An anion-dependent switch in selectivity results from a change of C-H activation mechanism in the reaction of an imidazolium salt with IrH5(PPh3)2

Changing the counteranion along the series Br, BF4, PF6, SbF6 in their ion-paired 2-pyridylmethyl imidazolium salts causes the kinetic reaction products with IrH5(PPh3)2 to switch from chelating N-heterocyclic carbenes (NHCs) having normal C2 (N path) to abnormal C5 binding (AN path). Computational work (DFT) suggests that the AN path involves C-H oxidative addition to Ir(III) to give Ir(V) with little anion dependence. The N path, in contrast, goes by heterolytic C-H activation with proton transfer to the adjacent hydride. The proton that is transferred is accompanied by the counteranion in an anion-coupled proton transfer, leading to an anion dependence of the N path, and therefore of the N/AN selectivity. The N path goes via Ir(III), not Ir(V), because the normal NHC is a much less strong donor ligand than the abnormal NHC. PGSE NMR experiments support the formation of ion-pair in both the reactants and the products. 19F,1H-HOESY NMR experiments indicate an ion-pair structure for the products that is consistent with the computational prediction (ONIOM(B3PW91/UFF)).     

Surface Changes at Platinized Platinum Based Hydrogen Gas Electrodes Following Use in Highly Saline Aqueous Solutions

Platinized platinum based hydrogen gas electrodes, Pt(Pt)|H₂(g)|H⁺(aq), and silver‐silver chloride electrodes, Ag|AgCl|Cl^? (aq), make up the Harned cell, without transfer, working in the potentiometric mode at Cl^? concentrations and ionic strengths, I, below 0.1 mol kg^?1, for assigning primary pH values to reference pH buffer solutions. This work reports on experiments performed at higher I and Cl^? solutions up to 0.7 mol kg^?1, aiming at addressing seawater conditions with results of equally high quality. In the course of measurements, the occasional occurrence of highly unstable potentials denoted electrode malfunction; Pt metal surfaces observed by SEM/EDS and XRD exhibit strong Ag and Cl peaks corresponding to the presence of AgCl crystals deposited at both surfaces.     

Particle methods for stochastic optimal control problems

When dealing with numerical solution of stochastic optimal control problems, stochastic dynamic programming is the natural framework. In order to try to overcome the so-called curse of dimensionality, the stochastic programming school promoted another approach based on scenario trees which can be seen as the combination of Monte Carlo sampling ideas on the one hand, and of a heuristic technique to handle causality (or nonanticipativeness) constraints on the other hand. However, if one considers that the solution of a stochastic optimal control problem is a feedback law which relates control to state variables, the numerical resolution of the optimization problem over a scenario tree should be completed by a feedback synthesis stage in which, at each time step of the scenario tree, control values at nodes are plotted against corresponding state values to provide a first discrete shape of this feedback law from which a continuous function can be finally inferred. From this point of view, the scenario tree approach faces an important difficulty: at the first time stages (close to the tree root), there are a few nodes (or Monte-Carlo particles), and therefore a relatively scarce amount of information to guess a feedback law, but this information is generally of a good quality (that is, viewed as a set of control value estimates for some particular state values, it has a small variance because the future of those nodes is rich enough); on the contrary, at the final time stages (near the tree leaves), the number of nodes increases but the variance gets large because the future of each node gets poor (and sometimes even deterministic). After this dilemma has been confirmed by numerical experiments, we have tried to derive new variational approaches. First of all, two different formulations of the essential constraint of nonanticipativeness are considered: one is called algebraic and the other one is called functional. Next, in both settings, we obtain optimality conditions for the corresponding optimal control problem. For the numerical resolution of those optimality conditions, an adaptive mesh discretization method is used in the state space in order to provide information for feedback synthesis. This mesh is naturally derived from a bunch of sample noise trajectories which need not to be put into the form of a tree prior to numerical resolution. In particular, an important consequence of this discrepancy with the scenario tree approach is that the same number of nodes (or points) are available from the beginning to the end of the time horizon. And this will be obtained without sacrifying the quality of the results (that is, the variance of the estimates). Results of experiments with a hydro-electric dam production management problem will be presented and will demonstrate the claimed improvements. A more realistic problem will also be presented in order to demonstrate the effectiveness of the method for high dimensional problems.     

Picomolar quantitation of free sulfite in foods by means of [57Co]hydroxocobalamin and radiometric chromatography of [57Co]sulfitocobalamin. Method, applications and significance of coexisting sulfides

The concentration dependent reaction of sulfite with 57Co-labeled hydroxocobalamin (OH57CoCbl) to produce a sulfitocobalamin (SO(3)57CoCbl) adduct served as a quantification strategy for foodborne sulfite residues freely extracted into pH 5.2, 0.05 M acetate buffer. SO(3)57CoCbl was then resolved using SP-Sephadex C-25 gel chromatography and its radiometric detection allowed calculation of a standard logit plot from which unknown sulfite concentrations could be determined. The sulfite detection range was 6.0 nM-0.3 pM with respective relative standard deviations of 4.4-29.4% for 50-microl samples. Individual incidences of foodborne sulfite intolerances provoked by L-cysteine or sulfite additive use in bakery products, which remained undetected using conventional sulfite analytical methods, underscored the quantitative value of the method. The analytical significance and occurrences of detectable sulfides coexisting with foodborne sulfite residues was also addressed.     

