Article

Determination of the Effective Hydrodynamic Radii of Small Molecules by Viscometry

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Abstract

The effective hydrodynamic radii of small uncharged molecules in dilute aqueous solution were determined using Einstein's classical theory of viscosity. The radii thus obtained are those of a hypothetical sphere whose hydrodynamic behavior is the same as that of the solute molecule plus that water of hydration which is too firmly bound to partake in the viscous shearing process. The results obtained compare favorably with radii determined from molecular models constructed in accordance with atomic dimensions compiled by Pauling. Although the application of the Einstein theory to molecules whose size is comparable to that of water represents a considerable extrapolation, the results suggest that this deviation from the assumptions of the theory, in the case of the molecules studied, is of second order importance. Employing the viscometric radii, we have formulated an empirical correction of the Stokes-Einstein diffusion equation. This correction is similar in form to those previously proposed by Cunningham (22) and Millikan (21) and is of particular significance when the solute molecule is comparable in size to the discontinuities of the surrounding medium. The molecular radii of a number of small organic molecules obtained by means of the corrected Stokes-Einstein equation do not differ significantly from the radii obtained from molecular models of these compounds.

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... Le rayon hydrodynamique a caractérise alors la taille que la molécule aurait si elle se comportait comme une sphère rigide et impénétrable. On peut donc voir la relation I.13 comme un moyen de déterminer la taille d'une molécule [80]. Par la suite, on retiendra plutôt que la relation de Stokes-Einstein pour l'auto-diffusion a la forme : ...
... Le cas du glycérol est très intéressant car il montre une variété de comportements plus grande encore. Tout d'abord, on constate que pour toutes les concentrations, la plupart des valeurs du rayon hydrodynamique du glycérol (a g w (T )) sont inférieures à la valeur de référence a g ref = 300 pm, mais d'environ 15%, alors que la valeur de référence est elle-même connue avec une précision de 10% environ [80]. Pour T < 280 K, la valeur du rayon hydrodynamique diminue quand la concentration augmente, de façon analogue au comportement de l'eau (équation IV.4) avec une distinction plus tranchée entre w = 1% et w = 10% cependant. ...
Thesis
L’eau est le liquide le plus commun qui soit mais l’ensemble de ses propriétés ne sont toujours pas élucidées. En particulier, l’eau présente un grand nombre d’anomalies par rapport aux autres liquides, certaines se trouvant particulièrement exacerbées dans l’état surfondu (liquide à une température inférieure à celle de fusion). Au cours de ce travail, on introduit du glycérol dans l’eau en faible quantité (entre 10% et 50% en masse), ce qui a pour conséquence de repousser le point de fusion et celui de nucléation homogène. On mesure deux propriétés de ces solutions : la viscosité et l’auto-diffusion. La première caractérise la propriété macroscopique de résistance à l’écoulement, tandis que la seconde caractérise le phénomène microscopique de diffusion des molécules dans la solution. Ces deux grandeurs sont habituellement liées par la relation de Stokes-Einstein (RSE) dans des conditions usuelles de température et de pression au sein des liquides. La viscosité des solutions eau-glycérol est mesurée par une technique optique : la Microscopie Dynamique Différentielle (DDM). Le mouvement brownien de colloïdes dans la solution eau-glycérol est caractérisé par un coefficient de diffusion dont la mesure permet de déduire la viscosité. La viscosité des mélanges eau-glycérol croît quand la température décroît. À température donnée, elle augmente quand la concentration augmente. L’évolution de la viscosité en fonction de la température des solutions de faible concentration (< 20% en masse) suit le même type de loi que pour l’eau pure. Pour des concentrations plus élevées, la viscosité suit un autre type de comportement. L’augmentation de la concentration en glycérol cause donc un changement de dynamique des solutions surfondues. La diffusion mutuelle des molécules caractérise leur mobilité. Elle est caractérisée par le coefficient d’intra-diffusion dans un mélange et d’auto-diffusion pour un corps pur. On mesure l’intra-diffusion dans des solutions de glycérol, de concentrations allant de 1% à 50% en masse, grâce à la technique NMR-PGSE. La diffusion de l’eau et du glycérol dans le mélange augmentent avec la température quelle que soit la concentration. À haute température, la diffusion diminue quand la concentration en glycérol augmente. À basse température, dans l’état surfondu et pour de faibles concentrations (1% en masse de glycérol) la diffusion du glycérol connaît une diminution plus rapide que pour les autres concentrations et la même tendance se dessine pour l’eau dans les mêmes conditions. Connaissant désormais la viscosité des solutions eau-glycérol à basse température et le coefficient de diffusion des molécules il est possible de déterminer l’évolution de la RSE en fonction de la température. Elle systématiquement violée pour les molécules d’eau, quelle que soit la concentration pour des températures inférieures à 273 K. Les molécules de glycérol présentent le même type de violation de la RSE que l’eau pour des concentrations de 30% et 50% en masse. À 10% en masse, la relation est cependant respectée jusqu’aux plus basses températures mesurées (243 K). Enfin, à 1% de glycérol une violation de la RSE se produit, mais en sens inverse. L’interprétation microscopique de ces résultats demeure spéculative. Enfin, des mesures de viscosité et d’auto-diffusion ont réalisées sur l’eau pure mais pour des pressions allant jusqu’à 150 MPa. La RSE est également testée jusqu’à des températures de 228 K, permettant ainsi la comparaison avec les prévisions de récents modèles numériques
... The translational diffusion coefficient for 80 µM Aβ40 peptide increases in a concentration-dependent manner from 6.7 to 7.0 x 10 -11 m 2 /s upon increasing Ag(I) concentration from 0 to 50 µM (Fig. 3A). From the translational diffusion coefficient, the hydrodynamic radius (RH) can be calculated using the Stokes-Einstein equation (58,59). The apparent hydrodynamic radius decreases from 17.0 Å for Aβ40 alone to 16.3 Å in the presence of 50 µM Ag(I) ions, suggesting a slightly more compact Aβ peptide structure once bound to the Ag(I) ion, without significant changes in the secondary structure content (Fig. S11B). ...
... A standard sample of 1% H2O, 0.1% DSS and 0.1 mg ml -1 GdCl3 in D2O was used to calibrate the pulse field gradients. The translational diffusion coefficient (Dt) was determined by one-component analysis and hydrodynamic radius (rH) were determined from the diffusion coefficient (76) using the Stokes-Einstein relation relation (58,59). The diffusion data were further analyzed using a two-state model: ...
Article
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A detailed understanding of the molecular pathways for amyloid-β (Aβ) peptide aggregation from monomers into amyloid fibrils, a hallmark of Alzheimer’s disease, is crucial for the development of diagnostic and therapeutic strategies. We investigate the molecular details of peptide fibrillization in vitro by perturbing this process through addition of differently charged metal ions. Here, we used a monovalent probe, the silver ion, that, similarly to divalent metal ions, binds to monomeric Aβ peptide and efficiently modulates Aβ fibrillization. On the basis of our findings, combined with our previous results on divalent zinc ions, we propose a model that links the microscopic metal ion binding to Aβ monomers to its macroscopic impact on the peptide self-assembly observed in bulk experiments. We found that sub-stoichiometric concentrations of the investigated metal ions bind specifically to the N-terminal region of Aβ, forming a dynamic, partially compact complex. The metal ion bound state appears to be incapable of aggregation, effectively reducing the available monomeric Aβ pool for incorporation into fibrils. This is especially reflected in a decreased fibril-end elongation rate. However, since the bound state is significantly less stable than the amyloid state, Aβ peptides are only transiently redirected from fibril formation and eventually almost all Aβ monomers are integrated into fibrils. Taken together, these findings unravel the mechanistic consequences of delaying Aβ aggregation via weak metal ion binding, quantitatively linking the contributions of specific interactions of metal ions with monomeric Aβ to their effects on bulk aggregation.
... The effective hydrodynamic radius is usually regarded as a constant when the three variants of the SE relation are employed. However, it was reported to change its value with different volume fractions or ions in diluted organic solution and aqueous ionic solution (3,(39)(40)(41)(42). Therefore, the effective hydrodynamic radius in supercooled water may also change when the correlation between the central molecule and its surrounding shell increases as temperature decreases. ...
