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1.
As part of a study of factors controlling biological redox reactions of nicotinamide cofactors [nicotinamide adenine dinucleotide (phosphate) NAD(P)H], we have investigated the effect on a model reaction of the conformational state (cis or trans) of the carboxamide side chain, using quantum chemical methods. The reaction is that for the enzyme dihydrofolate reductase between the NADPH analogue, 1-methyl-dihydronicotinamide, and the protonated forms of the folate and dihydrofolate substrate analogues, pyrazine and dihydropyrazine. Some calculations on pterin and dihydropterin substrate analogues were also carried out in order to gauge the effects of inter-ring coupling. The influence of carboxamide side-chain conformation of nicotinamide on the energetics of the hydride-ion transfer, and on the structures of the transition states and stable intermolecular-interaction complexes, are examined as a function of the orientation of approach of the reactants. These approach geometries include those corresponding to the observed binding of cofactor and either substrate or inhibitor in the enzyme active site. Reactant, product, reactants-complex, and transition-state geometries were optimized at the semiempirical AM1 level, while ab initio SCF/STO-3G and SCF/3-21G single-point calculations were carried out at the AM1 optimized geometries for all species, as well as full geometry optimizations for isolated reactants and products. The results show that reactants-complex and transition-state energies are lower for the trans conformer of dihydronicotinamide than for the cis conformer, due to more favorable H-bonding or electrostatic interactions with the protonated substrate. Also, consideration of the structural parameters, including reaction coordinate bond lengths, ring geometries, and charge distributions, indicate that the trans transition states are more product-like than those for the cis. For the (trans) approaches corresponding to the enzymic orientation for substrate, the intermolecular interaction for the folate reaction lacks the stabilizing influence of the formal H-bond which is present for the dihydrofolate reaction, and consequently the reactants-complex and transition state are less stable.  相似文献   

2.
New liquid triarylamine-siloxane hybrid materials are produced using the Piers-Rubinsztajn reaction. Under mild conditions, liquid analogues of conventional and commonly crystalline triarylamines are easily synthesized from readily available or accessible intermediates. Using a diverse selection of triarylamines, we explored the effects of siloxane group and substitution pattern on the physical properties of these materials, and we have demonstrated that relatively large molecular liquids with desirable electrochemical properties can be produced. The interactions between the strongly Lewis acidic catalyst used for this transformation, tris(pentafluorophenyl)borane (BCF), and the Lewis basic triarylamine substrates were studied. Through UV-vis-NIR and (19)F NMR spectroscopy, we have proposed that the catalyst undergoes a reversible redox reaction with the substrates to produce a charge transfer complex. The formation of this charge transfer complex is sensitive to the oxidation potential of the triarylamine and can greatly affect the kinetics of the Piers-Rubinsztajn reaction.  相似文献   

3.
The current ideas of organic chemists based on the work of Ingold and his school are applied to heterogeneous catalytic eliminations (mostly from haloalkanes and aliphatic alcohols). It is deduced from the activity of the catalysts, the reactivity of the substrates (reactants), and the primary product distribution that these eliminations proceed by a heterolytic mechanism similar to that involved in the liquid phase. The activity of the catalysts (salts and oxides) increases with increasing charge and decreasing radius of the cations and with increasing basicity of the anions. The reactivity of the substrates behaves in much the same manner as in the liquid phase. In contrast with the liquid-phase reaction, the cis-olefins are frequently favored as primary products. The stereospecificity of the reaction is determined from the relative strengths of the interactions between the catalyst cation and the leaving group X?, and between the catalyst anion and the leaving proton. Only trans elimination has so far been found in the concerted mechanism.  相似文献   

4.
We discuss a model for the autocatalytic reaction A + B→ 2A on substrates where the reactants perform a compact exploration of the space, i.e., on lattices whose spectral dimension d͂ is < 2. For finite systems, the total time τ for the reaction to end scales according to two different regimes, for high and low concentrations of reactants. The functional dependence of τ on the volume of the substrate and the concentration of reactants is discussed within a mean-field approximation. Possible applications are discussed.  相似文献   

