters formed by electrospray ionization. Broad distributions of cluster sizes and charge states are observed, ranging from clusters containing only a few proline units to clusters that contain more than 100 proline units (i.e., protonated clusters of the form [xPro + nH](n+) with x = 1 to >100 and n = 1-7). As the sizes of clusters increase, there is direct evidence for nanometer scale, chirally induced organization into specific structures. For n = 4 and 5, enantiopure clusters of approximately 50 to 100 prolines assemble into structures that are more elongated than the most compact structure that is observed from the racemic proline clusters. A molecular analogue, cis-4-hydroxy-proline, displays significantly different behavior, indicating that in addition to the rigidity of the side chain ring, intermolecular interactions are important in the formation of chirally directed clusters. This is the first case in which assemblies of chirally selective elongated structures are observed in this size range of amino acid clusters. Relationships between enantiopurity, cluster shape, and overall energetics are discussed.

Fast characterization of C-glycoside acetophenones in Medemia argun male racemes (an Ancient Egyptian palm) using LC-MS analyses and computational study with their antioxidant effect

NASA Astrophysics Data System (ADS)

Ben Said, Ridha; Hamed, Arafa I.; Essalah, Khaled; Al-Ayed, Abdullah S.; Boughdiri, Salima; Tangour, Bahoueddine; Kowalczyk, Mariusz; Moldoch, Jaroslaw; Mahalel, Usama A.; Olezek, Wolesow; Stochmal, Anna

2017-10-01

Medemia argun is an ancient endemic palm growing in Nubian Desert of Egypt and Sudan. Liquid chromatography coupled with mass spectrometry in negative ion mode (LC/ESI-MS) has proved to be a potent tool for rapid identification and characterization of complex phytochemicals in male racemes of M. argun. A total of seven compounds were tentatively identified comprising of two C-glycoside acetophenones, along with the known compounds one stilbene derivative and four known flavonol derivatives from 40% methanolic portion. The product ions of acetophenone derivatives [M-H]- were shown to be cross-ring cleavages of the hexoside moiety [M-(90/120)-H]- characteristic for C-glycoside linkage. The position of Csbnd C-linkage was elucidated by DFT study using the Fukui functions and descriptors. The results revealed that hexose was conjugated with aglycones at C3 or C5. In addition, the theoretical antioxidant activity of compounds 6 and 7 was evaluated by using Bond Dissociation Enthalpy (BDE).

Enhancement of epoxide hydrolase production by 60 Co gamma and UV irradiation mutagenesis of Aspergillus niger ZJB-09103.

PubMed

Jin, Huo-Xi; OuYang, Xiao-Kun; Hu, Zhong-Ce

2017-05-01

An effective epoxide hydrolase (EH) production strain was mutagenized using 60 Co gamma and UV irradiation. Among positive mutant strains, the EH activity of C2-44 reached 33.7 U/g, which was 267% as much as that of the original Aspergillus niger ZJB-09103. Compared with the wild type, there were significant changes in morphology for C2-44, including the color of mycelia on the slants and the shape of conidial head. In addition, glucose and soybean cake were the optimal carbon and nitrogen source in terms of EH activity for the mutant C2-44 instead of soluble starch and peptone for the wild-type strain. The reaction time required to reach 99% enantiomeric excesses of (S)-epichlorohydrin from racemic substrate was shortened significantly by the mutant C2-44. This phenomenon was probably explained by the higher V max for hydrolysis of racemic epichlorohydrin by C2-44 compared with Aspergillus niger ZJB-09103. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Enantioresolution of (RS)-baclofen by liquid chromatography: A review.

PubMed

Batra, Sonika; Bhushan, Ravi

2017-01-01

Baclofen is a commonly used racemic drug and has a simple chemical structure in terms of the presence of only one stereogenic center. Since the desirable pharmacological effect is in only one enantiomer, several possibilities exist for the other enantiomer for evaluation of the disposition of the racemic mixture of the drug. This calls for the development of enantioselective analytical methodology. This review summarizes and evaluates different methods of enantioseparation of (RS)-baclofen using both direct and indirect approaches, application of certain chiral reagents and chiral stationary phases (though very expensive). Methods of separation of diastereomers of (RS)-baclofen prepared with different chiral derivatizing reagents (under microwave irradiation at ease and in less time) on reversed-phase achiral columns or via a ligand exchange approach providing high-sensitivity detection by the relatively less expensive methods of TLC and HPLC are discussed. The methods may be helpful for determination of enantiomers in biological samples and in pharmaceutical formulations for control of enantiomeric purity and can be practiced both in analytical laboratories and industry for routine analysis and R&D activities. Copyright © 2016 John Wiley & Sons, Ltd.

Optically active bis(β-diketonate) complexes of titanium.

PubMed

Kongprakaiwoot, Natcharee; Armstrong, Jack B; Noll, Bruce C; Brown, Seth N

2010-11-14

The 2,2'-bis(methylene)biphenyl bridged bis(diketonate) (Tol(2)Bob)Ti(IV) fragment is resolved by reaction of the isopropoxide complex with (R)-1,1'-bi-2-naphthol, which selectively forms (S,Δ)-(Tol(2)Bob)Ti(R-BINOL). The binaphtholate ligand can be cleaved from titanium by careful treatment with trifluoromethanesulfonic acid to give (S,Δ)-(Tol(2)Bob)Ti(OTf)(2), which has a half-life toward racemization of at least 34 h at 51 °C. Racemization of the (Tol(2)Bob)Ti(IV) fragment is strongly accelerated under protic conditions, probably due to protonolysis of one of the diketonate ligands. Analogous optically active titanium bis(diketonates) can also be prepared by using an optically active 2,2'-bis(methylene)-1,1'-binaphthyl bridged bis(diketonate) ligand, Tol(2)Bobbinap, prepared from (R)-BINOLH2. Complexation of (R)-Tol(2)BobbinapH(2) with Ti(OiPr)(4) gives only a single diastereomer with the Λ configuration at titanium. The bis(diketonate)titanium(IV) fragment gives rise to characteristic signals in circular dichroism spectra which can be used to identify the configuration at the metal centre.

Narcolepsy Treated with Racemic Amphetamine during Pregnancy and Breastfeeding.

PubMed

Öhman, Inger; Wikner, Birgitta Norstedt; Beck, Olof; Sarman, Ihsan

2015-08-01

This case report describes a woman with narcolepsy treated with racemic amphetamine (rac-amphetamine) during pregnancy and breastfeeding with follow-up on the infant's development up to 10 months of age. The pregnancy outcome and the pharmacokinetics of rac-amphetamine were studied during breastfeeding. The pregnancy and the delivery were uneventful. Concentrations of rac-amphetamine were determined in the plasma of the mother and infant, and in the breast milk with a liquid chromatography-mass spectrometry method. Samples were obtained at 2, 5, and 9 weeks postpartum. The transfer of rac-amphetamine to the breast milk was extensive (mean milk/maternal plasma concentration ratio approximately 3). The breastfed infant had a low plasma concentration of rac-amphetamine (about 9% of the maternal plasma level) and the calculated relative infant dose was low (2%). No adverse effects were observed in the breastfed infant. The infant's somatic and psychomotor development up to 10 months of age was normal. Further studies of amphetamine prescribed for medical reasons during pregnancy and lactation are needed. © The Author(s) 2015.

From Mesocates to Helicates: Structural, Magnetic and Chiro-Optical Studies on Nickel(II) Supramolecular Assemblies Derived from Tetradentate Schiff Bases.

PubMed

Mayans, Júlia; Font-Bardia, Mercè; Di Bari, Lorenzo; Arrico, Lorenzo; Zinna, Francesco; Pescitelli, Gennaro; Escuer, Albert

2018-05-28

The systematic reactions of a family of tetradentate pyridyl/imine and quinolyl/imine racemic or enantiopure Schiff bases with Ni(NO 3 ) 2 or Ni(ClO 4 ) 2 in the presence of sodium azide yielded, as a function of the starting racemic, chiral or achiral base, a set of chiral, meso or achiral complexes. In all cases, the compounds consist of two Ni II cations linked by a double azido bridge in its end-on coordination mode. All the dimers exhibit a mesocate supramolecular structure and one of them, the unprecedented mix of helicate and mesocate in 2:1 ratio. The transition from mesocate to helicate conformation has been reached by tuning the flexibility of the central spacers of the Schiff bases and the size of the substituents. Electronic circular dichroism (ECD) studies have been performed for two pairs of enantiomers and interpreted by means of DFT calculations. Susceptibility measurements show a ferromagnetic coupling between the Ni II cations mediated by the end-on azido bridges. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

(+)-Meyeniins A-C, Novel Hexahydroimidazo[1,5-c]thiazole Derivatives from the Tubers of Lepidium meyenii: Complete Structural Elucidation by Biomimetic Synthesis and Racemic Crystallization.

PubMed

Zhou, Min; Ma, Hang-Ying; Liu, Zhi-Hua; Yang, Guang-Yu; Du, Gang; Ye, Yan-Qing; Li, Gan-Peng; Hu, Qiu-Fen

2017-03-08

(+)-Meyeniins A-C (1-3), a novel class of sulfur-containing hexahydroimidazo[1,5-c]thiazole derivatives, were isolated from the tubers of Lepidium meyenii (maca) cultivated in Lijiang, Yunnan province, China. Guided by their biosynthetic hypothesis, a stereocontrolled biomimetic synthesis of meyeniins A-C and their individual enantiomers was efficiently accomplished by a combination of a condensation reaction and Edman degradation. The formation of high-quality crystals for X-ray crystallography occurred much more readily from a racemic mixture of (±)-meyeniin A than with the single enantiomer alone in this case. These extensive strategies, combined with circular dichroism (CD) spectra, allowed the complete structural assignments of (+)-meyeniins A-C. Among them, (+)-meyeniin A showed moderate selective cytotoxicities against the HL-60, A549 and MCF-7 human cell lines with IC 50 values of 14.41, 32.22, and 33.14 μM, respectively. To some extent, these findings support traditional applications of maca as healthy nutritional supplements or functional foods for cancer prevention.

Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine.

PubMed

Leone, Stefania; Di Cianni, Simone; Casati, Andrea; Fanelli, Guido

2008-08-01

Levobupivacaine and ropivacaine, two new long-acting local anesthetics, have been developed as an alternative to bupivacaine, after the evidence of its severe toxicity. Both of these agents are pure left-isomers and, due to their three-dimensional structure, seem to have less toxic effects on the central nervous system and on the cardiovascular system. Many clinical studies have investigated their toxicology and clinical profiles: theoretically and experimentally, some differences have been observed, but the effects of these properties on clinical practice have not been shown. By examining randomised, controlled trials that have compared these three local agents, this review supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences reported between the three anesthetics are mainly related to the slightly different anesthetic potency, with racemic bupivacaine > levobupivacaine > ropivacaine. However, the reduced toxic potential of the two pure left-isomers suggests their use in the clinical situations in which the risk of systemic toxicity related to either overdosing or unintended intravascular injection is high, such as during epidural or peripheral nerve blocks.

Bupivacaine, levobupivacaine and ropivacaine: are they clinically different?

PubMed

Casati, Andrea; Putzu, Marta

2005-06-01

Two new, long-acting local anaesthetics have been developed after the evidence of bupivacaine-related severe toxicity: levobupivacaine and ropivacaine. Both these agents are pure left-isomers and, based on their three-dimensional structure, they have less toxic potential both on the central nervous system and on the heart. Several clinical studies have evaluated their toxicology and clinical profiles: theoretically and experimentally, some differences can be seen, but the reflections of these characteristics into clinical practice have not been evident. Evaluating randomised, controlled trials that have compared these three local anaesthetics, this chapter supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences observed between the three agents are mainly related to the slightly different anaesthetic potency, with racemic bupivacaine>levobupivacaine>ropivacaine. However, the reduced toxic potential of the two pure left-isomers supports their use in those clinical situations in which the risk of systemic toxicity related to either overdosing or unwanted intravascular injection is high, such as during epidural or peripheral nerve blocks.

Separation of drug stereoisomers by the formation of. beta. -cyclodextrin inclusion complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armstrong, D.W.; Ward, T.J.; Armstrong, R.D.

For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized ..beta..-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as ..beta..-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of ..beta..-cyclodextrin complexes ofmore » propanol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of ..beta..-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiometric drugs. 27 references, 3 figures, 2 tables.« less

The Role of Carbohydrates at the Origin of Homochirality in Biosystems

NASA Astrophysics Data System (ADS)

Toxvaerd, Søren

2013-10-01

Pasteur has demonstrated that the chiral components in a racemic mixture can separate in homochiral crystals. But with a strong chiral discrimination the chiral components in a concentrated mixture can also phase separate into homochiral fluid domains, and the isomerization kinetics can then perform a symmetry breaking into one thermodynamical stable homochiral system. Glyceraldehyde has a sufficient chiral discrimination to perform such a symmetry breaking. The requirement of a high concentration of the chiral reactant(s) in an aqueous solution in order to perform and maintain homochirality; the appearance of phosphorylation of almost all carbohydrates in the central machinery of life; the basic ideas that the biochemistry and the glycolysis and gluconeogenesis contain the trace of the biochemical evolution, all point in the direction of that homochirality was obtained just after- or at a phosphorylation of the very first products of the formose reaction, at high concentrations of the reactants in phosphate rich compartments in submarine hydrothermal vents. A racemic solution of D,L-glyceraldehyde-3-phosphate could be the template for obtaining homochiral D-glyceraldehyde-3-phosphate(aq) as well as L-amino acids.

A computational study on the role of chiral N-oxides in enantioselective Pauson-Khand reactions.

PubMed

Fjermestad, Torstein; Pericàs, Miquel A; Maseras, Feliu

2011-08-29

Density functional calculations were carried out to ascertain the origin of enantioselectivity in the brucine N-oxide (BNO)-assisted enantioselective Pauson-Khand reaction (PKR) of norbornene with 2-methyl-3-butyn-2-ol. The computed ee value in acetone is 68 % (R), which compares well to the previously reported experimental value of 58 % (R). In DME the computed ee value of 76 % (R) is in excellent agreement with the experimentally determined value of 78 % (R). The mechanism of enantioselectivity consists of several steps. First, the dicobalt complex is activated by BNO with chirality transfer from enantiopure BNO to the dicobalt complex. Second, competition occurs between a racemization process and complexation with the olefin reagent, which leads to the products. The lower ee value in acetone is due to the lower energy barrier of the racemization process. Calculations show that replacement of BNO by a hypothetical more enantioselective chiral N-oxide will hardly increase the ee value beyond 90 %. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparative enantioseparation of propafenone by counter-current chromatography using di-n-butyl L-tartrate combined with boric acid as the chiral selector.

PubMed

Tong, Shengqiang; Shen, Mangmang; Zheng, Ye; Chu, Chu; Li, Xing-Nuo; Yan, Jizhong

2013-09-01

This paper extends the research of the utilization of borate coordination complexes in chiral separation by counter-current chromatography (CCC). Racemic propafenone was successfully enantioseparated by CCC with di-n-butyl l-tartrate combined with boric acid as the chiral selector. The two-phase solvent system was composed of chloroform/ 0.05 mol/L acetate buffer pH 3.4 containing 0.10 mol/L boric acid (1:1, v/v), in which 0.10 mol/L di-n-butyl l-tartrate was added in the organic phase. The influence of factors in the enantioseparation of propafenone were investigated and optimized. A total of 92 mg of racemic propafenone was completely enantioseparated using high-speed CCC in a single run, yielding 40-42 mg of (R)- and (S)-propafenone enantiomers with an HPLC purity over 90-95%. The recovery for propafenone enantiomers from fractions of CCC was in the range of 85-90%. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Templated native silk smectic gels

NASA Technical Reports Server (NTRS)

Park, Jae-Hyung (Inventor); Valluzzi, Regina (Inventor); Jin, Hyoung-Joon (Inventor)

2009-01-01

One aspect of the present invention relates to a method of preparing a fibrous protein smectic hydrogel by way of a solvent templating process, comprising the steps of pouring an aqueous fibrous protein solution into a container comprising a solvent that is not miscible with water; sealing the container and allowing it to age at about room temperature; and collecting the resulting fibrous protein smectic hydrogel and allowing it to dry. Another aspect of the present invention relates to a method of obtaining predominantly one enantiomer from a racemic mixture, comprising the steps of pouring an aqueous fibrous protein solution into a container comprising a solvent that is not miscible with water; sealing the container and allowing it to age at about room temperature; allowing the enantiomers of racemic mixture to diffuse selectively into the smectic hydrogel in solution; removing the smectic hydrogel from the solution; rinsing predominantly one enantiomer from the surface of the smectic hydrogel; and extracting predominantly one enantiomer from the interior of the smectic hydrogel. The present invention also relates to a smectic hydrogel prepared according to an aforementioned method.

Experimental and DFT study of cyclodehydration and acetylation of ferrocenyl diols

NASA Astrophysics Data System (ADS)

Lapić, Jasmina; Višnjevac, Aleksandar; Cetina, Mario; Djaković, Senka; Vrček, Valerije; Rapić, Vladimir

2012-07-01

Racemic ferrocenyl diols, i.e. ferrocenyl(2-hydroxymethylphenyl)methanol (2), ferrocenyl-2-(2-hydroxymethylphenyl)ethanol (7), and ferrocenyl(2-(2-hydroxyethyl)phenyl)methanol (9) have been prepared by reduction of corresponding ketoesters using NaBH4 in a mixture EtOH and Et2O. In the course of these reactions new cyclic ethers 1-ferrocenyl-2-oxaindane (3), 3-ferrocenylisochromane (8), and 1-ferrocenylisochromane (10) have been isolated as side-products. Intramolecular cyclizations of ferrocenyl diols occur in both acidic and neutral medium. Density functional theory (BP86) calculations were used to explain the mechanism of these cyclodehydrations. Acid catalyzed reaction follows the classical SN1 mechanism, whereas the cyclodehydration in neutral medium is described as an SN2 reaction. X-ray diffraction analysis of new cyclic ether products has been performed. Monoacetates 11, 13 and 15 have been obtained in the reaction of ferrocenyl diols 2, 7, and 9, respectively, and acetic anhydride. Stereoselective acylation of racemic diols by vinyl acetate have been catalyzed by various lipases, and the best stereoselectivity has been observed for the diol 2 in the presence of Penicillium camembertii lipase.

Characterization of a single-isomer carboxymethyl-beta-cyclodextrin in chiral capillary electrophoresis.

PubMed

Fejős, Ida; Varga, Erzsébet; Benkovics, Gábor; Malanga, Milo; Sohajda, Tamás; Szemán, Julianna; Béni, Szabolcs

2017-08-01

In this work, the synthesis, characterization, and chiral capillary electrophoretic study of heptakis-(2,3-di-O-methyl-6-O-carboxymethyl)-β-CD (HDMCM), a single-isomer carboxymethylated CD, are presented. The pH-dependent and selector concentration-dependent enantiorecognition properties of HDMCM were investigated and discussed herein. The enantioseparation was assessed applying a structurally diverse set of noncharged, basic, and zwitterionic racemates. The increase in the selector concentration and gross negative charge of HDMCM improved the enantioseparation that could be observed in the majority of the cases. HDMCM was also successfully applied as BGE additive in NACE using a methanol-based system in order to prove the separation selectivity features and to highlight the broad applicability of HDMCM. Over 25 racemates showed partial or baseline separation with HDMCM under the conditions investigated, among which optimal enantiomer migration order was found for the four stereoisomers of tadalafil, tapentadol, and dapoxetine, offering the possibility of a chiral CE method development for chiral purity profiling of these drugs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optical resolution by preferential crystallization of (RS)-2-benzoylamino-2-benzyl-3-hydroxypropanoic acid and its use in synthesizing optically active 2-amino-2-methyl-3-phenylpropanoic acid.

PubMed

Shiraiwa, Tadashi; Suzuki, Masahiro; Sakai, Yoshio; Nagasawa, Hisashi; Takatani, Kazuhiro; Noshi, Daisuke; Yamanashi, Kenji

2002-10-01

To synthesize optically active 2-amino-2-methyl-3-phenylpropanoic acid (1), (RS)-2-benzoylamino-2-benzyl-3-hydroxypropanoic acid [(RS)-2] was first optically resolved using cinchonidine as a resolving agent to yield optically pure (S)- and (R)-2 in yields of about 70%, based on half of the starting amount of (RS)-2. Next, the racemic structure of (RS)-2 was examined based on melting point, solubility, IR spectrum, and binary and ternary phase diagrams, with the aim of optical resolution by preferential crystallization of (RS)-2. Results indicated that the (RS)-2 exists as a conglomerate at room temperature, although it forms a racemic compound at the melting point. The optical resolution by preferential crystallization yielded (S)- and (R)-2 with optical purities of about 90%, which were fully purified by recrystallization. After O-tosylation of (S)- and (R)-2, reduction by zinc powder and sodium iodide gave (R)- and (S)-1, respectively.

Fully convergent chemical synthesis of ester insulin: determination of the high resolution X-ray structure by racemic protein crystallography.

PubMed

Avital-Shmilovici, Michal; Mandal, Kalyaneswar; Gates, Zachary P; Phillips, Nelson B; Weiss, Michael A; Kent, Stephen B H

2013-02-27

Efficient total synthesis of insulin is important to enable the application of medicinal chemistry to the optimization of the properties of this important protein molecule. Recently we described "ester insulin"--a novel form of insulin in which the function of the 35 residue C-peptide of proinsulin is replaced by a single covalent bond--as a key intermediate for the efficient total synthesis of insulin. Here we describe a fully convergent synthetic route to the ester insulin molecule from three unprotected peptide segments of approximately equal size. The synthetic ester insulin polypeptide chain folded much more rapidly than proinsulin, and at physiological pH. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin (i.e., [Asp(B10), Lys(B28), Pro(B29)]ester insulin) were prepared by total chemical synthesis. The atomic structure of the synthetic ester insulin molecule was determined by racemic protein X-ray crystallography to a resolution of 1.6 Å. Diffraction quality crystals were readily obtained from the racemic mixture of {D-DKP ester insulin + L-DKP ester insulin}, whereas crystals were not obtained from the L-ester insulin alone even after extensive trials. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin were assayed for receptor binding and in diabetic rats, before and after conversion by saponification to the corresponding DKP insulin enantiomers. L-DKP ester insulin bound weakly to the insulin receptor, while synthetic L-DKP insulin derived from the L-DKP ester insulin intermediate was fully active in binding to the insulin receptor. The D- and L-DKP ester insulins and D-DKP insulin were inactive in lowering blood glucose in diabetic rats, while synthetic L-DKP insulin was fully active in this biological assay. The structural basis of the lack of biological activity of ester insulin is discussed.

