Small Charge Differences Research Articles

Introducing Structures from Hexagonal Borophene to Nitrophene and Their Thermal Conductivity Investigation Using a Reactive Molecular Dynamics Simulation.

In the present work, the thermal conductivity (TC) of hexagonal structures of boron nitride and borophene was investigated by a reactive molecular dynamics (MD) simulation. Also, to figure out the effect of the boron and nitrogen in the hexagonal structure, five other hypothetical structures were created (in addition to the structure of boron nitride and borophene) and their structures were represented by the symbol BxNy, where x refers to the number of boron atoms and y refers to the number of nitrogen atoms. In this regard, B6N0 refers to borophene, B3N3 is boron nitride, and B0N6 is called nitrophene. The TC of B6N0 and B3N3 structures was calculated and compared with the literature values. Besides these two compounds, the five other structures have not been experimentally synthesized yet, so the TC of the five other hypothetical structures were predicted in the present work. The lowest TC belonged to B3N3, and the highest one was for B0N6. Based on the inherent potential of reactive MD simulation, during TC calculation, atoms' coordination and partial charges are changed and new bonds, rings, or even defects were automatically created on the surfaces. The coordination contour map showed that in B3N3, the atoms have collective movements like a large and single wave, while B0N6 and B6N0 have small group movements as vibrations. So, it became clear that the higher stability of structures caused more curved movements. In addition, the contour map of partial charges is calculated, and the results showed that the high differences in partial charge between atoms in the structure cause high TC, while small charge differences in the structure inhibit heat transfer and cause lower TC.

Unexpected large impact of small charges on surface frictions with similar wetting properties

Generally, the interface friction on solid surfaces is regarded as consistent with wetting behaviors, characterized by the contact angles. Here using molecular dynamics simulations, we find that even a small charge difference (≤0.36 e) causes a change in the friction coefficient of over an order of magnitude on two-dimensional material and lipid surfaces, despite similar contact angles. This large difference is confirmed by experimentally measuring interfacial friction of graphite and MoS2 contacting on water, using atomic force microscopy. The large variation in the friction coefficient is attributed to the different fluctuations of localized potential energy under inhomogeneous charge distribution. Our results help to understand the dynamics of two-dimensional materials and biomolecules, generally formed by atoms with small charge, including nanomaterials, such as nitrogen-doped graphene, hydrogen-terminated graphene, or MoS2, and molecular transport through cell membranes.

Manipulating adenoviral vector ion-exchange chromatography: Hexon versus fiber.

The serotype specificity of adenovirus ion-exchange chromatography has previously been studied using standard particle-based columns, and the hexon protein has been reported to determine retention time. In this study, we have submitted Adenovirus type 5 recombinants to anion-exchange chromatography using methacrylate monolithic supports. Our experiments with hexon-modified adenoviral vectors show more precisely that the retention time is affected by the substitution of amino acids in hypervariable region 5, which lies within the hexon DE1 loop. By exploring the recombinants modified in the fiber protein, we have proven the previously predicted chromatographic potential of this surface constituent. Modifications that preserve the net charge of the hexon protein, or those that cause only a small charge difference in the fiber protein, in addition to shortening the fiber shaft, did not change the chromatographic behavior of the adenovirus particles. However, modifications that include the deletion of just two negatively charged amino acids in the hexon protein, or the introduction of a heterologous fiber protein, derived from another serotype, revealed recognizable changes in anion-exchange chromatography. This could be useful in facilitating chromatography-approach purification by creating targeted capsid modifications, thereby shifting adenovirus particles away from particular interfering substances present in the crude lysate.

Reduction of product‐related species during the fermentation and purification of a recombinant IL‐1 receptor antagonist at the laboratory and pilot scale

Through a parallel approach of tracking product quality through fermentation and purification development, a robust process was designed to reduce the levels of product-related species. Three biochemically similar product-related species were identified as byproducts of host-cell enzymatic activity. To modulate intracellular proteolytic activity, key fermentation parameters (temperature, pH, trace metals, EDTA levels, and carbon source) were evaluated through bioreactor optimization, while balancing negative effects on growth, productivity, and oxygen demand. The purification process was based on three non-affinity steps and resolved product-related species by exploiting small charge differences. Using statistical design of experiments for elution conditions, a high-resolution cation exchange capture column was optimized for resolution and recovery. Further reduction of product-related species was achieved by evaluating a matrix of conditions for a ceramic hydroxyapatite column. The optimized fermentation process was transferred from the 2-L laboratory scale to the 100-L pilot scale and the purification process was scaled accordingly to process the fermentation harvest. The laboratory- and pilot-scale processes resulted in similar process recoveries of 60 and 65%, respectively, and in a product that was of equal quality and purity to that of small-scale development preparations. The parallel approach for up- and downstream development was paramount in achieving a robust and scalable clinical process.

