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Two-step Mechanism (two-step + mechanism)
Selected AbstractsComplete reconstruction of the retinal laminar structure from a cultured retinal pigment epithelium is triggered by altered tissue interaction and promoted by overlaid extracellular matricesDEVELOPMENTAL NEUROBIOLOGY, Issue 14 2009Fusako Kuriyama Abstract The retina regenerates from retinal pigment epithelial (RPE) cells by transdifferentiation in the adult newt and Xenopus laevis when it is surgically removed. This was studied under a novel culture condition, and we succeeded, for the first time, in developing a complete retinal laminar structure from a single epithelial sheet of RPE. We cultured a Xenopus RPE monolayer sheet isolated from the choroid on a filter cup with gels overlaid and found that the retinal tissue structure differentiated with all retinal layers present. In the culture, RPE cells isolated themselves from the culture substratum (filter membrane), migrated, and reattached to the overlaid gel, on which they initiated transdifferentiation. This was exactly the same as observed during in vivo retina regeneration of X. laevis. In contrast, when RPE monolayers were cultured similarly without isolation from the choroid, RPE cells proliferated, but remained pigmented instead of transdifferentiating, indicating that alteration in tissue interaction triggers transdifferentiation. We then examined under the conventional tissue culture condition whether altered RPE-choroid interaction induces Pax6 expression. Pax6 was upregulated in RPE cells soon after they were removed from the choroid, and this expression was not dependent of FGF2. FGF2 administration was needed for RPE cells to maintain Pax6 expression. From the present results, in addition to our previous ones, we propose a two-step mechanism of transdifferentiation: the first step is a reversible process and is initiated by the alteration of the cell-extracellular matrix and/or cell,cell interaction followed by Pax6 upregulation. FGF2 plays a key role in driving RPE cells into the second step, during which they differentiate into retinal stem cells. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] Alternative Mechanistic Paths in the Hetero-Diels,Alder Reaction of ,-Oxothiones: A Theoretical StudyEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 21 2007Laura Legnani Abstract DFT calculations at the B3LYP/6-311+G(d,p) level for the C, H, and O atoms and at the 6-311+G(2df,p) level for the S atom were used to study the hetero-Diels,Alder reactions between several ,-oxothiones and ethylene or methyl vinyl ether (MVE). All the transition states and the intermediates along the reaction pathways, as well as the reaction products, were located. The reactions with ethylene are all concerted though asynchronous whereas in the reactions with MVE the electron-releasing character of the methoxy substituent lowers the energy barriers and enhances the asynchronicity and the charge transfer process to such an extent that the reaction may become unconcerted and exhibit a two-step mechanism with a zwitterionic intermediate derived from nucleophilic attack of electron-rich MVE to the sulfur atom of the strongly electrophilically activated ,-oxothiones. The reactions are also favored by the conjugation of the newly formed C=C bond. Moreover, the geometric features of the diene exert a nonnegligible role, as dienes that are planar or almost planar in their ground state show a lower energy barrier. Thus, both geometric and electronic features of the dienes as well as of the dienophiles play a significant role in the easiness of the reactions and in their mechanism. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Lewis Acid Induced [2+2] Cycloadditions of Silyl Enol Ethers with ,,,-Unsaturated Esters: A DFT AnalysisEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2005Manuel Arnó Abstract The Lewis acid (LA) induced cycloaddition of trimethysilyl vinyl ether with methyl acrylate has been studied by DFT methods at the B3LYP/6-31G* level. In the absence of an LA, a [4+2] cycloaddition between the silyl enol ether and methyl acrylate in the s-cis conformation takes place through an asynchronous, concerted bond-formation process. This cycloaddition presents a large activation enthalpy of 21.1 kcal,mol,1. Coordination of the LA AlCl3 to the carbonyl oxygen atom of methyl acrylate yields a change of molecular mechanism from a concerted to a two-step mechanism and produces a drastic reduction of the activation energy. This stepwise mechanism is initialized by the nucleophilic attack of the enol ether at the ,-position of methyl acrylate in a Michael-type addition. The very low activation energy (7.1 kcal,mol,1)associated with this nucleophilic attack can be related to the increase of the electrophilicity of the LA-coordinated ,,,-unsaturated ester, which favors the cycloaddition through a polar process. The subsequent ring-closure allows the formation of the corresponding [2+2] and [4+2] cycloadducts. While the [4+2] cycloadduct is formed by kinetic control, the [2+2] cycloadducts are formed by thermodynamic control. The energetic results provide an explanation for the conversion of [4+2] cycloadducts into the thermodynamically more stable [2+2] ones. The cis/trans ratio found for the catalytic [2+2] process is in agreement with the experimental outcome. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Addition Reactions of Sulfenyl and Sulfinyl Chlorides with 3-Phenyl-1-azabicyclo[1.1.0]butaneHELVETICA CHIMICA ACTA, Issue 8 2008Grzegorz Mlosto Abstract The reactions of 3-phenyl-1-azabicyclo[1.1.0]butane with , -chlorosulfenyl chlorides and sulfinyl chlorides lead to the corresponding sulfenamides and sulfinamides, respectively, which possess an azetidine ring. It is proposed that a two-step mechanism occurs involving an intermediate carbenium ion, which is formed by the addition of the electrophile at the N-atom and cleavage of the N(1)C(3) bond. The structures of 9b and 10b are established by X-ray crystallography. [source] Interactions of the "piano-stool" [ruthenium(II) (,6 -arene)(en)CL]+ complexes with water and nucleobases; ab initio and DFT studyJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 12 2009k Futera Abstract Piano stool ruthenium complexes of the composition [Ru(II)(,6 -arene)(en)Cl]+/2+ (en = ethylenediamine) represent an emerging class of cisplatin-analogue anticancer drug candidates. In this study, we use computational quantum chemistry to characterize the structure, stability and reactivity of these compounds. All these structures were optimized at DFT(B3LYP)/6-31G(d) level and their single point properties were determined by the MP2/6-31++G(2df,2pd) method. Thermodynamic parameters and rate constants were determined for the aquation process, as a replacement of the initial chloro ligand by water and subsequent exchange reaction of aqua ligand by nucleobases. The computations were carried out at several levels of DFT and ab initio theories (B3LYP, MP2 and CCSD) utilizing a range of bases sets (from 6-31G(d) to aug-cc-pVQZ). Excellent agreement with experimental results for aquation process was obtained at the CCSD level and reasonable match was achieved also with the B3LYP/6-31++G(2df,2pd) method. This level was used also for nucleobase-water exchange reaction where a smaller rate constant for guanine exchange was found in comparison with adenine. Although adenine follows a simple replacement mechanism, guanine complex passes by a two-step mechanism. At first, Ru-O6(G) adduct is formed, which is transformed through a chelate TS2 to the Ru-N7(G) final complex. In case of guanine, the exchange reaction is more favorable thermodynamically (releasing in total by about 8 kcal/mol) but according to our results, the rate constant for guanine substitution is slightly smaller than the analogous constant in adenine case when reaction course from local minimum is considered. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009 [source] Effects of entropy on the gas-phase pyrolysis of ethyl N,N -dimethylcarbamateJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 3 2007Chang K. Kim Abstract In this study, we examined the gas-phase pyrolysis of ethyl N,N -dimethylcarbamate theoretically at various theoretical levels. The reaction consists of a two-step mechanism, with N,N -dimethylcarbamic acid and ethylene as reaction intermediates. In the first step, the reaction proceeds via a six-membered cyclic transition state (TS), which is more favorable than that via a four-membered cyclic TS. Here, the contribution of entropy to the overall potential energy surface was found to play an important role in determining the rate-limiting step, which was found to be the second step when viewed in terms of the enthalpy of activation (,H,), but the first step when entropy changes (,T,S,) were considered. These results are consistent with experimental findings. Moreover, the experimental activation entropy can be reproduced by using the hindered rotor approximation, which converts some low vibration frequencies that correspond to internal rotational modes into hindered rotors. © 2006 Wiley Periodicals, Inc. J Comput Chem 28: 625,631, 2007 [source] Kinetic study of the decomposition of 2-butanol on carbon-based acid catalystAICHE JOURNAL, Issue 6 2010J. Bedia Abstract The catalytic conversion of 2-butanol on a carbon-based acid catalyst prepared by chemical activation of olive stone with phosphoric acid was investigated. The carbon catalyst showed a considerable amount of surface phosphorus, presumably in form of phosphate groups, as revealed by XPS, despite a washing step carried out after the activation process. Conversion of 2-butanol yields mainly dehydration products, mostly cis-2-butene and trans-2-butene with lower amounts of 1-butene, and a very small amount of mek as dehydrogenation product. Kinetic interpretation of the experimental data was performed using two elimination mechanisms for the dehydration reaction; an E1-mechanism (two-step mechanism) and an E2-mechanism (one-step mechanism). The rate expressions derived from both models fit properly the experimental results, suggesting that probably the two mechanisms occur simultaneously. This is supported by the similar rate constant obtained for the formation of the carbocation and the olefins in the E1 and E2 mechanisms, respectively. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] On the possibility of self-induction of drug protein bindingJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2010Leonid M. Berezhkovskiy Abstract The equilibrium unbound drug fraction (fu) is an important pharmacokinetic parameter, which influences drug elimination and distribution in the body. Commonly the drug plasma concentration is substantially less then that of drug binding proteins, so that fu can be assumed constant independent of drug concentration. A general consideration of protein binding based on the mass-action law provides that the unbound drug fraction increases with the increase of drug concentration, which is also a usual experimental observation. For several drugs, though, a seemingly unusual sharp decrease of the unbound drug fraction with the increase of total drug concentration (Ro) in the interval 0,<,Ro,,,5,µM was experimentally observed. A possible explanation of this apparently strange phenomenon is presented. The explanation is based on the consideration of a two-step mechanism of drug protein binding. The first step occurs as a drug binding to the site with relatively low affinity. Consequently this binding leads to the activation of a high affinity site, which otherwise is not available for binding. The suggested binding scheme yields the curves for fu dependence on the total drug concentration that are in good agreement with experimental measurements. The interpretation of pharmacokinetic data for the drugs with such unusual concentration dependence of fu appears to be a formidable problem. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4400,4405, 2010 [source] Theoretical evidence on O,N type smiles rearrangement mechanism: a computational study on the intramolecular cyclization of N -methyl-2-(2-chloropyridin-3-yloxy)-acetamide anionJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 3 2008Hui Sun Abstract Smiles rearrangement (SR) falls under a broad category of organic synthesis for many important compounds. A complete understanding toward SR process appeals to the assistance of theoretical research. Herein, by performing quantum chemistry calculations, we give a theoretical evidence for the mechanism of a representative O,N type SR, the intramolecular cyclization of N -methyl-2-(2-chloropyridin-3-yloxy)acetamide anion. It is found that the SR to the ipso -position involves a two-step mechanism and is energetically more favorable than the direct nucleophilic attack by N atom on the ortho -position. The present result rationalizes well the experimentally observed ipso -SR product and provides a consistent picture of the O,N SR process. Copyright © 2008 John Wiley & Sons, Ltd. [source] Insights into phase stability of anhydrous/hydrate systems: a Raman-based methodologyJOURNAL OF RAMAN SPECTROSCOPY, Issue 3 2010Mariela M. Nolasco Abstract FT-Raman spectroscopy turns out to be a powerful technique to evaluate the amount of polymorphic and pseudopolymorphic forms in crystalline samples,which is particularly relevant in pharmaceutical sciences. This paper presents a methodology that allows successful quantitative evaluation of the solid-state hydration and dehydration processes, using FT-Raman spectroscopy. All the steps required for a reliable evaluation of the hydration/dehydration process are illustrated for the caffeine system, a particularly challenging system presenting limited spectral differences between the pseudopolymorphs. The hydration process of caffeine was found to occur in a single-step process with a half-life time of ca 13 h, while the dehydration occurs through a two-step mechanism. The critical relative humidity was found to be at ca 81 and 42% for anhydrous and hydrate caffeine forms, respectively. Copyright © 2009 John Wiley & Sons, Ltd. [source] Undersampled radial MRI with multiple coils.MAGNETIC RESONANCE IN MEDICINE, Issue 6 2007Iterative image reconstruction using a total variation constraint Abstract The reconstruction of artifact-free images from radially encoded MRI acquisitions poses a difficult task for undersampled data sets, that is for a much lower number of spokes in k-space than data samples per spoke. Here, we developed an iterative reconstruction method for undersampled radial MRI which (i) is based on a nonlinear optimization, (ii) allows for the incorporation of prior knowledge with use of penalty functions, and (iii) deals with data from multiple coils. The procedure arises as a two-step mechanism which first estimates the coil profiles and then renders a final image that complies with the actual observations. Prior knowledge is introduced by penalizing edges in coil profiles and by a total variation constraint for the final image. The latter condition leads to an effective suppression of undersampling (streaking) artifacts and further adds a certain degree of denoising. Apart from simulations, experimental results for a radial spin-echo MRI sequence are presented for phantoms and human brain in vivo at 2.9 