On the role of the conserved aspartate in the hydrolysis of the phosphocysteine intermediate of the low molecular weight tyrosine phosphatase

The usual rate-determining step in the catalytic mechanism of the low molecular weight tyrosine phosphatases involves the hydrolysis of a phosphocysteine intermediate. To explain this hydrolysis, general base-catalyzed attack of water by the anion of a conserved aspartic acid has sometimes been invoked. However, experimental measurements of solvent deuterium kinetic isotope effects for this enzyme do not reveal a rate-limiting proton transfer accompanying dephosphorylation. Moreover, base activation of water is difficult to reconcile with the known gas-phase proton affinities and solution phase pK(a)'s of aspartic acid and water. Alternatively, hydrolysis could proceed by a direct nucleophilic attack by a water molecule. To understand the hydrolysis mechanism, we have used high-level density functional methods of quantum chemistry combined with continuum electrostatics models of the protein and the solvent. Our calculations do not support a catalytic activation of water by the aspartate. Instead, they indicate that the water oxygen directly attacks the phosphorus, with the aspartate residue acting as a H-bond acceptor. In the transition state, the water protons are still bound to the oxygen. Beyond the transition state, the barrier to proton transfer to the base is greatly diminished; the aspartate can abstract a proton only after the transition state, a result consistent with experimental solvent isotope effects for this enzyme and with established precedents for phosphomonoester hydrolysis.     

Effect of the choice of the pressure coupling method on the spontaneous aggregation of DPPC molecules

The self-assembly of DPPC molecules starting from a random, solution-like configuration in the presence of water molecules is described in the present MD simulation study. Simulations were performed with either anisotropic or isotropic pressure coupling. Use of anisotropic pressure coupling led to the formation of a bilayer/bilayerlike aggregate; the features of the bilayer are in agreement with those reported from earlier simulation and experimental studies. In contrast, simulating the same system with isotropic pressure coupling led to the formation of a cylindrical micelle/lamellar structure with a large water hole. The formation of micelles seems unrealistic since diacylphosphatidylcholines having hydrocarbon tails with nine or more carbon atoms have been shown to form only bilayers. Simulations were also performed with preformed bilayerlike configurations with either anisotropic or isotropic pressure coupling. The bilayer characteristics deduced from simulations using anisotropic pressure coupling are in better agreement with those reported from earlier experimental and simulation studies. Thus, the choice of the pressure coupling method has a significant effect on the spontaneous aggregation of DPPC molecules but makes relatively lesser effect if the bilayer has formed already.     

Koopmans-like approximation in the Kohn-Sham method and the impact of the frozen core approximation on the computation of the reactivity parameters of the density functional theory

A Koopmans-like approximation is introduced in the spin-polarized version of the Kohn-Sham (KS) density functional theory to obtain a relation between KS orbital energies and vertical ionization potential and electron affinity. Expressions for reactivity indexes (like electronegativity, hardness, electrophilicity, and excitation energies) include KS frontier orbital energies and additional contributions associated with the self-interaction correction. Those reactivity parameters were computed with different exchange-correlation functionals to test the approach for a set of small molecules. The results show that the present approximation provides a better way to estimate hardness, electronegativity, and electrophilicity than just the use of frontier orbital energy values. However KS HOMO and LUMO energy gap gives a better agreement with excitation energies.     

Application of the chiral base desymmetrisation of imides to the synthesis of the alkaloid jamtine and the antidepressant paroxetine

The synthesis of the alkaloid jamtine and the antidepressant paroxetine have been addressed by a strategy involving asymmetric desymmetrisation of prochiral imides by a chiral lithium amide base. A short reaction sequence, starting with a cyclohexane fused succinimide, led to the structures originally reported for the alkaloid jamtine and its derived N-oxide. The structures synthesised are shown not to correspond with those originally reported. A second sequence involves desymmetrisation of a 4-arylglutarimide, and provides a short enantioselective synthesis of the drug substance paroxetine.     

Towards the electrochemical quantification of the strength of garlic

A simple but sensitive technique has been demonstrated towards the electroanalytical quantification of the strength of garlic. This technique can also be used to quantify dialkyldisulfides. The cyclic voltammetry of bromide was found to be a sensitive electrochemical probe, electrogenerated bromine reacting with dialkyldisulfides to catalytically regenerate bromide, resulting in a significant increase in peak current. A linear response of current vs. concentration was observed between 0.1 and 15 mM dipropyldisulfide at edge plane pyrolytic graphite (EPPG) electrodes; a smaller range up to ca. 5 mM was available at screen printed carbon electrodes (SPCEs), with a detection limit (from 3σ) of 0.067 mM. The response of diallyldisulfide was found to be essentially identical. Shaking garlic puree in acetonitrile for 5 minutes, followed by dilution with water then recording the voltammetry at the cheap, disposable SPCE gave a linear trend in current with respect to the quantity of garlic present, corresponding to the diallyldisulfide extracted. This has potential applications in monitoring the garlic content of medicinal supplements, batch-to-batch variation and the stability of garlic during storage.     