... Based on both experimental and simulation results, Xu and coworkers(15) have further concluded that the breakdown and the associated fractional form are due to the two-state transformation related with the crossing of the Windom line when water undergoes supercooling.All the above works identify the breakdown of the SE relation in supercooled water by monitoring the validity of the three variants without direct test of the original SE relation questionable because the equivalence of the three variants to the original SE form is on the basis of various assumptions, while there are some evidences showing that those assumptions may not be valid all the time. For instance, a for organic molecules varies with volume fraction in their diluted solutions(3), and the behavior of ions in aqueous solutions is observed to deviate from the SE relation by taking a as a constant but the original SE relation actually holds if a is allowed to change(39)(40)(41)(42)(43). It is revealed that the variation of a is caused by the fact that molecules or ions in solutions move effectively with their surrounding shells. ...
Preprint
The Stokes-Einstein (SE) relation has three commonly used variants: D~1/{\tau}, D~T/{\tau} and D~T/{\eta}. In this work, the consistency of the original SE relation and its three variants in supercooled water is examined by molecular dynamics simulation with the TIP5P and Jagla water models, respectively. It is found that the original SE relation remains valid even when the three variants are all invalid in the simulated temperature ranges: D~1/{\tau} and D~T/{\tau} follow the fractional forms D~(1/{\tau}){\zeta} and D~(T/{\tau}){\zeta} with a crossover temperature, at which the wavevector-dependent exponent {\zeta} changes its value; D~T/{\eta} is equivalent to the original SE relation only when the effective hydrodynamic radius a is a constant, which is however found to decrease with decreasing temperature T. Therefore, care should be taken when employing its variants to judge the validity of the original SE relation in supercooled water.
... From transcription kinetics assays under crowding, we know that the same amount of RNA is synthesized regardless of the crowder's size and / or concentration (Fig. 2B): Hydrodynamic radii of all crowders were obtained from references (17)(18)(19)(20)(21). ...
... Such technique has demonstrated its full relevance to deal with very similar systems. [58][59][60][61] The selected solutes were classified according to their diameter ( Table 2) considering that they adopt a spherical shape in water, [59][60][61][62][63][64][65][66][67] of course this approximation becomes less accurate as PEG length increases. ...
Article
As it forms water‐filled channel in the mitochondria outer membrane and diffuses essential metabolites such as NADH and ATP, the VDAC (voltage‐dependent anion channel) protein family plays a central role in all eukaryotic cells. In comparison with their mammalian homologues, little is known about the structural and functional properties of plant VDACs. In the present contribution, one of the two VDACs isoforms of Solanum tuberosum, stVDAC36, has been successfully overexpressed and refolded by an in‐house method, as demonstrated by the information on its secondary and tertiary structure gathered from circular dichroism and intrinsic fluorescence. Cross‐linking and molecular modelling studies have evidenced the presence of dimers and tetramers, and they suggest the formation of an intermolecular disulphide bond between two stVDAC36 monomers. The pore‐forming activity was also assessed by liposome swelling assays, indicating a typical pore diameter between 2.0 and 2.7 nm. Finally, insights about the ATP binding inside the pore are given by docking studies and electrostatic calculations. This article is protected by copyright. All rights reserved.
... Our previous work showed that the FMN -heme IET rate value of an iNOS oxyFMN was decreased with added sucrose, 39 the monomeric form of Ficoll 70. Addition of sucrose only increases the solution viscosity, but should not give macromolecular crowding effect because its hydrodynamic diameter in water (1.00 -1.12 nm) 48 is much smaller than the size of NOS protein noted in the Introduction section. We here observed that the IET rates of human iNOS oxyFMN were noticeably increased with added Ficoll 70 (Table 1), which brings forth both crowding and viscosity effects, while the rate was decreased by ~ 50 % when only viscosity effect is involved by adding sucrose (to give the same viscosity of 2.7 cP). 39 This indicates that excluded volume has a more substantial effect on the FMN -heme IET kinetics than solution viscosity. ...
Article
Full-text available
Current biochemical studies of nitric oxide synthase enzymes (NOSs) are conducted in diluted solutions. However, the intracellular milieu where the proteins perform their biological functions is crowded with macromolecules. The crowding effect on the electron transfer kinetics of multidomain proteins is much less understood. Herein, we investigated the effect of macromolecular crowding on the FMN ‒ heme intraprotein interdomain electron transfer (IET), an obligatory step in NOS catalysis. A noticeable increase in the IET rate in the bi-domain oxygenase/FMN (oxyFMN) and the holoprotein of human inducible NOS (iNOS) was observed upon addition of Ficoll 70 in a non-saturatable manner. Additionally, the magnitude of IET enhancement for the holoenzyme is much higher than that that of the oxyFMN construct. Importantly, the enhancing extent is similar for the iNOS oxyFMN protein with added Ficoll 70 and Dextran 70, showing that specific interactions do not exist between the NOS protein and the crowder. The crowding effect is also evident under different ionic strength. Moreover, the population of the docked FMN-heme state is significantly increased upon adding Ficoll 70. The steady-state cytochrome c reduction by the holoenzyme is noticeably enhanced by the crowder, while the ferricyanide reduction is unchanged. The NO production activity of the iNOS holoenzyme is stimulated by Ficoll 70. The effect of macromolecular crowding on the kinetics can be rationalized based on excluded volume effect, with an entropic origin. The results indicate that the macromolecular crowding influences the NOS electron transfer through multiple pathways.
... CAA was calculated using Chem 3D Ultra Software (8.0.3 version, Cambridge-Soft, MA, USA). Energy minimization with MM2 method was performed to generate the structure of wellstudied molecules, including glycerol, dextrose, Fe(CN) 6 3− , sucrose, lactose, raffinose and Ru(II) 6,32,33 . The equivalent spherical radius (CAA radius) of molecule was derived from CAA and then plotted as a function of hydrated radius, which is shown in Supplementary Fig. 9. ...
Article
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Precise control of interlayer spacing and functionality is crucial in two-dimensional material based membrane separation technology. Here we show anion intercalation in protonated graphite phase carbon nitride (GCN) that tunes the interlayer spacing and functions of GCN-based membranes for selective permeation in aqueous/organic solutions. Sulfate anion intercalation leads to a crystalline and amphipathic membrane with an accessible interlayer spacing at ~10.8 Å, which allows high solvent permeability and sieves out the solutes with sizes larger than the spacing. We further extend the concept and illustrate the example of GCN-based chiral membrane via incorporating (1R)-(-)-10-camphorsulfonic anion into protonated GCN layers. The membrane exhibits a molecular weight cutoff around 150 among various enantiomers and highly enantioselective permeation towards limonene racemate with an enantiomeric excess value of 89%. This work paves a feasible way to achieve water purification and chiral separation technologies using decorated laminated membranes.
... Finally, whereas cells preincubated with AbCC (Fig. 6C) and AcCC (Fig. 6E) became highly permeable to KCl, those exposed to AbCC, in contrast with those exposed to AcCC, acquired a slight permeability to glucose, evidenced by the fact that their volume stabilized at a higher level than that of control cells (Fig. 6A) (53). Based on the hydrodynamic radii of these sugar molecules (25,45), the diameters of the pores formed by Cry1C and CCAb are between 1.0 and 1.2 nm and those of the pores made by AbCC and CCE are between 0.8 and 1.0 nm. The pore generated by AcCC has a diameter of less than 0.8 nm. ...
... Here, r p is the hydrodynamic radius, and MW is the molecular weight of the dextran. Diameter of sucrose is based on hydrodynamic radii found in literature [54]. ...
Article
Nanoporous metal–polymer composite membranes for organics separations and catalysis - Michael J. Detisch, Thomas John Balk, Mariah Bezold, Dibakar Bhattacharyya
... Therefore, the differences of the R ap values observed in disaccharides of the same molecular weight can be attributed to differences in their r s . This latter parameter is also known as the effective hydrodynamic radius, which is defined as the radius of a rigid uncharged sphere which exhibits the same hydrodynamic behaviour as the solvated molecule in solution, thus including the water of hydration [48]. There are different mathematical approaches for estimating this value, most of them based on the Stoke-Einstein equation. ...
