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Mechanistic Details (mechanistic + detail)
Selected AbstractsEnantioselective [4+2]-Cycloaddition Reaction of a Photochemically Generated o -Quinodimethane: Mechanistic Details, Association Studies, and Pressure EffectsCHEMISTRY - A EUROPEAN JOURNAL, Issue 9 2004Benjamin Grosch Dipl. Abstract 1,2,3,4-Tetrahydro-2-oxoquinoline-5-aldehyde (2) was prepared from m -aminobenzoic acid and 3-ethoxyacryloyl chloride (4) in 19,% overall yield. Compound 2 underwent a photochemically induced [4+2]-cycloaddition reaction with various dienophiles upon irradiation in toluene solution. The exo product 10,a was obtained with acrylonitrile (9,a) as the dienophile, whereas methyl acrylate (9,b) and dimethyl fumarate (9,c) furnished the endo products 11,b and 11,c (69,77,% yield). The reactions proceeded at ,60,°C in the presence of the chiral complexing agent 1 (1.2 equiv) with excellent enantioselectivity (91,94,% ee). The enantiomeric excess increases in the course of the photocycloaddition as a result of the lower product association to 1. The intermediate (E)-dienol 8 was spectroscopically detected at ,196,°C in an EPA (diethyl ether/isopentane/ethanol) glass matrix. The association of the substrate 2 to the complexing agent 1 was studied by circular dichroism (CD) titration. The measured association constant (KA) was 589,M,1 at room temperature (25,°C) and normal pressure (0.1 MPa). An increase in pressure led to an increased association. At 400 MPa the measured value of KA was 703,M,1. Despite the stronger association the enantioselectivity of the reaction decreased with increasing pressure. At 25,°C the enantiomeric excess for the enantioselective reaction 2 + 9,a,10,a decreased from 68,% ee at 0.1 MPa to 58,% ee at 350 MPa. This surprising behavior is explained by different activation volumes for the diastereomeric transition states leading to 10,a and ent - 10,a. 1,2,3,4-Tetrahydro-2-oxochinolin-5-aldehyd (2) wurde ausgehend von m -Aminobenzoesäure und 3-Ethoxyacryloylchlorid (4) in fünf Schritten und einer Gesamtausbeute von 19,% hergestellt. Die Verbindung ließ sich in Toluol als Lösungsmittel mit verschiedenen Dienophilen in einer photochemisch induzierten [4+2]-Cycloaddition umsetzen (69,77,% Ausbeute), wobei als Hauptprodukt mit Acrylnitril (9,a) das exo -Produkt 10,a entstand. Methylacrylat (9,b) und Dimethylfumarat (9,c) lieferten die endo -Produkte 11,b and 11,c. In Gegenwart des chiralen Komplexierungsreagenz, 1 (1.2 Äquiv.) verliefen die Reaktionen mit exzellenter Enantioselektivität (91,94,% ee). Der Enantiomerenüberschuß nahm im Verlauf der photochemischen Umsetzung zu, was man auf die relativ zum Substrat 2 niedrigere Assoziation des Produkts zurückführen kann. Das intermediär gebildete (E)-Dienol 8 wurde spektroskopisch in einer EPA (Ether/i -Pentan/Ethanol) Glasmatrix bei ,196,°C nachgewiesen. Die Assoziation des Substrats 2 an das Komplexierungsreagenz 1 wurde durch CD-Titration genauer untersucht. Die Assoziationskonstante (KA) wurde bei Zimmertemperatur (25,°C) und Normaldruck (0.1 MPa) zu 589,M,1bestimmt. Bei höherem Druck beobachtete man eine verstärkte Assoziation und bei 400 MPa wurde eine Assoziationskonstante von KA=703,M,1bestimmt. Trotz der stärkeren Assoziaion nahm die Enantioselektivität mit wachsendem Druck ab. Bei 25,°C sank der Enantiomerenüberschuß der enantioselektiven Reation 2 + 9,a,10,a von 68,% ee bei 0.1 MPa auf 58,% ee bei 350 MPa. Dieses überraschende Verhalten läßt sich möglicherweise durch die unterschiedlichen Aktivierungsvolumina für die Übergangszustände erklären, die zu 10,a und ent - 10,a führen. [source] Pyrazole formation: Examination of kinetics, substituent effects, and mechanistic pathways,INTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 7 2008Joseph C. Sloop Reaction kinetics for the condensation of 1,3-diketones 1a,o with selected arylhydrazines (aryl = Ph, 4-NO2Ph, 4-CH3OPh, and 2,4-diNO2Ph) was studied using 19F NMR spectroscopy. Product regioselectivity is modulated by reactant ratios, substituents, and acidity. Reaction rates were found to be influenced by substituents on the diketones and on phenylhydrazines as well as by acidity of the reaction medium with rates varying as much as 1000-fold. Hammett , values for these cyclizations were determined. The reaction was found to be first order in both the diketone and arylhydrazine. The rate-determining step for pyrazole formation shifts as a function of pH. Mechanistic details and reaction pathways supporting these findings are proposed. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 40: 370,383, 2008 [source] Development of a coupled metal speciation-fate model for surface aquatic systemsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2004Satyendra P. Bhavsar Abstract A coupled metal transport and speciation model (TRANSPEC) has been developed for surface aquatic systems that explicitly considers the influence of metal speciation on fate. The TRANSPEC, which is general to most metal and surface aquatic systems, is constructed by sequentially coupling the speciation/complexation module (in this application MINEQL+) with the fugacity/aquivalence approach for the fate calculations. This model formulation increases the mechanistic detail, predictive power, and fidelity to reality of current fugacity-aquivalence fate models for metals by estimating aqueous speciation and complexation, rather than relying on empirically derived partition coefficients. A pseudo-steady state version of TRANSPEC was used to simulate Zn dynamics in Ross Lake (Flin Flon, MB, Canada) that received elevated metal and organic matter inputs for over 50 years. Field studies revealed that ZnS forms soluble ZnL, Zn2+, and ZnSO40 increasing pore water concentrations when surficial sediments turn oxic during fall. The model results for three seasonal scenarios suggest that Zn remobilization is driven by resuspension of insoluble ZnS and the contribution of diffusion is negligible, even during fall when ZnS dissolves to increase the concentration of soluble species under oxic conditions in the sediments. The low diffusive flux is due to the binding of Zn to colloidal dissolved organic matter (DOM) for which sediment-water diffusion is relatively slow, a result that was obtained as a result of considering metal speciation in the fate calculations. [source] Reconciling plant strategy theories of Grime and TilmanJOURNAL OF ECOLOGY, Issue 6 2005JOSEPH M. CRAINE Summary 1The theories of Grime and Tilman are ambitious attempts to unify disparate theories regarding the construction of plants, their interaction with the environment and the assembly of communities. After over two decades of parallel research, their ideas have not been reconciled, hindering progress in understanding the functioning of ecosystems. 2Grime's theories do not adequately incorporate the importance of non-heterogeneous supplies of nutrients and how these supplies are partitioned over long time scales, are inconsistent regarding the importance of disturbance in nutrient-limited habitats and need to reconsider the carbon economy of shade-tolerant plants. 3Failure to account for differences between aquatic and terrestrial systems in how resource supplies are partitioned led Tilman to develop a shifting set of theories that have become reduced in mechanistic detail over time. The most recent highlighted the reduction of nutrient concentrations in soil solution, although it can no longer be derived from any viable mechanistic model. The slow diffusion of nutrients in soils means that the reduction of average soil solution nutrient concentrations cannot explain competitive exclusion. 4Although neither theory, nor a union of the two, adequately characterizes the dynamics of terrestrial plant assemblages, the complementarity in their assumptions serve as an important foundation for future theory and research. 5Reconciling the approaches of Grime and Tilman leads to six scenarios for competition for nutrients and light, with the outcome of each depending on the ability of plants to pre-empt supplies. Under uniform supplies, pulses or patches, light competition requires leaf area dominance, while nutrient competition requires root length dominance. There are still important basic questions regarding the nature of nutrient supplies that will need to be answered, but recent research brings us closer to a unified set of theories on resource competition. [source] Specific Processes and Scrambling in the Dehydrogenation of Ethane and the Degenerate Hydrogen Exchange in the Gas-Phase Ion