Molecular simulation study of the effect of pressure on the vapor-liquid interface of the square-well fluid

We examine a model system to study the effect of pressure on the surface tension of a vapor-liquid interface. The system is a two-component mixture of spheres interacting with the square-well (A-A) and hard-sphere (B-B) potentials and with unlike (A-B) interactions ranging (for different cases) from hard sphere to strongly attractive square well. The bulk-phase and interfacial properties are measured by molecular dynamics simulation for coexisting vapor-liquid phases for various mixture compositions, pressures, and temperatures. The variation of the surface tension with pressure compares well to values given by surface-excess formulas derived from thermodynamic considerations. We find that surface tension increases with pressure only for the case of an inert solute (hard-sphere A-B interactions) and that the presence of A-B attractions strongly promotes a decrease of surface tension with pressure. An examination of density and composition profiles is made to explain these effects in terms of surface-adsorption arguments.     

On the Nature of the Temperature-Induced Transition From the Molten Globule to the Unfolded State of Globular Proteins

In this paper we try to perform a thermodynamic analysis of the temperature-induced transition from the molten globule to the unfolded state of globular proteins. A series of calorimetric investigations showed that this process is not associated with an excess heat capacity absorption peak, and cannot be regarded as a first-order phase transition. This result contrasts with the well-established conclusion that the thermal unfolding of the native tertiary structure of globular proteins is a first-order phase transition. First, the theoretical approach developed by Ikegami is outlined to emphasize that a second-order or gradual transition induced by temperature is expected for globular proteins when the various secondary structure elements do not interact cooperatively. Secondly, a simple thermodynamic model is presented which, taking into account the independence of the secondary structure elements among each other, is able to rationalize the shape of the experimental DSC profiles.This revised version was published online in November 2005 with corrections to the Cover Date.     

FTIR study of the mode of binding of the reactants on the Pd nanoparticle surface during the catalysis of the Suzuki reaction

In the Suzuki reaction between phenylboronic acid and iodobenzene catalyzed by palladium nanoparticles, our previous studies suggested that the phenylboronic acid adsorbs on the nanoparticle surface and then interacts with the iodobenzene that is present in solution. In the present study, FTIR is used to examine the change in the vibrational frequencies of phenylboronic acid in films with and without the addition of palladium nanoparticles. The large change in the B-O stretching frequency of phenylboronic acid from 1348 to 1376 cm(-1) in the presence of sodium acetate and palladium nanoparticles strongly suggests that the mode of binding of phenylboronic acid to the Pd nanoparticle surface involves a B-O-Pd type of bonding. Shifts in the B-C stretching mode and the out-of-plane phenyl C-C ring deformation bands associated with phenylboronic acid provide additional confirmations of the binding process. It is also shown that the phenylboronic acid needs to be in the deprotonated form in the presence of sodium acetate (phenylboronate anion) to bind to the palladium nanoparticle surface. No changes in the characteristic bands of iodobenzene were observed in films made in the presence of the palladium nanoparticles. The FTIR studies provide proof of the mode of binding that occurs in the nanoparticle surface for the first time and also confirms the mechanism of the Suzuki reaction that we proposed previously.     

Effects of the menstrual cycle on the red and near-infrared optical properties of the human breast

Time-resolved reflectance and transmittance spectroscopy was applied to measure in vivo the absorption and transport scattering spectra of the female breast from 610 to 1010 nm. Three measurement configurations were used to probe different breast regions, and data were collected two or three times in each of the five phases of the menstrual cycle. The absorption spectra were best-fitted with a linear combination of the spectra of the main tissue constituents (water, lipids, oxy- and deoxyhemoglobin). This allowed us to evaluate percentage contents of water and lipids, total hemoglobin content and hemoglobin oxygen saturation. The scattering spectra were interpreted with a function derived from Mie theory, providing information on the density and average size of the tissue scatterers. Significant changes in the estimated variables were observed with measurement geometry, reflecting the heterogeneous nature of the breast, and with time, in agreement with expected physiological changes over the menstrual cycle.     