Article
Galacto-oligosaccharides (GOS) are short oligosaccharides chains containing several galactoses and one terminal glucose. Raw GOS are mixtures containing oligosaccharides, unreacted lactose and monosaccharides; hence nanofiltration is an alternative for product purification. However, poor membrane selectivity towards separation of lactose from GOS is the main drawback. So, in order to improve the purification of enzymatically-produced GOS by nanofiltration, the incorporation of a previous lactose hydrolysis step, to convert the remaining lactose into monosaccharides, is proposed. The purification of raw and hydrolyzed raw GOS was evaluated using two nanofiltration polymeric membranes (Synder NFG and TriSep XN45) at different transmembrane pressures (8-30 bar) in a stirred dead-end cell. Results indicate that the incorporation of the lactose hydrolysis step allows increasing GOS retention and monosaccharides and lactose removal, improving GOS purification. Best operational conditions for hydrolyzed raw GOS nanofiltration were obtained with the TriSep XN45 membrane at 20 bar, 45°C and 1500 rpm.
... We have used diffusion-ordered spectroscopy (66) to determine the translational diffusion coefficients for the different cosolutes under consideration that were used to estimate the hydrodynamic ratios (R h ) (Fig. 2 A; Table S4; Fig. S5). Because of fast signal exchange or the absence of an NMR observable, the R h -values for the ions and the guanidine and urea were taken from the literature (40,53,54). The extent to which a given cosolute affects the association rate (here measured as the difference between both rates in logarithm scale, logðk M/ðeqÞ;cosol: asc =k 0 asc Þ) shows a good linear correlation with the R h for most of the cosolutes (Fig. 4 B). ...
Article
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Protein oligomerization processes are widespread and of crucial importance to understand degenerative diseases and healthy regulatory pathways. One particular case is the homo-oligomerization of folded domains involving domain swapping, often found as a part of the protein homeostasis in the crowded cytosol, composed by a complex mixture of cosolutes. Here, we have investigated the effect of a plethora of cosolutes of very diverse nature on the kinetics of a protein dimerization by domain swapping. In the absence of cosolutes, our system exhibits slow interconversion rates, with the reaction reaching the equilibrium within the average protein homeostasis timescale (24-48 h). In the presence of crowders, though, the oligomerization reaction in the same time frame will, depending on the protein's initial oligomeric state, either reach a pure equilibrium state or get kinetically trapped into an apparent equilibrium. Specifically, when the reaction is initiated from a large excess of dimer, it becomes unsensitive to the effect of cosolutes and reaches the same equilibrium populations as in the absence of cosolute. Conversely, when the reaction starts from a large excess of monomer, the reaction during the homeostatic timescale occurs under kinetic control and it is exquisitely sensitive to the presence and nature of the cosolute. In this scenario (the most habitual case in intracellular oligomerization processes), the effect of cosolutes on the intermediate conformation and diffusion-mediated encounters will dictate how the cellular milieu affect the domain-swapping reaction.
... This study will concentrate on the diffusive clearance of small water-soluble compounds like urea (h d~0 .36 nm) (Schultz and Solomon 1961), and creatinine (h d~0 .6 nm) (Carrie et al. 1980), with minimum loss of blood proteins. ...
Article
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In-house fabricated silicon nanoporous membranes (SNMs), functionalized for efficient clearance of uremic toxins, can lead to compact and portable dialysis systems. Efficacy of 15 nm thick SNMs, with average pore diameter of 8 nm, was tested for dialysis of two uremic toxins - urea and creatinine using custom made teflon apparatus of 2, 10 and 30 ml. The apparatus consisted of two reservoirs, with the cis containing the uremic fluid, and the trans containing the dialysate. Peristalsis was found to enhance the clearance rate by a factor of four as compared to unstirred condition. Functionalisation of the SNMs reduced protein binding, and surface binding of urea from 23% to negligible values. A lateral array of nine SNMs and a new design for the dialysis apparatus, increased the clearance rate by a factor of twelve from that of the single SNM. The arrays cleared about 42% of urea and 48% of creatinine from 30 ml of diluted serum samples, in 15 min. Periodic replacement of the trans fluid cleared about 81% of high concentration uremic toxins from the cis reservoir in 45 mins. The SNM arrays are stable, reproducible, and with the superior clearance rates for urea and creatinine, they have the potential to be used as membranes for portable hemodialysers.
... In this regard, it has been applied to: explain the behaviour of surfactants in suspensions [21], register the diffusion coefficient of Xe in different solvents [22,23], and in liquid hydrogen [24], etc. It has been assumed for measuring the hydrodynamic radius of small molecules [25]. In most of those experiments, the dragging-force law is validated via the Stokes-Einstein equation for the diffusion of particles in a fluid with low Reynolds number. ...
Article
The molecular nature of the drag force exerted by a fluid on a body is revealed from a fundamental perspective. To do this, the Newtonian and Brownian theories are employed to simulate the falling of a body with atomic structure in a liquid with the explicit and implicit presence of the fluid molecules, respectively. The body reaches a terminal velocity in the way predicted for macroscopic spherical bodies by the Stokes law. In this respect, the present approach shows the hydrodynamic limit for very small objects. The values of the viscosity are found in good agreement with the experimental data. The present formulation not only complements the continuous-medium approach, traditionally employed to study fluids, but also opens new ways in the investigation of fluids and their effects on bodies with different shapes, sizes, and compositions, due to the atomic nature of the simulations.
... The opening of mPTP is associated with a decrease in the ∆Ψm, the release of accumulated Ca 2+ and Mg 2+ from mitochondria, and entry into the matrix of solutes with an average particle size of up to 1.5 kDa and even larger. The dissipation of ∆Ψm, swelling in KCl-BM, Ca 2+ /Mg 2+ release, and swelling in S-BM require pores with minimum radii of 0.14, 0.35, 0.42, and 0.52 nm, respectively, which correspond to the hydrodynamic radii of solvated particles [32,41,42]. However, the dissipation of ∆Ψm and the release of Ca 2+ and Mg 2+ can be separated in time from the initiation of the sucrose and mannitol entry into the matrix by classical mPTP inhibitors (EGTA, CsA, ADP, Mg 2+ , and BSA) [29,43]. ...
Article
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The opening of the permeability transition pore (mPTP) in mitochondria initiates cell death in numerous diseases. The regulation of mPTP by NAD(H) in the mitochondrial matrix is well established; however, the role of extramitochondrial (cytosolic) NAD(H) is still unclear. We studied the effect of added NADH and NAD+ on: (1) the Ca2+-retention capacity (CRC) of isolated rat liver, heart, and brain mitochondria; (2) the Ca2+-dependent mitochondrial swelling in media whose particles can (KCl) or cannot (sucrose) be extruded from the matrix by mitochondrial carriers; (3) the Ca2+-dependent mitochondrial depolarization and the release of entrapped calcein from mitochondria of permeabilized hepatocytes; and (4) the Ca2+-dependent mitochondrial depolarization and subsequent repolarization. NADH and NAD+ increased the CRC of liver, heart, and brain mitochondria 1.5–2.5 times, insignificantly affecting the rate of Ca2+-uptake and the free Ca2+ concentration in the medium. NAD(H) suppressed the Ca2+-dependent mitochondrial swelling both in KCl- and sucrose-based media but did not induce the contraction and repolarization of swollen mitochondria. By contrast, EGTA caused mitochondrial repolarization in both media and the contraction in KCl-based medium only. NAD(H) delayed the Ca2+-dependent depolarization and the release of calcein from individual mitochondria in hepatocytes. These data unambiguously demonstrate the existence of an external NAD(H)-dependent site of mPTP regulation.
... In the original work (Gebauer and others, 2008), the average PNC diameter was 2.1 nm from sedimentation coefficients, and 0.9 nm from diffusion coefficients, bringing the independently determined values into better accord when the viscosity is corrected. For very small species with radii up to 3 to 5 Å, an empirical correction formula for the hydrodynamic radius from the Stokes-Einstein equation was given by Schultz and Solomon (1961), who were misleadingly cited by Smeets and others (2017) postulating a "break-down" of the equation at small solute sizes. However, the PNC sizes are larger than the limit of 5 Å. ...