Behavioral and neurogenomic transcriptome changes in wild-derived zebrafish with fluoxetine treatment

PubMed Central

2013-01-01

Background Stress and anxiety-related behaviors are seen in many organisms. Studies have shown that in humans and other animals, treatment with selective serotonin reuptake inhibitors (e.g. fluoxetine) can reduce anxiety and anxiety-related behaviors. The efficacies and side effects, however, can vary between individuals. Fluoxetine can modulate anxiety in a stereospecific manner or with equal efficacy regardless of stereoisomer depending on the mechanism of action (e.g. serotonergic or GABAergic effects). Zebrafish are an emerging and valuable translational model for understanding human health related issues such as anxiety. In this study we present data showing the behavioral and whole brain transcriptome changes with fluoxetine treatment in wild-derived zebrafish and suggest additional molecular mechanisms of this widely-prescribed drug. Results We used automated behavioral analyses to assess the effects of racemic and stereoisomeric fluoxetine on male wild-derived zebrafish. Both racemic and the individual isomers of fluoxetine reduced anxiety-related behaviors relative to controls and we did not observe stereospecific fluoxetine effects. Using RNA-sequencing of the whole brain, we identified 411 genes showing differential expression with racemic fluoxetine treatment. Several neuropeptides (neuropeptide Y, isotocin, urocortin 3, prolactin) showed consistent expression patterns with the alleviation of stress and anxiety when anxiety-related behavior was reduced with fluoxetine treatment. With gene ontology and KEGG pathway analyses, we identified lipid and amino acid metabolic processes, and steroid biosynthesis among other terms to be over-enriched. Conclusion Our results demonstrate that fluoxetine reduces anxiety-related behaviors in wild-derived zebrafish and alters their neurogenomic state. We identify two biological processes, lipid and amino acid metabolic synthesis that characterize differences in the fluoxetine treated fish. Fluoxetine may be acting on several different molecular pathways to reduce anxiety-related behaviors in wild-derived zebrafish. This study provides data that could help identify common molecular mechanisms of fluoxetine action across animal taxa. PMID:23706039

Imitating prebiotic homochirality on Earth.

PubMed

Breslow, Ronald; Levine, Mindy; Cheng, Zhan-Ling

2010-02-01

We show how the amino acids needed on prebiotic earth in their homochiral L form can be produced by a reaction of L-alpha-methyl amino acids-that have been identified in the Murchison meteorite-with alpha-keto acids under credible prebiotic conditions. When they are simply heated together they perform a process of decarboxylative transamination but with almost no chiral transfer, and that in the wrong direction, producing D-amino acids from the L-alpha-methyl amino acids. With copper ion a square planar complex with two of the reaction intermediates is formed, and now there is the desired L to L transformation, producing small enantioexcesses of the normal L-amino acids. We also show how these can be amplified, not by making more of the L form but by increasing its concentration in water solution. The process can start with a miniscule excess and in one step generate water solutions with L/D ratios in the over 90% region. Kinetic processes can exceed the results from equilibria. We have also examined such amplifications with ribonucleosides, and have shown that initial modest excesses of the D-nucleosides can be amplified to afford water solutions with D to L ratios in the high 90's. We have shown that the homochiral compound has two effects on the solubility of the racemate. On one hand it decreases the solubility of the racemate by its role in the solubility product, as a theoretical equation predicts. On the other hand, it increases the solubility of the racemate by changing the nature of the solvent, acting as a cosolvent with the water. This explains why the amplification, while large, is not as large as the simple theoretical equation predicts. Thus when credible examples are produced where small enantioexcesses of D-ribose are created under credible prebiotic conditions, the prerequisites for the RNA world will have been exemplified.

Atropisomerization in N-aryl-2(1H)-pyrimidin-(thi)ones: a ring-opening/rotation/ring-closure process in place of a classical rotation around the pivot bond.

PubMed

Najahi, Ennaji; Vanthuyne, Nicolas; Nepveu, Françoise; Jean, Marion; Alkorta, Ibon; Elguero, José; Roussel, Christian

2013-12-20

Uncatalyzed racemization processes in atropisomeric diphenyl-like frameworks are classically described as the result of the rotation around the pivotal single bond linking two planar frameworks. Severe constraints leading to more or less distorted transition states account for the experimental barrier to atropenantiomerization. In 1988, one of us hypothesized that, in N-aryl-2(1H)-pyrimidin-(thi)ones, a ring-opening/ring-closure process was contributing to the observed racemization process accounting for the lower barriers in the sulfur analogues than in oxygen analogues. Now, a series of six novel 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones 5a-5f and two 6-amino-5-cyano-4-p-tolyl-1-substituted-2(1H)-pyrimidinethiones 6a and 6b were synthesized and characterized through spectroscopic and X-ray diffraction studies. Semipreparative HPLC chiral separation was achieved, and enantiomerization barriers were obtained by thermal racemization. The rotational barriers of 6-amino-5-cyano-1-o-tolyl-4-p-tolyl-2(1H)-pyrimidinone (5b) and 6-amino-5-cyano-1-(naphthalen-1-yl)-4-p-tolyl-2(1H)-pyrimidinone (5e) were found to be 120.4 and 125.1 kJ·mol(-1) (n-BuOH, 117 °C), respectively, and those of the corresponding thiones were 116.8 and 109.6 kJ·mol(-1) (EtOH, 78 °C), respectively. DFT calculations of the rotational barriers clearly ruled out the classical rotation around the pivotal bond with distorted transition states in the case of the sulfur derivatives. Instead, the ranking of the experimental barriers (sulfur versus oxygen, and o-tolyl versus 1-naphthyl in both series) was nicely reproduced by calculations when the rotation occurred via a ring-opened form in N-aryl-2(1H)-pyrimidinethiones.

Fully Convergent Chemical Synthesis of Ester Insulin: Determination of the High Resolution X-ray Structure by Racemic Protein Crystallography

PubMed Central

Avital-Shmilovici, Michal; Mandal, Kalyaneswar; Gates, Zachary P.; Phillips, Nelson B.; Weiss, Michael A.; Kent, Stephen B.H.

2013-01-01

Efficient total synthesis of insulin is important to enable the application of medicinal chemistry to the optimization of the properties of this important protein molecule. Recently we described ‘ester insulin’ – a novel form of insulin in which the function of the 35 residue C-peptide of proinsulin is replaced by a single covalent bond – as a key intermediate for the efficient total synthesis of insulin. Here we describe a fully convergent synthetic route to the ester insulin molecule from three unprotected peptide segments of approximately equal size. The synthetic ester insulin polypeptide chain folded much more rapidly than proinsulin, and at physiological pH. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin (i.e. [AspB10, LysB28, ProB29]ester insulin) were prepared by total chemical synthesis. The atomic structure of the synthetic ester insulin molecule was determined by racemic protein X-ray crystallography to a resolution of 1.6 Å. Diffraction quality crystals were readily obtained from the racemic mixture of {D-DKP ester insulin + L-DKP ester insulin}, whereas crystals were not obtained from the L-ester insulin alone even after extensive trials. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin were assayed for receptor binding and in diabetic rats, before and after conversion by saponification to the corresponding DKP insulin enantiomers. L-DKP ester insulin bound weakly to the insulin receptor, while synthetic L-DKP insulin derived from the L-DKP ester insulin intermediate was fully active in binding to the insulin receptor. The D- and L-DKP ester insulins and D-DKP insulin were inactive in lowering blood glucose in diabetic rats, while synthetic L-DKP insulin was fully active in this biological assay. The structural basis of the lack of biological activity of ester insulin is discussed. PMID:23343390

Stereochemical investigations of a novel class of chiral phosphapalladacycle complexes derived from 1-[(2,5-dimethyl)phenyl]ethyldiphenylphosphine.

PubMed

Ng, Joseph Kok-Peng; Li, Yongxin; Tan, Geok-Kheng; Koh, Lip-Lin; Vittal, Jagadese J; Leung, Pak-Hing

2005-12-26

The phosphapalladacycle derived from 1-(2',5'-dimethylphenyl)ethyldiphenylphosphine has been prepared in the optically active and racemic forms. The phosphine was synthesized as a racemate by the treatment of 1-chloro-1-(2',5'-dimethylphenyl)ethane with sodium diphenylphosphide in THF. The racemic phosphapalladacycle was subsequently obtained as the chloro-bridged dimer by the treatment of the phosphine with palladium(II) acetate followed by anion metathesis with lithium chloride. Alternatively, the phosphine could be optically resolved via metal complexation using (R,R)-bis(mu-chloro)bis{1-[1-(N,N-dimethylamino)ethyl]naphthyl-C(2),N}dipalladium(II) as the resolving agent. An efficient separation of the resulting diastereomeric complexes was achieved by silica gel chromatography. The obtained optically resolved diastereomers were next subject to chemoselective removal of the (R)-N,N-(dimethylamino)-1-(1-naphthyl)ethylaminate auxiliary by treatment with concentrated hydrochloric acid. This process yielded the binuclear dimer complexes containing the resolved eta(1)-P ligand. Cyclopalladation of the coordinated phosphine could next be performed by treatment of its eta(1)-P binuclear dimer with silver(I) hexafluorophosphate(V) in a dichloromethane/water mixture followed by treatment with lithium chloride, giving rise to a pair of optically pure enantiomeric dimers with [alpha](D) -322 and +319 degrees in CH(2)Cl(2). Despite the possibilities of the phosphine to attain a five- membered structure by ortho-palladation or a six-membered ring formation by aliphatic C-H bond activation, only the former was observed. X-ray crystallographic data of the meso dimer and an acetylacetonate derivative indicated that the phosphapalladacycle alpha-C methyl substituent was axially located. The 2-D (1)H-(1)H ROESY spectrum of the acetylacetonate derivative further revealed that the phosphapalladacycle was conformationally rigid in CDCl(3).

The change in management of bronchiolitis in the intensive care unit between 2000 and 2015.

PubMed

Mecklin, Minna; Heikkilä, Paula; Korppi, Matti

2018-05-15

This case-control study evaluated interventions for bronchiolitis in relation to time in the pediatric intensive care unit (PICU) during a 16-year surveillance period. Together, 105 infants aged < 12 months were treated for bronchiolitis in the PICU, and for them, we selected 210 controls admitted for bronchiolitis closest to cases. We collected data on treatments in the PICU, at the ward and in the emergency department for three periods: years 2000-2005, 2006-2010, and 2011-2015. Median hospital length of stay for PICU patients were 7 days (interquartile range 5-12), 5 days (4-8) and 8 days (4-12.5, p = 0.127), respectively. By time, the use of inhaled beta-agonist (68 vs. 44 vs. 38%, p = 0.019) and systemic corticosteroids (29 vs. 15 vs. 5%, p = 0.019) decreased, but that of racemic adrenaline (59 vs. 78 vs. 84%, p = 0.035) and hypertonic saline (0 vs. 0 vs. 54%, p < 0.001) inhalations increased in the PICU. Similar changes were seen at the ward. In the PICU, non-invasive ventilation therapies increased significantly, but intubation rates did not decline. Beta-agonists and systemic corticosteroids were used less by time in intensive care for infant bronchiolitis, but the use of hypertonic saline and racemic adrenaline increased, though their effectiveness has been questioned. What is Known: • Until now, studies have shown which treatments do not work in bronchiolitis, and so, there is no consensus how infants with bronchiolitis should be treated. In particular, there is no consensus on different interventions in intensive care for bronchiolitis. What is New: • During 2000-2015, treatments with inhaled beta-agonists and systemic corticosteroids decreased but treatments with racemic adrenaline and hypertonic saline inhalations increased in intensive care for bronchiolitis. Similar changes were seen at the ward. Though non-invasive ventilation therapies increased, the intubation rate did not decline.

Intrinsic chirality and prochirality at Air/R-(+)- and S-(-)-limonene interfaces: spectral signatures with interference chiral sum-frequency generation vibrational spectroscopy.

PubMed

Fu, Li; Zhang, Yun; Wei, Zhe-Hao; Wang, Hong-Fei

2014-09-01

We report in this work detailed measurements of the chiral and achiral sum-frequency vibrational spectra in the C-H stretching vibration region (2800-3050 cm(-1)) of the air/liquid interfaces of R-(+)-limonene and S-(-)-limonene, using the recently developed high-resolution broadband sum-frequency generation vibrational spectroscopy (HR-BB-SFG-VS). The achiral SFG spectra of R-limonene and S-limonene, as well as the RS racemic mixture (50/50 equal amount mixture), show that the corresponding molecular groups of the R and S enantiomers are with the same interfacial orientations. The interference chiral SFG spectra of the limonene enantiomers exhibit a spectral signature from the chiral response of the Cα-H stretching mode, and a spectral signature from the prochiral response of the CH(2) asymmetric stretching mode, respectively. The chiral spectral feature of the Cα-H stretching mode changes sign from R-(+)-limonene to S-(-)-limonene surfaces, and disappears for the RS racemic mixture surface. While the prochiral spectral feature of the CH(2) asymmetric stretching mode is the same for R-(+)-limonene and S-(-)-limonene surfaces, and also surprisingly remains the same for the RS racemic mixture surface. Therefore, the structures of the R-(+)-limonene and the S-(-)-limonene at the liquid interfaces are nevertheless not mirror images to each other, even though the corresponding groups have the same tilt angle from the interfacial normal, i.e., the R-(+)-limonene and the S-(-)-limonene at the surface are diastereomeric instead of enantiomeric. These results provide detailed information in understanding the structure and chirality of molecular interfaces and demonstrate the sensitivity and potential of SFG-VS as a unique spectroscopic tool for chirality characterization and chiral recognition at the molecular interface. © 2014 Wiley Periodicals, Inc.

Effects of molecular chirality on self-assembly and switching in liquid crystals at the cross-over between rod-like and bent shapes.

PubMed

Ocak, Hale; Poppe, Marco; Bilgin-Eran, Belkız; Karanlık, Gürkan; Prehm, Marko; Tschierske, Carsten

2016-09-21

A bent-core compound derived from a 4-cyanoresorcinol core unit with two terephthalate based rod-like wings and carrying chiral 3,7-dimethyloctyloxy side chains has been synthesized in racemic and enantiomerically pure form and characterized by polarizing microscopy, differential scanning calorimetry, X-ray diffraction and electro-optical investigations to study the influence of molecular chirality on the superstructural chirality and polar order in lamellar liquid crystalline phases. Herein we demonstrate that the coupling of molecular chirality with superstructural layer chirality in SmCsPF domain phases (forming energetically distinct diastereomeric pairs) can fix the tilt direction and thus stabilize synpolar order, leading to bistable ferroelectric switching in the SmC* phases of the (S)-enantiomer, whereas tristable modes determine the switching of the racemate. Moreover, the mechanism of electric field induced molecular reorganization changes from a rotation around the molecular long axis in the racemate to a rotation on the tilt-cone for the (S)-enantiomer. At high temperature the enantiomer behaves like a rod-like molecule with a chirality induced ferroelectric SmC* phase and an electroclinic effect in the SmA'* phase. At reduced temperature sterically induced polarization, due to the bent molecular shape, becomes dominating, leading to much higher polarization values, thus providing access to high polarization ferroelectric materials with weakly bent compounds having only "weakly chiral" stereogenic units. Moreover, the field induced alignment of the SmCsPF(()*()) domains gives rise to a special kind of electroclinic effect appearing even in the absence of molecular chirality. Comparison with related compounds indicates that the strongest effects of chirality appear for weakly bent molecules with a relatively short coherence length of polar order, whereas for smectic phases with long range polar order the effects of the interlayer interfaces can override the chirality effects.

Geranylated flavonoids from the roots of Campylotropis hirtella and their immunosuppressive activities.

PubMed

Shou, Qing-Yao; Fu, Run-Zhong; Tan, Qing; Shen, Zheng-Wu

2009-08-12

In an effort to identify new immunosuppressive agents from natural sources, 12 new geranylated flavonoids, 5,7,4'-trihydroxy-3'-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]isoflavone (1), a racemate of 5,7,2',4'-tetrahydroxy-3'-[7-hydroxy-3,7-dimethyl-2(E)-octenyl]isoflavanone (2), 2''(S)-5,7-dihydroxy-[2''-methyl-2''-(4-methyl-3-pentenyl)pyrano]-5'',6'':3',4'-isoflavone (3), (2''S,3''R,4''S)-5,7,3'',4''-tetrahydroxy[2''-methyl-2''-(4-methyl-3-pentenyl)pyrano]-5'',6'':3',4'-isoflavone (4), a racemate of 3'-geranyl-5,7,2',4'-tetrahydroxyisoflavanone (5), a racemate of 3'-geranyl-4'-methoxy-5,7,2'-trihydroxyisoflavanone (6), 3'-geranyl-5,7,4',5'-tetrahydroxyisoflavone (8), 3'-geranyl-5,7,2',5'-tetrahydroxyisoflavone (9), 3'-geranyl-4'-methoxy-5,7,2'-trihydroxyisoflavone (10), 2(R),3(R)-3'-geranyl-2,3-trans-5,7,4'-trihydroxyflavonol (12), (2R,3R)-6-methyl-3'-geranyl-2,3-trans-5,7,4'-trihydroxyflavonol (13), and 5,7-dihydroxy-4'-O-geranylisoflavone (14), were isolated from the roots of Campylotropis hirtella (Franch.) Schindl. together with three previously described flavonoids. Their structures were elucidated by spectroscopic measurements, including two-dimensional nuclear magnetic resonance (NMR) techniques. The immunosuppressive effects of these compounds were assessed using mitogen-induced splenocyte proliferation, and the cytotoxicity of the compounds was also examined. The IC50 values of the compounds were found to be in the range of 1.49-61.23 microM for T lymphocyte suppression and 1.16-73.07 microM for B lymphocyte suppression. An analysis of their structure-activity relationships revealed that an isoflavonoid carbon skeleton with a C10 substituent at the C3' position was necessary for the activity. As many of the compounds exhibited good immunosuppressive activities, they may be promising as novel immunosuppressive agents.

Stereoselective Formation of Mono- and Di-Hydroxylated Polychlorinated Biphenyls by Rat Cytochrome P450 2B1

PubMed Central

Lehmler, Hans-Joachim; Wong, Charles S.

2013-01-01

Changes in atropisomer composition of chiral polychlorinated biphenyls (PCBs) and their mono- and di- hydroxylated metabolites (OH- and diOH-PCBs) via rat cytochrome P450 2B1 (CYP2B1) mediated biotransformation were investigated in vitro. Rat CYP2B1 could stereoselectively biotransform chiral PCBs to generate meta-OH-PCBs as the major metabolites after 60 min incubations. Non-racemic enantiomer fractions (EFs: concentration ratios of the (+)-atropisomer or the first-eluting atropisomer over the total concentrations of two atropisomers) of 5-OH-PCBs, were 0.17, 0.20, 0.85, 0.77 and 0.41 for incubations with PCBs 91, 95, 132, 136 and 149, respectively. CYP-mediated stereoselective formation of diOH-PCBs from OH-PCBs was observed for the first time. After 60 min stereoselective biotransformation, the EFs of both 4-OH-PCB 95 and 5-OH-PCB 95 changed from racemic (i.e., 0.50) to 0.62 and 0.46, respectively. These transformations generated statistically non-racemic 4,5-diOH-PCB 95, with EFs of 0.53 and 0.58 for 4-OH-PCB 95 and 5-OH-PCB 95 incubations, respectively. Biotransformation of PCBs 91 and 136 also generated 4,5-diOH-PCB 91 and 4,5-diOH-PCB 136, respectively. These in vitro results were consistent with that observed for stereoselective PCB biotransformation by rat liver microsomes and in vivo. Biotransformation interference between two atropisomers of PCB 136 was investigated for the first time in this study. The biotransformation process of (−)-PCB 136 was significantly disrupted by the presence of (+)-PCB 136, but not the other way around. Thus, stereoselective metabolism of chiral PCBs and OH-PCBs by CYPs is a major mechanism for atropisomer composition change of PCBs and their metabolites in the environment, with the degree of composition change dependent, at least in part, on stereoselective interference of atropisomers with each other at the enzyme level. PMID:24060104

Chiral Symmetry Breaking and Complete Chiral Purity by Thermodynamic-Kinetic Feedback Near Equilibrium: Implications for the Origin of Biochirality

NASA Astrophysics Data System (ADS)

Viedma, Cristobal

2007-05-01

Chiral symmetry breaking occurs when a physical or chemical process spontaneously generates a large excess of one of the two enantiomers-left-handed (L) or right-handed (D)--with no preference as to which of the two enantiomers is produced. From the viewpoint of energy, these two enantiomers can exist with an equal probability, and inorganic processes that involve chiral products commonly yield a racemic mixture of both. The fact that biologically relevant molecules exist only as one of the two enantiomers is a fascinating example of complete symmetry breaking in chirality and has long intrigued the science community. The origin of this selective chirality has remained a fundamental enigma with regard to the origin of life since the time of Pasteur, some 140 years ago. Here, it is shown that two populations of chiral crystals of left and right hand cannot coexist in solution: one of the chiral populations disappears in an irreversible autocatalytic process that nurtures the other one. Final and complete chiral purity seems to be an inexorable fate in the course of the common process of growth-dissolution. This unexpected chiral symmetry breaking can be explained by the feedback between the thermodynamic control of dissolution and the kinetics of the growth process near equilibrium. This ``thermodynamic-kinetic feedback near equilibrium'' is established as a mechanism to achieve complete chiral purity in solid state from a previously solid racemic medium. The way in which this mechanism could operate in solutions of chiral biomolecules is described. Finally, based on this mechanism, experiments designed to search for chiral purity in a new way are proposed: chiral purity of amino acids or biopolymers is predicted in solid phase from a previously solid racemic medium. This process may have played a key role in the origin of biochirality.

Responses of Cerambycidae and Other Insects to Traps Baited With Ethanol, 2,3-Hexanediol, and 3,2-Hydroxyketone Lures in North-Central Georgia.

PubMed

Miller, D R; Crowe, C M; Mayo, P D; Silk, P J; Sweeney, J D

2015-10-01

In north-central Georgia, 13 species of woodboring beetles (Coleoptera: Cerambycidae: Cerambycinae) were attracted to multiple-funnel traps baited with ethanol and one of the following pheromones: (1) racemic 3-hydroxyhexan-2-one; (2) racemic 3-hydroxyoctan-2-one; and (3) syn-2,3-hexanediol. The following species were attracted to traps baited with ethanol and 3-hydroxyhexan-2-one: Anelaphus pumilus (Newman), Eburia quadrigeminata (Say), Euderces pini (Olivier), Knulliana cincta (Drury), Neoclytus mucronatus (F.), Neoclytus scutellaris (Olivier), and Xylotrechus colonus (F.). Clytus marginicollis Castelnau & Gory, and Anelaphus parallelus (Newman) were attracted to traps baited with ethanol and 3-hydroxyoctan-2-one, whereas traps baited with ethanol and syn-2,3-hexanediol were attractive to Anelaphus villosus (F.), A. parallelus, Neoclytus acuminatus (F.), Neoclytus jouteli jouteli Davis, and Megacyllene caryae (Gahan). Ethanol enhanced catches of seven cerambycid species in traps baited with syn-2,3-hexanediol and 3,2-hydroxyketones. Catches of bark and ambrosia beetles (Curculionidae: Scolytinae) in ethanol-baited traps were largely unaffected by the addition of syn-2,3-hexanediol and 3,2-hydroxyketone lures, except for two species. The mean catches of Hypothenemus rotundicollis Wood & Bright and Dryoxylon onoharaensum (Murayama) in ethanol-baited traps increased and decreased, respectively, with the addition of racemic 3-hydroxyoctan-2-one. Traps baited with ethanol and syn-2,3-hexanediol were attractive to Xylobiops basilaris (Say) (Bostrichidae) and Chariessa pilosa (Forster) (Cleridae), whereas Temnoscheila virescens (F.) (Trogossitidae) were attracted to traps baited with ethanol and 3-hydroxyhexan-2-one. The assassin bug, Apiomerus crassipes (F.) (Hemiptera: Reduviidae), was attracted to traps baited with ethanol and 3,2-hydroxyketones. Published by Oxford University Press on behalf of Entomological Society of America 2015. This work is written by US Government employees and is in the public domain in the US.