5.
The reduction of bis(2-hydroxyethyl)disulfide (HEDS) by reduced glutathione (GSH) is the most commonly used assay to analyze the presence and properties of enzymatically active glutaredoxins (Grx), a family of central redox proteins in eukaryotes and glutathione-utilizing prokaryotes. Enzymatically active Grx usually prefer glutathionylated disulfide substrates. These are converted via a ping-pong mechanism. Sequential kinetic patterns for the HEDS assay have therefore been puzzling since 1991. Here we established a novel assay and used the model enzyme ScGrx7 from yeast and PfGrx from Plasmodium falciparum to test several possible causes for the sequential kinetics such as pre-enzymatic GSH depletion, simultaneous binding of a glutathionylated substrate and GSH, as well as substrate or product inhibition. Furthermore, we analyzed the non-enzymatic reaction between HEDS and GSH by HPLC and mass spectrometry suggesting that such a reaction is too slow to explain high Grx activities in the assay. The most plausible interpretation of our results is a direct Grx-catalyzed reduction of HEDS. Physiological implications of this alternative mechanism and of the Grx-catalyzed reduction of non-glutathione disulfide substrates are discussed.  相似文献   

6.
A rare example of ion/ion reaction between species of like polarity was shown to take place during the transfer of metal cations from nucleic acid substrates to chelating agents in the gas phase. Gaseous anionic reactants were generated from separate solutions of analyte and chelator by using a dual nanospray setup. The respective multiply charged ions shared the same path and were allowed to react for a predetermined interval in an rf-only hexapole before high-resolution analysis by Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. Efficient transfer of sodium and magnesium ions was readily observed with significant reduction of the nonspecific adducts that are typically associated with decreased sensitivity and resolution in the analysis of nucleic acid samples. Metal cations were abstracted from the initial analyte without being replaced by protons, in a process that was clearly dependent on the concentration of chelator in the auxiliary emitter and on the time spent by the reactants in the hexapole element. A survey of the properties of selected anionic chelators showed that their known affinity for a target cation in solution was more critical than their maximum anionic charge in determining the outcome of the transfer process. The analysis of selected assemblies requiring divalent cations to preserve their structural integrity and functional properties demonstrated that ion/ion reactions were clearly capable of discriminating between nonspecific interactions and specific coordination based on transfer susceptibility. These examples demonstrated that the ability to selectively eliminate nonspecific adducts in the gas phase, after the desolvation process is complete, offers a unique opportunity for studying specific metal binding in biological systems without resorting to separation procedures that may adversely affect the position of binding equilibria in solution and disrupt the assemblies under investigation.  相似文献   

7.
Photocatalytic activity of microporous titanosilicate ETS-10 has been studied in water. The photoactivated ETS-10 shows catalytic activity driven by size and polarity of substrates. ETS-10 efficiently catalyzes a conversion of substrates with a size larger than the pore diameter of ETS-10. In contrast, the reactivity of small substrates depends strongly on substrate polarity; less polar substrates show higher reactivity on ETS-10. Electron spin resonance analysis reveals that large substrates or less polar substrates scarcely diffuse inside the highly polarized micropores of ETS-10 and, hence, react efficiently with hydroxyl radicals (*OH) formed on titanol (Ti-OH) groups exposed on the external surface of ETS-10. In contrast, small polar substrates diffuse easily inside the micropores of ETS-10 and scarcely react with *OH, resulting in low reactivity. The photocatalytic activity of ETS-10 is successfully applicable to selective transformations of large reactants or less polar reactants to small polar products, enabling highly selective dehalogenation and hydroxylation of aromatics.  相似文献   

8.
The knowledge of the structure and orientation of polymer chains adsorbed at an interface could be of major importance to predict the level of interfacial interactions and adhesion that depend strongly on the properties of the interface formed between the two materials (polymer and substrate) brought into contact. In this work, we were interested to study thin films of atactic polystyrene after adsorption (spin‐coating) on two chemically different substrates (inert and OH‐grafted gold substrates). The main aim is to analyze the resulting anisotropy due to the confinement in a quasi‐bidimensional geometry, as well as to investigate the incidence of the interfacial interactions, potentially established between the polymer and the surface, on the chain organization. Our infrared spectroscopy results allowed us to access the adsorption model of polystyrene chains and to highlight the relation between chain orientation and interfacial acid–base interactions. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1268–1276, 2006  相似文献   