Article
Full-text available
Classical nucleation theory (CNT) is based on the notion of critical nuclei serving as transition states between supersaturated solutions and growing particles. Their excess standard free energy depends on supersaturation, and determines the height of the barrier for phase separation. However, predictions of CNT nucleation rates can deviate from experimental observations by many orders of magnitude. We argue that this is due to oversimplifications within CNT, rendering the critical nucleus essentially a conceptual notion, rather than a truly existing physical entity. Still, given adequate parametrization, CNT is useful for predicting and explaining nucleation phenomena, since it is currently the only quantitative framework at hand. In the recent years, we have been introducing an alternative theory, the so-called pre-nucleation cluster (PNC) pathway. The truly “non-classical” aspect of the PNC pathway is the realization that critical nuclei, as defined within CNT, are not the key to nucleation, but that the transition state relevant for phase separation is based on a change in dynamics of PNCs rather than their size. We provide a summary of CNT and the PNC pathway, thereby highlighting this major difference. The discussion of recent works claiming to provide scientific evidence against the existence of PNCs reveals that such claims are indeed void. Moreover, we illustrate that an erroneous interpretation of the concentration dependence of the free energy has led to a postulated rationalization of the standard free energy of ion pairs and stable ion associates within CNT, which is not sustainable. In fact, stable ion associates are stuck in a free energy trap from the viewpoint of CNT and cannot be considered in a straightforward manner. On the other hand, the notions of the PNC pathway, by dismissing the idea of the CNT-type critical nucleus as a required transition state, overcome this issue. While a quantitative theory of the PNC pathway is eagerly anticipated, the rationalization of experimental observations that are inconsistent with CNT proves its qualitative explanatory power, underpinning great promise towards a better understanding of, for instance, polymorph selection and crystallization control by additives.
... To understand whether the structural parameters of the hydrogel and nanofiber may affect the analytical performance of the biosensor, we estimated the pore size of the PAG using available literature (Holmes and Stellwagen, 1991;Schultz and Solomon, 1961;Stellwagen, 1998). The most common composition of PAG in this work is 10% of total monomer concentration (%T), and 0.5-2% of crosslinker (%C). ...
Article
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We integrated a magnetohydrodynamic fluid extractor with an amperometric glucose biosensor to develop a wearable device for non-invasive glucose monitoring. Reproducible fluid extraction through the skin and efficient transport of the extracted fluid to the biosensor surface are prerequisites for non-invasive glucose monitoring. We optimized the enzyme immobilization and the interface layer between the sensing device and the skin. The monitoring device was evaluated by extracting fluid through porcine skin followed by glucose detection at the biosensor. The biosensor featured a screen-printed layer of Prussian Blue that was coated with a layer containing glucose oxidase. Both physical entrapment of glucose oxidase in chitosan and tethering of glucose oxidase to electrospun nanofibers were evaluated. Binding of glucose oxidase to nanofibers under mild conditions provided a stable biosensor with analytical performance suitable for accurate detection of micromolar concentrations of glucose. Hydrogels of varying thickness (95–2000 μm) as well as a thin (30 μm) nanofibrous polycaprolactone mat were studied as an interface layer between the biosensor and the skin. The effect of mass transfer phenomena at the biosensor-skin interface on the analytical performance of the biosensor was evaluated. The sensing device detected glucose extracted through porcine skin with an apparent (overall) sensitivity of −0.8 mA/(M·cm²), compared to a sensitivity of −17 mA/(M·cm²) for measurement in solution. The amperometric response of the biosensor correlated with the glucose concentration in the fluid that had been extracted through porcine skin with the magnetohydrodynamic technique.
... In the original work (Gebauer and others, 2008), the average PNC diameter was 2.1 nm from sedimentation coefficients, and 0.9 nm from diffusion coefficients, bringing the independently determined values into better accord when the viscosity is corrected. For very small species with radii up to 3 to 5 Å, an empirical correction formula for the hydrodynamic radius from the Stokes-Einstein equation was given by Schultz and Solomon (1961), who were misleadingly cited by Smeets and others (2017) postulating a "break-down" of the equation at small solute sizes. However, the PNC sizes are larger than the limit of 5 Å. ...
Article
Full-text available
Classical nucleation theory (CNT) is based on the notion of critical nuclei serving as transition states between supersaturated solutions and growing particles. Their excess standard free energy depends on supersaturation, and determines the height of the barrier for phase separation. However, predictions of CNT nucleation rates can deviate from experimental observations by many orders of magnitude. We argue that this is due to oversimplifications within CNT, rendering the critical nucleus essentially a conceptual notion, rather than a truly existing physical entity. Still, given adequate parametrization, CNT is useful for predicting and explaining nucleation phenomena, since it is currently the only quantitative framework at hand. In the recent years, we have been introducing an alternative theory, the so-called pre-nucleation cluster (PNC) pathway. The truly "non-classical" aspect of the PNC pathway is the realization that critical nuclei, as defined within CNT, are not the key to nucleation, but that the transition state relevant for phase separation is based on a change in dynamics of PNCs rather than their size. We provide a summary of CNT and the PNC pathway, thereby highlighting this major difference. The discussion of recent works claiming to provide scientific evidence against the existence of PNCs reveals that such claims are indeed void. Moreover, we illustrate that an erroneous interpretation of the concentration dependence of the free energy has led to a postulated rationalization of the standard free energy of ion pairs and stable ion associates within CNT, which is not sustainable. In fact, stable ion associates are stuck in a free energy trap from the viewpoint of CNT and cannot be considered in a straightforward manner. On the other hand, the notions of the PNC pathway, by dismissing the idea of the CNT-type critical nucleus as a required transition state, overcome this issue. While a quantitative theory of the PNC pathway is eagerly anticipated, the rationalization of experimental observations that are inconsistent with CNT proves its qualitative explanatory power, underpinning great promise towards a better understanding of, for instance, polymorph selection and crystallization control by additives.
... Such loss in contrast reflects the exchange between the sucrose and glucose solutions. This occurs because during photooxidation, the pores must open, enabling the traffic of sugar molecules of approximately 0.5 nm [109,110]. Eventually, these pores can be visualized at the micron scale before the total collapse of the GUV [86] or not [80], depending on the experimental conditions (e.g., PS concentration and level of oxidative stress). ...
Article
In this review, we describe how photooxidation changes membrane properties that can ultimately lead to permanent membrane damage. Lipid photooxidation occurs in the presence of reactive oxygen species such as singlet oxygen and by direct reactions of lipids with a photosensitizer in the excited state. Indeed, lipid oxidation triggers chemical transformations that can alter lipid packing; change the membrane surface area, thickness and elastic modulus; and induce pore formation and phase separation. Here, we highlight how lipid hydroperoxides promote membrane remodelling and phase separation. Further, we emphasize the alterations caused by truncated oxidized lipids that lead to increased membrane permeability. Finally, the consequences of lipid photooxidation on cell functions are also discussed.
... Thus, we determined to use the a value of galactose for the estimation of P of GalCer-based associates as the reference. By using the reported hydrodynamic radius (R h ) of galactose, 4.2 Å, 44 we calculated the a value of galactose to be 55.4 Å 2 . As a result, we estimated P for the associates comprising GalCer to be less than 0.76. ...
... All permeability (P) values are experimentally determined and reported in literature as effective permeability, which account for convective and diffusive contributions. Molecular radii of compounds for kidney and pancreas permeability were compiled from literature 204,205 . For tumor permeability, molecular radii of compounds were calculated based on previously reported methods for globular proteins and PEG chains when not stated in the reference 25 . ...