The pharmacokinetic behavior of the soy isoflavone metabolite S-(-)equol and its diastereoisomer R-(+)equol in healthy adults determined by using stable-isotope-labeled tracers.

PubMed

Setchell, Kenneth Dr; Zhao, Xueheng; Jha, Pinky; Heubi, James E; Brown, Nadine M

2009-10-01

The nonsteroidal estrogen equol occurs as diastereoisomers, S-(-)equol and R-(+)equol, both of which have significant biological actions. S-(-)equol, the naturally occurring enantiomer produced by 20-30% of adults consuming soy foods, has selective affinity for estrogen receptor-beta, whereas both enantiomers modulate androgen action. Little is known about the pharmacokinetics of the diastereoisomers, despite current interest in developing equol as a nutraceutical or pharmaceutical agent. The objective was to compare the pharmacokinetics of S-(-)equol and R-(+)equol by using [13C] stable-isotope-labeled tracers to facilitate the optimization of clinical studies aimed at evaluating the potential of these diastereoisomers in the prevention and treatment of estrogen- and androgen-dependent conditions. A randomized, crossover, open-label study in 12 healthy adults (6 men and 6 women) compared the plasma and urinary pharmacokinetics of orally administered enantiomeric pure forms of S-(-)[2-13C]equol, R-(+)[2-13C]equol, and the racemic mixture. Plasma and urinary [13C]R-equol and [13C]S-equol concentrations were measured by tandem mass spectrometry. Plasma [13C]equol concentration appearance and disappearance curves showed that both enantiomers were rapidly absorbed, attained high circulating concentrations, and had a similar terminal elimination half-life of 7-8 h. The systemic bioavailability and fractional absorption of R-(+)[2-13C]equol were higher than those of S-(-)[2-13C]equol or the racemate. The pharmacokinetics of racemic (+/-)[2-13C]equol were different from those of the individual enantiomers: slower absorption, lower peak plasma concentrations, and lower systemic bioavailability. The high bioavailability of both diastereoisomers contrasts with previous findings for the soy isoflavones daidzein and genistein, both of which have relatively poor bioavailability, and suggests that low doses of equol taken twice daily may be sufficient to achieve biological effects.

Kinetic resolution of racemic α-hydroxyphosphonates by asymmetric esterification using achiral carboxylic acids with pivalic anhydride and a chiral acyl-transfer catalyst.

PubMed

Shiina, Isamu; Ono, Keisuke; Nakahara, Takayoshi

2013-11-25

A practical protocol is developed to directly provide chiral α-acyloxyphosphonates and α-hydroxyphosphonates from (±)-α-hydroxyphosphonates utilizing the transacylation process to generate the mixed anhydrides from acid components and pivalic anhydride in the presence of organocatalysts (s-value = 33-518).

Experiments on the origins of optical activity. [in amino acids

NASA Technical Reports Server (NTRS)

Bonner, W. A.; Flores, J. J.

1975-01-01

An investigation was conducted concerning the asymmetric adsorption of phenylalanine enantiomers by kaolin. No preferential adsorption of either phenylalanine enantiomer could be detected and there was no resolution of the racemic phenylalanine by kaolin. The attempted asymmetric polymerization of aspartic acid by kaolin is also discussed along with a strontium-90 bremsstrahlung radiolysis of leucine.

Enantioselective Photochemical Organocascade Catalysis

PubMed Central

Woźniak, Łukasz; Magagnano, Giandomenico

2017-01-01

Abstract Reported herein is a photochemical cascade process that combines the excited‐state and ground‐state reactivity of chiral organocatalytic intermediates. This strategy directly converts racemic cyclopropanols and α,β‐unsaturated aldehydes into stereochemically dense cyclopentanols with exquisite stereoselectivity. Mechanistic investigations have enabled elucidating the origin of the stereoconvergence, which is governed by a kinetic resolution process. PMID:29205718

4,5-Dibromo-2,7-di-tert-butyl-9,9-dimethyl-9H-thioxanthene

PubMed Central

Rubio, Omayra H.; Fuentes de Arriba, Angel L.; Sanz, Francisca; Muniz, Francisco M.; Morán, Joaquín R.

2012-01-01

In the title compound, C23H28Br2S, the thioxanthene unit is twisted, showing a dihedral angle of 29.3 (5)° between the benzene rings. When projected along [001], the packing shows two types of channels. The crystal studied was a racemic twin. PMID:22719586

Transition-Metal Catalysis of Nucleophilic Substitution Reactions: A Radical Alternative to SN1 and SN2 Processes.

PubMed

Fu, Gregory C

2017-07-26

Classical methods for achieving nucleophilic substitutions of alkyl electrophiles (S N 1 and S N 2) have limited scope and are not generally amenable to enantioselective variants that employ readily available racemic electrophiles. Radical-based pathways catalyzed by chiral transition-metal complexes provide an attractive approach to addressing these limitations.

Transition-Metal Catalysis of Nucleophilic Substitution Reactions: A Radical Alternative to SN1 and SN2 Processes

PubMed Central

2017-01-01

Classical methods for achieving nucleophilic substitutions of alkyl electrophiles (SN1 and SN2) have limited scope and are not generally amenable to enantioselective variants that employ readily available racemic electrophiles. Radical-based pathways catalyzed by chiral transition-metal complexes provide an attractive approach to addressing these limitations. PMID:28776010

21 CFR 172.540 - DL-Alanine.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Agents and Related Substances § 172.540 DL-Alanine. DL-Alanine (a racemic mixture of D- and L-alanine; CAS Reg. No. 302-72-7) may be safely used as a flavor enhancer for sweeteners in pickling mixtures at a level not to exceed 1 percent of the pickling spice that is added to the pickling brine. [56 FR...

Field Response of Dendroctonus frontalis (Coleoptera: Scolytinae) to Synthetic Semiochemicals in Chiapas, Mexico.

Treesearch

Benjamin Moreno; Jorge Macias; Brian Sullivan; Stephen Clarke

2008-01-01

Dendroctonus frontalis Zimmermann (Coleoptera: Scolytinae) is the most serious pestof pines (Pinus spp.) in Mexico. ConspeciÞcs are attracted to trees undergoing colonization by the  aggregation pheromone frontalin, which is synergized by odors of pine oleoresin released from beetle-damaged host tissue. Synthetic racemic frontalin combined with turpentine has been the...

Direct HPLC separation of beta-aminoester enantiomers on totally synthetic chiral stationary phases.

PubMed

Gasparrini, F; D'Acquarica, I; Villani, C; Cimarelli, C; Palmieri, G

1997-01-01

The direct separation of beta-aminoester enantiomers by HPLC on synthetic chiral stationary phases based on a pi-acidic derivative of trans 1,2-diaminocyclohexane as selector is described. The application of different columns containing the stationary phase with opposite configurations and in the racemic form to the determination of enantiomeric excess in chemically impure samples is demonstrated.

The optical nature of methylsuccinic acid in human urine

NASA Technical Reports Server (NTRS)

Zeitman, B.; Lawless, J. G.

1975-01-01

Methylsuccinic acid was isolated from human urine, derivatized as the di-S-(+)-2-butyl ester, and analyzed using a gas chromatographic system capable of separating the enantiomers of the derivative. The R-(+)-isomer was found to be present. Methylsuccinic acid is potentially important as a criterion for abiogenicity, having been obtained as a racemic mixture from sources known to be abiotic.

Anti-cancer agents based on 6-trifluoromethoxybenzimidazole derivatives and method of making

DOEpatents

Gakh, Andrei A.; Vovk, Mykhaylo V.; Mel'nychenko, Nina V.; Sukach, Volodymyr A.

2012-08-14

The present disclosure relates to novel compounds having the structural Formulas (1a,1b), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof as chemotherapy agents for treating of cancer, particularly androgen-independent prostate cancer. The disclosure also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

Anti-cancer agents based on 6-trifluoromethoxybenzimidazole derivatives and method of making

DOEpatents

Gakh, Andrei A; Vovk, Mykhaylo V; Mel& #x27; nychenko, Nina V; Sukach, Volodymyr A

2012-10-23

The present disclosure relates to novel compounds having the structural Formulas (1a,1b), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof as chemotherapy agents for treating of cancer, particularly androgen-independent prostate cancer. The disclosure also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

Aminostratigraphy of Organisms in Antarctic and Siberian Permafrost Cores

NASA Technical Reports Server (NTRS)

Brinton, K. L. F.; Tsapin, A. I.; McDonald, G. D.; Gilichinsky, D.

1999-01-01

Amino acid racemization dating (or aminostratigraphy) in Antarctic and Siberian permafrost core samples can be used to evaluate the age of organisms in frozen environments. The potential for subsurface permafrost on Mars makes terrestrial permafrost an important source of information regarding the preservation of both living organisms and their remains. Additional information is contained in the original extended abstract.

Native chemical ligation at Asx-Cys, Glx-Cys: chemical synthesis and high-resolution X-ray structure of ShK toxin by racemic protein crystallography.

PubMed

Dang, Bobo; Kubota, Tomoya; Mandal, Kalyaneswar; Bezanilla, Francisco; Kent, Stephen B H

2013-08-14

We have re-examined the utility of native chemical ligation at -Gln/Glu-Cys- [Glx-Cys] and -Asn/Asp-Cys- [Asx-Cys] sites. Using the improved thioaryl catalyst 4-mercaptophenylacetic acid (MPAA), native chemical ligation could be performed at -Gln-Cys- and Asn-Cys- sites without side reactions. After optimization, ligation at a -Glu-Cys- site could also be used as a ligation site, with minimal levels of byproduct formation. However, -Asp-Cys- is not appropriate for use as a site for native chemical ligation because of formation of significant amounts of β-linked byproduct. The feasibility of native chemical ligation at -Gln-Cys- enabled a convergent total chemical synthesis of the enantiomeric forms of the ShK toxin protein molecule. The D-ShK protein molecule was ~50,000-fold less active in blocking the Kv1.3 channel than the L-ShK protein molecule. Racemic protein crystallography was used to obtain high-resolution X-ray diffraction data for ShK toxin. The structure was solved by direct methods and showed significant differences from the previously reported NMR structures in some regions of the ShK protein molecule.

Thyroxine revisited.

PubMed

Katrusiak, Andrzej; Katrusiak, Anna

2004-12-01

The crystal structure of the common therapeutic agent, the pentahydrated sodium salt of L-thyroxine hormone (3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]-L-alanine), has been determined and discussed in relation to the drug's stability. The stoichiometry and absolute configuration (-)-C(8)S-[C15H10I4NO4]-.Na+.5H2O have been confirmed. The crystals are built of a three-dimensional supramolecular network with two symmetry-independent L-thyroxine anions, in two distinct conformations not previously reported, linked by strong NH-O hydrogen bonds into dimers. Two independent sodium cations are fivefold and sixfold coordinated. The cations and two independent water molecules not involved in coordinating the Na cations form sheets along the crystallographic (001) planes. The presence of differently coordinated cations and non-coordinating water molecules may be responsible for water transport and loss, for decay of the crystals, and subsequent low stability of the drug. Only a conglomerate could be obtained when racemic sodium thyroxine was crystallized from ethanol and methanol solutions by evaporation, which explains the equal penta-hydration of the sodium salts of enantiomorphic and racemic thyroxine, and the fact that there are no apparent differences in their stability. (c) 2004 Wiley-Liss, Inc. and the American Pharmacists Association

Ultra-broad polypyrrole (PPy) nano-ribbons seeded by racemic surfactants aggregates and their high-performance electromagnetic radiation elimination.

PubMed

Jiao, Yingzhi; Wu, Fan; Zhang, Kun; Sun, Mengxiao; Xie, Aming; Dong, Wei

2017-08-04

Ribbon-like nano-structures possess high aspect ratios, and thus have great potential in the development of high-performance microwave absorption (MA) materials that can effectively eliminate adverse electromagnetic radiation. However, these nano-structures have been scarcely constructed in the field of MA, because of the lack of efficient synthetic routes. Herein, we developed an efficient method to successfully construct polypyrrole (PPy) nano-ribbons using the self-assembly aggregates of a racemic surfactant as the seeds. The frequency range with a reflection loss value of lower than -10 dB reached 7.68 GHz in the frequency range of 10.32-18.00 GHz, and surpassed all the currently reported PPy nano-structures, as well as most other MA nano-materials. Through changing the amount of surfactant, both the nano-structures and MA performance can be effectively regulated. Furthermore, the reason behind the high-performance MA of PPy nano-ribbons has been deeply explored. It opens up the opportunity for the application of conducting polymer nano-ribbons as a lightweight and tunable high-performance MA material, especially in applications of special aircraft and flexible electronics.

Effect of release rate and enantiomeric composition on response to pheromones of Megaplatypus mutatus (Chapuis) in poplar plantations of Argentina and Italy.

PubMed

Funes, Hernán; Zerba, Eduardo; Gonzalez-Audino, Paola

2013-10-01

Megaplatypus mutatus (=Platypus sulcatus Chapuis) is an Ambrosia beetle native to South America, which was recently introduced in Italy and its presence there is causing severe damage to the local poplar plantations. The male M. mutatus pheromone is composed of (S)-(+)-6-methyl-5-hepten-2-ol [(+)-sulcatol], 6-methyl-5-hepten-2-one (sulcatone) and 3-pentanol. A series of field trials testing dose, blend and enantiomer composition performed in Argentina and Italy evaluated attraction and found that the optimal release rate of pheromone components as baits in cross vane baited traps (CIPEIN-CV) was 6, 6 and 30 mg day−1 of sulcatone, (+)-sulcatol and 3-pentanol, respectively. It was also determined that racemic sulcatol is as effective as the pure (+)-isomer for the purpose of beetle catch, due to the inert nature of the (−)-isomer allowing the usage of low cost racemic sulcatol instead of highly expensive (+)-sulcatol. The results of our work contribute to the development of pheromone-based local technologies with low environmental impact and low cost for control or monitoring of an important pest.

Chiral-catalyst-based convergent synthesis of HIV protease inhibitor GRL-06579A.

PubMed

Mihara, Hisashi; Sohtome, Yoshihiro; Matsunaga, Shigeki; Shibasaki, Masakatsu

2008-02-01

Catalytic asymmetric synthesis of GRL-06579A (1), an HIV-1 protease inhibitor effective against multi-protease-inhibitor-resistant viruses, is described. A convergent strategy that utilizes heterobimetallic multifunctional catalysts developed in our group is a key feature of the synthesis. The chirality of the bicyclic tetrahydrofuran unit of 1 was introduced through Al-Li-bis(binaphthoxide) (ALB) catalyst-controlled Michael addition of dimethyl malonate to racemic 4-O-protected cyclopentenone. ALB afforded not only the trans adduct with up to 96% ee from a matched substrate through kinetic resolution, but also the cis adduct with 99% ee through a catalyst-controlled Michael addition to a mismatched substrate. The Michael addition to produce the unusual cis adduct is described in detail. The framework of the bicyclic tetrahydrofuran was constructed by an intramolecular oxy-Michael reaction. The amino alcohol unit was constructed by an La-Li3-tris(binaphthoxide) (LLB)-catalyzed diastereoselective nitroaldol reaction of N-Boc aldehyde (Boc = tert-butoxycarbonyl) derived from L-phenylalanine. LLB promoted the nitroaldol reaction without racemization of the chiral aldehyde to give the nitroaldol adduct in 85% yield and with 93:7 diastereoselectivity and over 99% ee.

The radiolysis and radioracemization of amino acids on silica surfaces

NASA Technical Reports Server (NTRS)

Bonner, W. A.; Lemmon, R. M.

1981-01-01

Results are presented of experiments on the radioracemization of amino acids in the presence of silica surfaces such as may have been found on the prebiotic earth. L-leucine and a DL-leucine mixture deposited on samples of 1-quartz and an amorphous silica preparation (Syloid 63) was subjected to Co-60 gamma-ray irradiation, then analyzed by gas chromatography to determine the radiolysis and racemization rates. The quartz surface is found to have a marginal efficacy in enhancing radiolysis when compared with a crystalline L-leucine control, although enhancing radioracemization symmetrically by a factor of two. Both the radiolysis and radioracemization of L-leucine and DL-leucine on a Syloid-63 silica surface are observed to increase with increasing radiation dose, and to be substantially greater than in the crystalline controls. Additional experiments with the nonprotein amino acid isovaline deposited on Syloid 63 confirm the greater radiolysis susceptibility of amino acids deposited on silica with respect to the crystalline state, although racemization is not observed. The observations suggest that the presence of a silica surface would have a deleterious effect on any mechanism for the origin of molecular chirality relying on stereoselective beta-radiolysis.

Thz Spectroscopy and DFT Modeling of Intermolecular Vibrations in Hydrophobic Amino Acids

NASA Astrophysics Data System (ADS)

Williams, michael R. C.; Aschaffenburg, Daniel J.; Schmuttenmaer, Charles A.

2013-06-01

Vibrations that involve intermolecular displacements occur in molecular crystals at frequencies in the 0.5-5 THz range (˜15-165 cm^{-1}), and these motions are direct indicators of the interaction potential between the molecules. The intermolecular potential energy surface of crystalline hydrophobic amino acids is inherently interesting simply because of the wide variety of forces (electrostatic, dipole-dipole, hydrogen-bonding, van der Waals) that are present. Furthermore, an understanding of these particular interactions is immediately relevant to important topics like protein conformation and pharmaceutical polymorphism. We measured the low-frequency absorption spectra of several polycrystalline hydrophobic amino acids using THz time-domain spectroscopy, and in addition we carried out DFT calculations using periodic boundary conditions and an exchange-correlation functional that accounts for van der Waals dispersion forces. We chose to investigate a series of similar amino acids with closely analogous unit cells (leucine, isoleucine, and allo-isoleucine, in racemic or pseudo-racemic mixtures). This allows us to consider trends in the vibrational spectra as a function of small changes in molecular arrangement and/or crystal geometry. In this way, we gain confidence that peak assignments are not based on serendipitous similarities between calculated and observed features.

Controlled synthesis and chiral recognition of immobilized cellulose and amylose tris(cyclohexylcarbamate)s/3-(triethoxysilyl)propylcarbamates as chiral packing materials for high-performance liquid chromatography.

PubMed

Shen, Jun; Liu, Shuangyan; Li, Pengfei; Shen, Xiande; Okamoto, Yoshio

2012-07-13

The cyclohexylcarbamates of cellulose and amylose bearing a controlled amount of 3-(triethoxysilyl)propyl residue were synthesized by a one-pot process and efficiently immobilized onto silica gel through the intermolecular polycondensation of triethoxysilyl group. Their chiral recognition abilities were evaluated as chiral packing materials (CPMs) for high-performance liquid chromatography (HPLC). The immobilized CPMs exhibited comparable or higher recognition abilities than the conventional coated-type CPMs. The universal solvent compatibility of the immobilized CPMs clearly contributes to the improvement of chiral recognition for most racemates used in the present study. Interestingly, a significantly improved resolution for racemic trans-stilbene oxide (α=2.23) could be attained on the immobilized CPM using the eluent containing 30 vol.% chloroform in hexane, which cannot be used for the conventional coated-type CPMs. On the CPMs, almost no resolution of trans-stilbene oxide was attained by a typical eluent, hexane-2-propanol mixture (90/10, v/v). The novel immobilized CPM can also be used in thin-layer chromatography (TLC) due to the absence of an aromatic group. Copyright © 2012 Elsevier B.V. All rights reserved.

Enrichment of Non-Terrestrial L-Proteinogenic Amino Acids by Aqueous Alteration on the Tagish Lake Meteorite Parent Body

NASA Technical Reports Server (NTRS)

Glavin, Daniel P.; Elsila, Jamie E.; Burton, Aaron S.; Callahan, Michael P.; Dworkin, Jason P.; Herd, Christopher D. K.

2012-01-01

The distribution and isotopic and enantiomeric compositions of amino acids found in three distinct fragments of the Tagish Lake C2-type carbonaceous chondrite were investigated via liquid chromatography fluorescence detection time-of-flight mass spectrometry and gas chromatography isotope ratio mass spectrometry. Large L-enantiomeric excesses (L(sub ee) approx. 43 to 59%) of the a-hydrogen aspartic and glutamic amino acids were measured in Tagish Lake, whereas alanine, another alpha-hydrogen protein amino acid, was found to be nearly racemic (D approx. L) using both techniques. Carbon isotope measurements of D- and L-aspartic acid and D- and L-alanine in Tagish Lake fall well outside of the terrestrial range and indicate that the measured aspartic acid enantioenrichment is indigenous to the meteorite. Alternate explanations for the Lexcesses of aspartic acid such as interference from other compounds present in the sample, analytical biases, or terrestrial amino acid contamination were investigated and rejected. These results can be explained by differences in the solid-solution phase behavior of aspartic acid, which can form conglomerate enantiopure solids during crystallization, and alanine, which can only form racemic crystals.

Age estimation based on aspartic acid racemization in elastin from the yellow ligaments.

PubMed

Ritz-Timme, S; Laumeier, I; Collins, M

2003-04-01

The yellow ligaments of the spine are characterized by an exceptionally high content of elastin, a protein with a proved longevity in several human tissues. This unique biochemical composition suggested a suitability of yellow ligaments for age estimation based on aspartic acid racemization (AAR), which was tested by determination of AAR in total tissue specimens and in purified elastin from yellow ligaments of individuals of known age. AAR was found to increase with age in both sample sets. The purified elastin samples exhibited a much faster kinetics than the total tissue, with ca. 3.7-4.6-fold higher apparent rates. The relationship between AAR and age was much closer in the purified elastin samples ( r=0.96-0.99) and it can therefore be used as a basis for biochemical age estimation. The analysis of total tissue samples cannot be recommended since the AAR values can be strongly influenced even by slight, histologically non-detectable variations in the collagen content. Age estimation based on AAR in purified elastin from yellow ligaments may be a valuable additional tool in the identification of unidentified cadavers, especially in cases where other methods cannot be applied (e.g. no available teeth, body parts).