T using 24, 48, and 96 spokes with 256 data samples. In comparison to conventional reconstructions (regridding) the proposed method yielded visually improved image quality in all cases. Magn Reson Med 57:1086,1098, 2007. © 2007 Wiley-Liss, Inc. [source] Oxidation behaviour of Fe-Cr-Al alloys during resistance and furnace heatingMATERIALS AND CORROSION/WERKSTOFFE UND KORROSION, Issue 2 2006H. Echsler Abstract The behaviour of thin Fe-Cr-Al heating element strips was investigated with respect to the oxidation limited life times and geometrical changes during resistance and furnace heating. For this purpose, isothermal and cyclic oxidation tests varying in their total exposure time and cycle duration were performed in the temperature range 1050,1200 °C. Specimens subjected to rapid cyclic, resistance heating revealed shorter life times than calculated for specimens subjected to isothermal exposure. The life times were found to increase with increasing cycle duration and hence decreasing number of cycles for a given time at temperature. This life time decrease is related to an "hour glass" waviness of the specimens, which develops during prolonged thermal cycling. The development of this plastic deformation also occurred during furnace heated, thermal cycling tests. A two-step mechanism is introduced combining an oxidation kinetics related time to the onset of significant waviness with an enhancement of this waviness as a result of a ratcheting effect. The latter seems to strongly depend on the number of cycles and on the plastic deformation generated during each cycle rather than on the total time at temperature. The development of an "hour glass" waviness leads to an enhanced aluminium depletion due to an increase of the specimen surface area. Additional deformation phenomena like "hot tube" or "corkscrew" behaviour occur during the resistance heating tests. These are related to a temperature gradient that develops over the specimen width due to the poor aspect ratio of the specimens. [source] The Comparative Analysis of Osmotins and Osmotin-Like PR-5 ProteinsPLANT BIOLOGY, Issue 2 2003S. An, lovar Abstract: One of the ways that plants respond to biotic and/or abiotic stress factors is the accumulation of pathogenesis-related proteins of class 5 (PR-5), which are evolutionary conserved in the plant kingdom. Within the PR-5 family, a distinct subgroup of osmotin and closely related proteins has been characterized. In contrast to the extracellular forms of PR-5 proteins, osmotins presumably accumulate in the vacuole of the cell. They contain a C-terminal propeptide that is considered to be a determinant for vacuolar targeting. The comparison of the three-dimensional structure of tobacco PR-5 d with the sequences of some osmotins showed that the proteins consist of three conserved domains, with the acidic cleft between domains I and II. Besides the constitutive species and tissue-specific presence, the osmotins are also induced by several abiotic and biotic stresses. Among them, fungal infections can elicit osmotin gene expression, and most known proteins from the family have antifungal activity in in vitro assays. In agreement with the osmotin structure and data on the activity of similar proteins, a two-step mechanism, which involves reaction of osmotins with the fungal wall and the permeabilization of fungal membranes, is discussed. [source] Conformational polymorphism in a Schiff-base macrocyclic organic ligand: an experimental and theoretical studyACTA CRYSTALLOGRAPHICA SECTION B, Issue 5 2010Leonardo Lo Presti Polymorphism in the highly flexible organic Schiff-base macrocycle ligand 3,6,9,17,20,23-hexa-azapentacyclo(23.3.1.111,15.02,6.016,20)triaconta-1(29),9,11,13,15(30),23,25,27-octaene (DIEN, C24H30N6) has been studied by single-crystal X-ray diffraction and both solid-state and gas-phase density functional theory (DFT) calculations. In the literature, only solvated structures of the title compound are known. Two new polymorphs and a new solvated form of DIEN, all obtained from the same solvent with different crystallization conditions, are presented for the first time. They all have symmetry, with the macrocycle positioned on inversion centres. The two unsolvated polymorphic forms differ in the number of molecules in the asymmetric unit Z,, density and cohesive energy. Theoretical results confirm that the most stable form is (II°), with Z, = 1.5. Two distinct molecular conformations have been found, named `endo' or `exo' according to the orientation of the imine N atoms, which can be directed towards the interior or the exterior of the macrocycle. The endo arrangement is ubiquitous in the solid state and is shared by two independent molecules which constitute an invariant supramolecular synthon in all the known crystal forms of DIEN. It is also the most stable arrangement in the gas phase. The exo form, on the other hand, appears only in phase (II°), which contains both the conformers. Similarities and differences among the occurring packing motifs, as well as solvent effects, are discussed with the aid of Hirshfeld surface fingerprint plots and correlated to the results