Suppression of Liquid-Liquid Phase Separation and Aggregation of Antibodies by Modest Pressure Application

The high colloidal stability of antibody (immunoglobulin) solutions is important for pharmaceutical applications. Inert cosolutes, excipients, are generally used in therapeutic protein formulations to minimize physical instabilities, such as liquid–liquid phase separation (LLPS), aggregation and precipitation, which are often encountered during manufacturing and storage. Despite their widespread use, a detailed understanding of how excipients modulate the specific protein-protein interactions responsible for these instabilities is still lacking. In this work, we demonstrate the high sensitivity to pressure of globulin condensates as a suitable means to suppress LLPS and subsequent aggregation of concentrated antibody solutions. The addition of excipients has only a minor effect. The high pressure sensitivity observed is due to the fact that these flexible Y-shaped molecules create a considerable amount of void volume in the condensed phase, leading to an overall decrease in the volume of the system upon dissociation of the droplet phase by pressure already at a few tens of to hundred bar. Moreover, we show that immunoglobulin molecules themselves are highly resistant to unfolding under pressure, and can even sustain pressures up to about 6 kbar without conformational changes. This implies that immunoglobulins are resistant to the pressure treatment of foods, such as milk, in high-pressure food-processing technologies, thereby preserving their immunological activity.     

Electrodes based on zeolites modified with cobalt and/or molybdenum for pesticide degradation: part II—2,4,6-trichlorophenol degradation

Journal of Solid State Electrochemistry - 2,4,6-trichlorophenol (TCP) is a persistent pollutant introduced in water by industrial processes and pesticides. We have studied the electrooxidation of...     

Green Synthesis of Cuprous Oxide Nanoparticles Using Andean Capuli (Prunus serotina Ehrh. var. Capuli) Cherry

Journal of Cluster Science - Copper oxide nanoparticles have gained considerable attention in the past two decades due to their simplicity and exhibit a range of potentially useful physical...     

Critical clusters in interdependent economic sectors

In this paper we develop a data-driven hierarchical clustering methodology to group the economic sectors of a country in order to highlight strongly coupled groups that are weakly coupled with other groups. Specifically, we consider an input-output representation of the coupling among the sectors and we interpret the relation among sectors as a directed graph; then we recursively apply the spectral clustering methodology over the graph, without a priori information on the number of groups that have to be obtained. In order to do this, we resort to the eigengap criterion, where a suitable number of groups is selected automatically based on the intensity and structure of the coupling among the sectors. We validate the proposed methodology considering a case study for Italy, inspecting how the coupling among clusters and sectors changes from the year 1995 to 2011, showing that in the years the Italian structure underwent deep changes, becoming more and more interdependent, i.e., a large part of the economy has become tightly coupled.     

Liquid transport due to light scattering

Using experiments and theory, we show that light scattering by inhomogeneities in the index of refraction of a fluid can drive a large-scale flow. The experiment uses a near-critical, phase-separated liquid, which experiences large fluctuations in its index of refraction. A laser beam traversing the liquid produces a interface deformation on the scale of the experimental setup and can cause a liquid jet to form. We demonstrate that the deformation is produced by a scattering-induced flow by obtaining good agreements between the measured deformations and those calculated assuming this mechanism.     

Homogeneous and unimolecular gas‐phase thermal decomposition kinetics of methyl benzoylformate: experimental and theoretical study