Thesis
Type 1 diabetes affects over one million Americans and an additional 40,000 new cases are diagnosed each year. The disease is characterized by the destruction of insulin-secreting beta cells in the pancreas by the immune system. Consequently, patients with type 1 diabetes rely on exogenous insulin for life. Due to the small volume of beta cells in healthy pancreas, it is extremely challenging to monitor disease progression (particularly at early stages when adequate control of blood sugar levels is still maintained) and assess treatment efficacy in patients with type 1 diabetes. Therefore, an accurate method to monitor and quantify the beta cell mass (BCM) through imaging has been an important goal of the diabetes community. This thesis describes the unique anatomy and physiology of the beta cells within the Islets of Langerhans and calculates the optimal physicochemical properties needed for a BCM molecular imaging probe. The molecular weight of exendin probes are near ideal for targeting the endocrine pancreas, and this molecule was analyzed in more detail. Receptor trafficking properties and plasma clearance play a major role in determining beta cell targeting versus background signal and were measured for a series of probes. Due to rapid downregulation of the receptor, slow plasma clearance does not allow for continual beta cell uptake and increases background, so more rapid clearance results in higher target to background signal. Additionally, the receptor expression of GLP1-R was measured for the first time and provided evidence for low exocrine expression of GLP1-R in addition to the high endocrine expression. Because this could explain poor clinical contrast of exendin probes, exocrine expression was investigated in more detail. Using a transgenic mouse model, a very low expression of GLP1-R was confirmed on exocrine cells. Although absolute expression is very low (850 receptors per cell on exocrine cells versus 53,000 receptors per cell on beta cells), the much higher prevalence of exocrine cells (99%) relative to beta cells (1%) results in a significant total signal from the exocrine pancreas. Preliminary results show it is possible to preferentially block exocrine uptake to provide more specific beta cell signal. Multiple doses were administered to first saturate the exocrine with non-detectable peptide followed by a imaging agent dose to label the beta cells. The dosing strategy completely blocked exocrine GLP-1R in healthy animal models. Because peptides often have poor stability and lower affinity due to the lack of secondary structure, exendin was used as a model system to study the impact of helix stabilization on improving peptide physicochemical properties. Using a unique cross-linker with exendin and GLP1 peptides, the helicity, protease stability, and affinity could be improved. The increase protease stability of the cross-linked peptides and use of exendin as a therapeutic led us to test the subcutaneous bioavailability. Near-100% bioavailability was achieved through peptide stabilization, and the bioavailability of a slow-clearing version was also improved. The linker lipophilicity could be controlled to modulate the absorption and clearance rates of the fluorescent peptide. Overall, this thesis provides a theoretical analysis of imaging BCM, novel tools to manipulate peptide image probe properties, and experimental evidence of methods to improve the design of molecular imaging agents for beta cell mass.
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In the present work, we employ broadband dielectric spectroscopy to study the molecular dynamics of the prototypical glass former glycerol confined in two microporous zeolitic imidazolate frameworks (ZIF-8 and ZIF-11) with well-defined pore diameters of 1.16 and 1.46 nm, respectively. The spectra reveal information on the modified α relaxation of the confined supercooled liquid, whose temperature dependence exhibits clear deviations from the typical super-Arrhenius temperature dependence of the bulk material, depending on the temperature and pore size. This allows assigning well-defined cooperativity length scales of molecular motion to certain temperatures above the glass transition. We relate these and previous results on glycerol confined in other host systems to the temperature-dependent length scale deduced from nonlinear dielectric measurements. The combined experimental data can be consistently described by a critical divergence of this correlation length as expected within theoretical approaches assuming that the glass transition is due to an underlying phase transition.
Preprint
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The effect of macromolecular crowding on the structure and function of Escherichia coli prolyl-tRNA synthetase (Ec ProRS) has been investigated using a combined experimental and theoretical method. Ec ProRS is a multi-domain enzyme; coupled-domain dynamics is essential for efficient catalysis. To gain an insight into the mechanistic detail of the crowding effect, kinetic studies were conducted with varying concentrations and sizes of crowders. In parallel, spectroscopic and quantum chemical studies were employed to probe the "soft-interactions" between crowders and protein side chains. Finally, the dynamics of the dimeric protein was examined in the presence of crowders using a long-duration (70 ns) classical molecular dynamic simulations. The results of the simulations revealed a significant shift in the conformational ensemble, which is consistent with the "soft-interactions" model of the crowding effect and explained the observed alteration in kinetic parameters. Collectively, the present study demonstrated that the effects of molecular crowding on both conformational dynamics and catalytic function, are correlated. This is the first report where molecular crowding has been found to impact the conformational ensemble in the multi-domain Ec ProRS, a member of aminoacyl-tRNA synthetase family, which is central to protein synthesis in all living cells. The present study affirmed that the effect of crowders should be considered while investigating the structure-dynamics-function relationship in modular enzymes.
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Aquaporins are water channel proteins in cell membrane, highly specific for water molecules while restricting the passage of contaminants and small molecules, such as urea and boric acid. Cysteine functional groups were installed on aquaporin Z for covalent attachment to the polymer membrane matrix so that the proteins could be immobilized to the membranes and aligned in the direction of the flow. Depth profiling using x-ray photoelectron spectrometer (XPS) analysis showed the presence of functional groups corresponding to aquaporin Z modified with cysteine (Aqp-SH). Aqp-SH modified membranes showed a higher salt rejection as compared to unmodified membranes. For 2 M NaCl and CaCl 2 solutions, the rejection obtained from Aqp-SH membranes was 49.3 ± 7.5% and 59.1 ± 5.1%. On the other hand, the rejections obtained for 2 M NaCl and CaCl 2 solutions from unmodified membranes were 0.8 ± 0.4% and 1.3 ± 0.2% respectively. Furthermore, Aqp-SH membranes did not show a significant decrease in salt rejection with increasing feed concentrations, as was observed with other membranes. Through simulation studies, it was determined that there was approximately 24% capping of membrane pores by dispersed aquaporins.
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Enthusiasm for photodynamic therapy (PDT) as a promising technique to eradicate various cancers has increased exponentially in recent decades. The majority of clinically approved photosensitizers are hydrophobic in nature, thus, the effective delivery of photosensitizers at the targeted site is the main hurdle associated with PDT. Temoporfin (mTHPC, medicinal product name: Foscan®), is one of the most potent clinically approved photosensitizers, is not an exception. Successful temoporfin-PDT requires nanoscale delivery systems for selective delivery of photosensitizer. Over the last 25 years, the number of papers on nanoplatforms developed for mTHPC delivery such as conjugates, host-guest inclusion complexes, lipid-and polymer-based nanoparticles and carbon nanotubes is burgeoning. However, none of them appeared to be "ultimate". The present review offers the description of different challenges and achievements in nanoparticle-based mTHPC delivery focusing on the synergetic combination of various nano-platforms to improve temoporfin delivery at all stages of biodistribution. Furthermore, the association of different nanoparticles in one nanoplatform might be considered as an advanced strategy allowing the combination of several treatment modalities.
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Early- and late-stage formulation development for biopharmaceuticals (e.g. therapeutic proteins) remains a challenging task, especially when one has to select suitable excipients to solubilize and stabilize the protein in solution. State-of-the-art formulation development includes cost-intensive high-throughput screening methods to identify suitable excipients and formulation conditions. These methods often deliver a “working” formulation but unlikely the “optimal” formulation. Within this work, we developed a novel method that allows identifying suitable excipients based on the second osmotic virial coefficient B22 as the measure of choice for protein-protein interactions in aqueous solution in the presence of excipients (salts, sugars, amino acids, etc.). B22 is easily accessible by light scattering methods and advanced thermodynamic models like the extended mxDLVO model. Aqueous immunoglobulin G solutions including sugars, amino acids, surfactants and salts as excipients were used as model systems within this work. Applying the extended mxDLVO, the model allows predicting protein-protein interactions with high accuracy for mixtures of up to three excipients in one formulation. These measurements allow for quick identification of suitable excipients and their concentrations and are giving a greater insight in molecular interactions under the respective formulation conditions. An application of this method in future formulation development has the potential to reduce time-consuming and cost-intensive screening methods and finally lead to optimal formulations.
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Surface-modified EDTA-reduced graphene oxide (EDTA-rGO) membranes with high rejection rates, for monovalent ions in particular, were fabricated from graphene oxide (GO) for nanofiltration. The EDTA-rGO membrane surface was treated with oxygen plasma to enhance its water permeability (P-EDTA-rGO). The resulting P-EDTA-rGO membranes demonstrated rejection rates of more than 80% for NaCl and water permeabilities of approximately 150 LMH bar-1, which are approximately 15 times higher than those before the treatment, without sacrificing the ion rejection performance for small ions. The high rejection rates and permeabilities of the P-EDTA-rGO membranes are presumed to originate from the small interlayer spacing (remains comparably small even in a wetted state; 5.7 Å) resulting from EDTA functionalization and the enhanced hydrophilicity due to plasma treatment. In addition, the membrane impeded bacterial adhesion.