Influence of Structural Parameters on the Self‐Association Properties of Anti‐HIV Catanionic Dendrimers

The self‐association properties of anti‐HIV catanionic dendrimers as multivalent galactosylceramide (GalCer)‐derived inhibitors are presented. The study was designed to elucidate the origin of the relatively high cytotoxicity values of these anti‐HIV catanionic dendrimers, which have previously been found to exhibit in vitro anti‐HIV activity in the submicromolar range. The physicochemical properties of these catanionic dendrimers were studied to tentatively correlate the structural parameters with self‐association and biological properties. We can conclude from this study that the absence of correlation between the hydrophobicity and the cytotoxicity of the catanionic systems could be explained by the partial segregation of the different partners of the catanionic entities.     

Comparison of stability predictions and simulated unfolding of rhodopsin structures

Developing a better mechanistic understanding of membrane protein folding is urgently needed because of the discovery of an increasing number of human diseases, where membrane protein instability and misfolding is involved. Towards this goal, we investigated folding and stability of 7-transmembrane (TM) helical bundles by computational methods. We compared the results of three different algorithms for predicting changes in stability of proteins against an experimental mutation dataset obtained for bacteriorhodopsin (BR) and mammalian rhodopsin and find that 61.6% and 70.6% of the mutation results can potentially be explained by known local contributors to the stability of the folded state of BR and mammalian rhodopsin, respectively. To obtain further information on the predicted folding pathway of 7-TM proteins, we conducted simulated thermal unfolding experiments of all available rhodopsin structures with resolution better than 3 angstroms using the Floppy Inclusions and Rigid Substructure Topography (FIRST) method (Jacobs, D. J., A. J. Rader, L. A. Kuhn and M. F. Thorpe [2001] Proteins 44, 150) described previously for a single mammalian rhodopsin structure (Rader et al. [2004] PNAS 101, 7246). In statistical comparison we found that structures of mammalian rhodopsin have a stability core that is characterized by long-range interactions involving amino acids close in space but distant in sequence comprising positions from both extracellular loop and TM regions. In contrast, BR-simulated unfolding does not reveal such a core but is dominated by interactions within individual and groups of TM helices, consistent with the two-stage hypothesis of membrane protein folding. Similar results were obtained for halo- and sensory rhodopsins as for BRs. However, the average folding core energies of sensory rhodopsins were in between those observed for mammalian rhodopsins and BRs hinting at a possible evolution of these structures toward a rhodopsin-like behavior. These results support the conclusion that although the two-stage model can explain the mechanisms of folding and stability of BR, it fails to account for the folding and stability of mammalian rhodopsin, even though the two proteins are structurally related.     

Synthesis and antiproliferative activity of (Z + E)‐1‐[4‐(2‐(cyclopentadienyltricarbonylmanganese)‐2‐oxo‐ethoxy)phenyl]‐1,2‐di(p‐hydroxyphenyl)‐but‐1‐ene against breast cancer cells

This paper describes the synthesis of (Z + E)‐1‐[4‐(2‐(cyclopentadienyltricarbonylmanganese)‐2‐oxo‐ethoxy)phenyl]‐1,2‐di(p‐hydroxyphenyl)‐but‐1‐ene. Two synthetic pathways were explored. The best pathway consisted of the alkylation of 1,2‐bis‐[4‐(tert‐butyl‐dimethylsilyloxy)phenyl]‐1‐(4‐hydroxyphenyl)but‐1‐ene with BrCH₂COOEt. The ester obtained was transformed into the Weinreb amide by reaction with HN(OMe)Me–HCl. The reaction of lithium manganese tricarbonylcyclopentadienide with the Weinreb amide produced 1‐[4‐(2‐(cyclopentadienyltricarbonylmanganese)‐2‐oxo‐ethoxy)phenyl]‐1,2‐di(p‐tert‐butyldimethylsiloxyphenyl)‐but‐1‐ene. The deprotection of phenolic functions of the latter compound led to the formation of the final compound. The Z and E isomers could be separated but the isomerization of these isomers from one to another is an easy process. The Z + E compound 2 was tested against the hormone‐dependent MCF‐7 and hormone‐independent MDA‐MB‐231 breast cancer cell lines. The IC₅₀ values of compound 2 were 4.80 ± 2.00 µm and 4.79 ± 0.70 µm for MCF‐7 cells and MDA‐MB‐231 cells, respectively, which was three times better than the ferrocenyl analogue. Copyright © 2012 John Wiley & Sons, Ltd.     