Chemical chiral pollution: Impact on the society and science and need of the regulations in the 21st century.

PubMed

Basheer, Al Arsh

2018-04-01

The chiral pollution is a serious issue for our health and environment due to the enantio-selective biodegradation of the chiral pollutants. It has adverse impact on our society and science. There is a big loss of our economy due to the use of racemic agrochemicals. The most notorious chiral pollutants are pesticides, polychloro biphenyls, polyaromatic hydrocarbons, brominated flame retardants, drugs, and pharmaceuticals. More than 1500 chiral pollutants are present in the environment. Unfortunately, there is no regulation and control of the chiral pollutants. Therefore, it is an urgent need of the present 21st century to develop a data bank on the chiral pollutants, guidelines for controlling the production, sale and use of the racemic agrochemicals and the other industrial products. The Governments of the different countries should come forward to initiate the regulations. US, FDA, US EPA, and WHO are the most important regulatory authorities and should think about the chiral pollutants. The present article highlights the impact of the chiral pollution on the society and science. Besides, the efforts have also been made to emphasize the need of the regulations to control the chiral pollution. © 2017 Wiley Periodicals, Inc.

Preparative and mechanistic studies toward the rational development of catalytic, enantioselective selenoetherification reactions.

PubMed

Denmark, Scott E; Kalyani, Dipannita; Collins, William R

2010-11-10

A systematic investigation into the Lewis base catalyzed, asymmetric, intramolecular selenoetherification of olefins is described. A critical challenge for the development of this process was the identification and suppression of racemization pathways available to arylseleniranium ion intermediates. This report details a thorough study of the influences of the steric and electronic modulation of the arylselenenyl group on the configurational stability of enantioenriched seleniranium ions. These studies show that the 2-nitrophenyl group attached to the selenium atom significantly attenuates the racemization of seleniranium ions. A variety of achiral Lewis bases catalyze the intramolecular selenoetherification of alkenes using N-(2-nitrophenylselenenyl)succinimide as the electrophile along with a Brønsted acid. Preliminary mechanistic studies suggest the intermediacy of ionic Lewis base-selenium(II) adducts. Most importantly, a broad survey of chiral Lewis bases revealed that 1,1'-binaphthalene-2,2'-diamine (BINAM)-derived thiophosphoramides catalyze the cyclization of unsaturated alcohols in the presence of N-(2-nitrophenylselenenyl)succinimide and methanesulfonic acid. A variety of cyclic seleno ethers were produced in good chemical yields and in moderate to good enantioselectivities, which constitutes the first catalytic, enantioselective selenofunctionalization of unactivated olefins.

Effect of chirality and lipophilicity in the functional activity of evodiamine and its analogues at TRPV1 channels.

PubMed

De Petrocellis, Luciano; Schiano Moriello, Aniello; Fontana, Gabriele; Sacchetti, Alessandro; Passarella, Daniele; Appendino, Giovanni; Di Marzo, Vincenzo

2014-05-01

Evodiamine, a racemic quinazolinocarboline alkaloid isolated from the traditional Chinese medicine Evodiae fructus, has been reported to act as an agonist of the transient receptor potential vanilloid type-1 (TRPV1) cation channel both in vitro and in vivo. Evodiamine is structurally different from all known TRPV1 activators, and has significant clinical potential as a thermogenic agent. Nevertheless, the molecular bases for its actions are still poorly understood. To investigate the structure-activity relationships of evodiamine, the natural racemate was resolved, and a series of 23 synthetic analogues was prepared, using as the end point the intracellular Ca(2+) elevation in HEK-293 cells stably overexpressing either the human or the rat recombinant TRPV1. S-(+) evodiamine was more efficacious and potent than R-(-) evodiamine, and a new potent lead (Evo30) was identified, more potent than the reference TRPV1 agonist, capsaicin. In general, potency and efficacy correlated with the lipophilicity of the analogues. Like other TRPV1 agonists, several synthetic analogues could efficiently desensitize TRPV1 to activation by capsaicin. Evodiamine qualifies as structurally unique lead structure to develop new potent TRPV1 agonists/desensitizers. © 2013 The British Pharmacological Society.

Ultra-broad polypyrrole (PPy) nano-ribbons seeded by racemic surfactants aggregates and their high-performance electromagnetic radiation elimination

NASA Astrophysics Data System (ADS)

Jiao, Yingzhi; Wu, Fan; Zhang, Kun; Sun, Mengxiao; Xie, Aming; Dong, Wei

2017-08-01

Ribbon-like nano-structures possess high aspect ratios, and thus have great potential in the development of high-performance microwave absorption (MA) materials that can effectively eliminate adverse electromagnetic radiation. However, these nano-structures have been scarcely constructed in the field of MA, because of the lack of efficient synthetic routes. Herein, we developed an efficient method to successfully construct polypyrrole (PPy) nano-ribbons using the self-assembly aggregates of a racemic surfactant as the seeds. The frequency range with a reflection loss value of lower than -10 dB reached 7.68 GHz in the frequency range of 10.32-18.00 GHz, and surpassed all the currently reported PPy nano-structures, as well as most other MA nano-materials. Through changing the amount of surfactant, both the nano-structures and MA performance can be effectively regulated. Furthermore, the reason behind the high-performance MA of PPy nano-ribbons has been deeply explored. It opens up the opportunity for the application of conducting polymer nano-ribbons as a lightweight and tunable high-performance MA material, especially in applications of special aircraft and flexible electronics.

Binding of [alpha, alpha]-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ilies, Monica; Di Costanzo, Luigi; Dowling, Daniel P.

Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of {alpha},{alpha}-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase Imore » and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional {alpha}-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase.« less

Enantioconvergent production of (R)-1-phenyl-1,2-ethanediol from styrene oxide by combining the Solanum tuberosum and an evolved Agrobacterium radiobacter AD1 epoxide hydrolases.

PubMed

Cao, Li; Lee, Jintae; Chen, Wilfred; Wood, Thomas K

2006-06-20

Soluble epoxide hydrolase (EH) from the potato Solanum tuberosum and an evolved EH of the bacterium Agrobacterium radiobacter AD1, EchA-I219F, were purified for the enantioconvergent hydrolysis of racemic styrene oxide into the single product (R)-1-phenyl-1,2-ethanediol, which is an important intermediate for pharmaceuticals. EchA-I219F has enhanced enantioselectivity (enantiomeric ratio of 91 based on products) for converting (R)-styrene oxide to (R)-1-phenyl-1,2-ethanediol (2.0 +/- 0.2 micromol/min/mg), and the potato EH converts (S)-styrene oxide primarily to the same enantiomer, (R)-1-phenyl-1,2-ethanediol (22 +/- 1 micromol/min/mg), with an enantiomeric ratio of 40 +/- 17 (based on substrates). By mixing these two purified enzymes, inexpensive racemic styrene oxide (5 mM) was converted at 100% yield to 98% enantiomeric excess (R)-1-phenyl-1,2-ethanediol at 4.7 +/- 0.7 micromol/min/mg. Hence, at least 99% of substrate is converted into a single stereospecific product at a rapid rate. 2006 Wiley Periodicals, Inc.

Structural and functional characterization of the enantiomers of the antischistosomal drug oxamniquine

DOE PAGES

Taylor, Alexander B.; Pica-Mattoccia, Livia; Polcaro, Chiara M.; ...

2015-10-20

For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. mansoni sulfotransferase (SmSULT) was identified as the target of OXA action. Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, whilemore » R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA•SmSULT and S-OXA•SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA. Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. In conclusion, these findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds.« less

(±)-MDMA and its enantiomers: potential therapeutic advantages of R(-)-MDMA.

PubMed

Pitts, Elizabeth G; Curry, Daniel W; Hampshire, Karly N; Young, Matthew B; Howell, Leonard L

2018-02-01

The use of (±)-3,4-methylenedioxymethamphetamine ((±)-MDMA) as an adjunct to psychotherapy in the treatment of psychiatric and behavioral disorders dates back over 50 years. Only in recent years have controlled and peer-reviewed preclinical and clinical studies lent support to (±)-MDMA's hypothesized clinical utility. However, the clinical utility of (±)-MDMA is potentially mitigated by a range of demonstrated adverse effects. One potential solution could lie in the individual S(+) and R(-) enantiomers that comprise (±)-MDMA. Individual enantiomers of racemic compounds have been employed in psychiatry to improve a drug's therapeutic index. Although no research has explored the individual effects of either S(+)-MDMA or R(-)-MDMA in humans in a controlled manner, preclinical research has examined similarities and differences between the two molecules and the racemic compound. This review addresses information related to the pharmacodynamics, neurotoxicity, physiological effects, and behavioral effects of S(+)-MDMA and R(-)-MDMA that might guide preclinical and clinical research. The current preclinical evidence suggests that R(-)-MDMA may provide an improved therapeutic index, maintaining the therapeutic effects of (±)-MDMA with a reduced side effect profile, and that future investigations should investigate the therapeutic potential of R(-)-MDMA.

Performance of soil-applied FeEDDHA isomers in delivering Fe to soybean plants in relation to the moment of application.

PubMed

Schenkeveld, Walter D C; Reichwein, Arjen M; Bugter, Marcel H J; Temminghoff, Erwin J M; van Riemsdijk, Willem H

2010-12-22

FeEDDHA (iron(3+) ethylenediamine-N,N'-bis(hydroxyphenylacetic acid) products are commonly applied to mend and prevent Fe deficiency chlorosis in soil-grown crops. Plants mainly take up Fe in the progressed vegetative and in the reproductive stages. This study examined which of the principal constituents of FeEDDHA products (the isomers racemic o,o-FeEDDHA, meso o,o-FeEDDHA, and o,p-FeEDDHA), most effectively meets the Fe requirements of soybean plants (Glycine max (L.) Merr.) grown on calcareous soil in the aforementioned growth stages. FeEDDHA isomers were applied once, separately or in mixtures, at t = 0, in the progressed vegetative stage or in the reproductive stage. o,p-FeEDDHA did not significantly contribute to Fe uptake in either growth stage. Both racemic and meso o,o-FeEDDHA were effective in supplying plants with Fe, approximately to the same extent. The moment of application had a significant effect on yield and FeEDDHA pore water concentrations at harvest, but not on Fe uptake. To optimize yield while minimizing FeEDDHA dosage, FeEDDHA is best applied to soybean plants prior to the onset of chorosis.

Search for extraterrestrial life using chiral molecules: mandelate racemase as a test case.

PubMed

Thaler, Tracey L; Gibbs, Phillip R; Trebino, Rick P; Bommarius, Andreas S

2006-12-01

We have investigated an enzymatic racemization reaction as a marker for extraterrestrial life, which resulted in a change in optical rotation of a mandelic acid over time, as measured by polarimetry. Mandelate racemase was active in aqueous buffer in a temperature range between 0 degrees C and 70 degrees C and also in concentrated ammonium salt solutions and water-in-oil microemulsions in a temperature range between -30 degrees C and 60-70 degrees C; however, the enzyme was not active in several organic cryosolvents. Thus, we have demonstrated that concentrated ammonium salt solutions and water-in-oil microemulsions, both of which are able to form on extraterrestrial planets and moons in the presence of liquid water, are suitable media for enzyme reactions at subzero temperatures. Kinetic data for the mandelate racemase reaction obtained by polarimetry, while reproducible and internally consistent, differed significantly from several sets of data obtained previously by other methods such as chromatography and hydrogen-deuterium exchange. However, we conclude that reactions yielding a polarimetric signal, such as the racemizations employed in this work, are suitable mechanisms by which to utilize a change in chirality over time as a tool to detect signs of life.

Enzyme catalysis with small ionic liquid quantities.

PubMed

Fischer, Fabian; Mutschler, Julien; Zufferey, Daniel

2011-04-01

Enzyme catalysis with minimal ionic liquid quantities improves reaction rates, stereoselectivity and enables solvent-free processing. In particular the widely used lipases combine well with many ionic liquids. Demonstrated applications are racemate separation, esterification and glycerolysis. Minimal solvent processing is also an alternative to sluggish solvent-free catalysis. The method allows simplified down-stream processing, as only traces of ionic liquids have to be removed.

Enzymatic Resolution of 1-Phenylethanol and Formation of a Diastereomer: An Undergraduate [superscript 1]H NMR Experiment to Introduce Chiral Chemistry

ERIC Educational Resources Information Center

Faraldos, Juan A.; Giner, Jos-Luis; Smith, David H.; Wilson, Mark; Ronhovde, Kyla; Wilson, Erin; Clevette, David; Holmes, Andrea E.; Rouhier, Kerry

2011-01-01

This organic laboratory experiment introduces students to stereoselective enzyme reactions, resolution of enantiomers, and NMR analysis of diastereomers. The reaction between racemic 1-phenylethanol and vinyl acetate in hexane to form an ester is catalyzed by acylase I. The unreacted alcohol is then treated with a chiral acid and the resulting…

Silica-Immobilized Enzyme Reactors (Postprint)

DTIC Science & Technology

2007-09-01

mode of action of drugs such as aspirin and ibuprofen .[61] Serotonin reuptake inhibitors and monoamine oxidase inhibitors can function as...immobilizing PGA onto chromatography supports and using the enantiomeric selectivity of the enzyme to resolve racemic mixtures.[100] Immobilization onto...column. J. Chroma- togr. B. Biomed. Sci. Appl. 2001, 753, 375–383. 37. Jadaud, P.; Wainer, I.W. The stereochemical resolution of the enantiomers of

Enantioselective Photochemical Organocascade Catalysis.

PubMed

Woźniak, Łukasz; Magagnano, Giandomenico; Melchiorre, Paolo

2018-01-22

Reported herein is a photochemical cascade process that combines the excited-state and ground-state reactivity of chiral organocatalytic intermediates. This strategy directly converts racemic cyclopropanols and α,β-unsaturated aldehydes into stereochemically dense cyclopentanols with exquisite stereoselectivity. Mechanistic investigations have enabled elucidating the origin of the stereoconvergence, which is governed by a kinetic resolution process. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Enantioselective Reduction of Ketones and Imines Catalyzed by (CN-Box)Re(V)-Oxo Complexes

PubMed Central

Nolin, Kristine A.; Ahn, Richard W.; Kobayashi, Yusuke; Kennedy-Smith, Joshua J.

2012-01-01

The development and application of chiral, non-racemic Re(V)-oxo complexes to the enantioselective reduction of prochiral ketones is described. In addition to the enantioselective reduction of prochiral ketones, we report the application of these complexes to (1) a tandem Meyer-Schuster rearrangement/reduction to access enantioenriched allylic alcohols and (2) the enantioselective reduction of imines. PMID:20623567

Recent advances in biotechnological applications of alcohol dehydrogenases.

PubMed

Zheng, Yu-Guo; Yin, Huan-Huan; Yu, Dao-Fu; Chen, Xiang; Tang, Xiao-Ling; Zhang, Xiao-Jian; Xue, Ya-Ping; Wang, Ya-Jun; Liu, Zhi-Qiang

2017-02-01

Alcohol dehydrogenases (ADHs), which belong to the oxidoreductase superfamily, catalyze the interconversion between alcohols and aldehydes or ketones with high stereoselectivity under mild conditions. ADHs are widely employed as biocatalysts for the dynamic kinetic resolution of racemic substrates and for the preparation of enantiomerically pure chemicals. This review provides an overview of biotechnological applications for ADHs in the production of chiral pharmaceuticals and fine chemicals.

Metal-free one-pot oxidative amination of aldehydes to amides.

PubMed

Ekoue-Kovi, Kekeli; Wolf, Christian

2007-08-16

Metal-free oxidative amination of aromatic aldehydes in the presence of TBHP provides convenient access to amides in 85-99% under mild reaction conditions within 5 h. This method avoids free carboxylic acid intermediates and integrates aldehyde oxidation and amide bond formation, which are usually accomplished separately, into a single operation. Proline-derived amides can be prepared in excellent yields without noticeable racemization.

(R)-albuterol for asthma: pro [a.k.a. (S)-albuterol for asthma: con].

PubMed

Ameredes, Bill T; Calhoun, William J

2006-11-01

Is there scientific evidence to support the replacement of the beta-agonist racemic albuterol with levalbuterol--that is, (R)-albuterol? The argument presented further refines the question as "Do we wish to continue to treat asthma with a mixture of albuterol, of which half is an agent with no known benefit--that is, (S)-albuterol--and which may exacerbate the disease?"

Stereodivergent Synthesis of Chromanones and Flavanones via Intramolecular Benzoin Reaction.

PubMed

Wen, Genfa; Su, Yingpeng; Zhang, Guoxiang; Lin, Qiqiao; Zhu, Yujin; Zhang, Qianqian; Fang, Xinqiang

2016-08-19

The strategy of stereodivergent reactions on racemic mixtures (stereodivergent RRM) was employed for the first time in intramolecular benzoin reactions and led to the rapid access of chromanones/flavanones with two consecutive stereocenters. The easily separable stereoisomers of the products were obtained with moderate to excellent enantioselectivities in a single step. Catechol type additives proved crucial in achieving the desired diastereo- and enantioselectivities.

Enantiomeric metabolic interactions and stereoselective human methadone metabolism.

PubMed

Totah, Rheem A; Allen, Kyle E; Sheffels, Pamela; Whittington, Dale; Kharasch, Evan D

2007-04-01

Methadone is administered as a racemate, although opioid activity resides in the R-enantiomer. Methadone disposition is stereoselective, with considerable unexplained variability in clearance and plasma R/S ratios. N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. CYP2B6 metabolism was stereoselective. CYP2C19 was less active, and stereoselectivity was opposite that for CYP2B6. CYP3A4 was not stereoselective. With all three isoforms, enantiomer N-dealkylation rates in the racemate were lower than those of (R)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (R-methadone) or (S)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (S-methadone) alone, suggesting an enantiomeric interaction and mutual metabolic inhibition. For CYP2B6, the interaction between enantiomers was stereoselective, with S-methadone as a more potent inhibitor of R-methadone N-demethylation than R-of S-methadone. In contrast, enantiomer interactions were not stereoselective with CYP2C19 or CYP3A4. For all three cytochromes P450, methadone N-demethylation was best described by two-site enzyme models with competitive inhibition. There were minor model differences between cytochromes P450 to account for stereoselectivity of metabolism and enantiomeric interactions. Changes in plasma R/S methadone ratios observed after rifampin or troleandomycin pretreatment in humans in vivo were successfully predicted by CYP2B6- but not CYP3A4-catalyzed methadone N-demethylation. CYP2B6 is a predominant catalyst of stereoselective methadone metabolism in vitro. In vivo, CYP2B6 may be a major determinant of methadone metabolism and disposition, and CYP2B6 activity and stereoselective metabolic interactions may confer variability in methadone disposition.

The Clinical Pharmacokinetics of Amphetamines Utilized in the Treatment of Attention-Deficit/Hyperactivity Disorder.

PubMed

Markowitz, John S; Patrick, Kennerly S

2017-10-01

Amphetamine (AMP), an indirectly acting psychostimulant approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults, is among the most long-standing therapeutic agents in all of clinical psychopharmacology. This review focuses on AMP absorption, metabolism, and elimination brought to bear on comparative pharmacokinetics in its various formulations. A comprehensive search of the published literature was conducted using MEDLINE (PubMed) and Google Scholar databases through April 2017 to retrieve all pertinent in vitro and human studies for review and synthesis. Additionally, Food and Drug Administration (FDA) databases were accessed for otherwise unavailable data when possible. Initially available as racemic (dl)-AMP, this drug was later supplanted by enantiopure (d)-AMPH or enantioenriched (75:25 dl)-AMP formulations; although racemic AMP returned as an approved drug to treat ADHD in 2014. Presently, there are several immediate-release (IR) formulations available, including d-AMP, dl-AMP, and mixed amphetamine salts, which are neither racemic nor the pure d-enantiomer (i.e., a 3:1 mixture of d-AMP and l-AMP). Furthermore, new modified-release AMP formulations, including an oral suspension and an orally disintegrating tablet, are now available. A lysine-bonded prodrug form of d-AMP also serves as a treatment option. Oral AMP is rapidly absorbed, with high absolute bioavailability, followed by extensive metabolism involving multiple enzymes. Some metabolic pathways exhibit stereoselective biotransformations favoring the l-isomer substrate. Drug exposure exhibits dose-proportional pharmacokinetics. Body weight is a fundamental determinant of differences in observed AMP plasma concentrations. IR formulations typically provide a T max from 2 to 3 hours. In replicated studies, children exhibit a shorter plasma T 1/2 (∼7 hours) relative to adults (∼10 to 12 hours). There are few documented pharmacokinetic drug interactions of clinical significance beyond influences of drug-induced alteration of urinary pH. The array of AMP formulations addressed in this review offer flexibility in dosing, drug onset, and offset to assist in individualized pharmacotherapy of ADHD.

The Next Generation MOD: A Microchip Amino Acid Analyzer for Detecting Extraterrestrial Life

NASA Technical Reports Server (NTRS)

Mathies, R. A.; Hutt, L. D.; Bada, J. L.; Glavin, D.; Grunthaner, F. J.; Grunthaner, P. J.

2000-01-01

The MOD (Mars Organic Detector) instrument which has selected for the definition phase of the BEDS package on the 2005 Mars Explorer Program spacecraft is designed to simply detect the presence of amino acids in Martian surface samples at a sensitivity of a few parts per billion (ppb). An additional important aspect of amino acid analyses of Martian samples is identifying and quantifying which compounds are present, and also distinguishing those produced abiotically from those synthesized by either extinct or extant life. Amino acid homochirality provides an unambiguous way of distinguishing between abiotic vs. biotic origins. Proteins made up of mixed D- and L-amino acids would not likely have been efficient catalysts in early organisms because they could not fold into bioactive configurations such as the a-helix. However, enzymes made up of all D-amino acids function just as well as those made up of only L-amino acids, but the two enzymes use the opposite stereoisomeric substrates. There are no biochemical reasons why L-amino acids would be favored over Damino acids. On Earth, the use of only L-amino acids in proteins by life is probably simply a matter of chance. We assume that if proteins and enzymes were a component of extinct or extant life on Mars, then amino acid homochirality would have been a requirement. However, the possibility that Martian life was (or is) based on D-amino acids would be equal to that based on L-amino acids. The detection of a nonracemic mixture of amino acids in a Martian sample would be strong evidence for the presence of an extinct or extant biota on Mars. The finding of an excess of D-amino acids would provide irrefutable evidence of unique Martian life that could not have been derived from seeding the planet with terrestrial life (or the seeding of the Earth with Martian life). In contrast, the presence of racemic amino acids, along with non-protein amino acids such as alpha-aminoisobutyric acid and isovaline, would be indicative of an abiotic origin, although we have to consider the possibility that the racemic amino acids were generated from the racemization of biotically produced amino acids.