Article
Functional polymers or copolymers have been added to separations membranes by incorporating them in the membrane dope prior to casting, by in situ polymerization, and by postsynthesis surface modification of existing membranes. Here, a postsynthesis membrane functionalization that targeted decreasing the molecular weight cutoff (MWCO) and increasing the hydrophilicity without significantly decreasing the operating flux was studied. Hybrid bisamide molecules with added amine and carboxylic acid functionalities as end groups were synthesized to form a selective layer on membrane surface via covalent attachment to the membrane. Fourier transform infrared spectroscopy analysis showed the functional groups corresponding to bisamide molecules were present on modified membranes. Furthermore, modified membranes displayed MWCO of 400 Da as compared to 1000 Da MWCO of unmodified membranes, along with an increase in the hydrophilicity of modified membranes. Modified membranes showed an improvement in divalent salt rejection and percent flux recovered after reverse‐flow filtration as compared to unmodified membranes. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48327. Schematic of membrane surface containing artificial bisamide molecules
Article
The uniform size and complex chemical topology of the pores formed by self-assembled amphiphilic molecules such as liquid crystals make them promising candidates for selective separations. In this work, we observe transport of water, sodium ions and 20 small polar solutes within the pores of a lyotropic liquid crystal (LLC) membrane using atomistic molecular simulations. We find that the transport of a species is dependent not only on molecular size, but on chemical functionality as well. The membrane’s inhomogeneous composition gives rise to radially dependent transport mechanisms with respect to the pore centers. We observe that all solutes perform intermittent hops between lengthy periods of entrapment. Three different trapping mechanisms are responsible for this behavior. First, solutes that drift out of the pore can become entangled among the dense monomer tails. Second, solutes can donate hydrogen bonds to the monomer head groups. Third, solutes can coordinate with sodium counter ions. The degree to which a solute is affected by each mechanism is dependent on the chemical functionality of the solute. Using the insights developed in this study, we can begin to think about how to redesign existing LLC membranes in order to perform solute-specific separations.
Article
The friction coefficient of molecular solutes depends on the solute, on the solvent, and on the solute-solvent interactions, but is typically assumed to not depend on an externally applied force that acts on the solute. In this paper we compute the friction memory function from molecular dynamics simulations and show that the friction coefficients of harmonically confined methane, water, Na+, an artificial Na− ion, and glycerol in water in fact increase with confinement strength. The results show that the friction increase with confinement strength is a fundamental effect that occurs for hydrophobic, hydrophilic, as well as charged molecules. We demonstrate that a parameter-free extraction of the running integral over the memory function yields the most robust results when compared to methods based on parametrization or Fourier transforms. In all systems, this friction increase is accompanied by a slowdown of the solvent dynamics in the first hydration shell of the solutes. By simulations of a confined glycerol molecule in water-glycerol mixtures, we furthermore demonstrate that the friction dependence on the confining potential is magnified in more viscous solvents, which suggests that this effect plays an important role for larger molecules in highly viscous solutions like polymer melts, in line with dynamic scaling arguments.
Article
Two commercially available nanofiltration membranes (NF99HF, NP010) were investigated in order to separate In and Ge from pregnant leaching solutions (PLS) resulting from a bioleaching process. The PLS contains Zn, Cu and Fe as major components while In and Ge are minor constituents. In and Ge are assessed as critical raw materials (CRM) by the European Commission since there reliable and unhindered access is of growing concern for the European economy. NF experiments were conducted in cross-flow mode for model solutions containing equal concentrations and a model PLS at pH 2, respectively. Experiments with model solutions of increasing solute content revealed a negligible effect on ion retention and permeate flux. In order to discuss transport phenomena, diffusion coefficients of In ³⁺ and Ge(OH) 4⁰ were researched or estimated. Ge(OH) 4⁰ revealed high diffusivity and hence mass transfer is primarily favored due to its low diffusion resistance. Owing to its Stokes radius which is greater than all the other species considered, In ³⁺ revealed noticeable steric hindrance beside electrostatic interactions. The considered membrane NF99HF is able to selectively separate In and Ge in a PLS by accumulating In, Zn, Cu and Fe in the retentate, while Ge is enriched in the permeate.
Article
Still today, high–concentration protein formulations are often developed based on high-throughput experimental screening approaches. Although likely delivering working formulations, these approaches do not lead to a deep / mechanistic understanding of the protein phase behavior in solution. Within this work, we thus optimized and enhanced a recent approach for an initial low effort selection of potential excipients and excipient mixtures to be used in high concentration protein formulations. This approach considers both: molecular interactions and thermodynamic determinants to access the phase behavior of the proteins in solution, as well as pharmaceutical engineering boundaries (such as osmotic pressure and osmolality) to deliver on optimal formulation conditions. Water activity coefficient γW–calculations (used to describe the protein environment in solution), unfolding temperature (conformational stability) and protein–protein interactions (colloidal stability) are used as determinants. Amino acids (20 proteinogenic amino acids), selected amino acid mixtures, as well as mixtures of amino acids and trehalose (l-arginine-trehalose; l-histidine-trehalose) are considered as model excipients. The approach is extends by studying the long-term stability of the predicted formulation conditions for a γ globulin from human blood and denosumab. The results reveal, that by combining protein-specific experiments as well as model-based studies for the selection of excipient mixtures in high concentration protein formulations, the effort as well as the resource requirements can be reduced significantly.
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The effect of molecular crowding on the structure and function of Escherichia coli prolyl-transfer RNA synthetase (Ec ProRS), a member of the aminoacyl-transfer RNA synthetase family, has been investigated using a combined experimental and theoretical method. Ec ProRS is a multidomain enzyme; coupled-domain dynamics are essential for efficient catalysis. To gain insight into the mechanistic detail of the crowding effect, kinetic studies were conducted with varying concentrations and sizes of crowders. In parallel, spectroscopic and quantum chemical studies were employed to probe the "soft interactions" between crowders and protein side chains. Finally, the dynamics of the dimeric protein was examined in the presence of crowders using a long-duration (70 ns) classical molecular dynamic simulations. The results of the simulations revealed a shift in the conformational ensemble, which is consistent with the preferential exclusion of cosolutes. The "soft interactions" model of the crowding effect also explained the alteration in kinetic parameters. In summary, the study found that the effects of molecular crowding on both conformational dynamics and catalytic function are correlated in the multidomain Ec ProRS, an enzyme that is central to protein synthesis in all living cells. This study affirmed that large and small cosolutes have considerable impacts on the structure, dynamics, and function of modular proteins and therefore must be considered for stabilizing protein-based pharmaceuticals and industrial enzymes.
Article
Limiting the diffusion of small-sized substances (Dh< 5 nm) through hydrogels is particularly difficult to achieve. Herein, we demonstrate the utility of a comb architecture to systematically reduce the mesh size of a double network (DN) hydrogel to between ∼1 and 3 nm, without loss of hydration. Combs of varying charge, length, and concentration were introduced during the formation of the first network of the DN hydrogel based on thermoresponsive N-isopropylacrylamide and negatively charged 2-acrylamido-2-methylpropane sulfonic acid. The resulting hydrogels' mesh sizes were characterized with a size-exclusion test. Negatively charged combs were the most effective in reducing mesh size, attributed to electrostatic repulsive forces with the DN. Due to a lack of interaction and attractive forces to the first network, respectively, neutral and particularly positively charged combs were less effective.
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The study deals with nanofiltration for separating saccharides from phenolics and considers permeation of each individual sugar (mono- or disaccharide) from a plant hydrolysate compared to a model sugar solution. Experiments are carried out in a cross-flow flat-sheet cell (MaxiMem, Prozesstechnik GmbH) equipped with Nadir® NP030 P membrane. Nanofiltration in concentration and diafiltration mode has been investigated. It has been found that diafiltration mode ensures the appropriate conditions in the concentration polarization layer of the membrane that favours the sugar diffusion but prevents critical deposition and fouling. Due to the different mass transfer rates of sugars, a stepwise purification of phenolics in the retentate is obtained. Phenolics are first purified from galactose and mannose due to the negative rejections of these sugars at the beginning of diafiltration. Then purification from disaccharides increases with the increase in concentration polarization effect on diffusive transport of disaccharides through the membrane. At the same time purification from glucose also increases and becomes significant. Purification factors achieved in diafiltration mode vary from 3.9 to 10.2 and are up to 6.4-fold higher than in concentration mode.
