Different NMR approaches to the chiral analysis of trisubstituted allenes devoid of polar functional groups and aromatic hydrocarbons

The use of permethylated beta-cyclodextrin as chiral solvating agent for NMR spectroscopy allowed us to determine the enantiomeric purity of chiral aromatic hydrocarbons as well as the enantiomeric purity and absolute configuration of chiral trisubstituted allenes devoid of polar functional groups. The enantiomeric excesses of the trisubstituted allenes have been also determined by 195Pt NMR spectroscopy of the diastereoisomeric trans-dichloro[(S)-alpha-phenylethyl-amine](allene)Pt(II) complexes.     

Novel Chiral PNNP-Ru Complexes:Synthesis and Application in Asymmetric Transfer Hydrogenation of Ketones

The efficient catalytic systems generated in situ from RuCl2(PPh3)3 and chiral ligands N,N-bis[2-(di-otolylphosphino)-benzyl]cyclohexane-1,2-diamine(2) were employed for asymmetric transfer hydrogenation of aromatic ketones, giving the corresponding optically active alcohols with high activities(up to 99% conversion) and excellent enantioselectivities(up to 96% e.e.) under mild conditions. The chiral ruthenium(Ⅱ) complex (R.,R)-3 has been prepared and characterized by NMR and X-ray crystallography.     

The design of chiral separation media using monodisperse functionalized macroporous beads: effects of polymer matrix, tether, and linkage chemistry

Porous size monodisperse methacrylate beads containing amino and hydroxyl groups, which can be used as a platform for the production of chiral separation media, have been prepared using the staged templated suspension polymerization process. The monomers 2-hydroxyethyl methacrylate and several tert-butoxycarbonyl-protected aminoalkyl methacrylates were used for the preparation of both hydroxyl- and amino-functionalized beads. Attachment of a chiral selector based on L-valine-3,5-dimethylanilide through a carbamate and a urea linkage, respectively, provides chiral stationary phases with excellent enantioselectivities in the separation of the enantiomers of 3,5-dinitrobenzamido derivatives of alpha-amino acids. For comparison purposes, a separation medium was also prepared by the direct polymerization of a chiral monomer analogous to the hydroxyethyl methacrylate-based stationary phase. The chiral stationary phases prepared with the N-methyl-2-aminoethyl methacrylate platform exhibit the best selectivity, and separation factors as high as 15 were achieved under normal-phase HPLC conditions.     

Stereocontrolled phosphorothioate synthesis using chiral phosphite triesters

We describe stereocontrolled synthesis of phosphorothioate oligonucleotides including stereospecific transesterification to form chiral phosphite triester backbone under basic conditions. Substrate phosphite triesters with phenoxy derivative substituents as leaving groups were separated into individual stereoisomers and reacted with hydroxyl-containing compounds to form chiral phosphite triester backbone. Subsequent stereoretentive sulfurization and deprotection gave desired stereocontrolled phosphorothioate linkages.     

Enantioselective bioanalysis of beta-blocking agents: focus on atenolol, betaxolol, carvedilol, metoprolol, pindolol, propranolol and sotalol

The recent developments in enantioselective HPLC-separation techniques are impressive and are driven by industrial and academic interests; thus there is for instance a high demand for developing stereoselective assays for chiral drugs in biological fluids. The beta-blocking agents, which possess an amino-propanol- or -ethanol side chain with at least one chiral centre, represent one of the most intensively investigated groups of more than 40 drugs introduced world wide. Seven of the most popular beta-blockers were chosen as representatives: atenolol; betaxolol; carvedilol; metoprolol; pindolol; propranolol; and sotalol, these span the whole range of lipophilicity to hydrophilicity (polarity). Enantioselective HPLC bioassays for these beta-blockers published so far, including techniques based on chiral derivatizing agents (CDAs), chiral stationary phases (CSPs) and chiral mobile phase additives (CMPAs) have been reviewed and documented in the light of general aspects together with pharmacokinetic and pharmacodynamic considerations.     

Borna disease virus--a possible etiological agent of human psychoneurological disorders?