The kinetics of the gas‐phase thermal decomposition of the α‐ketoester methyl benzoylformate was carried out in a static system with reaction vessel deactivated with allyl bromide, and in the presence of the free radical inhibitor propene. The rate coefficients were determined over the temperature range of 440–481 °C and pressures from 32 to 80 Torr. The reaction was found to be homogenous, unimolecular and obey a first‐order rate law. The products are methyl benzoate and CO. The temperature dependence of the rate coefficient gives the following Arrhenius parameters: log₁₀ k (s^?1) = 13.56 ± 0.31 and E_a (kJ mol^?1) = 232.6 ± 4.4. Theoretical calculations of the kinetic and thermodynamic parameters are in good agreement with the experimental values using PBE1PBE/6‐311++g(d,p). A theoretical Arrhenius plot was constructed at this level of theory, and the good agreement with the experimental Arrhenius plot suggests that this model of transition state may describe reasonably the elimination process. These results suggest a concerted non‐synchronous semi‐polar three‐membered cyclic transition state type of mechanism. The most advanced coordinate is the bond breaking C^δ+‐‐‐^δ‐OCH₃ with an evolution of 66.7%, implying this as the limiting factor of the elimination process. Copyright © 2014 John Wiley & Sons, Ltd.     

Gas‐phase elimination kinetics of selected aliphatic α,β‐unsaturated aldehydes catalyzed by hydrogen chloride

The gas‐phase elimination of 2‐methyl‐2‐propenal catalyzed by HCl yields propene and CO gas, while E‐2‐pentenal with the same catalyst gives butene and CO gas. The kinetics determinations were carried out in a static system with the reaction vessels deactivated with allyl bromide and the presence of the free radical inhibitor toluene. Temperature and pressure ranges were 350.0–410.0 °C and 34–76 Torr. The elimination reactions are homogeneous and unimolecular, and follow a first‐order rate law. The rate coefficients for the reactions are expressible by the following Arrhenius equations: Data from the kinetic and thermodynamic parameters of these catalyzed elimination reactions implies a mechanism of a concerted five‐membered cyclic transition state structure for the formation of the corresponding olefin and carbon monoxide. Copyright © 2015 John Wiley & Sons, Ltd.     

Electron irradiation-enhanced core/shell organization of Al(Cr,Fe, Mn)Si dispersoids in Al–Mg–Si alloys

The age hardening 6061-T6 aluminium alloy has been chosen as structural material for the core vessel of the material testing Jules Horowitz nuclear reactor. The alloy contains incoherent Al(Cr, Fe, Mn)Si dispersoids whose characterization by energy-filtered transmission electron microscopy (EFTEM) analysis shows a core/shell organization tendency where the core is (Mn, Fe) rich, and the shell is Cr rich. The present work studies the stability of this organization under irradiation. TEM characterization on the same particles, before and after 1 MeV electron irradiation, reveals that the core/shell organization is enhanced after irradiation. It is proposed that the high level of point defects, created by irradiation, ensures a radiation-enhanced diffusion process favourable to the unmixing forces between (Fe, Mn) and Cr. Shell formation may result in the low-energy interface segregation of Cr atoms within the (Fe, Mn) system combined with the unmixing of Cr, Fe and Mn components.     

Functionalized Graphene as a Gatekeeper for Chiral Molecules: An Alternative Concept for Chiral Separation

We propose a new method of chiral separation using functionalized nanoporous graphene as an example. Computational simulations based on density functional theory show that the attachment of a suitable chiral “bouncer” molecule to the pore rim prevents the passage of the undesired enantiomer while letting its mirror image through.     

Asymmetric Transfer Hydrogenation of gem-Difluorocyclopropenyl Esters: Access to Enantioenriched gem-Difluorocyclopropanes

Catalytic enantioselective access to disubstituted functionalized gem-difluorocyclopropanes, which are emerging fluorinated motifs of interest in medicinal chemistry, was achieved through asymmetric transfer hydrogenation of gem-difluorocyclopropenyl esters, catalyzed by a Noyori–Ikariya (p-cymene)-ruthenium(II) complex, with (N-tosyl-1,2-diphenylethylenediamine) as the chiral ligand and isopropanol as the hydrogen donor. The resulting cis-gem-difluorocyclopropyl esters were obtained with moderate to high enantioselectivity (ee=66–99 %), and post-functionalization reactions enable access to valuable building blocks incorporating a cis- or trans-gem-difluorocyclopropyl motif.