Chemistry of the Ni(C,H3,O)+/C2H6 CoupleHELVETICA CHIMICA ACTA, Issue 5 2007Maria Schlangen Abstract A mechanistically unprecedented situation characterizes the gas-phase ion chemistry of Ni(C,H3,O)+ when reacted under thermal, single-collision conditions with ethane. A dehydrogenation channel leading to Ni(C3,H7,O)+ is to 90% preceded by a complete loss of positional identity of all nine H-atoms of the encounter complex (,scrambling'), whereas ca. 10% of the reaction exhibit a selective CH bond activation of the alkane. In addition, a degenerate H exchange between ethane and the (C,H3,O) unit occurs as a side reaction, the mechanistic details of which remain unknown for the time being. [source] On the Scope of a Prins -Type Cyclization of Oxonium IonsHELVETICA CHIMICA ACTA, Issue 11 2004Georg Fráter The Prins cyclization of an aldehyde 1 with a homoallylic alcohol 2, affording tetrahydro-2H -pyrans 4via the oxonium ion 3 as central intermediate, was conceptually transferred to (alk-3-enyloxy)acrylates 6, which form a related oxonium ion 7 upon treatment with acids (Scheme,1). The scope and utility of this modification of the Prins -type cyclization of oxonium ions is discussed exemplarily by means of the syntheses of ten tetrahydro-2H -pyran and tetrahydrofuran derivatives, featuring diverse substitution patterns as well as different degrees of molecular complexity. These target structures include (±)-ethyl (2RS)-2-[(2RS,4SR,6RS)- and (2SR,4RS,6SR)-2-tetahydro-4-hydroxy-6-methylpyran-2-yl]propanoate (23), (±)-ethyl [(2RS, 3RS)-tetrahydro-3-isopropenylfuran-2-yl]acetate (32), (±)-ethyl (2Z)-3-(tetrahydro-2,2-dimethylfuran-3-yl)acrylate (37), (±)-(3aRS,6RS, 7aRS)-octahydro-7a-methylbenzofuran-6-yl formate (42), (±)-ethyl (2RS,3RS,4aRS,8SR,8aRS)-hexahydro-2,5,5,8-tetramethyl-7-oxo-2H,5H -pyrano[4,3- b]pyran-3-carboxylate (48), and (±)-ethyl (2RS,3RS,6SR)-tetrahydro-6-(2-methoxy-2-oxoethyl)-3-methyl-2H -pyran-2-carboxylate (53) (see Schemes,3 and 5,8). Besides the stereochemistry and mechanistic details of this versatile oxonium-ion cyclization, the synthesis of suitable starting materials is also described. [source] Mechanism of the Asymmetric Sulfoxidation in the Esomeprazole Process: Effects of the Imidazole Backbone for the EnantioselectionADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 6 2009Muthu Seenivasaperumal Abstract The asymmetric sulfoxidation reaction of imidazole-based prochiral sulfides was studied to explore the mechanistic details of the highly efficient esomeprazole process, which is one of the few industrial scale catalytic asymmetric procedures. The synthetic studies revealed that the smallest subunit governing the selectivity in the esomeprazole process is an imidazole ring. Thus, by using the esomeprazole procedure methyl imidazole sulfide could be oxidized as efficiently as its several functionalized derivatives, including pyrmetazol. However, alkylation of the imidazole nitrogen led to a major drop of the enantioselectivity. Our atmospheric pressure chemical ionization-mass spectrometry (APCI/MS) studies indicate that addition of small amounts of water to the reaction mixture facilitates the formation of mononuclear titanium species, which are the active catalytic intermediates of the selective oxidation reaction. One of the most important features of the esomeprazole procedure is that amine additives increase the enantioselectivity of the oxidation process. The NMR studies of the presumed reaction intermediates show that under catalytic conditions the amines are able to coordinate to titanium and dissociate the coordinated imidazole substrate. The density functional theory (DFT) modelling studies provided new insights in the mechanism of the asymmetric induction. It was found that the oxidation requires a lower activation energy if the imidazole sulfide precursor does not coordinate to titanium. Two possible reaction paths were explored for this out of sphere oxidation mechanism. The most important interaction governing the enantioselection is hydrogen bonding between the NH of the imidazole ring and the chiral tartrate ligand on titanium. Furthermore, the oxidation reaction imposes an important structural constraint to the TS structure involving a linear arrangement of the peroxide oxygens and the sulfur