The effect of three different feeding techniques (electronic automated feeder, teat bucket and bucket with floating teat) on oral activities, skin condition, health and performance of 144 German Holstein group housed veal calves was investigated. About 21% of the observed time over 24 hours was spent on oral activities and only about 1% with the particularly health-relevant activities at prepuce, navel or scrotum. As a consequence of sucking activities at pen mates in most cases reddening of the skin and, with low incidence (about 7%), additional loss of hair could be found. Altogether about 74% of the calves were affected with the highest incidence in the electronic automated feeder groups. Calves of these groups had, moreover, higher disease incidences and a lower weight gain and feed conversion rate than those fed by teat bucket or by bucket with floating teat. Altogether results show that in terms of behaviour and health it is possible to keep calves at the age of two weeks in groups, even in conventional veal calf production, when satisfactory management is applied. The electronic automated feeder still needs further technical development for use with veal calves.     

Influence of neonatal idiopathic respiratory distress syndrome on serum enzyme activities in premature healthy and asphyxiated newborns

Elevated serum aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), and hydroxybutyrate dehydrogenase (HBDH) activities are highly predictive for the development of hypoxia-related neurologic disorders in asphyxiated newborns. Little is known about the influence of the idiopathic respiratory distress syndrome (IRDS) on the serum profile of these enzymes. In a prospective study we measured ASAT, LDH, and HBDH activities in asphyxiated newborns with (n = 12) and without (n = 12) IRDS as well as non-asphyxiated newborns with IRDS (n = 16). Blood samples were taken serially at five fixed times: 0 (cord), 12, 24, 72, and 144 hours postpartum. Whereas both study groups of asphyxiated newborns showed significantly elevated enzyme activities as compared with the non-asphyxiated controls, the fundamental influence of perinatal hypoxic-ischemic events on neonatal serum enzyme profiles and activities of all three enzymes was not significantly altered by the development of IRDS. Therefore, the predictive value of these enzymes for the development of neurologic disorders in asphyxiated newborns is not adversely affected by the development of an immediately and effectively treated IRDS. It is concluded that elevated ASAT, LDH, and HBDH activities can be used as predictors for neurologic disorders in asphyxiated newborns even in the presence of IRDS.     

Strategies for capillary electrophoresis: method development and validation for pharmaceutical and biological applications

This review is in support of the development of selective, reproducible and validated capillary electrophoretis (CE) methods. Focusing on pharmaceutical and biological applications, the successful use of CE is demonstrated by more than 800 references, mainly from 1994 until 1998. Approximately 80 recent reviews have been catalogued. These articles sum up the existing strategies for method development in CE, especially in the search for generally accepted concepts, but also looking for new, promising reagents and ideas. General strategies for method development were derived not only with regard to selectivity and efficiency, but also with regard to precision, short analysis time, limit of detection, sample pretreatment requirements and validation. Standard buffer recipes, surfactants used in micellar electrokinetic capillary chromatography (MEKC), chiral selectors, useful buffer additives, polymeric separation media, electroosmotic flow (EOF) modifiers, dynamic and permanent coatings, actions to deal with complex matrices and aspects of validation are collected in 20 tables. Detailed schemes for the development of MEKC methods and chiral separations, for optimizing separation efficiency, means of troubleshooting, and other important information for key decisions during method development are given in 19 diagrams. Method development for peptide and protein separations, possibilities to influence the EOF and how to stabilize it, as well as indirect detection are considered in special sections.     

Patterns of adolescents' participation in organized activities: Are sports best when combined with other activities?

Although many adolescents participate in sports and other types of organized activities, little extant research explores how youth development outcomes may vary for youth involved in different combinations of activities. The present study uses the Child Development Supplement of the Panel Study of Income Dynamics, a large, nationally representative sample, to compare activity patterns of adolescents ages 10–18 years (n = 1,711). A cluster analytic technique revealed 5 activity clusters: sports-focused, sports plus other activities, primarily school-based activities, primarily religious youth groups, and low activity involvement. Activity patterns were examined in conjunction with 5 categories of youth development outcomes, including competence (e.g., academic ability), confidence (e.g., self-concept of ability), connections (e.g., talking with friends), character (e.g., externalizing behavior problems), and caring (e.g., prosocial behavior). Results showed that those who participated only in sports had more positive outcomes compared with those who had little or no involvement in organized activities, but less positive outcomes compared with those who participated in sports plus other activities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immobilized enzymes--learning from past successes and failures

The use of immobilized enzymes in the food, pharmaceutical and chemical industries has increased steadily during the past decade. Further research and development in enzyme technology is expected to expand their use in the synthesis of chiral drugs, complex organic compounds and fine chemicals, and lead to the construction of novel, specific biosensors.     