Compatibility of activity coefficients estimated experimentally and by Pitzer equations for the assessment of seawater pH

Calibration of pH meters is usually performed with reference pH buffer solutions of low ionic strength, I ≤ 0.1 mol kg^?1. For seawater pH measurements (I ≈ 0.7 mol kg^?1), calibration buffers in high ionic strength matrix are required. The Harned cell, in association with the Nernst equation and a model for estimating the chloride ion activity coefficient, \(\gamma_{{{\text{Cl}}^{ - } }} ,\) is the basis of the primary method for pH assignment to reference pH buffers. The semi-empirical Pitzer model is, in principle, adequate to estimate \(\gamma_{{{\text{Cl}}^{ - } }}\) of complex solutions, namely seawater. Nevertheless, no assessment of the validity of the model for this matrix is known to the authors. This work aims at estimating the adequacy of the Pitzer model by assessing the metrological compatibility of mean activity coefficients, in this case \(\gamma_{ \pm } = \sqrt {\gamma_{{{\text{H}}^{ + } }} \gamma_{{{\text{Cl}}^{ - } }} }\) estimated experimentally with the Harned cell, \(\gamma_{ \pm }^{\text{Exp}} ,\) and using the Pitzer model, \(\gamma_{ \pm }^{\text{Ptz}}\). The measurement uncertainty considered in the compatibility test was estimated using the bottom-up approach, where components were combined by the numerical Kragten method after checking its adequacy. The compatibility of the estimated \(\gamma_{ \pm }\) was assessed for solutions with increasing complexity and an ionic strength of 0.67 mol kg^–1. \(\gamma_{ \pm }^{\text{Exp}}\) and \(\gamma_{ \pm }^{Ptz}\) are metrologically compatible for a confidence level of 95 % where the relative standard uncertainty of their difference ranged from 1.1 % to 3.1 % in all chloride solutions to approximately 6.3 % when sodium sulfate was also present. This led to assume the validity of the Pitzer model equations to estimate \(\gamma_{{{\text{Cl}}^{ - } }} ,\) required to define reference pH values of buffer solutions with high ionic strength.     

Abnormal ligand binding and reversible ring hydrogenation in the reaction of imidazolium salts with IrH(5)(PPh(3))(2)

We show that imidazolium salts do not always give normal or even aromatic carbenes on metalation, and the chemistry of these ligands can be much more complicated than previously thought. N,N'-disubstituted imidazolium salts of type [(2-py)(CH(2))(n)(C(3)H(3)N(2))R]BF(4) react with IrH(5)(PPh(3))(2) to give N,C-chelated products (n = 0, 1; 2-py = 2-pyridyl; C(3)H(3)N(2) = imidazolium; R = mesityl, n-butyl, i-propyl, methyl). Depending on the circumstances, three types of kinetic products can be formed: in one, the imidazole metalation site is the normal C2 as expected; in another, the metalation occurs at the abnormal C4 site; and in the third, C4 metalation is accompanied by hydrogenation of the imidazolium ring. The bonding mode is confirmed by structural studies, and spectroscopic criteria can also distinguish the cases. Initial hydrogen transfer can take place from the metal to the carbene to give the imidazolium ring hydrogenation product, as shown by isotope labeling; this hydrogen transfer proves reversible on reflux when the abnormal aromatic carbene is obtained as final product. Care may therefore be needed in the future in verifying the structure(s) formed in cases where a catalyst is generated in situ from imidazolium salt and metal precursor.     

Investigation of the curing kinetics of polyurethane/nitrocellulose blends through FT-IR measurements

Polyester (HTPS) based polyurethane (PU) elastomers were currently established to be effective binders for high-energy composites with improved performances. Conventional PU binders are mostly non-energetic materials, and consequently reduce the energy performance significantly. Nitrocellulose (NC), is an energetic polymer widely used as an ingredient in propellants, explosives, fireworks, and gas generators, it may be introduced in PU-based compositions to overcome their performance drawback. Kinetic parameters must be specified in order to build PU binders with the most convenient and appropriate features. Therefore, the cure kinetics of polyester based polyurethane binder systems were investigated by Fourier transform infrared spectroscopy (FT-IR) isothermal method. The polyester prepolymer (Desmophen^® 1200) was cured with hexamethylene diisocyanate (HDI: Desmodur^® N100) at various molar ratios (R_[NCO]/[OH] = 0.6, 1, 1.25, and 1.5) and under different isothermal conditions (T = 60°C, 80°C, 100°C, and 120°C). In addition, the effect of the addition of nitrocellulose on the kinetics of polymerization of PU was investigated. The progression of the reaction was followed based on the decrease of the peak intensity of –NCO group at 2271 cm⁻¹ as a function of the reaction time. The curing kinetic model and the apparent activation energy (E_α) were determined by the use of Kamal autocatalytic model and Friedman isoconversional method, respectively.