Structural Transitions from Triangular to Square Molecular Arrangements in the Quasi-One-Dimensional Molecular Conductors (DMEDO-TTF)2XF6 (X = P, As, and Sb)

A series of quasi-one-dimensional molecular conductors (DMEDO-TTF)(2)XF(6) (X = P, As, and Sb), where DMEDO-TTF is dimethyl(ethylenedioxy)tetrathiafulvalene, undergo characteristic structural transitions in the range of 130-195 K for the PF(6) salt and 222-242 K for the AsF(6) salt. The dramatic structural transition is induced by the order of the ethylenedioxy moiety, and the resulting anion rotation leads to the reconstruction of the H···F interaction between the methyl groups and the anions. The unique hydrogen bonds play a crucial role in the transition. As a result, the molecular packing is rearranged entirely; the high-temperature molecular stacks with an ordinary quasi-triangular molecular network transforms to a quasi-square-like network, which has never been observed among organic conductors. Nonetheless, the low-temperature phase exhibits a good metallic conductivity as well, so the transition is a metal-metal (MM) transition. The resistivity measured along the perpendicular direction to the conducting ac-plane (ρ(⊥)) and the calculation of the Fermi surface demonstrate that the high-temperature metal phase is a one-dimensional metal, whereas the low-temperature metal phase has considerable interchain interaction. In the SbF(6) salt, a similar structural transition takes place around 370 K, so that the quasi-square-like lattice is realized even at room temperature. Despite the largely different MM transition temperatures, all these salts undergo metal-insulator (MI) transitions approximately at the same temperature of 50 K. The low-temperature insulator phase is nonmagnetic, and the reflectance spectra suggest the presence of charge disproportionation with small charge difference (0.14).

Silver Melonates and Coordination Modes of the Multidentate [C6N7(NCN)3]3– Anion

AbstractThree different silver melonates, Ag3[C6N7(NCN)3]·H2O (2a), Ag3[C6N7(NCN)3]·0.5NH3 (2b) and Ag3[C6N7(NCN)3]·2C2H8N2 (2c), and a nickel melonate, Ni3[C6N7(NCN)3]2·10NH3·6H2O (3), have been synthesised by the reaction of potassium melonate with silver nitrate either in an aqueous solution (2a), aqueous ammonia solution (2b) or an aqueous solution of ethylenediamine (2c) and with nickel nitrate in an aqueous ammonia solution (3). The crystal structure of 2c was determined by XRD [triclinic, P$\bar {1}$, a = 7.5499(4), b = 11.3438(6), c = 12.5741(7) Å, α = 72.138(4), β = 80.148(4), γ = 75.945(4)°, V = 984.90(9) Å3]. Silver atoms are coordinated to the terminal nitrogen atom of the cyanamide substituent as well as directly to the N atoms of the s‐heptazine core. Complex 2c crystallises in a layered structure. Adjacent Ag–melonate cation–anion units are connected by Ag–Ag interactions. The preferred coordination mode of metal ions at the melonate anion has been considered by quantum chemical calculations. Natural atomic charges calculated for the four nonequivalent, nucleophilic N atoms of the [C6N7(NCN)3]3– anion are (a) –0.596, (b) –0.619, (c) –0.675 and (d) –0.644. The metal coordination found experimentally in the melonates correlates with these relatively small charge differences and with the hard‐soft acid–base concept. However, (mono)protonation of the [C6N7(NCN)3]3– anion exclusively occurs at the terminal N atoms (b) of the s‐heptazine core, which is indicated experimentally and theoretically. Silver melonates 2a, 2b and 2c and nickel melonate 3 were further characterised by FTIR and 13C solid‐state magic‐angle spinning NMR spectroscopy, thermogravimetric/differential thermal analysis and elemental analysis. Solvent‐free complexes 2a and 2b, i.e. Ag3[C6N7(NCN)3], are thermally stable up to 500 °C. In contrast, 2c and 3 are thermally less stable.