Article
Polyethyleneimine (PEI), a potent architecture backbone was explored for the synthesis of novel polymeric ionic liquids (PolyE‐ILs) with protagonist properties. The simple quaternization of PEI dendrimer with Bronsted acids (H2SO4, H3PO4, CH3SO3H, CF3COOH and TsOH) leads to formation of series of protic PolyE‐ILs with corresponding counter anions [HSO4]−, [H2PO4]−, [CH3SO3]−, [CF3COO]− and [TsO]−. The physicochemical properties of synthesized PolyE‐ILs were studied by using TGA, Hammett acidity, hydrodynamic radii, solubility, and elemental analysis. PolyE‐ILs showed characteristic Hammett acidity (0.94–1.78), good thermal stability (<250 °C) and enhanced hydrodynamic radii. However, use of PolyE‐IL can be promoted for their wide applications as an acid catalysts. The reported PolyE‐IL‐1 with sulfonic acid counter ion was explored as catalyst for esterification of (E)‐cinnamic acids and it showed good catalytic activity. The enhanced hydrodynamic radii due to the branched architecture of PEI dendrimers facilities the separation process via Nanofiltration (NF) membrane with no membrane fouling. Thus, PolyE‐ILs can be highly active, easily recoverable, and reusable catalyst for esterification reactions with superior sustainability and economics. In addition to this the present one pot PolyE‐IL synthesis process is non‐complex and simple as compared to conventional post polymerization, ion exchange, and nucleophilic addition etc., strategies for synthesis of PILs. In the present study, PolyE‐ILs were synthesized via simple quaternization of polyethyleneimine by using series of Bronsted acids. Synthesized PolyE‐ILs have showed protagonist properties for acid catalysis with ease of separation characteristics. The tested PolyE‐IL with [HsO4]− counter ion showed excellent performance for esterification of (E)‐cinnamic acid and its derivatives with remarkable recyclability and comparable yields of corresponding cinnamic acid ester.
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This work demonstrates that an additional resistance term should be included in the Navier–Stokes equation when fluids and objects are in relative motion. This is based on an observation that the effect of the microscopic molecular random velocity component parallel to the macroscopic flow direction is neglected. The two components of the random velocity perpendicular to the local mean flow direction are accounted for by the viscous resistance, e.g., by Stokes’ law for spherical objects. The relationship between the mean- and the random velocity in the longitudinal direction induces differences in molecular collision velocities and collision frequency rates on the up- and downstream surface areas of the object. This asymmetry therefore induces flow resistance and energy dissipation. The flow resistance resulting from the longitudinal momentum transfer mode is referred to as thermal resistance and is quantified by calculating the net difference in pressure up- and downstream the surface areas of a sphere using a particle velocity distribution that obeys Boltzmann’s transport equation. It depends on the relative velocity between the fluid and the object, the number density and the molecular fluctuation statistics of the fluid, and the area of the object and the square root of the absolute temperature. Results show that thermal resistance is dominant compared to viscous resistance considering water and air in slow relative motion to spherical objects larger than nanometer-size at ambient temperature and pressure conditions. Including the thermal resistance term in the conventional expression for the terminal velocity of spherical objects falling through liquids, the Stokes–Einstein relationship and Darcy’s law, corroborates its presence, as modified versions of these equations fit observed data much more closely than the conventional expressions. The thermal resistance term can alternatively resolve d’Alembert’s paradox as a finite flow resistance is predicted at both low and high relative fluid–object velocities in the limit of vanishing fluid viscosity. Link to paper presentation at PoreLab NTNU-UIO 15th. Sept. 2021: https://www.youtube.com/watch?v=LRhi53tpyDc&t=143s
Article
Hydrophobic, chemically resistant nanofiltration (NF) polymeric membranes could provide major improvements to a wide range of processes, from pharmaceutical manufacturing to hazardous waste treatment. Here, we report the fabrication of the first poly (vinylidene fluoride) (PVDF) NF membranes retaining their hydrophobicity and surface chemistry. This was achieved by incorporating in the polymer 2D siloxene, which induce a compaction of the PVDF chains, resulting in low free volume and a highly ordered microstructure. Siloxene nanosheets were obtained from deintercalation of Ca from CaSi2 using HCl, followed by exfoliation and size fractionation, with average lateral dimension of 1–2 μm and thickness of 3–4 nm. The resulting membranes, containing 0.075 wt% of siloxene, have a pure water permeance of 22 ± 2 L m⁻² h⁻¹ bar⁻¹ and molecular weight cut-off (MWCO) of 530 Da. The same membrane also showed stable hexane permeance of 11 L m⁻² h⁻¹ bar⁻¹ for 24 h with MWCO of around 535 Da. These results supersede the performance of commercial NF membranes, expanding the potential application of nanofiltration to processes requiring stable, chemically resistant and hydrophobic nanofiltration membranes.
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Tecoma capensis is one of relatively few dicotyledonous plants in which the phloem in the veins of leaves, contain specialized parenchyma cells (called intermediary cells) in addition to sieve tubes and companion cells. These plants convert sucrose to the raffinose family oligosaccharides (RFOs), which form the primary transport sugar. The fact that the interface between bundle sheath and intermediary cells in RFO-transporting species always contain high numbers of plasmodesmata (Pd) in the BS-IC interface raises questions on the mechanism driving RFO accumulation and the subsequent loading of the RFOs into the phloem. Our primary focus was thus to make a detailed study of the plasmodesmata in the phloem loading pathway in Tecoma to determine (a) plasmodesmatal frequencies at all cell-to-cell interfaces in the phloem loading pathway and (b) to undertake a comprehensive study of the ultrastructure of plasmodesmata in the loading pathway. We noted that the average plasmodesmatal total diameter decreased from 49.5 nm in the common walls between mesophyll cells, to 47.5 nm between mesophyll and bundle sheath cells, to 31.2 nm at the interface between bundle sheath and intermediary cells and was reduced further to 9.7 nm in the IC. From our observations the radius of the cytoplasmic sleeve (through which intercellular transport takes place), was condensed to approximately 1.5 nm across, and there are indications that the plasma membrane and/ or the desmotubule may be lost within these PD.
Preprint
Biological reactions in the cellular environment differ physicochemically from those performed in dilute buffer solutions due to, in part, slower diffusion of various components in the cellular milieu, increase in their chemical activities, and modulation of their binding affinities and conformational stabilities. In vivo transcription is therefore expected to be strongly influenced by the ‘crowdedness’ of the cell. Previous studies of transcription under macromolecular crowding conditions have focused mainly on multiple cycles of RNAP-Promoter associations, assuming that the association is the rate-determining step of the entire transcription process. However, recent reports demonstrated that late initiation and promoter escape could be the rate-determining steps for some promoter DNA sequences. The investigation of crowding effects on these steps under single-round conditions is therefore crucial for better understanding of transcription initiation in vivo . Here, we have implemented an in vitro transcription quenched-kinetics single-molecule assay to investigate the dependence of transcription reaction rates on the sizes and concentrations of crowders. Our results demonstrate an expected slowdown of transcription kinetics due to increased viscosity, and an unexpected enhancement in transcription kinetics by large crowding agents (at a given viscosity). More importantly, the enhancement’s dependence on crowder size significantly deviates from hard-sphere model (scaled-particle theory) predictions, commonly used for description of crowding effects. Our findings shed new light on how enzymatic reactions are affected by crowding conditions in the cellular milieu.
Article
Uhl et al. studied the molecular dynamics of glycerol confined in the microporous zeolitic imidazolate framework (ZIF-8) with well-defined pore diameters of 1.16 nm by broadband dielectric spectroscopy. Of interest is a fast process in the central part of the pores identified as the α-relaxation of the confined supercooled glycerol with relaxation times τα,conf(T) reduced from τα,bulk(T) of bulk glycerol and have temperature dependence different from the super-Arrhenius temperature of the latter. The focus of Uhl et al. was relating the confined molecular dynamics to the cooperativity length scales Lcorr(T) of molecular motion above the glass transition, and deducing the limiting high-temperature value of the correlation length of about 1.22 nm. Not yet considered by anyone is the observed values of τα,conf(T) and temperature dependence. Since the cooperativity length scales Lcorr(T) were found to be larger than the pore size of ZIF-8 over the temperature range studied and the density of the glycerol in the pore is significantly lower than bulk, cooperativity of the -relaxation of glycerol confined in ZIF-8 is drastically reduced. Thus, within the framework of the Coupling Model (CM), τα,conf(T) should be nearly the same as the primitive relaxation time τ0(T) for glycerol when devoid of intermolecular coupling and cooperativity. Consistent with the absence of cooperativity of the glycerol confined in ZIF-8, we find the calculated τα,conf(T) are either the same or slightly longer than the calculated values of τ0(T). The quantitative prediction of the CM is verified. At this time we know of no other theory that can make such quantitative prediction.