9.
EPR/ENDOR studies have been carried out on oxyferrous cytochrome P450cam one-electron cryoreduced by gamma-irradiation at 77 K in the absence of substrate and in the presence of a variety of substrates including its native hydroxylation substrate, camphor (a), and the alternate substrates, 5-methylenyl-camphor (b), 5,5-difluorocamphor (c), norcamphor (d), and adamantanone (e); the equivalent experiments have been performed on the T252A mutant complexed with a and b. The present study shows that the properties and reactivity of the oxyheme and of both the primary and the annealed intermediates are modulated by a bound substrate. This includes alterations in the properties of the heme center itself (g tensor; (14)N, (1)H, hyperfine couplings). It also includes dramatic changes in reactivity: the presence of any substrate increases the lifetime of hydroperoxoferri-P450cam (2) no less than ca. 20-fold. Among the substrates, b stands out as having an exceptionally strong influence on the properties and reactivity of the P450cam intermediates, especially in the T252A mutant. The intermediate, 2(T252A)-b, does not lose H(2)O(2), as occurs with 2(T252A)-a, but decays with formation of the epoxide of b. Thus, these observations show that substrate can modulate the properties of both the monoxygenase active-oxygen intermediates and the proton-delivery network that encompasses them.  相似文献   

10.
Phase-vanishing reactions are triphasic reactions, which involve a reagent, a liquid perfluoroalkane as a phase screen and a substrate. Aromatization, isomerization and halogenation of neat substrates under phase-vanishing conditions gave the expected products in good to excellent yields. In tandem single-phase-phase-vanishing reaction, two reactants, placed in the top phase, afforded the intermediate, which in a subsequent phase-vanishing reaction reacted with the reagent from the bottom phase to give the final product. The reaction worked well under solvent-free conditions on liquid substrates and intermediates. With solids, results were better if an additional solvent was employed.  相似文献   

11.
Ornithine decarboxylase is the first and the rate-controlling enzyme in polyamine biosynthesis; it decarboxylates l-ornithine to form the diamine putrescine. We present calculations performed using a combined quantum mechanical and molecular mechanical (QM/MM) method with the AM1 semiempirical Hamiltonian for the wild-type ornithine decarboxylase reaction with ornithine (the physiological substrate) and lysine (a "slow" substrate) and for mutant E274A with ornithine substrate. The dynamical method is variational transition state theory with quantized vibrations. We employ a single reaction coordinate equal to the carbon-carbon distance of the dissociating bond, and we find a large difference between the intrinsic kinetic isotope effect for the physiological substrate, which equals 1.04, and that for the slow substrate, which equals 1.06. This shows that, contrary to a commonly accepted assumption, kinetic isotope effects on slow substrates are not always good models of intrinsic kinetic isotope effects on physiological substrates. Furthermore, analysis of free-energy-based samples of transition state structures shows that the differences in kinetic isotope effects may be traced to different numbers of hydrogen bonds at the different transition states of the different reactions.  相似文献   

12.
In this article we present computational studies of horse liver alcohol dehydrogenase (HLADH). The computations identify a rate-promoting vibration that is symmetrically coupled to the reaction coordinate. In HLADH a bulky amino acid (Val203) is positioned at the face of the nicotinamide adenine dinucleotide (NAD(+)) cofactor distal to alcohol substrate to restrict the separation of reactants and control the stereochemistry. Molecular dynamics simulations were performed on the dimeric HLADH, including the NAD cofactor, the substrate, and the crystallographic waters, for three different configurations, reactants, products, and transition state. From the spectral density for the substrate-NAD relative motion, and that for the NAD-Val203 relative motion, we find that the two motions are in resonance. By computing the associated spectrum, we find that the reaction coordinate is coupled with the substrate-NAD motion, and from the fact that the coupling vanishes at or near the transition state (demonstrated by the disappearance of strong features in the spectral density), we conclude that the substrate-NAD motion plays the role of a promoting vibration symmetrically coupled to the reaction coordinate.  相似文献   

