Cyclopalladation and Reactivity of Amino Esters through C?H Bond Activation: Experimental,Kinetic, and Density Functional Theory Mechanistic Studies

The orthopalladation, through C? H bond activation, of a large number of amino esters and amino phosphonates derived from phenylglycine, and having different substituents at the aryl ring and the C‐α atom, as well as on the N‐amine atom, has been studied. The experimental observations indicated an improvement in the yields of the orthopalladated compounds when the N‐amine and/or the C‐α atom are substituted, when compared with the unsubstituted methyl phenylglycinate derivatives. In contrast, substitutions at the aryl ring do not promote significant changes in the orthometalation results. Furthermore, the use of hydrochloride salts of the amino esters has also been shown to have a remarkably favorable effect on the process. All these observations have been fully quantified at different temperatures and pressures by a detailed kinetic study in solution in different solvents and in the presence and absence of added Brønsted acids and chloride anions. The data collected indicate relevant changes in the process depending on these conditions, as expected from the general background known for cyclopalladation reactions. An electronic mechanism of the orthopalladation has been proposed based on DFT calculations at the B3LYP level, and a very good agreement between the trends kinetically measured and the theoretically calculated activation barriers has been obtained. The reactivity of the new orthopalladated amino phosphonate derivatives has been tested and it was found that their halogenation, alkoxylation and carbonylation resulted in formation of the corresponding functionalized ortho‐haloaminophosphonates, ortho‐alkoxyaminophosphonates and oxoisoindolinylphosphonates.     

Long-Range proton-proton coupling constants. I. Propanic coupling involving a methyl group 4JMeH

An equation is formulated on the basis of theoretical INDO/FPT calculations which describes the angular dependence of the propanic long-range coupling constant ⁴J_MeH in substituted HCCCH₃ fragments. This equation is a truncated Fourier series in the torsion angle ?, HCCMe, which takes into account the dependence of the Fourier coefficients on the bond angle θ, CCMe. The substituent effects are assumed to be additive. Some parameters in the equation may be obtained from the ⁴J_MeH couplings in propane and neopentane derivatives. The calculated effect upon ⁴J_MeH of changes in the bond angle θ is significant and it seems to be in part the cause of some effects which have been attributed to conformational dependence.     

Determination of complex formation constants by phase sensitive alternating current polarography: Cadmium-polymethacrylic acid and cadmium-polygalacturonic acid

The use of phase sensitive alternating current polarography (ACP) for the evaluation of complex formation constants of systems where electrodic adsorption is present has been proposed. The applicability of the technique implies the previous selection of the phase angle where contribution of capacitive current is minimized. This is made using Multivariate Curve Resolution by Alternating Least Squares (MCR-ALS) in the analysis of ACP measurements at different phase angles. The method is checked by the study of the complexation of Cd by polymethacrylic (PMA) and polygalacturonic (PGA) acids, and the optimal phase angles have been ca. −10° for Cd-PMA and ca. −15° for Cd-PGA systems. The goodness of phase sensitive ACP has been demonstrated comparing the determined complex formation constants with those obtained by reverse pulse polarography, a technique that minimizes the electrode adsorption effects on the measured currents.     

A class of small molecules that inhibit TNFalpha-induced survival and death pathways via prevention of interactions between TNFalphaRI, TRADD, and RIP1

Small-molecule library screening to find compounds that inhibit TNFalpha-induced, but not interleukin 1beta (IL-1beta)-induced, intercellular adhesion molecule 1 (ICAM-1) expression in lung epithelial cells identified a class of triazoloquinoxalines. These compounds not only inhibited the TNFalpha-induced nuclear factor kappaB (NFkappaB) survival pathway but also blocked death-pathway activation. Such dual activity makes them unique against other known NFkappaB-pathway inhibitors that inhibit only a subset of TNFalpha signals leading to increased TNFalpha-induced cytotoxicity. Interestingly, these compounds inhibited association of TNFalpha receptor (TNFalphaR) I with TNFalphaR-associated death domain protein (TRADD) and receptor interacting protein 1 (RIP1), the initial intracellular signaling event following TNFalpha stimulation. Further study showed that they blocked ligand-dependent internalization of the TNFalpha-TNFalphaR complex, thereby inhibiting most of the TNFalpha-induced cellular responses. Thus, compounds with a triazoloquinoxaline scaffold could be a valuable tool to investigate small molecule-based anti-TNFalpha therapies.     

Mixing Closures for Conservation Laws in Stratified Flows

A closure for shocks involving the mixing of the fluids in two-layer stratified flows is proposed. The closure maximizes the rate of mixing, treating the dynamical hydraulic equations and entropy conditions as constraints. This closure may also be viewed as yielding an upper bound on the mixing rate by internal shocks. It is shown that the maximal mixing rate is accomplished by a shock moving at the fastest allowable speed against the upstream flow. Depending on whether the active constraint limiting this speed is the Lax entropy condition or the positive dissipation of energy, we distinguish precisely between internal hydraulic jumps and bores. Maximizing entrainment is shown to be equivalent to maximizing a suitable entropy associated to mixing. By using the latter, one can describe the flow globally by an optimization procedure, without treating the shocks separately. A general mathematical framework is formulated that can be applied whenever an insufficient number of conservation laws is supplemented by a maximization principle.     

Size-exclusion chromatographic protein refolding: fundamentals, modeling and operation

Size-exclusion chromatography (SEC) has proven its capability to refold a variety of proteins using a range of gel filtration column materials, demonstrated in the growing body of experimental evidence. However, little effort has been allocated to the development of mechanistic models describing size-exclusion chromatographic refolding reactors (SECRR). Mechanistic models are important since they provide a link between process variables like denatured and reduced protein feed concentration (C_f,D&;R), flow rate, column length, etc., and performance indicators like refolding yield (Y_N), thereby opening the possibility for in silico design of SECRRs. A critical step, in the formulation of such models, is the selection of an adequate reaction mechanism, which provides the direct link between the separation and the refolding yield. Therefore, in this work we present a methodology using a SEC refolding reactor model, supported by a library of reaction mechanisms, to estimate a suitable reaction scheme using experimental SEC refolding data. SEC refolding data is used since it provides information about the mass distribution of monomers and aggregates after refolding, information not readily available from batch dilution refolding data alone. Additionally, this work presents (1) a systematic analysis of the reaction mechanisms considered using characteristic time analysis and Damköhler maps, revealing (a) the direct effect of a given reaction mechanism on the shape of the SEC refolding chromatogram (number of peaks and resolution) and (b) the effect that the competition between convection, refolding and aggregation is likely to have on the SEC refolding yield; (2) a comparison between the SECR reactor and the batch dilution refolding reactor based on mechanistic modeling, quantitatively showing the advantages of the former over the latter; and (3) the successful application of the modeling based strategy to study the SEC refolding data of an industrially relevant protein. In principle, the presented modeling strategy can be applied to any protein refolded using any gel filtration material, providing the proper mass balances and activity measurements are available.     

Synthesis of rGO–Nps hybrids with electrocatalytic activity for hydrogen evolution reaction

Journal of Solid State Electrochemistry - A hybrid nanomaterial with palladium nanoparticles (PdNps) supported on reduced graphene oxide (rGO) flakes, dispersed in an aqueous solution was...