Treatment of PCP addiction and PCP addiction-related behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dewey, Stephen L.; Brodie, Jonathan D.; Ashby, Jr., Charles R.

2002-01-01

The present invention provides a method for changing addiction-related behavior of a mammal suffering from addiction to phencyclidine (PCP). The method includes administering to the mammal an effective amount of gamma vinylGABA (GVG) or a pharmaceutically acceptable salt thereof, or an enantiomer or a racemic mixture thereof, wherein the effective amount is sufficient to diminish, inhibit or eliminate behavior associated with craving or use of PCP.

How to prepare a chiral Grignard reagent: a theoretical proposal.

PubMed

Chen, Zhe-Ning; Fu, Gang; Xu, Xin

2011-04-15

It is shown that two competitive pathways (T2 vs T4) exist for Grignard reagent formation. While the nonradical pathway T2 leads to retention of the configuration, the radical pathway T4 gives racemization. Our calculations suggest the way that T2 can be enhanced, which should be of significance to prompt new synthesis approaches for the preparation of chiral Grignard reagents. © 2011 American Chemical Society

[Chemistry of alpha-aminonitriles. Aziridine-2-carbonitrile: photochemical formation from 2-aminopropenenitrile

NASA Technical Reports Server (NTRS)

Drenkard, S.; Ferris, J.; Eschenmoser, A.

1990-01-01

2-Aminopropenenitrile in solvents such as MeCN, MeOH, or H2O is photoisomerized by UV light to racemic aziridine-2-carbonitrile (rac-2); the larger part of the starting material, however, fragments to HCN and MeCN. The observed photocyclization constitutes a structural connection within an ensemble of C3H4N2 compounds considered to be potentially relevant to prebiotic chemistry.

Highly efficient temperature-dependent chiral separation with a nucleotide-based coordination polymer.

PubMed

Bruno, Rosaria; Marino, Nadia; Bartella, Lucia; Di Donna, Leonardo; De Munno, Giovanni; Pardo, Emilio; Armentano, Donatella

2018-06-05

We report a new chiral coordination polymer, prepared from the cytidine 5'-monophosphate (CMP) nucleotide, capable of separating efficiently (enantiomeric excess of ca. 100%) racemic mixtures of l- and d-Asp in a temperature-dependent manner. The crystal structure of the host-guest adsorbate, with the d-Asp guest molecules loaded within its channels, could be solved allowing a direct visualization of the chiral recognition process.

Enantioselective α-Vinylation of Aldehydes Via the Synergistic Combination of Copper and Amine Catalysis

PubMed Central

Skucas, Eduardas; MacMillan, David W. C.

2012-01-01

The enantioselective α-vinylation of aldehydes using vinyl iodonium triflate salts has been accomplished via the synergistic combination of copper and chiral amine catalysis. These mild catalytic conditions provide a direct route for the enantioselective construction of enolizable α-formyl vinylic stereocenters without racemization or olefin transposition. These high-value coupling adducts are readily converted into a variety of useful olefin synthons. PMID:22616631

Enantioselective Synthesis of Aminodiols by Sequential Rhodium-Catalysed Oxyamination/Kinetic Resolution: Expanding the Substrate Scope of Amidine-Based Catalysis.

PubMed

Guasch, Joan; Giménez-Nueno, Irene; Funes-Ardoiz, Ignacio; Bernús, Miguel; Matheu, M Isabel; Maseras, Feliu; Castillón, Sergio; Díaz, Yolanda

2018-03-26

Regio- and stereoselective oxyamination of dienes through a tandem rhodium-catalysed aziridination-nucleophilic opening affords racemic oxazolidinone derivatives, which undergo a kinetic resolution acylation process with amidine-based catalysts (ABCs) to achieve s values of up to 117. This protocol was applied to the enantioselective synthesis of sphingosine. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Model-based identification of optimal operating conditions for amino acid simulated moving bed enantioseparation using a macrocyclic glycopeptide stationary phase.

PubMed

Fuereder, Markus; Majeed, Imthiyas N; Panke, Sven; Bechtold, Matthias

2014-06-13

Teicoplanin aglycone columns allow efficient separation of amino acid enantiomers in aqueous mobile phases and enable robust and predictable simulated moving bed (SMB) separation of racemic methionine despite a dependency of the adsorption behavior on the column history (memory effect). In this work we systematically investigated the influence of the mobile phase (methanol content) and temperature on SMB performance using a model-based optimization approach that accounts for methionine solubility, adsorption behavior and back pressure. Adsorption isotherms became more favorable with increasing methanol content but methionine solubility was decreased and back pressure increased. Numerical optimization suggested a moderate methanol content (25-35%) for most efficient operation. Higher temperature had a positive effect on specific productivity and desorbent requirement due to higher methionine solubility, lower back pressure and virtually invariant selectivity at high loadings of racemic methionine. However, process robustness (defined as a difference in flow rate ratios) decreased strongly with increasing temperature to the extent that any significant increase in temperature over 32°C will likely result in operating points that cannot be realized technically even with the lab-scale piston pump SMB system employed in this study. Copyright © 2014. Published by Elsevier B.V.

Development and Validation of a Reversed-Phase Chiral HPLC Method to Determine the Chiral Purity of Bulk Batches of (S)-Enantiomer in Afoxolaner.

PubMed

Padivitage, Nilusha; Kumar, Satish; Rustum, Abu

2017-01-01

Afoxolaner is a new antiparasitic molecule from the isoxazoline family that acts on insect acarine g-aminobutyric acid and glutamate receptors. Afoxolaner is a racemic mixture, which has a chiral center at the isoxazoline ring. A reversed-phase chiral HPLC method has been developed to determine the chiral purity of bulk batches of (S)-enantiomer in afoxolaner for the first time. This method can also be used to verify that afoxolaner is a racemic mixture, which was demonstrated by specific rotation. ChromSword, an artificial intelligence method development tool, was used for initial method development. The column selected for the final method was CHIRALPAK AD-RH (150 × 4.6 mm, 5 μm particle size), maintained at 45°C, and isocratic elution using water-isopropanol-acetonitrile (40 + 50 + 10, v/v/v) as the mobile phase with a detection wavelength of 312 nm. The run time for the method was 11 min. The resolution and selectivity factors of the two enantiomers were 2.3 and 1.24, respectively. LOQ and LOD of the method were 1.6 and 0.8 μg/mL, respectively. This method was appropriately validated according to International Conference on Harmonization guidelines for its intended use.

Racemic hemiacetals as oxygen-centered pronucleophiles triggering cascade 1,4-addition/Michael reaction through dynamic kinetic resolution under iminium catalysis. Development and mechanistic insights† †Electronic supplementary information (ESI) available: Detailed experimental procedures and characterization of all new compounds, including copies of NMR spectra and HPLC chromatograms traces, computational details and Cartesian coordinates of all stationary points. CCDC 1525188 (4l), 1525189 (6a) and 1525190 (9a). For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc00009j Click here for additional data file. Click here for additional data file.

PubMed Central

Orue, Ane; Uria, Uxue; Roca-López, David; Delso, Ignacio; Reyes, Efraím; Carrillo, Luisa

2017-01-01

2-Hydroxydihydropyran-5-ones behave as excellent polyfunctional reagents able to react with enals through oxa-Michael/Michael process cascade under the combination of iminium and enamine catalysis. These racemic hemiacetalic compounds are used as unconventional O-pronucleophiles in the initial oxa-Michael reaction, also leading to the formation of a single stereoisomer under a dynamic kinetic resolution (DKR) process. Importantly, by using β-aryl or β-alkyl substituted α,β-unsaturated substrates as initial Michael acceptors either kinetically or thermodynamically controlled diastereoisomers were formed with high stereoselection through the careful selection of the reaction conditions. Finally, a complete experimental and computational study confirmed the initially proposed DKR process during the catalytic oxa-Michael/Michael cascade reaction and also explained the kinetic/thermodynamic pathway operating in each case. PMID:28451356

Stereochemically probing the photo-Favorskii rearrangement: a mechanistic investigation.

PubMed

Givens, Richard S; Rubina, Marina; Stensrud, Kenneth F

2013-03-01

Using model (R)-2-acetyl-2-phenyl acetate esters of (S)- or (R)-α-substituted-p-hydroxybutyrophenones (S,R)-12a and (R,R)-12b, we have shown that a highly efficient photo-Favorskii rearrangement proceeds through a series of intermediates to form racemic rearrangement products. The stereogenic methine on the photoproduct, rac-2-(p-hydroxyphenyl)propanoic acid (rac-9), is formed by closure of a phenoxy-allyloxy intermediate 17 collapsing to a cyclopropanone, the "Favorskii" intermediate 18. These results quantify the intermediacy of a racemized triplet biradical (3)16 on the major rearrangement pathway elusively to the intermediate 18. Thus, intersystem crossing from the triplet biradical surface to the ground state generates a planar zwitterion prior to formation of a Favorskii cyclopropanone that retains no memory of its stereochemical origin. These results parallel the mechanism of Dewar and Bordwell for the ground state formation of cyclopropanone 3 that proceeds through an oxyallyl zwitterionic intermediate. The results are not consistent with the stereospecific S(N)2 ground state Favorskii mechanism observed by Stork, House, and Bernetti. Interconversion of the diastereomeric starting esters of (S,R)-12a and (R,R)-12b during photolysis did not occur, thus ruling out leaving group return prior to rearrangement.

Stereochemically Probing the photo-Favorskii Rearrangement: A Mechanistic Investigation

PubMed Central

Givens, Richard S.; Rubina, Marina; Stensrud, Kenneth F.

2012-01-01

Using model (R)-2-acetyl-2-phenyl acetate esters of (S)- or (R)-α-substituted-p-hydroxybutyrophenones (S,R)-12a and (R,R)-12b, we have shown that a highly efficient photo-Favorskii rearrangement proceeds through a series of intermediates to form racemic rearrangement products. The stereogenic methine on the photoproduct, rac-2-(p-hydroxyphenyl)propanoic acid (rac-9), is formed by closure of a phenoxy-allyloxy intermediate 17 collapsing to a cyclopropanone, the “Favorskii” intermediate 18. These results quantify the intermediacy of a racemized triplet biradical 316 on the major rearrangement pathway elusively to the intermediate 18. Thus, intersystem crossing from the triplet biradical surface to the ground state generates a planar zwitterion prior to formation of a Favorskii cyclopropanone that retains no memory of its stereochemical origin. These results parallel the mechanism of Dewar and Bordwell for the ground state formation of cyclopropanone 3 that proceed through an oxyallyl zwitterionic intermediate. The results are not consistent with the stereospecific SN2 ground state Favorskii mechanism observed by Stork, House, and Bernetti. Interconversion of the diastereomeric starting esters of (S,R)-12a and (R,R)-12b during photolysis did not occur thus ruling out leaving group return prior to rearrangement. PMID:23057737

Chromatographic enantioseparation by poly(biphenylylacetylene) derivatives with memory of both axial chirality and macromolecular helicity.

PubMed

Ishidate, Ryoma; Ikai, Tomoyuki; Kanoh, Shigeyoshi; Yashima, Eiji; Maeda, Katsuhiro

2017-03-01

Novel poly(biphenylylacetylene) derivatives bearing two acetyloxy groups at the 2- and 2'-positions and an alkoxycarbonyl group at the 4'-position of the biphenyl pendants (poly-Ac's) were synthesized by the polymerization of the corresponding biphenylylacetylenes using a rhodium catalyst. The obtained stereoregular (cis-transoidal) poly-Ac's folded into a predominantly one-handed helical conformation accompanied by a preferred-handed axially twisted conformation of the biphenyl pendants through noncovalent interactions with a chiral alcohol and both the induced main-chain helicity and the pendant axial chirality were maintained, that is, memorized, after complete removal of the chiral alcohol. The stability of the helicity memory of the poly-Ac's in a solution was lower than that of the analogous poly(biphenylylacetylene)s bearing two methoxymethoxy groups at the 2- and 2'-positions of the biphenyl pendants (poly-MOM's). In the solid state, however, the helicity memory of the poly-Ac's was much more stable and showed a better chiral recognition ability toward several racemates than that of the previously reported poly-MOM when used as a chiral stationary phase for high-performance liquid chromatography. In particular, the poly-Ac-based CSP with a helicity memory efficiently separated racemic benzoin derivatives into enantiomers. © 2017 Wiley Periodicals, Inc.

Optimization of experimental conditions for the monitoring of nucleation and growth of racemic Diprophylline from the supercooled melt

NASA Astrophysics Data System (ADS)

Lemercier, Aurélien; Viel, Quentin; Brandel, Clément; Cartigny, Yohann; Dargent, Eric; Petit, Samuel; Coquerel, Gérard

2017-08-01

Since more and more pharmaceutical substances are developed as amorphous forms, it is nowadays of major relevance to get insights into the nucleation and growth mechanisms from supercooled melts (SCM). A step-by-step approach of recrystallization from a SCM is presented here, designed to elucidate the impact of various experimental parameters. Using the bronchodilator agent Diprophylline (DPL) as a model compound, it is shown that optimal conditions for informative observations of the crystallization behaviour from supercooled racemic DPL require to place samples between two cover slides with a maximum sample thickness of 20 μm, and to monitor recrystallization during an annealing step of 30 min at 70 °C, i.e. about 33 °C above the temperature of glass transition. In these optimized conditions, it could be established that DPL crystallization proceeds in two steps: spontaneous nucleation and growth of large and well-faceted particles of a new crystal form (primary crystals: PC) and subsequent crystallization of a previously known form (RII) that develops from specific surfaces of PC. The formation of PC particles therefore constitutes the key-step of the crystallization events and is shown to be favoured by at least 2.33 wt% of the major chemical impurity, Theophylline.

Stereospecificity of phenylalanine plasma kinetics and hydroxylation in man following oral application of a stable isotope-labelled pseudo-racemic mixture of L- and D-phenylalanine.

PubMed

Lehmann, W D; Theobald, N; Fischer, R; Heinrich, H C

1983-03-14

L-[15N]Phenylalanine and D-[2H5]phenylalanine have been administered orally to two healthy adult volunteers as a pseudo-racemic mixture at a dose of 25 mg/kg each. After oral application, the plasma kinetics of phenylalanine and tyrosine have been followed by the combined use of high pressure liquid chromatography and field desorption mass spectrometry. Additional incubation with D-amino acid oxidase was used to determine the enantiomeric composition of the differently labelled species of phenylalanine and tyrosine. D-Phenylalanine plasma levels show a faster rise to higher maximum values compared to L-phenylalanine (D/L ratio at maximum 3.19, 3.26). L-Phenylalanine is efficiently hydroxylated to L-tyrosine. In contrast, conversion of D-phenylalanine to the L-form with subsequent hydroxylation to L-tyrosine was observed. From the plasma kinetics it is estimated that about 1/3 of the applied dose of 25 mg/kg of D-phenylalanine is converted to the L-isomer. Of the administered dose of L-phenylalanine only very small amounts are excreted into urine as such (0.25%, 0.8%), whereas a substantial amount of the D-phenylalanine dose is found in urine (27.4%, 38.0%).

Synthesis and Biological Assessment of Racemic Benzochromenopyrimidinimines as Antioxidant, Cholinesterase, and Aβ1-42 Aggregation Inhibitors for Alzheimer's Disease Therapy.

PubMed

Dgachi, Youssef; Ismaili, Lhassane; Knez, Damijan; Benchekroun, Mohamed; Martin, Hélène; Szałaj, Natalia; Wehle, Sarah; Bautista-Aguilera, Oscar M; Luzet, Vincent; Bonnet, Alexandre; Malawska, Barbara; Gobec, Stanislav; Chioua, Mourad; Decker, Michael; Chabchoub, Fakher; Marco-Contelles, José

2016-06-20

Given the complex nature of Alzheimer's disease (AD), compounds that are able to simultaneously address two or more AD-associated targets show greater promise for development into drugs for AD therapy. Herein we report an efficient two-step synthesis and biological evaluation of new racemic benzochromene derivatives as antioxidants, inhibitors of cholinesterase and β-amyloid (Aβ1-42 ) aggregation. Based on the results of the primary screening, we identified 15-(3-methoxyphenyl)-9,11,12,15-tetrahydro-10H,14H-benzo[5,6]chromeno[2,3-d]pyrido[1,2-a]pyrimidin-14-imine (3 e) and 16-(3-methoxyphenyl)-9,10,11,12,13,16-hexahydro-15H-benzo[5',6']chromeno[2',3':4,5]pyrimido[1,2-a]azepin-15-imine (3 f) as new potential multitarget-directed ligands for AD therapy. Further in-depth biological analysis showed that compound 3 f is a good human acetylcholinesterase inhibitor [IC50 =(0.36±0.02) μm], has strong antioxidant activity (3.61 μmol Trolox equivalents), and moderate Aβ1-42 antiaggregating power (40.3 %). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Separation of hydroxynorketamine stereoisomers using capillary electrophoresis with sulfated β-cyclodextrin and highly sulfated γ-cyclodextrin.

PubMed

Sandbaumhüter, Friederike A; Theurillat, Regula; Thormann, Wolfgang

2017-08-01

The racemic N-methyl-d-aspartate receptor antagonist ketamine is used in anesthesia, analgesia and the treatment of depressive disorders. It is known that interactions of hydroxylated norketamine metabolites and 5,6-dehydronorketamine (DHNK) with the α 7 -nicotinic acetylcholine receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are responsible for the antidepressive effects. Ketamine and its first metabolite norketamine are not active on these receptors. As stereoselectivity plays a role in ketamine metabolism, a cationic capillary electrophoresis based method capable of resolving and analyzing the stereoisomers of four hydroxylated norketamine metabolites, norketamine and DHNK was developed. The assay is based on liquid/liquid extraction of the analytes from the biological matrix, electrokinetic sample injection across a buffer plug and analysis of the stereoisomers in a phosphate background electrolyte (BGE) at pH 3 comprising a mixture of sulfated β-cyclodextrin (5 mg/mL) and highly sulfated γ-cyclodextrin (0.1%). The method was used to analyze samples of an in vitro study in which ketamine was incubated with equine liver microsomes and in plasma samples of dogs and horses that were collected after an i.v. bolus injection of racemic ketamine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Origin of Amino Acids in Lunar Regolith Samples

NASA Technical Reports Server (NTRS)

Cook, Jamie E.; Callahan, Michael P.; Dworkin, Jason P.; Glavin, Daniel P.; McLain, Hannah L.; Noble, Sarah K.; Gibson, Everett K., Jr.

2016-01-01

We analyzed the amino acid content of seven lunar regolith samples returned by the Apollo 16 and Apollo 17 missions and stored under NASA curation since collection using ultrahigh-performance liquid chromatography with fluorescence detection and time-of-flight mass spectrometry. Consistent with results from initial analyses shortly after collection in the 1970s, we observed amino acids at low concentrations in all of the curated samples, ranging from 0.2 parts-per-billion (ppb) to 42.7 ppb in hot-water extracts and 14.5 ppb to 651.1 ppb in 6M HCl acid-vapor-hydrolyzed, hot-water extracts. Amino acids identified in the Apollo soil extracts include glycine, D- and L-alanine, D- and L-aspartic acid, D- and L-glutamic acid, D- and L-serine, L-threonine, and L-valine, all of which had previously been detected in lunar samples, as well as several compounds not previously identified in lunar regoliths: -aminoisobutyric acid (AIB), D-and L-amino-n-butyric acid (-ABA), DL-amino-n-butyric acid, -amino-n-butyric acid, -alanine, and -amino-n-caproic acid. We observed an excess of the L enantiomer in most of the detected proteinogenic amino acids, but racemic alanine and racemic -ABA were present in some samples.

Synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid vinyl-ACCA) derivatives: key intermediates for the preparation of inhibitors of the hepatitis C virus NS3 protease.

PubMed

Beaulieu, Pierre L; Gillard, James; Bailey, Murray D; Boucher, Colette; Duceppe, Jean-Simon; Simoneau, Bruno; Wang, Xiao-Jun; Zhang, Li; Grozinger, Karl; Houpis, Ioannis; Farina, Vittorio; Heimroth, Heidi; Krueger, Thomas; Schnaubelt, Jürgen

2005-07-22

(1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is a key building block in the synthesis of potent inhibitors of the hepatitis C virus NS3 protease such as BILN 2061, which was recently shown to dramatically reduce viral load after administration to patients infected with HCV genotype 1. We have developed a scalable process that delivers derivatives of this unusual amino acid in >99% ee. The strategy was based on the dialkylation of a glycine Schiff base using trans-1,4-dibromo-2-butene as an electrophile to produce racemic vinyl-ACCA, which was subsequently resolved using a readily available, inexpensive esterase enzyme (Alcalase 2.4L). Factors that affect diastereoselection in the initial dialkylation steps were examined and the conditions optimized to deliver the desired diastereomer selectively. Product inhibition, which was encountered during the enzymatic resolution step, initially resulted in prolonged cycle times. Enrichment of racemic vinyl-ACCA through a chemical resolution via diastereomeric salt formation or the use of forcing conditions in the enzymatic reaction both led to improvements in throughput and the development of a viable process. The chemistry described herein was scaled up to produce multikilogram quantities of this building block.

Treatment of addiction and addiction-related behavior

DOEpatents

Dewey, Stephen L.; Brodie, Jonathan D.; Ashby, Jr., Charles R.

2003-07-15

The present invention provides a method for changing addiction-related behavior of a mammal suffering from addiction to a combination of abused drugs. The method includes administering to the mammal an effective amount of gamma vinylGABA (GVG) or a pharmaceutically acceptable salt thereof, or an enantiomer or a racemic mixture thereof, wherein the effective amount is sufficient to diminish, inhibit or eliminate behavior associated with craving or use of the combination of abused drugs.

Novel odd/even effect of alkylene chain length on the photopolymerizability of organogelators.

PubMed

Aoki, Ken'ichi; Kudo, Masabumi; Tamaoki, Nobuyuki

2004-10-28

[reaction: see text] Starting from diactylene diacarboxylic acids, we have synthesized a series of photopolymerizable organogelators that possess simple amide structures, different alkylene chain lengths, and either optically active or racemic 3,7-dimethyl-1-octylamine units. The alkylene chain length of these compounds exhibits a prominent odd/even effect with respect to the photopolymerization in the gel state and is accompanied by a stereostructural effect on the gelation ability.

2-Amino-2,3-dimethyl­butanamide

PubMed Central

Yin, Yongbiao

2010-01-01

The title compound, C6H14N2O, was synthesized by the reaction between 2-amino-2,3-dimethyl­butanonitrile and oil of vitriol (sulfuric acid). A racemic mixture of L- and R-2-amino-2,3-di­methyl­butanamide was characterized crystallographically. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds link the two enanti­omers into a three-dimensional network. PMID:21579361

Ring-Opening Cycloaddition of Aziridines to Ketenimines.

