Diffusion Coefficients Of Small Molecules Research Articles

Coarse-grained force field for ZIF-8: A study on adsorption, diffusion, and structural properties.

Metal-organic frameworks (MOFs) are revolutionizing a spectrum of industries, from groundbreaking gas storage solutions to transformative biological system applications. The intricate architecture of these materials necessitates the use of advanced computational techniques for a comprehensive understanding of their molecular structure and prediction of their physical properties. Coarse-grained (CG) simulations shine a spotlight on the often-neglected influences of defects, pressure effects, and spatial disorders on the performance of MOFs. These simulations are not just beneficial but indispensable for high-demand applications, such as mixed matrix membranes and intricate biological system interfaces. In this work, we propose an optimized CG force field tailored for ZIF-8. Our work provides a deep dive into sorption isotherms and diffusion coefficients of small molecules. We demonstrate the structural dynamics of ZIF-8, particularly how it responds to pressurization, which affects its crystal structure and leads to local changes in aperture size and area. Emphasizing the game-changing potential of CG simulations, we explore the characteristics of amorphization in ZIF-8. Through computational exploration, we aim to bridge the knowledge gap, enhancing the potential applications of nanoporous materials for various applications.

Raman Diffusion-Ordered Spectroscopy.

The Stokes-Einstein relation, which relates the diffusion coefficient of a molecule to its hydrodynamic radius, is commonly used to determine molecular sizes in chemical analysis methods. Here, we combine the size sensitivity of such diffusion-based methods with the structure sensitivity of Raman spectroscopy by performing Raman diffusion-ordered spectroscopy (Raman-DOSY). The core of the Raman-DOSY setup is a flow cell with a Y-shaped channel containing two inlets: one for the sample solution and one for the pure solvent. The two liquids are injected at the same flow rate, giving rise to two parallel laminar flows in the channel. After the flow stops, the solute molecules diffuse from the solution-filled half of the channel into the solvent-filled half at a rate determined by their hydrodynamic radius. The arrival of the solute molecules in the solvent-filled half of the channel is recorded in a spectrally resolved manner by Raman microspectroscopy. From the time series of Raman spectra, a two-dimensional Raman-DOSY spectrum is obtained, which has the Raman frequency on one axis and the diffusion coefficient (or equivalently, hydrodynamic radius) on the other. In this way, Raman-DOSY spectrally resolves overlapping Raman peaks arising from molecules of different sizes. We demonstrate Raman-DOSY on samples containing up to three compounds and derive the diffusion coefficients of small molecules, proteins, and supramolecules (micelles), illustrating the versatility of Raman-DOSY. Raman-DOSY is label-free and does not require deuterated solvents and can thus be applied to samples and matrices that might be difficult to investigate with other diffusion-based spectroscopy methods.

Anisotropy growth of perovskite crystal induced by layered double hydroxide for efficiency enhancement of solar cell

The anisotropy of perovskite (PVK) crystals is important for charge carrier transport and light absorption. In this regard, organic small molecules are most commonly used to induce the orientation growth of PVK. However, the high volatility and high diffusion coefficient of small molecules hinders its practical application. Here, inorganic layered double hydroxide nanosheets (LDHs-NS) is introduced into the PVK solution, where both micro and macro anisotropy of LDHs-NS guide the anisotropic growth of PVK crystals. Based on this, the efficiency of assembled perovskite solar cells (PSC) in an all-air environment can reach 12.26% with excellent thermal stability. The orderly arrangement of –OH on LDHs-NS surfaces can induce orderly growth of PVK crystals by interacting with Pb2+; the anisotropy stacking of LDHs-NS ensured the orderly growth of PVK crystals on a large scale. Our work has important guiding implications for the anisotropy growth of PVK crystal, resulting in more efficient PSCs.

Estimation of the Diffusion Coefficients of Small Molecules by Diffusion Measurements with Agar-gel and Theoretical Molecular Modeling

Diffusion is a spontaneous process and one of the physicochemical phenomena responsible for molecular transport, the rate of which is governed mainly by the diffusion coefficient; however, few coefficients are available for small molecules. We have constructed a simple and convenient experimental system with agar-gel to measure the diffusion coefficients of sugars.