Programmed changes of cell cycle regulators by serum deprivation regardless of skeletal myocyte differentiation

Permanent withdrawal of skeletal myoblasts from the cell cycle precedes differentiation. We examined the changes of protein levels of cell cycle regulators and the activities of CDKs in differentiating (by serum deprivation) or in differentiation-inhibited (by serum deprivation + TGF-beta1 treated) C2C12 skeletal myocytes. Regardless of differentiation, protein levels of most cyclins declined over time while this effect was delayed slightly by TGF-beta1 for cyclins D1 and F. Although the protein levels of CDKs gradually decreased over time, the activities of CDK2 and cdc2 decreased dramatically between 0 and 12 h after serum deprivation in both groups. Decreased CDK2 and cdc2 activities were temporally related to decreased DNA synthesis. While the p27KIP1 protein increased in both groups, the p21CIP1 protein increased only in differentiating cells. In vivo, protein expressions of cyclins, CDKs, and p21CIP1 were high in fetal, but almost undetectable in adult skeletal muscle. In contrast, the levels of p27KIP1 protein in skeletal muscle were high throughout development. Thus, changes of cell cycle regulators in differentiating C2C12 myocytes paralleled those during skeletal muscle development of mice. These results suggest that the rapid reduction of DNA synthesis and activities of CDKs slow reduction of protein levels of cyclins and CDKs, and that the increase of p27KIP1 are programmed mechanisms upon mitogen deprivation regardless of differentiation in skeletal myocytes.     

A forty-year follow-up on the vocational interests of psychologists and their relationship to career development.

Studied a career development questionnaire completed by 37 male psychologists, and SVIBs which they completed on 3 occasions between 1927 and 1968. Test and retest profiles for the sample were similar over the 40-yr period, but interest in strenuous activities and in activities requiring association with other people decreased with age. No 1 factor seemed to have been dominant in leading Ss to become psychologists. Career development had most often been influenced by major position changes, many affected by environmental factors. Some individual profiles changed markedly over time. 2 groups of 10 Ss each, representing Ss with stable and unstable interests, were compared. The "stable" Ss tended to prefer academic and artistic activities and centered their careers around teaching and research. The "unstable" Ss were more interested in working with people in managerial or supervisory relationships and tended to move from teaching toward administration or business. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Coupled achiral/chiral column techniques in subcritical fluid chromatography for the separation of chiral and nonchiral compounds

A multicolumn approach was developed to address the limited achiral selectivity of chiral stationary phases. Groups of structurally related compounds, including beta-blockers and 1,4-benzodiazepines, were separated using coupled achiral/chiral stationary phases under subcritical fluid conditions. The achiral selectivity of amino and cyano stationary phases was used to modify the resolution of compounds on a Chiralcel OD chiral stationary phase by combining the achiral and chiral columns in series. In the case of the benzodiazepines, separation of achiral compounds was performed concurrently with the enantioseparation of chiral molecules. The separation of components of a multidrug cough and cold medication was also demonstrated on a cyano column coupled with a Chiralpak AD chiral stationary phase. The use of modified carbon dioxide eluents eliminated the mobile phase incompatibility problems associated with column coupling in liquid chromatography and incorporated the high efficiency of sub- and supercritical fluid chromatography.     

Isosteres of chiral clofibric acid analogs: synthesis, resolution, absolute configuration and HPLC detection of the optical purity

Both racemic and enantiomeric forms of some isosteres of chiral clofibric acid analogs have been synthesized. Also, the absolute configuration has been established by chemical correlation and the optical purity determined by a simple HPLC procedure. Moreover, these studies show that the isosteric substitution of the ether oxygen atom of alpha-aryloxy-alkanoic acids with sulfur, amino and methylene groups lead to compounds in which both biological activity and stereoselectivity regarding chloride channel are highly reduced.     

Chiral PAF agonists: synthesis, theoretical analysis of their stereoelectronic properties and structure activity relationships

A series of chiral PAF agonists were synthesized. Modifications at the PAF structure were undertaken as far as the C2 substituents and the onium head groups are concerned. In parallel, molecular modelling studies including a MOPAC geometry optimization and the analysis of the electrostatic potential were performed on the newly synthesized and on already known PAF agonists, in order to gain a better insight into the stereoelectronic features required for interaction with the PAF receptor.     