atom. This constraint and the N coordination of imidazole leads to a very strained structure for the inner sphere mechanism of the oxidation, which leads to a much higher activation barrier than the corresponding out of sphere process, and therefore it is unlikely. [source] Experimental demonstration of population extinction due to a predator-driven Allee effectJOURNAL OF ANIMAL ECOLOGY, Issue 3 2010Andrew M. Kramer Summary 1. Allee effects may result in negative growth rates at low population density, with important implications for conservation and management of exploited populations. Theory predicts prey populations will exhibit Allee effects when their predator exhibits a Type II functional response, but empirical evidence linking this positively density-dependent variation in predator-induced individual mortality to population growth rate and probability of extinction is lacking. 2. Here, we report a demonstration of extinction due to predator-driven Allee effects in an experimental Daphnia-Chaoborus system. A component Allee effect caused by higher predation rates at low Daphnia density led to positive density dependence in per capita growth rate and accelerated extinction rate at low density. 3. A stochastic model of the process revealed how the critical density below which population growth is negative depends on the mechanistic details of the predator,prey interaction. 4. The ubiquity of predator,prey interactions and saturating functional responses suggests predator-driven Allee effects are potentially important in determining extinction risk of a large number of species. [source] Mechanistic insights into oxidosqualene cyclizations through homology modelingJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2003Gasch, Tanja Schulz Abstract 2,3-Oxidosqualene cyclases (OSC) are key enzymes in sterol biosynthesis. They catalyze the stereoselective cyclization and skeletal rearrangement of (3S)-2,3-oxidosqualene to lanosterol in mammals and fungi and to cycloartenol in algae and higher plants. Sequence information and proposed mechanism of 2,3-oxidosqualene cyclases are closely related to those of squalene-hopene cyclases (SHC), which represent functional analogs of OSCs in bacteria. SHCs catalyze the cationic cyclization cascade converting the linear triterpene squalene to fused ring compounds called hopanoids. High stereoselectivity and precision of the skeletal rearrangements has aroused the interest of researchers for nearly half a century, and valuable data on studying mechanistic details in the complex enzyme-catalyzed cyclization cascade has been collected. Today, interest in cyclases is still unbroken, because OSCs became targets for the development of antifungal and hypocholesterolemic drugs. However, due to the large size and membrane-bound nature of OSCs, three-dimensional structural information is still not available, thus preventing a complete understanding of the atomic details of the catalytic mechanism. In this work, we discuss results gained from homology modeling of human OSC based on structural information of SHC from Alicyclobacillus acidocaldarius and propose a structural model of human OSC. The model is in accordance with previously performed experimental studies with mechanism-based suicide inhibitors and mutagenesis experiments with altered activity and product specificity. Structural insight should strongly stimulate structure-based design of antifungal or cholesterol-lowering drugs. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 741,753, 2003 [source] Understanding the Chemistry of the Development of Latent Fingerprints by Superglue FumingJOURNAL OF FORENSIC SCIENCES, Issue 5 2007Stephen P. Wargacki Ph.D. Abstract:, Cyanoacrylate fuming is a widely used forensic tool for the development of latent fingerprints, however the mechanistic details of the reaction between the fingerprint residue and the cyanoacrylate vapor are not well understood. Here the polymerization of ethyl-cyanoacrylate vapor by sodium lactate or alanine solutions, two of the major components in fingerprint residue, has been examined by monitoring the time dependence of the mass uptake and resultant polymer molecular weight characteristics. This data provides insight into the molecular level actions in the efficient development of