PubMed

Maas, Heiko; Bensimon, Corinne; Alper, Howard

1998-01-09

The Lewis acid-catalyzed addition of aziridines to ketenimines gave substituted pyrrolidonimines in 47-87% yields. The hard Lewis acid LiClO(4) proved to be superior to the soft [(PhCN)(2)PdCl(2)], affording higher yields under milder conditions. The reaction is regioselective and occurs with complete stereoselectivity using [(PhCN)(2)PdCl(2)] and with a small amount of racemization in the case of LiClO(4).

Development of Asymmetric Deacylative Allylation

PubMed Central

Grenning, Alexander J.; Van Allen, Christie K.; Maji, Tapan; Lang, Simon B.

2013-01-01

Herein we present the development of asymmetric deacylative allylation of ketone enolates. The reaction directly couples readily available ketone pronucleophiles with allylic alcohols using facile retro-Claisen cleavage to form reactive intermediates in situ. The simplicity and robustness of the reaction conditions is demonstrated by the preparation of > 6 grams of an allylated tetralone from commercially available materials. Furthermore, use of non-racemic PHOX ligands allows intermolecular formation of quaternary stereocenters directly from allylic alcohols. PMID:23734611

Synthesis and Biological Evaluation of Benzochromenopyrimidinones as Cholinesterase Inhibitors and Potent Antioxidant, Non-Hepatotoxic Agents for Alzheimer's Disease.

PubMed

Dgachi, Youssef; Bautista-Aguilera, Oscar M; Benchekroun, Mohamed; Martin, Hélène; Bonet, Alexandre; Knez, Damijan; Godyń, Justyna; Malawska, Barbara; Gobec, Stanislav; Chioua, Mourad; Janockova, Jana; Soukup, Ondrej; Chabchoub, Fakher; Marco-Contelles, José; Ismaili, Lhassane

2016-05-14

We report herein the straightforward two-step synthesis and biological assessment of novel racemic benzochromenopyrimidinones as non-hepatotoxic, acetylcholinesterase inhibitors with antioxidative properties. Among them, compound 3Bb displayed a mixed-type inhibition of human acetylcholinesterase (IC50 = 1.28 ± 0.03 μM), good antioxidant activity, and also proved to be non-hepatotoxic on human HepG2 cell line.

Identification and characterization of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones as inhibitors of the fatty acid transporter FATP4.

PubMed

Blackburn, Christopher; Guan, Bing; Brown, James; Cullis, Courtney; Condon, Stephen M; Jenkins, Tracy J; Peluso, Stephane; Ye, Yingchun; Gimeno, Ruth E; Punreddy, Sandhya; Sun, Ying; Wu, Hui; Hubbard, Brian; Kaushik, Virendar; Tummino, Peter; Sanchetti, Praveen; Yu Sun, Dong; Daniels, Tom; Tozzo, Effie; Balani, Suresh K; Raman, Prakash

2006-07-01

Several potent, cell permeable 4-aryl-dihydropyrimidinones have been identified as inhibitors of FATP4. Lipophilic ester substituents at the 5-position and substitution at the para-position (optimal groups being -NO(2) and CF(3)) of the 4-aryl group led to active compounds. In two cases racemates were resolved and the S enantiomers shown to have higher potencies.

The Screening and Evaluation of Experimental Antiparasitic Drugs

DTIC Science & Technology

1990-09-27

ester concentrate of fish oil containing 68% total eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) did not exert an increase in...to induce resistance to the R- stereoisomer than the S-stereoisomer of a floxacrine racemate analog. In a modified multidose MM test artelinic acid ...is the most active analog of artemisin. When the fatty acids in the membranes 14. SUBJECT TERMS 15. NUMBER OF PAGES Lab Animals; mice; RA I; Parasitic

GCMS/MS Analyses of Biological Samples in Support of Evaluation of Toxicity Associated with Intravenous Exposure to VX Stereoisomers in Guinea Pigs

DTIC Science & Technology

2017-07-01

14. ABSTRACT: This report documents the results of the gas chromatography–tandem mass spectrometry analyses of blood, tissues, and organs (heart...quantified using chemical ionization mass spectrometry with isotope dilution. 15. SUBJECT TERMS Gas chromatography–tandem mass spectrometry (GC–MS...characterize the pharmacokinetics of the individual stereoisomers and their racemic mixtures. This report details the results of gas chromatography–tandem

Size and Carbon Content of Sub-seafloor Microbial Cells

NASA Astrophysics Data System (ADS)

Braun, S.; Morono, Y.; Littmann, S.; Jørgensen, B. B.; Lomstein, B. A.

2015-12-01

Into the seafloor, a radical decline in nutrient and energy availability poses strong metabolic demands to any residing life. However, a sedimentary microbial ecosystem seems to maintain itself close to what we understand to be the energetic limit of life. Since a complex sediment matrix is interfering with the analysis of whole cells and sub-cellular compounds such as cell wall and membrane molecules, little is known about the physiological properties of cells in the deep biosphere. Here we focus on the size and carbon content of cells from a 90-m sediment drill core retrieved in October 2013 at Landsort Deep, Baltic Sea, in 437 meters water depth. To determine their shape and volume, cells were separated from the sediment matrix by multi-layer density centrifugation and visualized via fluorescence microscopy (FM), scanning electron microscopy (SEM), and stimulated emission depletion microscopy (STED). Total cell-carbon was calculated from amino acid-carbon, which was analyzed by high-performance liquid chromatography after cells had additionally been purified by fluorescence activated cell sorting (FACS). Cell-carbon turnover times were estimated using an amino acid racemization model that is based on the built-in molecular clock of aspartic acid, which due to racemization alternates between the D- and L-isomeric configurations over timescales of thousands of years at low in-situ temperatures (≈4˚C). We find that the majority of microbial cells in the sediment have coccoid or rod-shaped morphology, and that absolute values for cell volume are strongly dependent on the method used, spanning three orders of magnitude from approximately 0.001 to 1 µm3 for both coccoid and rod-shaped cells. From the surface to the deepest sample measured (≈60 mbsf), cell volume decreases by an order of magnitude, and carbon content is in the lower range (<20 fg C cell-1) of what has been reported in the literature as conversion factors. Cell-carbon is turned over approximately every 50-600 years, and total carbon oxidation rates decrease from ≈3400 to <60 nmol cm-3 yr-1 with depth, as inferred from amino acid racemization modeling. Given the large extent of marine sediments on Earth, our data will shed light on the energetic limits of life on our planet and will be important for estimating global biomass budgets.

Isoleucine epimerization in the high-molecular-weight fraction of pleistocene Arctica

NASA Astrophysics Data System (ADS)

Kaufman, Darrell S.; Sejrup, Hans-Petter

The extent of amino acid racemization, as traditionally determined in the entire (total acid hydrolysate) pool of amino acids comprising the organic remains of fossils, is a function of the integrated effects of a complex diagenetic reaction network. We investigated the possibility that some of the complications involved in protein diagenesis might be circumvented by isolating one component of the reaction network and studying the extent of racemization in that fraction alone. We used gel-filtration to extract the high-molecular-weight (HMW) fraction of proteinaceous matter from fossil and modem molluscan shells. This fraction contains the largest (ca. > 15,000 MW), most-pristine macromolecules and has been less affected by diagenesis than the more-degraded, lower molecular-weight fractions. Variations in the extent of racemization (isoleucine epimerization; alle/Ile) measured in the HMW fraction of subsamples taken along cross sections of Arctica shells from two interglacial sites, Bø and Fjøsanger, southwestern Norway, are within the range of analytical uncertainty [coefficient of variation (cv) = 5-8%], despite the strong gradient (cv = 20-24%) in alle/Ile of the total amino acid population. Because there is no age difference across a shell, this finding supports the idea that the HMW fraction contains more geochronologically reliable proteinaceous matter than the total amino acid pool. Weighted mean alle/Ile ratios in the HMW fraction of aliquots of powdered sample from the two shells overlap at ± 1σ, despite significantly different alle/Ile ratios in the total amino acid population of some shells from the two sites. The difference in alle/Ile ratios in the total population is attributed to a greater proportion of low-molecular-weight (ca. 300 MW), and hence, extensively epimerized molecules measured in gel-filtered samples from the Fjøsanger shell. Because the rate of epimerization in the HMW fraction is much lower than in the total population, the temporal resolution of the HMW technique is limited, particularly at these high-latitude sites. Therefore, we cannot use the aIle/Ile HMW data to exclude the possibility that the two sites are significantly different ages. Analyses of shells ranging in age from late Pliocene to Holocene indicate that reaction rate in the HMW fraction is about one-fifth the rate in the total amino acid population, although the difference is expected to decrease with increasing aIle/Ile.

Aminostratigraphy of surface and subsurface Quaternary sediments, North Carolina coastal plain, USA

USGS Publications Warehouse

Wehmiller, John F.; Thieler, E. Robert; Miller, D.; Pellerito, V.; Bakeman, Keeney V.; Riggs, S.R.; Culver, S.; Mallinson, D.; Farrell, K.M.; York, L.L.; Pierson, J.; Parham, P.R.

2010-01-01

The Quaternary stratigraphy and geochronology of the Albemarle Embayment of the North Carolina (NC) Coastal Plain is examined using amino acid racemization (AAR) in marine mollusks, in combination with geophysical, lithologic, and biostratigraphic analysis of 28 rotasonic cores drilled between 2002 and 2006. The Albemarle Embayment is bounded by structural highs to the north and south, and Quaternary strata thin westward toward the Suffolk paleoshoreline, frequently referred to as the Suffolk Scarp. The Quaternary section is up to ∼90 m thick, consists of a variety of estuarine, shelf, back-barrier, and lagoonal deposits, and has been influenced by multiple sea-level cycles. The temporal resolution of the amino acid racemization method is tested statistically and with the stratigraphic control provided by this geologic framework, and it is then applied to the correlation and age estimation of subsurface units throughout the region. Over 500 specimens (primarily Mercenaria and Mulinia) from the subsurface section have been analyzed using either gas chromatographic (GC) or reverse-phase liquid chromatographic (RPLC) techniques. The subsurface stratigraphic data are compared with AAR results from numerous natural or excavated exposures from the surrounding region, as well as results from NC beach collections, to develop a comprehensive aminostratigraphic database for the entire Quaternary record within the NC coastal system. Age mixing, recognized in the beach collections, is also seen in subsurface sections, usually where major seismic reflections or core lithology indicate the presence of stratigraphic discontinuities. Kinetic models for racemization are tested within the regional stratigraphic framework, using either radiocarbon or U-series calibrations or comparison with regional biostratigraphy. Three major Pleistocene aminozones [AZ2, AZ3, and AZ4] are found throughout the region, all being found in superposition in several cores. Each can be subdivided, yielding a total of at least eight stratigraphically and statistically distinct aminozones. Kinetic modeling, supplemented with local calibration, indicates that these aminozones represent depositional events ranging from ∼80 ka to nearly 2 Ma. Three prominent seismic reflections are interpreted to represent the base of the early, middle, and late Pleistocene, respectively, roughly 2 Ma, 800 ka, and 130 ka. The large number of samples and the available stratigraphic control provide new insights into the capabilities and limitations of aminostratigraphic methods in assessing relative and numerical ages of Atlantic Coastal Plain Quaternary deposits.

Kinetic Resolution of Secondary Alcohols Using Amidine-Based Catalysts

PubMed Central

Li, Ximin; Jiang, Hui; Uffman, Eric W.; Guo, Lei; Zhang, Yuhua; Yang, Xing; Birman, Vladimir B.

2012-01-01

Kinetic resolution of racemic alcohols has been traditionally achieved via enzymatic enantioselective esterification and ester hydrolysis. However, there has long been considerable interest in devising nonenzymatic alternative methods for this transformation. Amidine-Based Catalysts (ABCs), a new class of enantioselective acyl transfer catalysts developed in our group, have demonstrated, inter alia, high efficacy in the kinetic resolution of benzylic, allylic and propargylic secondary alcohols and 2-substituted cycloalkanols, and thus provide a viable alternative to enzymes. PMID:22283696

Olefin Metathesis in Peptidomimetics, Dynamic Combinatorial Chemistry, and Molecular Imprinting

DTIC Science & Technology

2006-08-01

aryl iodide to the Grignard reagent . Treatment of the magnesium compound with allyl bromide and CuCN·2LiCl afforded benzoate 4-11, which was then...cyclization of a linear peptide by conventional coupling agents to form a new amide bond (Scheme 1-12)36,44 Some common reagents are...dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), and expensive reagents such as HATU or PyBroP, which are more efficient.44 Racemization of the chiral

Mixed La-Li heterobimetallic complexes for tertiary nitroaldol resolution.

PubMed

Tosaki, Shin-ya; Hara, Keiichi; Gnanadesikan, Vijay; Morimoto, Hiroyuki; Harada, Shinji; Sugita, Mari; Yamagiwa, Noriyuki; Matsunaga, Shigeki; Shibasaki, Masakatsu

2006-09-13

A kinetic resolution of tertiary nitroaldols derived from simple ketones is described. Mixed BINOL/biphenol La-Li heterobimetallic complexes gave the best selectivity in retro-nitroaldol reactions of racemic tertiary nitroaldols. By using a mixture of La-Li3-(1a)3 complex (LLB 2a) and La-Li3-(1b)3 (LLB* 2b) complex in a ratio of 2/1, chiral tertiary nitroaldols were obtained in 80-97% ee and 30-47% recovery yield.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagaoka, Masataka; Core Research for Evolutional Science and Technology; ESICB, Kyoto University, Kyodai Katsura, Nishikyo-ku, Kyoto 615-8520

A new efficient hybrid Monte Carlo (MC)/molecular dynamics (MD) reaction method with a rare event-driving mechanism is introduced as a practical ‘atomistic’ molecular simulation of large-scale chemically reactive systems. Starting its demonstrative application to the racemization reaction of (R)-2-chlorobutane in N,N-dimethylformamide solution, several other applications are shown from the practical viewpoint of molecular controlling of complex chemical reactions, stereochemistry and aggregate structures. Finally, I would like to mention the future applications of the hybrid MC/MD reaction method.

rac-(S,S)-Bis(1-ferrocenylbut-3-en-yl) ether.

PubMed

Xie, Hao-Jun; Zhao, Chun-Zheng; Sun, Jun; Chen, Si; Wang, Jian-Jun

2013-01-01

The title complex, [Fe2(C5H5)2(C18H20O)], formed by dehydration of 1-ferrocenylbut-3-en-1-ol, crystallizes as a racemic compound. The central C-O-C fragment, in which the C atoms are the chiral centers, is characterized by an angle of 116.26 (10)° at the O atom. One ferrocene group shows a staggered conformation whereas the other shows an eclipsed conformation.

Light-induced racemization: artifacts in the analysis of the diastereoisomeric pairs of thioridazine 5-sulfoxide in the plasma and urine of patients treated with thioridazine.

PubMed

Eap, C B; Souche, A; Koeb, L; Baumann, P

1991-07-01

The ring sulfoxidation of thioridazine (THD), a widely used neuroleptic agent, yields two diastereoisomeric pairs, fast- and slow-eluting (FE and SE) thioridazine 5-sulfoxide (THD 5-SO). Until now, studies in which concentrations of these metabolites were measured in THD-treated patients have revealed no significant differences in their concentrations. Preliminary experiments in our laboratory had shown that sunlight and, to a lesser extent, dim daylight led to racemization and probably also to photolysis of the diastereoisomeric pairs as measured by high-performance liquid chromatography. Similar results were also obtained with direct UV light (UV lamp). In appropriate light-protected conditions, THD, northioridazine, mesoridazine, sulforidazine, and FE and SE THD 5-SO were measured in 11 patients treated with various doses of THD for at least 1 week. Significantly higher concentrations of the FE stereoisomeric pair were found. The concentration ratios THD 5-SO (FE)/THD 5-SO (SE) ranged from 0.89 to 1.75 in plasma and from 1.15 to 2.05 in urine. Because it is known that the ring sulfoxide contributes to the cardiotoxicity of the drug even more potently than the parent compound does, these results justify further studies to determine whether there is stereoselectivity in the cardiotoxicity of THD 5-SO.

Analysis of metalaxyl racemate using high performance liquid chromatography coupled with four kinds of detectors.

PubMed

Chen, Tao; Fan, Jun; Gao, Ruiqi; Wang, Tai; Yu, Ying; Zhang, Weiguang

2016-10-07

Chiral stationary phase-high performance liquid chromatography coupled with various detectors has been one of most commonly used methods for analysis and separation of chiral compounds over the past decades. Various detectors exhibit different characteristics in qualitative and quantitative studies under different chromatographic conditions. Herein, a comparative evaluation of HPLC coupled with ultraviolet, optical rotation, refractive index, and evaporative light scattering detectors has been conducted for qualitative and quantitative analyses of metalaxyl racemate. Effects of separation conditions on the peak area ratio between two enantiomers, including sample concentration, column temperature, mobile phase composition, as well as flow rate, have been investigated in detail. In addition, the limits of detection, the limits of quantitation, quantitative range and precision for these two enantiomers by using four detectors have been also studied. As indicated, the chromatographic separation conditions have been slight effects on ultraviolet and refractive index detections and the peak area ratio between two enantiomers remains almost unchanged, but the evaporative light scattering detection has been significantly affected by the above-mentioned chromatographic conditions and the corresponding peak area ratios varied greatly. Moreover, the limits of detection, the limits of quantitation, and the quantitative ranges of two enantiomers with UV detection were remarkably lower by 1-2 magnitudes than the others. Copyright © 2016 Elsevier B.V. All rights reserved.

Spontaneously amplified homochiral organic-inorganic nano-helix complexes via self-proliferation.

PubMed

Zhai, Halei; Quan, Yan; Li, Li; Liu, Xiang-Yang; Xu, Xurong; Tang, Ruikang

2013-04-07

Most spiral coiled biomaterials in nature, such as gastropod shells, are homochiral, and the favoured chiral feature can be precisely inherited. This inspired us that selected material structures, including chirality, could be specifically replicated into the self-similar populations; however, a physicochemical understanding of the material-based heritage is unknown. We study the homochirality by using calcium phosphate mineralization in the presence of racemic amphiphilic molecules and biological protein. The organic-inorganic hybrid materials with spiral coiling characteristics are produced at the nanoscale. The resulted helixes are chiral with the left- and right-handed characteristics, which are agglomerated hierarchically to from clusters and networks. It is interesting that each cluster or network is homochiral so that the enantiomorphs can be separated readily. Actually, each homochiral architecture is evolved from an original chiral helix, demonstrating the heritage of the matrix chirality during the material proliferation under a racemic condition. By using the Ginzburg-Landaue expression we find that the chiral recognition in the organic-inorganic hybrid formation may be determined by a spontaneous chiral separation and immobilization of asymmetric amphiphilic molecules on the mineral surface, which transferred the structural information from the mother matrix to the descendants by an energetic control. This study shows how biomolecules guide the selective amplification of chiral materials via spontaneous self-replication. Such a strategy can be applied generally in the design and production of artificial materials with self-similar structure characteristics.

The effects of low concentrations of the enantiomers of mushroom alcohol (1-octen-3-ol) on Arabidopsis thaliana

PubMed Central

Hung, Richard; Lee, Samantha; Bennett, Joan W.

2014-01-01

“Mushroom alcohol,” or 1-octen-3-ol, is a common fungal volatile organic compound (VOC) that has been studied for its flavor properties, its effects on fungal spore germination, mushroom development, and as a signaling agent for insects. Far less is known about its effects on plants. We exposed Arabidopsis thaliana seeds, under conditions conducive to germination, to high (10 and 100 mg/1) and low concentrations (1, 2, and 3 mg/1) of racemic, S, and R forms of 1-octen-3-ol for 3 days. In addition, 1-, 2-, 3-, and 4-week-old A. thaliana plants also were exposed to 1 mg/1 of the compounds for the same period of time. Seedling formation was retarded with all tested levels of exposure to 1-octen-3-ol for both enantiomers and the racemer, while 95% of unexposed control seeds germinated to seedling within 3 days. There was a dose-dependent response in the reduction of seedling formation between 1 mg/1 and 3 mg/1 of exposure. When exposed seeds were removed from the VOC, nearly all resumed germination. Young plants exposed to 1 mg/1 of the R and S enantiomers of 1-octen-3-ol exhibited a mild inhibition of growth and chlorophyll production at 2 and 3 weeks but not at 4 weeks. PMID:24999439

Enantioselective Metabolism of Chiral 3-Phenylbutyric Acid, an Intermediate of Linear Alkylbenzene Degradation, by Rhodococcus rhodochrous PB1

PubMed Central

Simoni, S.; Klinke, S.; Zipper, C.; Angst, W.; Kohler, H. E.

1996-01-01

Rhodococcus rhodochrous PB1 was isolated from compost soil by selective culture with racemic 3-phenylbutyric acid as the sole carbon and energy source. Growth experiments with the single pure enantiomers as well as with the racemate showed that only one of the two enantiomers, (R)-3-phenylbutyric acid, supported growth of strain PB1. Nevertheless, (S)-3-phenylbutyric acid was cometabolically transformed to, presumably, (S)-3-(2,3-dihydroxyphenyl)butyric acid (the absolute configuration at the C-3 atom is not known yet) by (R)-3-phenylbutyric acid-grown cells of strain PB1, as shown by (sup1)H nuclear magnetic resonance spectroscopy of the partially purified compound and gas chromatography-mass spectrometry analysis of the trimethylsilyl derivative. Oxygen uptake rates suggest that either 3-phenylpropionic acid or cinnamic acid (trans-3-phenyl-2-propenoic acid) is the substrate for aromatic ring hydroxylation. This view is substantiated by the fact that 3-(2,3-dihydroxyphenyl)propionic acid was a substrate for meta cleavage in cell extracts of (R)-3-phenylbutyric acid-grown cells of strain PB1. Gas chromatography-mass spectrometry analysis of trimethylsilane-treated ethyl acetate extracts of incubation mixtures showed that both the meta-cleavage product, 2-hydroxy-6-oxo-2,4-nonadiene-1,9-dicarboxylic acid, and succinate, a hydrolysis product thereof, were formed during such incubations. PMID:16535265

Levorotatory carbohydrates and xylitol subdue Streptococcus mutans and Candida albicans adhesion and biofilm formation.