13.
A theoretical study of the hydride transfer between formate anion and nicotinamide adenine dinucleotide (NAD(+)) catalyzed by the enzyme formate dehydrogenase (FDH) has been carried out by a combination of two hybrid quantum mechanics/molecular mechanics techniques: statistical simulation methods and internal energy minimizations. Free energy profiles, obtained for the reaction in the enzyme active site and in solution, allow obtaining a comparative analysis of the behavior of both condensed media. Moreover, calculations of the reaction in aqueous media can be used to probe the dramatic differences between reactants state in the enzyme active site and in solution. The results suggest that the enzyme compresses the substrate and the cofactor into a conformation close to the transition structure by means of favorable interactions with the amino acid residues of the active site, thus facilitating the relative orientation of donor and acceptor atoms to favor the hydride transfer. Moreover, a permanent field created by the protein reduces the work required to reach the transition state (TS) with a concomitant polarization of the cofactor that would favor the hydride transfer. In contrast, in water the TS is destabilized with respect to the reactant species because the polarity of the solute diminishes as the reaction proceeds, and consequently the reaction field, which is created as a response to the change in the solute polarity, is also decreased. Therefore protein structure is responsible of both effects; substrate preorganization and TS stabilization thus diminishing the activation barrier. Because of the electrostatic features of the catalyzed reaction, both media preferentially stabilize the ground-state, thus explaining the small rate constant enhancement of this enzyme, but FDH does so to a much lower extent than aqueous solution. Finally, a good agreement between experimental and theoretical kinetic isotope effects is found, thus giving some credit to our results.  相似文献   

14.
Increasing emphasis has recently been placed on the development of synthetic methods which effectively couple chemical synthesis and purification. For example, new formats for parallel synthesis are being developed which involve attachment of chemical tags to both reagents, reactants, and substrates to permit their chemoselective removal from reaction mixtures. The driving force for the development of tagged organic reagents is the ability to use standard solution-phase chemistry methods and reaction monitoring techniques (e.g. TLC and HPLC). In this mini-review, we will outline recent developments on the growing class of chemically tagged reagents, reactants, and substrates and highlight examples of their use in multistep synthesis.  相似文献   

15.
Until relatively recently, modeling chemical reactivity in emulsions has proved refractory. The problem lies in developing good methods for determining the distributions of reactants because classical separation of the phases by physical methods do not work, which prevents measurement of the distributions of reactants and components between the oil, interfacial and aqueous regions in emulsions. Without this understanding, they cannot be used efficiently as reaction media. We are using a physical-organic chemistry approach grounded in thermodynamics and inspired by the prior success of pseudophase kinetic models developed for association colloids such as micelles microemulsions, and vesicles. In emulsions, as in association colloids, the observed rate constant depends on the concentrations of reactants in each region and on medium effects. The medium effects reflect the solvent properties of a reaction region and the distributions of reactants depend on their solubilities in each region. Here we introduce: (a) the current concepts and basic assumptions employed to interpret chemical reactivity in nonionic and ionic emulsions; (b) several approaches for estimating the partition constants for substrates between the oil-interfacial, POI, and water-interfacial, PWI, regions of the emulsions; and (c) methods for determining the rate constant in the interfacial region, kI. The results demonstrate that pseudophase kinetic analyses provide a unique, versatile, and robust solution to interpreting chemical reactivity in emulsions. The approach permits identifying the relative importance of various emulsion properties such as oil hydrophobicity, emulsifier structure and HLB, temperature, and acidity on reactant distributions. Representative results for antioxidants are included. The approach offers a new route for identifying most efficient antioxidant for a particular food application.  相似文献   

16.
The algorithm by Northrup, Allison, and McCammon [J. Chem. Phys. 80, 1517 (1984)] has been used for two decades for calculating the diffusion-influenced rate-constants of enzymatic reactions. Although many interesting results have been obtained, the algorithm is based on the assumption that substrate-substrate interactions can be neglected. This approximation may not be valid when the concentration of the ligand is high. In this work, we constructed a simulation model that can take substrate-substrate interactions into account. We first validated the model by carrying out simulations in ways that could be compared to analytical theories. We then carried out simulations to examine the possible effects of substrate-substrate interactions on diffusion-controlled reaction rates. For a substrate concentration of 0.1 mM, we found that the diffusion-controlled reaction rates were not sensitive to whether substrate-substrate interactions were included. On the other hand, we observed significant influence of substrate-substrate interactions on calculated reaction rates at a substrate concentration of 0.1M. Therefore, a simulation model that takes substrate-substrate interactions into account is essential for reliably predicting diffusion-controlled reaction rates at high substrate concentrations, and one such simulation model is presented here.  相似文献   