latent fingerprints by superglue fuming. The results show that the carboxylate moiety is the primary initiator of the polymerization process and that a basic environment inhibits chain termination while an acidic environment promotes it. The results also indicate that water cannot be the primary initiator in this forensic technique. [source] Calpain-mediated degradation of G-substrate plays a critical role in retinal excitotoxicity for amacrine cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2009Toru Nakazawa Abstract The role of neuronal N-methyl-D-aspartate (NMDA) receptor-mediated intracellular signaling has been elucidated in both physiological and pathological conditions. However, the details of relative vulnerability for excitotoxicity remain unknown. Retinal excitotoxicity is involved in various diseases leading to irreversible blindness. Here, we used the visual system and explored the mechanistic details of the NMDA-elicited intracellular events, especially in the amacrine cells, which are the most vulnerable type of neuron in the retina. G-substrate, a specific substrate of cyclic guanosine 3,,5,-monophosphate (cGMP)-dependent protein kinase, is colocalized with amacrine cells and acts as an endogenous inhibitor of protein phosphatase. To elucidate how G-substrate was involved in NMDA-induced amacrine cell death, the immunohistochemical analysis with G-substrate antibody was performed following NMDA injury. In vivo, NMDA immediately decreased G-substrate immunoreactivity, and the suppression of calpain activation using ALLN or calpain III, an inhibitor of calpain, blocked this decrease. In vitro, degraded fragments of G-substrate were detected within 10 min after coincubation of G-substrate and calpain. Moreover, G-substrate knockout (G-substrate,/,) mice were more susceptible to NMDA injury than wild-type mice. ALLN did not have a neuroprotective effect in G-substrate,/, mice. These data strongly suggest that calpain-mediated loss of G-substrate represents an important mechanism contributing to NMDA-induced amacrine cell death. © 2008 Wiley-Liss, Inc. [source] Ribosome's mode of function: myths, facts and recent results,JOURNAL OF PEPTIDE SCIENCE, Issue 3 2009Itai Wekselman Abstract Ribosomes translate the genetic code into proteins in all living cells with extremely high efficiency, owing to their inherent flexibility and to their spectacular architecture. During the last 6 decades, extensive effort has been made to elucidate the molecular mechanisms associated with their function, and a quantum jump has been made in recent years, once the three dimensional structures of ribosomes and their functional complexes have been determined. These illuminated key issues in ribosome function, confirmed various biochemical, genetic, and medical findings, and revealed mechanistic details beyond previous expectation, thus leading to conceptual revolutions, and turning old myths into actual facts. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. [source] Activity Switches of Rhodopsin,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2008Eglof Ritter Rhodopsin, the visual pigment of the rod photoreceptor cell contains as its light-sensitive cofactor 11- cis retinal, which is bound by a protonated Schiff base between its aldehyde group and the Lys296 side chain of the apoprotein. Light activation is achieved by 11- cis to all- trans isomerization and subsequent thermal relaxation into the active, G protein-binding metarhodopsin II state. Metarhodopsin II decays via two parallel pathways, which both involve hydrolysis of the Schiff base eventually to opsin and released all- trans retinal. Subsequently, rhodopsin's dark state is regenerated by a complicated retinal metabolism, termed the retinoid cycle. Unlike other retinal proteins, such as bacteriorhodopsin, this regeneration cycle cannot be short cut by light, because blue illumination of active metarhodopsin II does not lead back to the ground state but to the formation of largely inactive metarhodopsin III. In this review, mechanistic details of activating and deactivating pathways of rhodopsin, particularly concerning the roles of the retinal, are compared. Based on static and time-resolved UV/Vis and FTIR spectroscopic data, we discuss a model of the light-induced