Article
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Instant coffee manufacture involves the aqueous extraction of soluble coffee components followed by drying to form a soluble powder. Loss of volatile aroma compounds during concentration through evaporation can lower product quality. One method of retaining aroma is to steam stripping volatiles from the coffee and add them back to a concentrated coffee solution before the final drying stage. A better understanding of the impact of process conditions on the aroma content of the stripped solution will improve product design stages. In this context, we present a multi-scale model for aroma extraction describing (i) release from the matrix (ii) intra-particle diffusion (iii) transfer into water and steam and (iv) advection through the column mechanisms. Results revealed (i) the existence of three different types of compound behavior (ii) how aroma physiochemistry determines the limiting kinetics of extraction (iii) extraction for some aromas can be inhibited by interaction with other coffee components.
Article
When a charge selective surface consumes or transports only cations or anions in the electrolyte, biased ion rejection initiates hydrodynamic instability, resulting in vortical fluid motions called electroconvection. In this Letter, we describe the first laboratory observation of three-dimensional electroconvection on a charge selective surface. Combining experiment and scaling analysis, we successfully categorized three distinct patterns of 3D electroconvection according to [(RaE)/(Re2Sc)] [electric Rayleigh number (RaE), Reynolds number (Re), Schmidt number (Sc)] as (i) polygonal, (ii) transverse, or (iii) longitudinal rolls. If Re increases or RaE decreases, pure longitudinal rolls are presented. On the other hand, transverse rolls are formed between longitudinal rolls, and two rolls are transformed as polygonal one at higher RaE or lower Re. In this pattern selection scenario, Sc determines the critical electric Rayleigh number (RaE*) for the onset of each roll, resulting in RaE*∼Re2Sc. We also verify that convective ion flux by electroconvection (represented by an electric Nusselt number NuE) is fitted to a power law, NuE∼[(RaE−RaE*)/(Re2Sc)]α1Reα2Peα3 [Péclet number (Pe)], where each term represents the characteristics of electroconvection, shear flow, and ion transport.
Article
In this study we investigated the impact of sucrose on the rheological properties of high pressure homogenized citrus peel fiber suspensions before and after drying. Drying of such cellulose-rich microfibrillated systems often goes paired with structural collapse which leads to a product with sub-optimal functional properties (e.g. swelling, water holding …) upon reconstitution. The purpose was to better understand the role of sucrose on preventing structural collapse during drying and consequently identify the optimum fiber/sucrose mixing ratio allowing optimal recovery of the functional properties upon reconstitution. High pressure homogenized samples were prepared by fixing the fiber concentration at 1% w/w while varying sucrose content from 0% to ~60% w/w. Through these investigations, we demonstrated that the presence of sucrose (at the given concentrations) seems to have a negative impact on the functionalized fiber properties prior drying, whereas a positive effect could be observed for the dried functionalized fibers when they were co-dried in presence of 30% w/w sucrose. This sucrose concentration allowed recovery of the functionalized fiber properties prior drying. The initial fiber properties recovery suggests that sucrose can act as a hydrogen bond blocker or a spacer that limits the irreversible aggregation effect usually observed for plant cell wall-derived fibers upon drying.
Article
The molecular glass-former and pharmaceutical, prilocaine, distinguishes itself by exhibiting seven general and fundamental dynamic and thermodynamic properties [Z. Wojnarowska, et al. J. Phys. Chem. B, 2015, 39, 12699.], all of which had been explained by the Coupling Model. Not studied before and only until very recently is how the properties of prilocaine are changed when subjected to extreme nano-confinement in spaces with size of about 1 nm. The structural α-relaxation times of the 1 nm confined prilocaine, ,conf(T), were found by Ruis et al. [G. N. Ruiz, et al. Phys.Chem.Chem.Phys., 2019, 21, 15576.] to be significantly reduced from that of bulk prilocaine, τα,bulk(T). The data pose a challenge for any theory of glass transition to explain quantitatively. The Coupling Model was applied to this problem to predict the α-relaxation time of prilocaine when cooperativity is removed expected when only a few molecules can fit into the 1 nm pores. The results are in quantitative agreement with the experimental values of τα,conf(T). The success is nontrivial because no other theory can do the same to the best of knowledge.
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High flux nanofiltration (NF) membranes with tunable molecular weight cut-off (MWCO) are desired for energy-efficient separation processes in many industries. The separation mechanism of these membranes involves size sieving and charge-based Donnan exclusion. The precise control over the pore size of NF membranes would produce better solute-solute selectivity. Thus it is essential to know the pore size and its distribution to ideally custom-design them. In this article, the advantages and limitations of various mathematical models of pore size estimation are discussed. The probability density function (PDF) model, which is a simple and efficient model for estimating pore size distribution (PSD) based on the rejection of electroneutral solutes, is discussed in detail, along with the flaws in its usage. The model has been randomly used in the past, which makes it difficult to compare the results obtained in different studies. We have introduced some critical points to be contemplated for the standardization of the model.
Article
Three AFC membranes from PCI, of the thin film composite (TFC) nanofiltration type, have been characterized by using XPS, AFM, Contact angles, Zeta potential and permeation experiments. This plethora of complimentary methods portrays a deep and exhaustive description of these membranes that could be used to tune fabrication and modification of nanofiltration membranes to get better properties. Morphological properties, including porosity, water permeability, fractal dimension, Wenzel parameter and roughness, correlate well with pore sizes. While functional characteristics as, for example wettability correlate well with the O/N ratio. Increasing O/N ratios should be interpreted as caused by increasing PVA coverages. The charge on the membrane’s surface is ordered in a different way for different pH but are quite similar anyway. The effect of charges on retention of 1:1, 1:2 and 2:1 salts (as tested with NaCl, Na2SO4 and CaCl2) increases with increasing O/N and wettability. Consequently, the trend of salt retentions can be explained in terms of the PVA coverage and the details of the amphoteric behavior of the three AFC membranes studied.
Article
Nanofiltration for the fractionation of uncharged solutes has become more interesting in recent times, due to the goal of valorizing side-streams and by-products of the food industry. Since the membranes suitable for this purpose are mainly utilized for demineralization processes, the specifications given by the manufacturer are insufficient for the prediction of the rejection of uncharged solutes. Nine membranes with a molecular weight cut-off between 150 and 1000 Da were investigated showing differences in their rejection of fructose at a transmembrane pressure difference ΔpTM of 1.0 MPa. These values were correlated with the root-mean-square roughness Sq and apparent pore size dap determined by atomic force microscopy, while the determined contact angle Θ did not influence the rejection. Thereby, a correlation between membrane morphology and rejection behavior was established.
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In the present work, we employ broadband dielectric spectroscopy to study the molecular dynamics of the prototypical glass former glycerol confined in two microporous zeolitic imidazolate frameworks (ZIF-8 and ZIF-11) with well-defined pore diameters of 1.16 and 1.46 nm, respectively. The spectra reveal information on the modified alpha relaxation of the confined supercooled liquid, whose temperature dependence exhibits clear deviations from the typical super-Arrhenius temperature dependence of the bulk material, depending on temperature and pore size. This allows assigning well-defined cooperativity length scales of molecular motion to certain temperatures above the glass transition. We relate these and previous results on glycerol confined in other host systems to the temperature-dependent length scale deduced from nonlinear dielectric measurements. The combined experimental data can be consistently described by a critical divergence of this correlation length as expected within theoretical approaches assuming that the glass transition is due to an underlying phase transition.
Article
A new method has been developed to measure the equivalent pore radius in cellular membranes, and has been applied to human red cells. When red cells are suddenly introduced into a non-isosmolar concentration of non-lipid-soluble non-electrolyte molecules, water will enter or leave the cell. The rate of cell swelling or shrinking is determined and extrapolated to zero time to give the initial rate of volume change. By suitable adjustment of the concentration of the external solution the initial rate may be brought to zero. The transient equilibrium concentration, determined by interpolation from experimental data, gives a measure of Staverman's reflection coefficient, sigma. The zero time method has enabled us to determine sigma for nine permeant molecules. sigma is directly related to the equivalent pore radius; the experimental data lead to a value of 4.2 A for the equivalent pore radius in man, in good agreement with the previous figure of 3.5 A given by Paganelli and Solomon. The zero time method offers a number of advantages over previous methods for determination of this parameter. It requires no measurement of the rate of water entrance into the cell, and is essentially independent of the kinetics of cell swelling. It may be applied to a variety of living cells so that many additional membranes may now be characterized in terms of their equivalent pore radius.
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