Structural investigation on the adsorption of the MARCKS peptide on anionic lipid monolayers – effects beyond electrostatic

Abstract The presence of charged lipids in the cell membrane constitutes the background for the interaction with numerous membrane proteins. As a result, the valence of the lipids plays an important role concerning their lateral organization in the membrane and therefore the very manner of this interaction. This present study examines this aspect, particularly regarding to the interaction of the anionic lipid DPPS with the highly basic charged effector domain of the MARCKS protein, examined in monolayer model systems. Film balance, fluorescence microscopy and X-ray reflection/diffraction measurements were used to study the behavior of DPPS in a mixture with DPPC for its dependance on the presence of MARCKS (151–175). In the mixed monolayer, both lipids are completely miscible therefore DPPS is incorporated in the ordered crystalline DPPC domains as well. The interaction of MARCKS peptide with the mixed monolayer leads to the formation of lipid/peptide clusters causing an elongation of the serine group of the DPPS up to 7 Å in direction to surface normal into the subphase. The large cationic charge of the peptide pulls out the serine group of the interface which simultaneously causes an elongation of the phosphodiester group of the lipid fraction too. The obtained results were used to compare the interaction of MARCKS peptide with the polyvalent PIP 2 in mixed monolayers. On this way we surprisingly find out, that the relative small charge difference of the anionic lipids causes a significant different interaction with MARCKS (151–175). The lateral arrangement of the anionic lipids depends on their charge values and determines the diffusion of the electrostatic binding clusters within the membrane.

Dependency of ligand free energy landscapes on charge parameters and solvent models

We performed replica-exchange molecular dynamics (REMD) simulations of six ligands to examine the dependency of their free energy landscapes on charge parameters and solvent models. Six different charge parameter sets for each ligand were first generated by RESP and AM1-BCC methods using three different conformations independently. RESP charges showed some conformational dependency. On the other hand, AM1-BCC charges did not show conformational dependency and well reproduced the overall trend of RESP charges. The free energy landscapes obtained from the REMD simulations of ligands in vacuum, Generalized-Born (GB), and TIP3P solutions were then analyzed. We found that even small charge differences can produce qualitatively different landscapes in vacuum condition, but the differences tend to be much smaller under GB and TIP3P conditions. The simulations in the GB model well reproduced the landscapes in the TIP3P model using only a fraction of the computational cost. The protein-bound ligand conformations were rarely the global minimum states, but similar conformations were found to exist in aqueous solution without proteins in regions close to the global minimum, local minimum or intermediate states.

Analysis of Dyslipidemia in Nephrotic Syndrome by Capillary Isotachophoresis

Hyperlipidaemia is a secondary change in nephrotic syndrome (NS) patients. Recent studies have highlighted increased risks of atherosclerosis and progression of renal disease associated with nephrotic dyslipidemia. All apolipoprotein B (apoB)-containing lipoproteins, including very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and lipoprotein(a) [Lp(a)] are elevated in NS patients, while high-density lipoproteins (HDL) remain unchanged or even reduced. In addition, the lipoprotein composition undergoes a marked change, with a higher ratio of cholesterol to triglyceride in apoB-containing lipoproteins and an increase in the proportion of cholesterol, cholesterol ester, and phospholipids compared with proteins. This change in LDL and HDL cholesterol could no longer represent LDL and HDL particles exactly, underscoring the need for an easy and feasible means of analyzing lipoproteins effectively. Unlike capillary zone electrophoresis, cITP can separate mixed sample zones into pure zones of individual substances according to differences in their electrophoretic mobilities by using a discontinuous electrolyte system. Once the separation is completed, a steady state exists and the zones migrate in the order of decreasing mobilities but with the same velocity. The sharpening and self-focusing effect is another special feature of cITP, which improves resolution of small charge differences within lipoparticles and increases fluorescent detection sensitivity of minor lipoprotein subclasses. 1

The effect of membrane properties on the separation of protein charge variants using ultrafiltration

Recent experimental studies have demonstrated that membrane systems can be used to separate protein variants that differ by only a single amino acid residue, although the selectivity and purification factor were relatively low. The objective of this study was to examine theoretically the effects of the membrane surface charge density and pore size distribution on the separation of protein variants by high performance tangential flow filtration. Model calculations based on the partitioning of a charged sphere into a charged cylindrical pore, including a shift in pH within the pores due to preferential partitioning of the positive hydrogen ions, are in good agreement with literature data for the separation of myoglobin and a succinylated variant. Significantly greater selectivity was obtained by reducing the mean pore size and increasing the membrane surface charge density, both of which enhance the electrostatic interactions arising from the small charge difference between the native protein and the variant. Purification factor–yield plots were developed to evaluate the separation performance. Proper selection of membrane properties gave 100-fold purification at 90% product yield for the separation of variants differing at only a single lysine group.