PubMed

Brambilla, Eugenio; Ionescu, Andrei C; Cazzaniga, Gloria; Ottobelli, Marco; Samaranayake, Lakshman P

2016-05-01

Dietary carbohydrates and polyols affect the microbial colonization of oral surfaces by modulating adhesion and biofilm formation. The aim of this study was to evaluate the influence of a select group of l-carbohydrates and polyols on either Streptococcus mutans or Candida albicans adhesion and biofilm formation in vitro. S. mutans or C. albicans suspensions were inoculated on polystyrene substrata in the presence of Tryptic soy broth containing 5% of the following compounds: d-glucose, d-mannose, l-glucose, l-mannose, d- and l-glucose (raceme), d- and l-mannose (raceme), l-glucose and l-mannose, sorbitol, mannitol, and xylitol. Microbial adhesion (2 h) and biofilm formation (24 h) were evaluated using MTT-test and Scanning Electron Microscopy (SEM). Xylitol and l-carbohydrates induced the lowest adhesion and biofilm formation in both the tested species, while sorbitol and mannitol did not promote C. albicans biofilm formation. Higher adhesion and biofilm formation was noted in both organisms in the presence of d-carbohydrates relative to their l-carbohydrate counterparts. These results elucidate, hitherto undescribed, interactions of the individually tested strains with l- and d-carbohydrates, and how they impact fungal and bacterial colonization. In translational terms, our data raise the possibility of using l-form of carbohydrates and xylitol for dietary control of oral plaque biofilms. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preferential Stereocomplex Crystallization in Enantiomeric Blends of Cellulose Acetate-g-Poly(lactic acid)s with Comblike Topology.

PubMed

Bao, Jianna; Han, Lili; Shan, Guorong; Bao, Yongzhong; Pan, Pengju

2015-10-01

Although stereocomplex (sc) crystallization is highly effective for improving the thermal resistance of poly(lactic acid) (PLA), it is much less predominant than homocrystallization in high-molecular-weight (HMW) poly(l-lactic acid)/ poly(d-lactic acid) (PLLA/PDLA) racemic blends. In this contribution, the sc crystallization of HMW PLLA/PDLA racemic blends was facilitated by using comblike PLAs with cellulose acetate as the backbone. Competing crystallization kinetics, polymorphic crystalline structure, and structural transition of comblike PLLA/PDLA blends with a wide range of MWs were investigated and compared with the corresponding linear/comblike and linear blends. The HMW comblike blend is preferentially crystallized in sc polymorphs and exhibits a faster crystallization rate than does the corresponding linear blend. The sc crystallites are predominantly formed in nonisothermal cold crystallization and isothermal crystallization at temperatures above 120 °C for the comblike blends. Except for the facilitated sc formation in primary crystallization, synchrotron radiation WAXD analysis indicates that the presence of a comblike component also facilitates the transition or recrystallization from homocrystallite (hc) to sc crystallite upon heating. Preferential sc formation of comblike blends is probably attributable to the favorable interdigitation between enantiomeric branches and the increased mobility of polymer segments. After crystallization under the same temperature, the comblike blends, which mainly contain sc crystallites, show smaller long periods and thinner crystalline lamellae than do the corresponding PLLA with homocrystalline structures.

Influence of gasoline inhalation on the enantioselective pharmacokinetics of fluoxetine in rats.

PubMed

Cardoso, Juciane Lauren Cavalcanti; Lanchote, Vera Lucia; Pereira, Maria Paula Marques; Capela, Jorge Manuel Vieira; Lepera, José Salvador

2013-03-01

Fluoxetine is used clinically as a racemic mixture of (+)-(S) and (-)-(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose-only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10-mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC-MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)-(S)-fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.68). In animals exposed to gasoline, we observed an increase in AUC(0-∞) for both enantiomers, with a sharper increase seen for the (-)-(R)-fluoxetine enantiomer (enantiomeric ratio AUC((+)-(S)/(-)-(R)) = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (-)-(R)-fluoxetine enantiomer (55% vs. 30%). Copyright © 2013 Wiley Periodicals, Inc.

Role of Cytochrome P450 Hydroxylase in the Decreased Accumulation of Vitamin E in Muscle from Turkeys Compared to that from Chickens

PubMed Central

Perez, Dale M.; Richards, Mark P.; Parker, Robert S.; Berres, Mark E.; Wright, Aaron T.; Sifri, Mamduh; Sadler, Natalie C; Tatiyaborworntham, Nantawat; Li, Na

2016-01-01

Turkeys and chickens reared to 5 weeks of age and fed diets with feedstuffs low in endogenous tocopherols were examined. Treatments included feed supplemented with RRR (natural source vitamin E) alpha tocopheryl acetate (AcT, 35 mg/kg feed) and all-racemic (synthetic vitamin E) AcT (10 and 58 mg/kg feed). Alpha tocopherol hydroxylase activity was greater in liver microsomes prepared from turkeys compared to that from chickens (p < 0.01). Alpha and gamma tocopherol metabolites were higher in turkey bile than in chicken when assessing the RRR AcT diet and the all-racemic AcT diet at 58 mg/kg feed (p < 0.01). Turkey cytochrome P450 2C29 was increased relative to its chicken ortholog on the basis of RNA-Seq transcript abundance (p < 0.001) and activity-based protein profiling (p < 0.01) of liver tissue. Alpha tocopherol concentrations in plasma, liver, and muscle from turkey were lower than the respective tissues from chicken (p < 0.05). Lipid oxidation was greater in turkey thigh than in chicken (p < 0.05). These results suggest that elevated tocopherol metabolism by cytochrome P450 hydroxylase(s) in turkeys contributes to the decreased accumulation of alpha tocopherol in turkey tissues compared to that of chickens. PMID:26653675

Enantioselective separation of chiral aromatic amino acids with surface functionalized magnetic nanoparticles.

PubMed

Ghosh, Sudipa; Fang, Tan Hui; Uddin, M S; Hidajat, K

2013-05-01

Chiral resolution aromatic amino acids, DL-tryptophan (DL-Trp), DL-phenylalanine (DL-Phe), DL-tyrosine (DL-Tyr) from phosphate buffer solution was achieved in present study employing the concept of selective adsorption by surface functionalized magnetic nanoparticles (MNPs). Surfaces of magnetic nanoparticles were functionalized with silica and carboxymethyl-β-cyclodextrin (CMCD) to investigate their adsorption resolution characteristics. Resolution of enantiomers from racemic mixture was quantified in terms of enantiomeric excess using chromatographic method. The MNPs selectively adsorbed L-enantiomers of DL-Trp, DL-Phe, and DL-Tyr from racemic mixture and enantiomeric excesses (e.e.) were determined as 94%, 73% and 58%, respectively. FTIR studies demonstrated that hydrophobic portion of enantiomer penetrated into hydrophobic cavity of cyclodextrin molecules to form inclusion complex. Furthermore, adsorption site was explored using XPS and it was revealed that amino group at chiral center of the amino acid molecule formed hydrogen bond with secondary hydroxyl group of CMCD molecule and favorability of hydrogen bond formation resulted in selective adsorption of L-enantiomer. Finally, stability constant (K) and Gibbs free energy change (-ΔG°) for inclusion complexation of CMCD with L-/D-enantiomers of amino acids were determined using spectroflurometry in aqueous buffer solution. Higher binding constants were obtained for inclusion complexation of CMCD with L-enantiomers compared to D-enantiomers which stimulated enantioselective properties of CMCD functionalized magnetite silica nanoparticles. Copyright © 2013 Elsevier B.V. All rights reserved.

Enantioselective synthesis of (S)-naproxen using immobilized lipase on chitosan beads.

PubMed

Gilani, Saeedeh L; Najafpour, Ghasem D; Heydarzadeh, Hamid D; Moghadamnia, Aliakbar

2017-06-01

S-naproxen by enantioselective hydrolysis of racemic naproxen methyl ester was produced using immobilized lipase. The lipase enzyme was immobilized on chitosan beads, activated chitosan beads by glutaraldehyde, and Amberlite XAD7. In order to find an appropriate support for the hydrolysis reaction of racemic naproxen methyl ester, the conversion and enantioselectivity for all carriers were compared. In addition, effects of the volumetric ratio of two phases in different organic solvents, addition of cosolvent and surfactant, optimum pH and temperature, reusability, and inhibitory effect of methanol were investigated. The optimum volumetric ratio of two phases was defined as 3:2 of aqueous phase to organic phase. Various water miscible and water immiscible solvents were examined. Finally, isooctane was chosen as an organic solvent, while 2-ethoxyethanol was added as a cosolvent in the organic phase of the reaction mixture. The optimum reaction conditions were determined to be 35 °C, pH 7, and 24 h. Addition of Tween-80 in the organic phase increased the accessibility of immobilized enzyme to the reactant. The optimum organic phase compositions using a volumetric ratio of 2-ethoxyethanol, isooctane and Tween-80 were 3:7 and 0.1% (v/v/v), respectively. The best conversion and enantioselectivity of immobilized enzyme using chitosan beads activated by glutaraldehyde were 0.45 and 185, respectively. © 2017 Wiley Periodicals, Inc.

One-Pot Multicomponent Coupling Methods for the Synthesis of Diastereo- and Enantioenriched (Z)-Trisubstituted Allylic Alcohols

PubMed Central

Kerrigan, Michael H.; Jeon, Sang-Jin; Chen, Young K.; Salvi, Luca; Carroll, Patrick J.; Walsh, Patrick J.

2009-01-01

(Z)-Trisubstituted allylic alcohols are widespread structural motifs in natural products and biologically active compounds but are difficult to directly prepare. Introduced herein is a general one-pot multicomponent coupling method for the synthesis of (Z)-α,α,β-trisubstituted allylic alcohols. (Z)-Trisubstituted vinylzinc reagents are formed in situ by initial hydroboration of 1-bromo-1-alkynes. Addition of dialkylzinc reagents induces a 1,2-metallate rearrangement that is followed by a boron-to-zinc transmetallation. The resulting vinylzinc reagents add to a variety of prochiral aldehydes to produce racemic (Z)-trisubstituted allylic alcohols. When enantioenriched aldehyde substrates are employed (Z)-trisubstituted allylic alcohols are isolated with high dr (>20:1 in many cases). For example, vinylation of enantioenriched benzyl protected α- and β-hydroxy propanal derivatives furnished the expected anti-Felkin addition products via chelation control. Surprisingly, silyl protected α-hydroxy aldehydes also afford anti-Felkin addition products. A protocol for the catalytic asymmetric addition of (Z)-trisubstituted vinylzinc reagents to prochiral aldehydes with a (−)-MIB-based catalyst has also been developed. Several additives were investigated as inhibitors of the Lewis acidic alkylzinc halide byproducts, which promote the background reaction to form the racemate. α-Ethyl and α-cyclohexyl (Z)-trisubstituted allylic alcohols can now be synthesized with excellent levels of enantioselectivity in the presence of diamine inhibitors. PMID:19476375

Chiral-phase high-performance liquid chromatography of rotenoid racemates

USGS Publications Warehouse

Abidi, S.L.

1987-01-01

The high-performance liquid chromatograhic (HPLC) behavior of parent rotenoids (type I) and the hydroxyl-analogues (type II) on three different chiral stationary phases (CSPs) was studied. Separations of optical isomers were achieved in various degrees depending largely upon the rotenoidal structures and the CSP types employed. Enantiomers of all but elliptone compounds were separable on β-cyclodextrin-bonded silica (CDS). Without exception, the 12a-hydroxyrotenoid antipodes were resolved on Pirkle's phenylglycine-bonded silica (PGS) despite unsuccessful attenmpts to resolve the type I rotenoidal racemates. Conversely, optical resolution of the latter rotenoids was accomplished by using a helical polytriphenylmethylacrylate-coated silica (TPS) column and the observed separation factors (α values) ranged from 1.14 to 1.90. The results from HPLC of type II rotenoids on TPS (α = 1.00–1.63) suggested that variations in E-ring structures had profound influence on the resolution outcome. Conjugated double bonds on the E-ring and the desisopropylation of the five-membered E-ring ot type II rotenoids appeared to be important structural features for chiral recognition involving the TPS substrate. In both reversed-phase (CDS) and normal-pahse (PGS and TPS) HPLC modes, the less polar enantiomers were the 6aβ,12aβ-rotenoids as observed in most cases, though this relationship was reversed in the cases of deguelin and hydroxyelliptone probably due to conformational effects of rotenoidal ring systems.

Homochirality through Photon-Induced Denaturing of RNA/DNA at the Origin of Life.

PubMed

Michaelian, Karo

2018-06-06

Since a racemic mixture of chiral nucleotides frustrates the enzymeless extension of RNA and DNA, the origin of homochirality must be intimately connected with the origin of life. Homochirality theories have elected to presume abiotic mechanisms for prebiotic enantiomer enrichment and post amplification, but none, so far, has been generally accepted. Here I present a novel hypothesis for the procurement of homochirality from an asymmetry in right- over left-circularly polarized photon-induced denaturing of RNA and DNA at the Archean ocean surface as temperatures descended below that of RNA and DNA melting. This asymmetry is attributed to the small excess of right-handed circularly polarized submarine light during the afternoon, when surface water temperatures were highest and thus most conducive to photon-induced denaturing, and to a negative circular dichroism band extending from 230 to 270 nm for small oligos of RNA and DNA. Because D-nucleic acids have greater affinity for L-tryptophan due to stereochemistry, and because D-RNA/DNA+L-tryptophan complexes have an increased negative circular dichroism band between 230 and 270 nm, the homochirality of tryptophan can also be explained by this hypothesis. A numerical model is presented, demonstrating the efficacy of such a mechanism in procuring homochirality of RNA or DNA from an original racemic solution in as little as 270 Archean years.

Microwave Assisted Synthesis of Py-Im Polyamides

PubMed Central

2012-01-01

Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chemistry on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification. It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several additional coupling steps. PMID:22578091

Manganese-Catalyzed Carbonylative Annulations for Redox-Neutral Late-Stage Diversification.

PubMed

Liang, Yu-Feng; Steinbock, Ralf; Münch, Annika; Stalke, Dietmar; Ackermann, Lutz

2018-05-04

An inexpensive, nontoxic manganese catalyst enabled unprecedented redox-neutral carbonylative annulations under ambient pressure. The manganese catalyst outperformed all other typically used base and precious-metal catalysts. The outstanding versatility of the manganese catalysis manifold was reflected by ample substrate scope, setting the stage for effective late-stage manipulations under racemization-free conditions of a wealth of marketed drugs and natural products, including alkaloids, amino acids, steroids, and carbohydrates. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chiral recognition by formation of paramagnetic diastereomeric complexes

NASA Astrophysics Data System (ADS)

Scheffler, K.; Höfler, U.; Schuler, P.; Stegmann, H. B.

The chiral 4-(α-hydroxy-benzyl)-2,6-di-tert. butyl-phenoxyl has been examined in its racemic form in toluene and carbontetrachloride. On adding of chiral auxiliaries (R)-resp. (S)-N,N-dimethyl-1-phenylethylamine or (S)-phenylethyl-amine two different couplings of the β-proton are recorded by ENDOR spectroscopy. The experimental results are interpreted by a ternary equilibrium between radical, solvent and auxiliary. A model for the suggested association processes is given and equilibrium constants and corresponding enthalpies are calculated.

Potential for Terahertz/Optical, Two Color Non-linear Sensing of Liquid Biochemical Agents

DTIC Science & Technology

2011-05-18

through the geometry and phase matching dependencies in the setup using enantiomeric and racemic limonene as a me- dium. In completely identical...around the 532 nm 18 795.2 cm−1 YAG line generated in S- limonene by 0.61 THz 20.3 cm−1. The rotation angle was 27°. At each point, 500 mixing events...In the following, signals are extracted as the integral of the total sideband line. Sum frequency sidebands for both S- limonene and a ra- cemic

Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burks, Heather E.; Abrams, Tinya; Kirby, Christina A.

Tetrahydroisoquinoline 40 has been identified as a potent ERα antagonist and selective estrogen receptor degrader (SERD), exhibiting good oral bioavailability, antitumor efficacy, and SERD activity in vivo. We outline the discovery and chemical optimization of the THIQ scaffold leading to THIQ 40 and showcase the racemization of the scaffold, pharmacokinetic studies in preclinical species, and the in vivo efficacy of THIQ 40 in a MCF-7 human breast cancer xenograft model.

Diastereoselective cyclization of an aminobenzoic acid derivative and chiroptical properties of triple-stranded helical bis(phenylethynyl)benzene.

PubMed

Yamakado, Ryohei; Matsuoka, Shin-ichi; Suzuki, Masato; Takeuchi, Daisuke; Masu, Hyuma; Azumaya, Isao; Takagi, Koji

2015-04-04

The diastereoselective cyclization of 2,5-dibromo-4-hexylaminobenzoic acid was achieved by the microwave-assisted condensation using SiCl4. Moreover, the triple-stranded helical structure of bis(phenylethynyl)benzene units embedded in the cyclic tri(benzamide) scaffold was obtained by a Sonogashira-Hagihara coupling reaction. Two optically active enantiomers that do not racemize even at the elevated temperature were separated by chiral HPLC. The chiral helical topology was revealed by the spectroscopic data and theoretical calculation.

Total synthesis of the proposed structure of trichodermatide A.

PubMed

Myers, Eddie; Herrero-Gómez, Elena; Albrecht, Irina; Lachs, Jennifer; Mayer, Peter; Hanni, Matti; Ochsenfeld, Christian; Trauner, Dirk

2014-10-17

A short total synthesis of the published structure of racemic trichodermatide A is reported. Our synthesis involves a Knoevenagel condensation/Michael addition sequence, followed by the formation of tricyclic hexahydroxanthene-dione and a diastereoselective bis-hydroxylation. The final product, the structure of which was confirmed by X-ray crystallography, has NMR spectra that are very similar, but not identical, to those of the isolated natural product. Quantum chemically computed (13)C shifts agree well with the present NMR measurements.

Molecular Evolution of Human PON to Design Enhanced Catalytic Efficiency for Hydrolysis of Nerve Agents

DTIC Science & Technology

2011-12-01

8   C.   Catalytic activity of evolved variants with GA ................................................................. 11   D...several variants of rePON1 with enhanced activity towards a racemic mixture of CMP-Coumarin by screening ‘neutral drift’ libraries of rePON1 (e.g. 1G3, 2G9...22. The most active variant was 3B3, which had ~250-fold higher catalytic efficiency (kcat/Km 20x106 M-1min-1) compared to the wild-type-like

Environmental Impact Research Program. Doveweeds (Croton supp.) Section 7.4.2, US Army Corps of Engineers Wildlife Resources Management Manual.

DTIC Science & Technology

1986-07-01

inflorescences are formed. The inflorescence is an abbre-9viated terminal raceme with pistillate flowers below staminate flowers. The 3 -IC Figure 1...Distribution and distinguishing characteristics of woolly croton (Croton capitatus): (a) flowering branch, (b) fruit, and (c) seeds 4 ovary is 3- celled ...and the capsule is 3- celled and 3-seeded except for C. monanthogynus, which is 1-seeded. When seeds mature in late fall, they are forcefully ejected

Temperature calibration of amino acid racemization: age implications for the Yuha skeleton

USGS Publications Warehouse

Bischoff, J.L.; Childers, W.M.

1979-01-01

D/L of aspartic acid ranged from 0.52 to 0.56 for femur samples of the Yuha skeleton. Subsurface temperature measurements made at the burial site indicate average annual temperature is 18??C and diagenetic temperature is 21.6??C. These data and a relation derived for the dependence of the aspartic acid rate constant on diagenetic temperature indicate an age of 23,600. The result is consistent with 14C and 230Th dating of calcrete found coating the bones. ?? 1979.

Structural and magnetic properties of two- and three-dimensional molecule-based magnets (cat) +[M IIM III(C 2O 4) 3] -

NASA Astrophysics Data System (ADS)

Ovanesyan, Nikolai S.; Shilov, Gena V.; Pyalling, Alex A.; Train, Cyrille; Gredin, Patrick; Gruselle, Michel; Kiss, László F.; Bottyán, László

2004-05-01

We discuss the different structural arrangements of NBu 4[Fe IICr III(C 2O 4) 3] layered compounds in their racemic and enantiomeric forms and related magnetic properties. For [Mn IIFe III(C 2O 4) 3] networks of dimensionalities 2 and 3 Mössbauer spectroscopy was applied to study the Fe III sublattice magnetization. Unusual magnetic relaxation phenomena below TN were observed for both 2D and 3D networks.

Infrared-thermographic screening of the activity and enantioselectivity of enzymes.

PubMed

Reetz, M T; Hermes, M; Becker, M H

2001-05-01

The infrared radiation caused by the heat of reaction of an enantioselective enzyme-catalyzed transformation can be detected by modern photovoltaic infrared (IR)-thermographic cameras equipped with focal-plane array detectors. Specifically, in the lipase-catalyzed enantioselective acylation of racemic 1-phenylethanol, the (R)- and (S)-substrates are allowed to react separately in the wells of microtiter plates, the (R)-alcohol showing hot spots in the IR-thermographic images. Thus, highly enantioselective enzymes can be identified at kinetic resolution.

Effects of HMG-COA Reductase Inhibitor Therapy on LDL Cholesterol Blood Levels in Hyperlipidemia: A Longitudinal Retrospective Anlaysis Using a Department of Defense Integrated Database.

DTIC Science & Technology

1998-05-21

United States. They are atorvastatin (Lipitor® by Bristol-Myers Squibb), fluvastatin (Lescol® by Sandoz), lovastatin (Mevacor® by Merck), pravastatin...34first- and-a-half40 generation statin (semi-synthetic), fluvastatin being a second generation statin (a racemic synthetic), and atorvastatin being a...third generation 27 statin (a pure enantiomer synthetic). Atorvastatin , fluvastatin, and pravastatin are taken in the active hydroxy-acid form114

Protopine hydrochloride.

PubMed

Dostál, J; Zák, Z; Necas, M; Slavík, J; Potácek, M

2001-05-01

Protopine hydrochloride (5,6,14,14a-tetrahydro-14a-hydroxy-7-methyl-8H-bis[1,3]benzodioxolo[5,6-a:4,5-g]quinolizinium chloride, C20H20NO5(+)-Cl(-)) is the salt of the isoquinoline alkaloid protopine. It is formed by the action of dilute hydrochloric acid on the protopine free base. The N-methyl and hydroxyl groups are in a trans configuration in the quinolizine ring and the central quinolizine N-C bond is unusually long [1.579 (2) A]. The crystal is a racemate.

Raman spectroscopic study of DL valine under pressure up to 20 GPa

NASA Astrophysics Data System (ADS)

Rêgo, F. S. C.; Lima, J. A.; Freire, P. T. C.; Melo, F. E. A.; Mendes Filho, J.; Polian, A.

2016-04-01

DL-valine crystal was studied by Raman spectroscopy under hydrostatic pressure using a diamond anvil cell from ambient pressure up to 19.4 GPa in the spectral range from 40 to 3300 cm-1. Modifications in the spectra furnished evidence of the occurrence of two structural phase transitions undergone by this racemic amino acid crystal. The classification of the vibrational modes, the behavior of their wavenumber as a function of the pressure and the reversibility of the phase transitions are discussed.