deactivation. We describe properties and photoreactions of metarhodopsin III and suggest potential roles of this intermediate for vision. [source] Structure of dehaloperoxidase B at 1.58,Å resolution and structural characterization of the AB dimer from Amphitrite ornataACTA CRYSTALLOGRAPHICA SECTION D, Issue 5 2010Vesna De Serrano As members of the globin superfamily, dehaloperoxidase (DHP) isoenzymes A and B from the marine annelid Amphitrite ornata possess hemoglobin function, but they also exhibit a biologically relevant peroxidase activity that is capable of converting 2,4,6-trihalophenols to the corresponding 2,6-dihaloquinones in the presence of hydrogen peroxide. Here, a comprehensive structural study of recombinant DHP B, both by itself and cocrystallized with isoenzyme A, using X-ray diffraction is presented. The structure of DHP B refined to 1.58,Å resolution exhibits the same distal histidine (His55) conformational flexibility as that observed in isoenzyme A, as well as additional changes to the distal and proximal hydrogen-bonding networks. Furthermore, preliminary characterization of the DHP AB heterodimer is presented, which exhibits differences in the AB interface that are not observed in the A-only or B-only homodimers. These structural investigations of DHP B provide insights that may relate to the mechanistic details of the H2O2 -dependent oxidative dehalogenation reaction catalyzed by dehaloperoxidase, present a clearer description of the function of specific residues in DHP at the molecular level and lead to a better understanding of the paradigms of globin structure,function relationships. [source] Structure,function studies of the RNA polymerase II elongation complexACTA CRYSTALLOGRAPHICA SECTION D, Issue 2 2009Florian Brueckner RNA polymerase II (Pol II) is the eukaryotic enzyme that is responsible for transcribing all protein-coding genes into messenger RNA (mRNA). The mRNA-transcription cycle can be divided into three stages: initiation, elongation and termination. During elongation, Pol II moves along a DNA template and synthesizes a complementary RNA chain in a processive manner. X-ray structural analysis has proved to be a potent tool for elucidating the mechanism of Pol II elongation. Crystallographic snapshots of different functional states of the Pol II elongation complex (EC) have elucidated mechanistic details of nucleotide addition and Pol II translocation. Further structural studies in combination with in vitro transcription experiments led to a mechanistic understanding of various additional features of the EC, including its inhibition by the fungal toxin ,-amanitin, the tunability of the active site by the elongation factor TFIIS, the recognition of DNA lesions and the use of RNA as a template. [source] Influence of Ionization State on the Activation of Temocapril by hCES1: A Molecular-Dynamics StudyCHEMISTRY & BIODIVERSITY, Issue 11 2009Giulio Vistoli Abstract Temocapril is a prodrug whose hydrolysis by carboxylesterase 1 (CES1) yields the active ACE inhibitor temocaprilat. This molecular-dynamics (MD) study uses a resolved structure of the human CES1 (hCES1) to investigate some mechanistic details of temocapril hydrolysis. The ionization constants of temocapril (pK1 and pK3) and temocaprilat (pK1, pK2, and pK3) were determined experimentally and computationally using commercial algorithms. The constants so obtained were in good agreement and revealed that temocapril exists mainly in three ionic forms (a cation, a zwitterion, and an anion), whereas temocaprilat exists in four major ionic forms (a cation, a zwitterion, an anion, and a dianion). All these ionic forms were used as ligands in 5-ns MS simulations. While the cationic and zwitterionic forms of temocapril were involved in an ion-pair bond with Glu255 suggestive of an inhibitor behavior, the anionic form remained in a productive interaction with the catalytic center. As for temocaprilat, its cation appeared trapped by Glu255, while its zwitterion and anion made a slow departure from the catalytic site and a partial egress from the protein. Only its dianion was effectively removed from the catalytic site and attracted to the protein surface by Lys residues. A detailed mechanism of product egress emerges from the simulations. [source] | |||||||||||||