Measurement of the ground-state lambshift of hydrogenlike uranium at the electron cooler of the ESR

X-rays are emitted with the radiative recombination of free electrons in an electron cooler of a heavyion storage ring. Due to a small width of the X-ray lines, an observation angle close to 0° and an accurate determination of the ion velocity, the ground-state Lambshift of hydrogenlike uranium (470 ± 16) eV could be measured to an accuracy of 3.4%. A re-evaluation of a measurement of the 1s _1/2 Lambshift in hydrogenlike gold gave a new value of (202.3 ± 7.9) eV as compared to the former value of (212 ± 15) eV. The results are in excellent agreement with QED calculations and are more precise than any other measurements previously reported for a high-Z, hydrogenlike ion.     

Role of the conformation in the reactivity of 1,3-diphosphapropenes

The symmetrical and unsymmetrical 1,3-diphospha-propenes 3 and 4 were obtained from the corresponding diposphiranes 1 and 2 . The chemical behavior of these compounds has been studied. Phosphonium-phosphaalkenes 7a and 10a have been obtained in the reactions with aluminium trichloride. Whereas the symmetrical diphosphaallene 13 can be obtained by reaction of 1 or 3 with lithio compounds, the unsymmetrical diphosphaalene 14 cannot be prepared by a similar route. Reduction of 3a and 4a (obtained with a different conformation) by lithium aluminum hydride afforded phosphino-phosphaalkenes 17a and 18a (with a similar conformation); further dehydrochlorination with amines led to the symmetrical and unsymmetrical diphosphaalenes 13 and 14 , respectively. The formation of allenes strongly depends on the conformation of the starting diphosphapropenes.     

Enhancement of the third-order nonlinear optical properties in open-shell singlet transition-metal dinuclear systems: effects of the group, of the period, and of the charge of the metal atom

Metal-metal multiply bonded complexes in their singlet state have been predicted to form a novel class of "σ-dominant" third-order nonlinear optical compounds based on the results of dichromium(II) and dimolybdenum(II) systems (H. Fukui et al. J. Phys. Chem. Lett.2011, 2, 2063) whose second hyperpolarizabilities (γ) are enhanced by the contribution of the dσ electrons with an intermediate diradical character. In this study, using the spin-unrestricted coupled-cluster method with singles and doubles as well as with perturbative triples, we investigate the dependences of γ on the group and on the period of the transition metals as well as on their atomic charges in several open-shell singlet dimetallic systems. A significant enhancement of γ is observed in those dimetallic systems composed of (i) transition metals with a small group number, (ii) transition metals with a large periodic number, and (iii) transition metals with a small positive charge. From the decomposition of the γ values into the contributions of dσ, dπ, and dδ electrons, the γ enhancements are shown to originate from the dσ contribution, because it corresponds to the intermediate diradical character region. Furthermore, the amplitude of dσ contribution turns out to be related to the size of the d(z(2)) atomic orbital of the transition metal, which accounts for the dependence of γ on the group, on the period, and on the charge of the metal atoms. These dependences provide a guideline for an effective molecular design of highly efficient third-order nonlinear optical (NLO) systems based on the metal-metal bonded systems.     

Prediction of fatigue properties of natural rubber based on the descriptions of the cracks population and of the dissipated energy

The goal of this paper is to relate the fatigue lifetime to the energy dissipation and the crack population for a Natural Rubber (NR) compound filled with carbon black. First, the dissipated energy is measured by thermal measurements and its evolution with the local strain is described. Then, the crack population under fatigue loading is investigated thanks to interrupted fatigue tests and SEM measurements. The dependency of the evolution of the crack surface density on the local strain and number of cycles is described. Finally, a fatigue criterion is suggested, starting from the basic assumption of accumulation of dissipated energy along the fatigue cycles. Combining the evolution of the dissipated energy and the crack surface density, the energetic criterion can be written as a simple expression using a single parameter. The predictions obtained with the identified criterion are compared with the results from classic fatigue tests and very close agreement is found.     

Influence of the structure of the alcoholic modifier on the enantioselective separation of nadolol

The influence of the structure of the alcoholic modifier of the mobile phase on the liquid chromatographic separation of the optical isomers of nadolol on a Pirkle-type chiral stationary phase was investigated. The isomers were separated as their chiral 1-naphthylureides on a column consisting of 3,5-dinitrobenzoyl- -leucine covalently bound to 3-μm aminopropylsilica, using an eluent consisting of n-hexane modified with an alcohol. A number of straight-chain, branched and unsaturated alcohols with carbon numbers ranging from 1 to 8 were evaluated. The choice of alcohol influenced both retention and selectivity, with optimum stereoselectivity being observed for C₃. The alcoholic modifiers selectively affected the retention and resolution of the two pairs of enantiomers that constitute nadolol. Thus chromatograms displaying two, three or four peaks could be obtained, depending on which modifier was employed. The best separation of all four isomers was achieved with ethanol as the modifier.     