Affinity capillary electrophoresis in biomolecular recognition

Affinity capillary electrophoresis is a new method for studies of biomolecular recognition. Applications reported in the literature include chiral separation of racemic biomolecules, measurement of binding constants, estimation of kinetic on- and off-rate constants, determination of binding stoichiometries (a useful tool in examining electrostatic interactions), estimation of effective charges and molecular weights of proteins, characterization of enzymatic activities and library screening for tight-binding drug candidates in solution. This technique demands only small amounts of sample (nanolitre injection volumes, picograms of proteins), involves no radiolabelled materials or chemically immobilized ligands, and does not require changes in spectroscopic characteristics upon binding. This paper reviews the most recent applications of affinity capillary electrophoresis and its use in the analysis of biomolecules.     

Chiral surfactants in micellar electrokinetic capillary chromatography

Most biologically active molecules contain one or more chiral centres, giving rise to stereoisomeric forms which can behave differently in a chiral environment. Thus, only one of the enantiomers may show the desired physiological activity, whereas the other enantiomers may either be considerably less active or even show undesireable side effects. Establishing that a chiral drug consists of one single enantiomer is nowadays essential before it can be given to patients. Analytical tools that can discriminate between enantiomers play a very important role in determining the stereoisomeric composition of chiral molecules. Until recently chromatographic techniques were the most popular for enantiomeric separations. The increased use of capillary electrophoresis (CE) has provided complementary methodology for chiral discrimination. One mode of CE that has been used for this purpose is micellar electrokinetic capillary chromatography (MECC), where natural or synthetic chiral surfactants are added to the separation buffer.     

PARAGRAPH as a neuromuscular blockade monitor

In connection with the development of new anticonvulsant agents with a broad spectrum, we found that N-Cbz-alpha-amino-N-alkylsuccinimides showed significant anticonvulsant activities, and the pharmacological activities of these compounds were dependent on their stereochemistry and N-substituted alkyl group. These results prompted us to define the effects of other functional group on the anticonvulsant activities of these compounds. Therefore a series of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimide were prepared from N-Cbz-aspartic acid and were evaluated with their anticonvulsant activities against the MES and PTZ tests, in order to define the effect of N-substituted alkoxy carbonyl group with the anticonvulsant activities. From these studies, it was found that all the tested N-alkoxycarbonyl-alpha-amino-N-methylsuccinimides exhibited significant anticonvulsant activities in the PTZ test and were not active in the MES test. The most active compound in the PTZ test was (S) N-ethoxycarbonyl-alpha-amino-N-methyl-succinimide. We found that the pharmacological activities in the PTZ test were dependent on their N-alkoxycarbonyl groups. They follow as such; The order of anticonvulsant activities for (R) series as evaluated by ED50 was N-phenoxycarbonyl = N-4-nitrobenzyloxycarbonyl > N-ethoxycarbonyl > N-allyloxycarbonyl > N-tert. butoxycarbonyl compound; For the (S) series N-ethoxycarbonyl > N-phenoxycarbonyl > N-allyloxycarbonyl compound. From the above results, it was conceivable that N-substituted alkoxycarbonyl group had certain effects on the anticonvulsant activities of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimides.     

Recent progress in liquid chromatographic enantioseparation based upon diastereomer formation with fluorescent chiral derivatization reagents

Techniques for the resolution by liquid chromatography of racemic compounds based upon diastereomer formation with a fluorescent chiral reagent are outlined in this review. The tagging reagents for various functional groups, i.e. amine, carboxyl, hydroxyl and thiol, are evaluated in terms of optical purity, handling, flexibility, stability, sensitivity and selectivity. The applicabilities of the reagents to drugs and biologically important substances are included in the text. This review is limited to reagents with fluorophores and reagents that exhibit fluorescence.     

Chiral separation of pharmaceuticals possessing a carboxy moiety

The separation of carboxylic enantiomers in the pharmaceutical field using high-performance liquid chromatographic and capillary electrophoretic techniques is reviewed. The techniques used for chiral separation include diastereomer derivatization, a chiral mobile phase, a chiral stationary phase (high-performance liquid chromatography) and chiral additives (capillary electrophoresis). Practical and conventional separation systems for pharmaceutical applications, such as pharmacokinetics, optical purity testing and stability studies, are described. A comprehensive collection of applications to carboxylic drugs and other carboxylic compounds of pharmaceutical interest is listed in the tables. The characteristics of each enantioseparation method are also discussed briefly.