of the energy analysis. A possible interconversion path in the gas phase between the endo and the exo conformers has been found by DFT calculations; it consists of a two-step mechanism with activation energies of the order of 30,40,kJ,mol,1. These findings have been related to the empirical evidence that the most stable phase (II°) is also the last appearing one, in accordance with Ostwald's rule. [source] On the Dichotomic Reactivity of Lithiated Styrene Oxide: A Computational and Multinuclear Magnetic Resonance InvestigationCHEMISTRY - A EUROPEAN JOURNAL, Issue 32 2009Vito Capriati Prof. Abstract A multinuclear magnetic resonance investigation, supported by density functional theory calculations, has been synergically used to investigate the configurational stability, reactivity and aggregation states of ,-lithiated styrene oxide in THF at 173,K. NMR studies on ,-lithiated [,,,- 13C2]styrene oxide (also in an enantiomerically enriched form) proved that in THF this oxiranyllithium is mainly present as a solvated monomeric species in equilibrium with a complex mixture of stereoisomeric dimeric aggregates, as well as with bridged and tetrameric aggregates. The fact that some C,Li bonds are partially broken in some stereoisomers reduces their symmetry and complicates the NMR spectra: two diastereoisomers each having a pair of diastereotopic carbon atoms slowly inverting at the lithium atom in absence of tetramethylethylenediamine (TMEDA) have been detected. A (13C,7Li)-HMQC experiment to correlate 7Li and 13C resonances of the various aggregates has been performed for the first time. From natural bond analysis, the monomeric aggregate was proven to have a lower carbenoid character with respect to bridged O-coordinated dimeric aggregates. The employment of suitable experimental conditions in terms of concentration, temperature and the presence or not of TMEDA are crucial to mitigate at the best the "carbene-like" reactivity of lithiated styrene oxide toward intermolecular CLi insertions, eliminative dimerisation reactions and ring-opening reactions. A two-step mechanism for the deprotonation of styrene oxide by sBuLi in THF has been proposed and discussed as well as competitive side reactions. [source] Studies on Stereoselective [2+2] Cycloadditions between N,N-Dialkylhydrazones and KetenesCHEMISTRY - A EUROPEAN JOURNAL, Issue 23 2004Eloísa Martín-Zamora Dr. Abstract Staudinger-like cycloadditions between chiral, non-racemic N,N-dialkylhydrazones 1 and functionalized ketenes constitute an efficient methodology for the stereoselective construction of the ,-lactam ring. The potential for fine tuning of the dialkylamino auxiliary structure, the availability of a high-yielding deprotection method for the release of the free azetidinones, and the high thermal and chemical stability of hydrazones as N-dialkylamino imines are highlighted as the key elements for the success of the strategy. This last aspect is of particular importance concerning generality: even hydrazones from easily enolizable aldehydes or from formaldehyde reacted to afford the corresponding cycloadducts with high chemical and stereochemical yields. The syntheses of the ,-amino-,-hydroxyacids (2R,3S)-phenylisoserine (42) and (2R,3S)-norstatin (45) were accomplished as illustrative examples of the synthetic utility of this procedure. A model system for the cycloaddition of g series auxiliaries was studied by ab initio computational methods. The collected results support a two-step mechanism through zwitterionic intermediates, and explain the observed absolute and relative stereochemistry in terms of the preferred outward cycloaddition to the Re face of the hydrazone. La reacción de cicloadición [2+2] de tipo Staudinger entre cetenas funcionalizadas y las hidrazonas quirales 1 constituye un método eficiente para la construcción estereoselectiva del anillo de azetidinona. La modulación de la estructura del grupo dialquilamino empleado como auxiliar, la disponibilidad de un procedimiento eficiente para la desprotección de las , -lactamas libres y la alta estabilidad química y térmica de las hidrazonas como N-dialquilamino iminas son los puntos clave para el éxito de la estrategia. Este último aspecto es de particular importancia por su implicación en la generalidad del método: hidrazonas derivadas de aldehídos fácilmente enolizables o incluso las derivadas de formaldehído reaccionan para dar lugar a los correspondientes cicloaductos con excelentes rendimientos químicos y estereoquímicos. La síntesis de los , -amino- , -hidroxiácidos (2R,3S)-fenilisoserina (42) y (2R,3S)-norestatina (45) se llevaron a cabo como ejemplos ilustrativos del potencial sintético del método. Estudios computacionales ab initio realizados sobre una reacción modelo basada en los auxiliares de la serie g sugieren un mecanismo en dos pasos a través de intermedios zwitteriónicos. Los resultados obtenidos explican la estereoquímica absoluta y relativa, así como el alto grado de inducción observado para estos auxiliares, por la preferencia de la aproximación "outward" de la cetena sobre la cara Re de la hidrazona. [source] | ||||||||||||||||||||||