High-pressure Raman study of the charge ordering inα−(BEDT−TTF)2I3

Charge distributions in the donor layer for the paramagnetic semimetal-like and nonmagnetic insulating phases of the $\ensuremath{\alpha}\ensuremath{-}(\mathrm{B}\mathrm{E}\mathrm{D}\mathrm{T}\ensuremath{-}\mathrm{T}\mathrm{T}\mathrm{F}{)}_{2}{\mathrm{I}}_{3}$ single crystal [BEDT-TTF: bis(ethylenedithiolo)tetrathiafulvalene] were investigated under quasihydrostatic pressures up to 3.6 GPa using Raman spectroscopy. The results confirmed the appearance of charge disproportionation below the metal-insulator phase transition temperature ${(T}_{\mathrm{MI}}).$ The average charge-disproportionation ratio, 0.2--0.8, at ambient pressure was quite pressure sensitive and decreased by ca. $0.1e/\mathrm{GPa}$ with increasing pressure. This result is ascribed to the faster increase of the transfer integrals than the intersite Coulomb repulsions under pressure. The loss of the inversion centers in the nonmagnetic insulating phase, concluded by the selection rule, suggests that the charge is ordered such that it forms a so-called horizontal stripe. Nonuniform charge distributions were also found at temperatures above ${T}_{\mathrm{MI}}$ for the paramagnetic semimetal-like phase. The experimentally determined small charge difference among BEDT-TTF at crystallographically nonequivalent sites is consistent with the band calculations.

ALaFeVO6 (A=Ca, Sr): New Double-Perovskite Oxides

We describe the synthesis and structural characterization of two new double perovskites, ALaFeVO6 (A=Ca, Sr), where Fe3+/V4+ are partially ordered at the octahedral sites. The small charge difference between Fe3+/V4+ precludes the formation of a long-range ordered double-perovskite structure even on prolonged annealing at 1000°C. Electrical conductivity and magnetic susceptibility measurements show that both phases are weakly ferrimagnetic semiconductors where dis-ordered Fe3+–O–V4+ pairs persist even up to ∼350 K.

Protein focusing in a conductivity gradient.

Conductivity gradient focusing (CGF) is one member of a family of gradient focusing techniques, characterized by two opposing forces which produce a dynamic equilibrium and which are able to simultaneously separate and concentrate proteins. In CGF, the two counteracting forces result from a constant convective flow of buffer opposed by an electric field gradient. This gradient in the electric field is formed by gradually decreasing buffer conductivity, i.e., when a slow-moving, relatively high conductivity buffer is dialyzed against a low conductivity purge buffer. This paper presents the design of an analytical-scale CGF device and the results of several experiments with colored proteins, both in free solution and with the use of a 45 micron size-exclusion (SEC) packing to decrease dispersion. Experimental results with hemoglobin suggest that CGF may one day be capable of resolving proteins with small charge differences. A linear computer model of conductivity gradient focusing is derived, and some suggestions are made for further development of this new electrophoretic method.

PH titration curves of the desialylated human α 1-acid glycoprotein variants by combined isoelectrofocusing—electrophoresis: utilization in the development of a fractionation method for the protein variants by chromatography on immobilized metal affinity adsorbent

Using a two-dimensional isoelectrofocusing (IEF)—electrophoresis technique, the pH titration curves of the three main desialylated variants (F1, S and A) of human α 1-acid glycoprotein (AAG) were studied to assist in the development of a fractionation method for the AAG variants. For this purpose, different AAG samples, each corresponding to one of the three main phenotypes of the protein (F1S/A, F1/A and S/A), were first purified by chromatographic separation of individual human plasma samples on immobilized Cibacron Blue F3G-A. The purified AAG samples were then desialylated and their heterogeneity was checked by analytical IEF. The pH-mobility curves of the desialylated AAG samples were displayed in polyacrylamide gel slabs, under a constant set of experimental conditions, by carrying out electrophoresis of the protein samples perpendicularly to two stationary pH gradients: a large gradient (pH 3.5–9.5) and a narrow gradient (pH 5–8). The curves showed that all the desialylated variants of AAG exhibited small charge differences and moved closely together between about pH 3.5–5.5 and pH 7.5–9.5. However, the variants were found to show microheterogeneity in their total charge between about pH 5.5 and 7.5 due to the titrated ionizable groups involved along this pH zone. This microheterogeneity was assumed to be accounted for by the existence of differences between the titratable histidyl residues of the AAG variants. Consequently, the interactions of the variants with immobilized transition metal ions were studied at pH 7, using affinity chromatography on an iminodiacetate Sepharose—Cu(II) gel. It was found that the A variant was strongly bound by immobilized Cu(II) ions, whereas the F1 and S variants interacted non-specifically with the immobilized ligand. This finding allowed the development of a rapid and effective fractionation method for desialylated AAG into its A and F1 or S variants, depending on the AAG phenotype, by chromatography on an immobilized affinity Cu(II) adsorbent. The quantitative relationships between immobilized Cu(II) ions and desialylated AAG (the apparent association constant and gel protein-binding capacity) were also determined using a non-chromatographic equilibrium binding technique.

Identification of Ungulate Hemoglobins for Law Enforcement

Identification of Ungulate Hemoglobins for Law Enforcement