Median Lethal Doses Associated with Intravenous Exposure to the Optically Pure Enantiomers of VX in Guinea Pigs

DTIC Science & Technology

2017-03-01

highly toxic based on the U.S. Environmental Protection Agency’s Acute Toxicity Categories for Pesticide Products . 15. SUBJECT TERMS Guinea pig ...in Guinea Pigs 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Wright, Linnzi K. M.; Forster, Jeffry S...intravenous exposure of adult, male guinea pigs to the individual VX enantiomers, and we compared those potencies to that for a racemic mixture. The P

Total Syntheses of (-)-Mersicarpine, (-)-Scholarisine G, (+)-Melodinine E, (-)-Leuconoxine, (-)-Leuconolam, (-)-Leuconodine A, (+)-Leuconodine F, and (-)-Leuconodine C: Self-Induced Diastereomeric Anisochronism (SIDA) Phenomenon for Scholarisine G and Leuconodines A and C.

PubMed

Xu, Zhengren; Wang, Qian; Zhu, Jieping

2015-05-27

Enantioselective total syntheses of title natural products from a common cyclohexenone derivative (S)-18 were reported. Ozonolysis of (S)-18 afforded a stable diketo ester (R)-17 that was subsequently converted to two skeletally different natural products, i.e., (-)-mersicarpine (8) with a [6.5.6.7] fused tetracyclic ring system and (-)-scholarisine G (9) with a [6.5.6.6.5] fused pentacyclic skeleton, respectively. The postcyclization diversification was realized by taking advantage of the facile conversion of (+)-melodinine E (6) to N-acyliminium ion 7, from which a hydroxy group was selectively introduced to the C6, C7, C10 and the central C21 position of diazafenestrane system, leading to (-)-leuconodine A (11), (+)-leuconodine F (12), (-)-scholarisine G (9), (-)-leuconodine C (13), and skeletally different (-)-leuconolam (5). Furthermore, an unprecedented non-natural oxabridged oxadiazafenestrane 68 was formed by oxidation of (+)-melodinine E (6). During the course of this study, a strong self-induced diastereomeric anisochronism (SIDA) phenomenon was observed for scholarisine G (9), leuconodines A (11) and C (13). X-ray structures of both the racemic and the enantiopure natural products 9, 11, and 13 were obtained. The different crystal packing of these two forms nicely explained the chemical shift differences observed in the (1)H NMR spectra of the racemic and the enantio-enriched compounds in an achiral environment.

Simultaneous analysis of the enantiomers of verapamil and norverapamil in rat plasma by liquid chromatography-tandem mass spectrometry.

PubMed

Mateus, Fabiano Henrique; Lepera, José Salvador; Marques, Maria Paula; Boralli, Vanessa Bergamin; Lanchote, Vera Lucia

2007-12-21

An enantioselective micromethod for the simultaneous analysis of verapamil (VER) and norverapamil (NOR) in plasma was developed, validated and applied to the study of the kinetic disposition of VER and NOR after the administration of a single oral dose of racemic-VER to rats. VER, NOR and the internal standard (paroxetine) were extracted from only 100-microL plasma samples using n-hexane and the enantiomers were resolved on a Chiralpak AD column using n-hexane:isopropanol:ethanol:diethylamine (88:6:6:0.1) as the mobile phase. The analyses were performed in the selected reaction monitoring mode. Transitions 456>166 for VER enantiomers, 441>166 for NOR enantiomers and 330>193 for the internal standard were monitored and the method had a total chromatographic run time of 12 min. The method allows the determination of VER and NOR enantiomers at plasma levels as low as 1.0 ng/mL. Racemic VER hydrochloride (10mg/kg) was given to male Wistar rats by gavage and blood samples were collected from 0 to 6.0 h (n=6 at each time point). The concentration of (-)-(S)-VER was three folds higher than (+)-(R)-VER, with an AUC ratio (-)/(+) of 2.66. Oral clearance values were 12.17 and 28.77 L/h/kg for (-)-(S)-VER and (+)-(R)-VER, respectively. The pharmacokinetic parameters of NOR were not shown to be enantioselective.

Assessing ongoing sources of dissolved-phase polychlorinated biphenyls in a contaminated stream

USGS Publications Warehouse

Dang, Viet D.; Walters, David M.; Lee, Cindy M.

2013-01-01

Few studies assess the potential of ongoing sources of “fresh” polychlorinated biphenyls (PCBs) to aquatic systems when direct discharge to the environment has been eliminated. In the present study, the authors used single-layered, low-density polyethylene samplers (PEs) to measure total PCB concentrations, congener profiles, and enantiomeric fractions (EFs) in a contaminated stream and to provide multiple lines of evidence for assessing ongoing inputs of PCB. Concentrations were well above background levels that have been monitored for years. Concentrations significantly increased with distance, the farthest downstream PE concentrations being almost five times greater than those at 79 m downstream of a historical point source. The PCBs in the PEs at 79 m downstream of the contamination source were dominated by low KOW congeners, similar to those in the mixture of Aroclors 1016 and 1254 (4:1 v/v) historically released from the former capacitor manufacturer. The only two chiral congeners detected in the PEs downstream were PCBs 91 and 95. The EF values were nonracemic for PCB 91, while the values were either racemic or near racemic for PCB 95. Increased PCB concentrations with distance and a congener composition of predominantly low-weight congeners in the PEs at 79 m downstream of the plant site suggested an ongoing PCB source from the plant site. Chiral signatures suggested aerobic biotransformation of dissolved PCBs but did not shed any light on possible ongoing PCB inputs.

Trail pheromone of ponerine ant Gnamptogenys striatula: 4-methylgeranyl esters from Dufour's gland.

PubMed

Blatrix, Rumsaïs; Schulz, Claudia; Jaisson, Pierre; Francke, Wittko; Hefetz, Abraham

2002-12-01

Dufour's gland is the origin of the trail pheromone of Gnamptogenys striatula. Chemical analysis of the glandular extracts revealed a series of new natural products, especially esters of (2E)-3,4,7-trimethyl-2,6-octadien-1-ol (4-methylgeraniol), and (2E)-3,4,7-trimethyl-2,6-nonadien-1-ol (a bishomogeraniol isomer) with medium-chain fatty acids. Bioassays with synthetic racemates of the esters revealed that the 4-methylgeranyl esters are highly active as trail pheromones, while the bishomogeranyl esters are either marginally active or not active at all. Assays with the individual 4-methylgeranyl esters showed each of them to be inferior to the glandular secretion in eliciting trail following. However, the mixture of racemic 4-methylgeranyl octanoate and the corresponding decanoate and dodecanoate, the main Dufour's volatile constituents, is as active as the natural secretion at similar concentration. We conclude that the trail pheromone constitutes a mixture of at least the 4-methylgeranyl esters identified in the gland. Since G. striatula generally preys on small arthropods rather than monopolizing large resources, we assume that trails are rarely used during foraging, but more often during nest migration. Production of new societies in this species is generally performed by budding, a period of considerable predation risk. Utilizing trails for efficient displacement in this context is, therefore, highly adaptive. This behavioral repertoire may also provide the ants with additional means of food resource exploitation.

Oral versus rectal ibuprofen in healthy volunteers.

PubMed

Vilenchik, Rolanda; Berkovitch, Matitiahu; Jossifoff, Azaria; Ben-Zvi, Zvi; Kozer, Eran

2012-01-01

Ibuprofen is a safe and effective non steroidal anti-inflammatory drug (NSAID). Ibuprofen suppositories are marketed in Europe; but data regarding pharmacokinetics of rectal vs. oral ibuprofen in humans is scarce. The objective of this study is to compare the pharmacokinetics of single-dose rectal vs. oral ibuprofen in healthy adult volunteers. Ten healthy adult male volunteers, aged 20-37 years, received in a non-blind, cross-over setting, two formulations of ibuprofen. First, a 400 mg (about 5 mg/kg) of racemic ibuprofen suppository; second (after a three week washout period) the same dosage of ibuprofen syrup. Blood samples were collected before dosing and for 12 hours after administration. Pharmacokinetics analysis was preformed. Mean peak plasma concentration (Cmax) of rectal ibuprofen was considerably lower, and the mean time to peak (Tmax) considerably longer, compared to oral ibuprofen. Absorption of rectal ibuprofen was considerably lower than oral ibuprofen, with a relative bioequivalence of 63%. Rectal ibuprofen reached therapeutic plasma concentration (>10 µg/ml) 45 minutes after dosing and remained in that range for four hours. The values of Vd/F and CL/F also differ significantly after rectal and oral administration, while no difference was found in the elimination rate constant (Kel) or half-life elimination (t1/2). Racemic ibuprofen suppository has lower bioavailability compared with ibuprofen syrup. Therapeutic plasma concentrations of ibuprofen were reached 45 minutes after dosing and remained in that range for 4 hours. Ibuprofen suppositories can contribute to the management of fever and pain when the oral route is not available.

Enantiomeric Lignans and Neolignans from Phyllanthus glaucus: Enantioseparation and Their Absolute Configurations

NASA Astrophysics Data System (ADS)

Wu, Zhaodi; Lai, Yongji; Zhou, Lei; Wu, Ye; Zhu, Hucheng; Hu, Zhengxi; Yang, Jing; Zhang, Jinwen; Wang, Jianping; Luo, Zengwei; Xue, Yongbo; Zhang, Yonghui

2016-04-01

Eight pairs of enantiomeric neolignans, norlignans, and sesquineolignans (1a/1b-8a/8b), together with five known neolignans (9a/9b and 10-12), have been isolated from 70% acetone extract of the whole plants of Phyllanthus glaucus Wall. (Euphorbiaceae). The racemic or partial racemic mixtures were successfully separated by chiral HPLC using different types of chiral columns with various mobile phases. Their structures were elucidated on the basis of extensive spectroscopic data. The absolute configurations of 2a/2b were determined by computational analysis of their electronic circular dichroism (ECD) spectrum, and the absolute configurations of other isolates were ascertained by comparing their experimental ECD spectra and optical rotation values with those of structure-relevant compounds reported in literatures. Compounds 4a/4b featured unique sesquineolignan skeletons with a novel 7-4‧-epoxy-8‧-8‧‧/7‧-2‧‧ scaffold, consisting of an aryltetrahydronaphthalene and a dihydrobenzofuran moiety. The planar structures of compounds 2, 3, 7, and 8 were documented previously; however, their absolute configurations were established for the first time in this study. The antioxidant activities of 1a/1b-8a/8b were evaluated using DPPH free radical scavenging assay, and the results demonstrated that compounds 1b and 3b showed potent DPPH radical scavenging activities with IC50 values of 5.987 ± 1.212 and 9.641 ± 0.865 μg/mL, respectively.

Age-related accumulation of the advanced glycation endproduct pentosidine in human articular cartilage aggrecan: the use of pentosidine levels as a quantitative measure of protein turnover.

PubMed

Verzijl, N; DeGroot, J; Bank, R A; Bayliss, M T; Bijlsma, J W; Lafeber, F P; Maroudas, A; TeKoppele, J M

2001-11-01

During aging, non-enzymatic glycation results in the formation and accumulation of the advanced glycation endproduct pentosidine in long-lived proteins, such as articular cartilage collagen. In the present study, we investigated whether pentosidine accumulation also occurs in cartilage aggrecan. Furthermore, pentosidine levels in aggrecan subfractions of different residence time were used to explore pentosidine levels as a quantitative measure of aggrecan turnover. In order to compare protein turnover rates, protein residence time was measured as racemization of aspartic acid. As has previously been shown for collagen, pentosidine levels increase with age in cartilage aggrecan. Consistent with the faster turnover of aggrecan compared to collagen, the rate of pentosidine accumulation was threefold lower in aggrecan than in collagen. In the subfractions of aggrecan, pentosidine levels increased with protein residence time. These pentosidine levels were used to estimate the half-life of the globular hyaluronan-binding domain of aggrecan to be 19.5 years. This value is in good agreement with the half-life of 23.5 years that was estimated based on aspartic acid racemization. In aggrecan from osteoarthritic (OA) cartilage, decreased pentosidine levels were found compared with normal cartilage, which reflects increased aggrecan turnover during the OA disease process. In conclusion, we showed that pentosidine accumulates with age in aggrecan and that pentosidine levels can be used as a measure of turnover of long-lived proteins, both during normal aging and during disease.

Inflorescence development in petunia: through the maze of botanical terminology.

PubMed

Castel, Rob; Kusters, Elske; Koes, Ronald

2010-05-01

Flowering plants have developed many ways to arrange their flowers. A flower-bearing branch or system of branches is called an inflorescence. The number of flowers that an inflorescence contains ranges from a single flower to endless flower-clusters. Over the past centuries, botanists have classified inflorescences based on their morphology, which has led to an unfortunate maze of complex botanical terminology. With the rise of molecular developmental biology, research has become increasingly focused on how inflorescences develop, rather than on their morphology. It is the decisions taken by groups of stem cells at the growing tips of shoots, called meristems, on when and where to produce a flower or a shoot that specify the course of inflorescence development. Modelling is a helpful aid to follow the consequences of these decisions for inflorescence development. The so-called transient model can produce the broad inflorescence types: cyme, raceme, and panicle, into which most inflorescences found in nature can be classified. The analysis of several inflorescence branching mutants has led to a solid understanding of cymose inflorescence development in petunia (Petunia hybrida). The cyme of petunia is a distinct body plan compared with the well-studied racemes of Arabidopsis and Antirrhinum, which provides an excellent opportunity to study evolutionary developmental biology (evo-devo) related questions. However, thus far, limited use has been made of this opportunity, which may, at least in part, be due to researchers getting lost in the terminology. Some general issues are discussed here, while focusing on inflorescence development in petunia.

Effect of dimethicone (polysilane gel) on the stereoselective pharmacokinetics of ketoprofen.

PubMed

Presle, N; Lapicque, F; Gillet, P; Herrmann, M A; Bannwarth, B; Netter, P

1998-06-01

Since dimethicone may be employed to improve gastrointestinal tolerability of non steroidal anti-inflammatory drugs (NSAIDs), we studied its influence on the pharmacokinetics of ketoprofen in subjects receiving a single oral dose of racemic ketoprofen. In a cross-over experimental design, 12 healthy fasting volunteers were given a single oral dose (100 mg) of racemic ketoprofen, administered with or without dimethicone. The kinetic parameters measured were area under the concentration (AUC), maximum peak plasma concentration (Cmax), time to reach peak concentration (tmax), elimination half-life (t1/2), mean residence time (MRT) and urinary excretion for R and S enantiomers. Dimethicone reduced the peak concentration of both R and S ketoprofen by about 10% (P<0.05) and also induced a slight but non-significant increase in the mean time to achieve peak concentration. However, this treatment had no significant effect on the bioavailability and the elimination of R and S enantiomers, as shown by AUC, t1/2 and MRT values. The absorption patterns were equivalent for both ketoprofen isomers, since plasma pharmacokinetic parameters were similar. Nevertheless, the urinary recovery was significantly lower for R ketoprofen than for its antipode. The administration of dimethicone did not alter this stereoselectivity. The administration of dimethicone to alleviate the epigastralgic effects related to NSAIDs does not affect the efficacy of the treatment. Dimethicone did not significantly alter the bioavailability of ketoprofen, chosen as an example of an NSAID, especially that of the pharmacologically active S enantiomer.

Direct chiral determination of free amino acid enantiomers by two-dimensional liquid chromatography: application to control transformations in E-beam irradiated foodstuffs.

PubMed

Guillén-Casla, Vanesa; León-González, María Eugenia; Pérez-Arribas, Luis Vicente; Polo-Díez, Luis María

2010-05-01

Changes in free amino acids content and its potential racemization in ready-to-eat foods treated with E-beam irradiation between 1 and 8 kGy for sanitation purposes were studied. A simple heart cut two-dimensional high performance liquid chromatographic method (LC-LC) for the simultaneous enantiomeric determination of three pairs of amino acids used as markers (tyrosine, phenylalanine, and tryptophan) is presented. The proposed method involves the use of two chromatographs in an LC-LC achiral-chiral coupling. Amino acids and their decomposition products were firstly separated in a primary column (C(18)) using a mixture of ammonium acetate buffer (20 mM, pH 6) (94%) and methanol (6%) as the mobile phase. Then, a portion of each peak was transferred by heart cutting through a switching valve to a teicoplanin-chiral column. Methanol (90%)/water (10%) was used as the mobile phase. Ultraviolet detection was at 260 nm. Detection limits were between 0.16 and 3 mg L(-1) for each enantiomer. Recoveries were in the range 79-98%. The LC-LC method combined with the proposed sample extraction procedure is suitable for complex samples; it involves an online cleanup, and it prevents degradation of protein, racemization of L-enantiomers, and degradation of tryptophan. Under these conditions, D-amino acids were not found in any of the analyzed samples at detection levels of the proposed method.

Polymorphic Crystallization and Crystalline Reorganization of Poly(l-lactic acid)/Poly(d-lactic acid) Racemic Mixture Influenced by Blending with Poly(vinylidene fluoride).

PubMed

Yu, Chengtao; Han, Lili; Bao, Jianna; Shan, Guorong; Bao, Yongzhong; Pan, Pengju

2016-08-18

The effects of poly(vinylidene fluoride) (PVDF) on the crystallization kinetics, competing formations of homocrystallites (HCs) and stereocomplexes (SCs), polymorphic crystalline structure, and HC-to-SC crystalline reorganization of the poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemic mixture were investigated. Even though the PLLA/PDLA/PVDF blends are immiscible, blending with PVDF enhances the crystallization rate and SC formation of PLLA/PDLA components at different temperatures that are higher or lower than the melting temperature of the PVDF component; it also facilitates the HC-to-SC melt reorganization upon heating. The crystallization rate and degree of SC crystallinity (Xc,SC) of PLLA/PDLA components in nonisothermal crystallization increase after immiscible blending with PVDF. At different isothermal crystallization temperatures, the crystallization half-time of PLLA/PDLA components decreases; its spherulitic growth rate and Xc,SC increase as the mass fraction of PVDF increases from 0 to 0.5 in the presence of either a solidified or a molten PVDF phase. The HCs formed in primary crystallization of PLLA/PDLA components melt and recrystallize into SCs upon heating; the HC-to-SC melt reorganization is promoted after blending with PVDF. We proposed that the PVDF-promoted crystallization, SC formation, and HC-to-SC melt reorganization of PLLA/PDLA components in PLLA/PDLA/PVDF blends stem from the enhanced diffusion ability of PLLA and PDLA chains.

Urolithiasis in rats consuming a dl bitartrate form of choline in a purified diet.

PubMed

Newland, M Christopher; Reile, Phyllis A; Sartin, Eva A; Hart, Michael; Craig-Schmidt, Margaret C; Mandel, Ian; Mandel, Neil

2005-08-01

Urolithiasis appeared in rats maintained to study the effects of nutrients and methylmercury on development and aging. After a year, the mortality rate was approximately 10%, and by 2 years, it had increased to nearly 30%. Clinical signs and urinary tract pathology were examined as a function of diet, duration on diet, gender, methylmercury exposure, genetics, and other potential risk factors by using survival analyses and qualitative comparisons. Urolithiasis in female rats appeared 15 weeks after beginning a purified diet and after 5 weeks for male rats. After 97 weeks, the mortality rate of female rats was 22% and for male rats was 64%. Lifetime urolithiasis-associated mortality was about 2% in a group of rats that consumed the contaminated diet for < 30 weeks. No urolithiasis occurred in siblings or cohorts of the rats described here that were maintained on a standard rodent chow containing choline chloride. Urolithiasis was traced to racemic, rather than levo-, bitartaric acid in some purified diets shipped in 2001 and 2002. It is unknown when the impurity first appeared in the diet, so estimates of exposure duration are upper limits. Chronic methylmercury exposure increased vulnerability. Some families (dam + offspring) had multiple cases of urolithiasis, but probability models constructed to evaluate familial clustering revealed no evidence for a genetic predisposition to urolithiasis apart from gender. Removing racemic tartaric acid did not decrease mortality once rats had been on the diet for 20 to 30 weeks, but it helped when exposure duration was shorter.

The design, synthesis and pharmacological characterization of novel β2-adrenoceptor antagonists

PubMed Central

Hothersall, J Daniel; Black, James; Caddick, Stephen; Vinter, Jeremy G; Tinker, Andrew; Baker, James R

2011-01-01

BACKGROUND AND PURPOSE Selective and potent antagonists for the β2-adrenoceptor are potentially interesting as experimental and clinical tools, and we sought to identify novel ligands with this pharmacology. EXPERIMENTAL APPROACH A range of pharmacological assays was used to assess potency, affinity, selectivity (β2-adrenoceptor vs. β1-adrenoceptor) and efficacy. KEY RESULTS Ten novel compounds were identified but none had as high affinity as the prototypical β2-adrenoceptor blocker ICI-118,551, although one of the novel compounds was more selective for β2-adrenoceptors. Most of the ligands were inverse agonists for β2-adrenoceptor-cAMP signalling, although one (5217377) was a partial agonist and another a neutral antagonist (7929193). None of the ligands were efficacious with regard to β2-adrenoceptor-β-arrestin signalling. The (2S,3S) enantiomers were identified as the most active, although unusually the racemates were the most selective for the β2-adrenoceptors. This was taken as evidence for some unusual enantiospecific behaviour. CONCLUSIONS AND IMPLICATIONS In terms of improving on the pharmacology of the ligand ICI-118,551, one of the compounds was more selective (racemic JB-175), while one was a neutral antagonist (7929193), although none had as high an affinity. The results substantiate the notion that β-blockers do more than simply inhibit receptor activation, and differences between the ligands could provide useful tools to investigate receptor biology. PMID:21323900

Chiral ligand exchange high-speed countercurrent chromatography: mechanism, application and comparison with conventional liquid chromatography in enantioseparation of aromatic α-hydroxyl acids

PubMed Central

Tong, Shengqiang; Shen, Mangmang; Cheng, Dongping; Ito, Yoichiro; Yan, Jizhong

2014-01-01

This work concentrates on the separation mechanism and application of chiral ligand exchange high-speed countercurrent chromatography (HSCCC) in enantioseparations, and comparison with traditional chiral ligand exchange high performance liquid chromatography (HPLC). The enantioseparation of ten aromatic α-hydroxyl acids were performed by these two chromatographic methods. Results showed that five of the racemates were successfully enantioseparated by HSCCC while only three of the racemates could be enantioseparated by HPLC using a suitable chiral ligand mobile phase additive. For HSCCC, the two-phase solvent system was composed of butanol-water (1:1, v/v), to which N-n-dodecyl-L-proline was added in the organic phase as chiral ligand and cupric acetate was added in the aqueous phase as a transition metal ion. Various operation parameters in HSCCC were optimized by enantioselective liquid-liquid extraction. Based on the results of the present studies the separation mechanism for HSCCC was proposed. For HPLC, the optimized mobile phase composed of aqueous solution containing 6 mmol L−1 L-phenylalanine and 3 mmol L−1 cupric sulfate and methanol was used for enantioseparation. Among three ligands tested on a conventional reverse stationary phase column, only one was found to be effective. In the present studies HSCCC presented unique advantages due to its high versatility of two-phase solvent systems and it could be used as an alternative method for enantioseparations. PMID:25087742