17.
Selective catalytic oxidation of various organic substrates with O2 in the presence of aqueous solutions of Mo-V-P heteropoly acids (HPA) is carried out via two stages in separate reactors. In stage (1), a substrate is oxidized into a desired product while HPA is reduced. The reduced form of HPA is oxidized with O2 in stage (2). A set of the physicochemical properties of the homogeneous catalyst has been found to alter continuously during these redox processes. Using a solution of the modified high-vanadium HPA (H12P3Mo18V7O85), we demonstrate that the density, viscosity, and pH of this solution reach their maxima after reaction (1) and attain their minima after reaction (2). On the contrary, the redox potential of the solution is minimum after reaction (1), and maximum after reaction (2). All alterations of the physicochemical properties of the catalyst are found to be completely reversible.  相似文献   

18.
The addition of carbon nucleophiles to isocyanates represents a conceptually flexible and efficient approach to the preparation of amides. This general synthetic strategy has, however, been relatively underutilized owing to narrow substrate tolerance and the requirement for less favourable reaction conditions. Herein, we disclose a high‐yielding, mass‐efficient, and scalable method with appreciable functional group tolerance for the formation of amides by reaction of Grignard reagents with isocyanates. Through the application of flow chemistry and the use of substoichiometric amounts of CuBr2, this process has been developed to encompass a broad range of substrates, including reactants found to be incompatible with previously published procedures.  相似文献   

19.
To probe how the aerosol substrate influences heterogeneous polycyclic aromatic hydrocarbon (PAH) oxidation, we investigated the reaction of surface-bound anthracene with gas-phase ozone on phenylsiloxane oil and azelaic acid aerosols under dry conditions in an aerosol flow tube with offline analysis of anthracene. The reaction exhibited pseudo-first-order kinetics for anthracene loss, and the pseudo-first-order rate coefficients displayed a Langmuir-Hinshelwood dependence on the gas-phase ozone concentration on both aerosol substrates. The following parameters were found: for the reaction on phenylsiloxane oil aerosols, K(O3) = (1.0 +/- 0.4) x 10(-13) cm(3) and k(I)(max) = (0.010 +/- 0.003) s(-1); for the reaction on azelaic acid aerosols, K(O3) = (2.2 +/- 0.9) x 10(-15) cm(3) and k(I)(max) = (0.057 +/- 0.009) s(-1), where K(O3) is a parameter that describes the partitioning of ozone to the surface and k(I)(max) is the maximum pseudo-first-order rate coefficient at high ozone concentrations. The K(O3) value for the reaction of surface-bound anthracene and ozone on azelaic acid aerosols is similar to the K(O3) value that we obtained in our previous study for the reaction of surface-bound benzo[a]pyrene and ozone on the same substrate. This finding supports our earlier hypothesis that the substrate influences the partitioning of ozone to the surface irrespective of the organic species (i.e., PAH) adsorbed to it. Preliminary ab initio calculations were performed to investigate whether there is a relationship between the relative binding energies of the ozone-substrate complex and the K(O3) values for the different substrates studied. A comparison between kinetic results obtained on aerosol substrates and thin films is presented.  相似文献   

20.
Herein we demonstrate that an external electric field (EEF) acts as an accessory catalyst/inhibitor for Diels–Alder (DA) reactions. When the EEF is oriented along the “reaction axis” (the coordinate of approach of the reactants in the reaction path), the barrier of the DA reactions is lowered by a significant amount, equivalent to rate enhancements by 4–6 orders of magnitude. Simply flipping the EEF direction has the opposite effect, and the EEF acts as an inhibitor. Additionally, an EEF oriented perpendicular to the “reaction axis” in the direction of the individual molecule dipoles can change the endo/exo selectivity, favouring one or the other depending on the positive/negative directions of the EEF vis‐à‐vis the individual molecular dipole. At some critical value of the EEF along the “reaction axis”, there is a crossover to a stepwise mechanism that involves a zwitterionic intermediate. The valence bond diagram model is used to comprehend these trends and to derive a selection rule for EEF effects on chemical reactions: an EEF aligned in the direction of the electron flow between the reactants will lower the reaction barrier. It is shown that the exo/endo control by the EEF is not associated with changes in secondary orbital interactions.  相似文献   

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