Does the Sign of the Cu–Gd Magnetic Interaction Depend on the Number of Atoms in the Bridge?

Several theoretical investigations with CASSCF methods confirm that the magnetic behavior of Cu–Gd complexes can only be reproduced if the 5d Gd orbitals are included in the active space. These orbitals, expected to be unoccupied, do present a low spin density, which is mainly due to a spin polarization effect. This theory is strengthened by the experimental results reported herein. We demonstrate that Cu–Gd complexes characterized by Cu–Gd interactions through single‐oxygen and three‐atom bridges consisting of oxygen, carbon, and nitrogen atoms, present weak ferromagnetic exchange interactions, whereas complexes with bridges made of two atoms, such as the nitrogen–oxygen oximato bridge, are subject to weak antiferromagnetic exchange interactions. Therefore, a bridge with an odd number of atoms induces a weak ferromagnetic exchange interaction, whereas a bridge with an even number of atoms supports a weak antiferromagnetic exchange interaction, as observed in pure organic compounds and also, as in this case, in metal–organic compounds with an active spin polarization effect.     

Influence of the errors made in the measurement of the extra-column volume on the accuracies of estimates of the column efficiency and the mass transfer kinetics parameters

The influences of the errors made in the measurement of the extra-column volume of an instrument on the accuracies of the estimates made of the column efficiency and of the parameters of the mass transfer kinetics were investigated from an experimental point of view. A standard HP1090 apparatus (extra-column volume, approximately 50 micro L) was used to measure the efficiency of a Sunfire-C(18) RPLC column (column hold-up volume, approximately 1.50 mL). The first and second moments of the peaks of phenol (a retained compound) and of thiourea (a practically non-retained compound) were measured at six different temperatures between 22 and 78 degrees C, for flow rates between 0.10 and 4.70 mL/min (i.e., for linear velocities between 0.025 and 1.179 cm/s). Each series of measurements was successively made with the instrument being fitted with and without the column. The experimental HETP data must be corrected for the solute dispersion in the connected tubes in order properly to assess the true column efficiency. Even with a modern, high performance instrument, the dispersion of a non-retained compound is essentially due to the band broadening phenomena that take place in the extra-column volumes, the sum of all these extra-column band broadening contributions accounting for more than 80% of the total band broadening measured. The contribution of the sampling device is particularly deleterious since, for a 2 mu L injection, the maximum solute concentration in the peak that enters into the column is nearly ten-fold lower than that of the sample. Nevertheless, the impact of the extra-column volumes on the estimates of the kinetic parameters (e.g., molecular diffusion coefficient D(m) and effective particle diffusivity D(e)) remains negligible. Obviously, the relative error made on the column efficiency of a retained compound depends much on its retention factor. It decreases from 8 to 1% when the retention factor increases from 5 to 17.     

On the effectiveness of different additives and concentrations on the re-building of the molecular structure of degraded polyethylene

Mechanical recycling is an easy and economic way to re-use plastic waste as secondary materials, but, in general, their properties are worse with respect to the reclaimed materials and the virgin polymer. The aim of this work was to study the effect of concentration and reaction kinetics of two additives, an ethylene-co-glycidyl methacrylate (Lotader) and a hydroxylamine derivative (CGX), in the re-building of a degraded polyethylene. CGX is a nitroxyl radical generator able to form branching in polyolefins while the epoxy groups of Lotader can react with the functional groups present in the recycled polyethylene. The results indicate that the CGX has a higher reaction rate than Lotader, probably due to its lower molecular weight and the different reaction path. As for the effect of concentration, as expected, a higher amount of additive accelerates and increases re-building, especially when CGX is used. The melt strength increases with the additive content and the mechanical properties show a significant reduction at the highest concentrations of both additives due to excessive cross-linking.     

Influence of the morphology of samples in the pyrolysis of PVC

PVC was used as a model substance to study the dependence of thermal measurement data on the preparation and morphological characteristics of samples The PVC treated was a commercially available suspension polymer, Ongrovil S 155, produced by the Borsodi Vegyi Kombinát. The whole thermal process was followed by TG and DTG measurements in air and argon atmospheres by means of a Du Pont 990 Thermoanalyzer. Evolved-gas analysis was performed with a home-made apparatus. Pyrolysis gas chromatography was accomplished using a Hamilton type pyrolyzer and a Carlo Erba Chromatograph furnished with a flame ionization detector. The investigations showed benzene and other components to be evolved from the initial polymer and an alteration depending on the morphological characteristics of the samples. This was suggested to be due to the different mechanisms of thermal degradation of the PVC.