Unified Description of Diffusion Coefficients from Small to Large Molecules in Organic-Water Mixtures.

Diffusion coefficients in mixtures of organic molecules and water are needed for many applications, ranging from the environmental modeling of pollutant transport, air quality, and climate, to improving the stability of foods, biomolecules, and pharmaceutical agents for longer use and storage. The Stokes-Einstein relation has been successful for predicting diffusion coefficients of large molecules in organic-water mixtures from viscosity, yet it routinely underpredicts, by orders of magnitude, the diffusion coefficients of small molecules in organic-water mixtures. Herein, a unified description of diffusion coefficients of large and small molecules in organic-water mixtures, based on the fractional Stokes-Einstein relation, is presented. A fractional Stokes-Einstein relation is able to describe 98% of the observed diffusion coefficients from small to large molecules, roughly within the uncertainties of the measurements. The data set used in the analysis includes a wide range of radii of diffusing molecules, viscosities, and intermolecular interactions. As a case study, we show that the degradation of polycyclic aromatic hydrocarbons (PAHs) by O3 within organic-water particles in the planetary boundary layer is relatively short (≲1 day) when the viscosity of the particle is ≲102 Pa s. We also show that the degradation times predicted using the Stokes-Einstein relation and the fractional Stokes-Einstein relation can differ by up to a factor of 10 in this region of the atmosphere.

Thin Polymer Films: Simple Optical Determination of Molecular Diffusion Coefficients

The possibility to assess diffusion coefficients of small molecules in packaging polymer films directly on the shelf, or even along the fabrication line, without the use laboratory equipment commonly employed for gravimetric methods would represent a paradigm changer in the evaluation of barrier properties and byproduct formation in goods packaging and device encapsulation. In this work, we demonstrate a simple, effective and versatile method for the determination of the molecular diffusion coefficients that exploits simple UV-Vis spectroscopy and is suitable for any polymer film. This simple method also allows the direct identification of the intercalating molecule without the need for chemical targeting or of complex laboratory equipment. For this purpose, we report on the assessment of diffusion coefficients of both polar and non-polar molecules including water, ammonia, methanol, ethanol, toluene, and even hexafluorobenzene into polyvinyl chloride wrap commercialized for food packaging.

Flory-Huggins Photonic Sensors for the Optical Assessment of Molecular Diffusion Coefficients in Polymers.

The lack of cost-effective systems for the assessment of air pollutants is a concern for health and safety in urban and industrial areas. The use of polymer thin films as label-free colorimetric sensors featuring specific interactions with pollutants would then represent a paradigm shift in environmental monitoring and packaging technologies, allowing to assess air quality, formation of byproducts in closed environment, and the barrier properties of the polymers. To this end, all-polymer distributed Bragg reflectors represent a promising approach toward a reliable and cost-effective transduction of chemical stimuli and effective colorimetric label-free selective detectors. We show selectivity attained by specific interactions between the polymer and analytes. Such interactions drive the analyte intercalation through the polymer structure and its kinetics, converting it in a dynamic optical response which is at the basis of the Flory-Huggins photonic sensors. The multivariate analyses of the response kinetics also allow distinguishing binary mixtures. Additionally, we demonstrate that such optical responses can be used to esteem the diffusion coefficients of small molecules within polymer media via simple UV-vis spectroscopy retrieving data comparable to those obtained with state-of-the-art gravimetric procedures. Last, we assess the figures of merit of the sensors in terms of lower detection limit, sensitivity, and reversibility, demonstrating that such devices can pave the way to an innovative, simple, and low-cost detection method integrable to in situ assessment of barrier polymers used for the encapsulation of optoelectronic devices, food packaging, and goods storage in general.

Experimental Determination of Drug Diffusion Coefficients in Unstirred Aqueous Environments by Temporally Resolved Concentration Measurements.

The diffusion coefficient (also known as diffusivity) of an active pharmaceutical ingredient (API) is a fundamental physicochemical parameter that affects passive diffusion through biological barriers and, as a consequence, bioavailability and biodistribution. However, this parameter is often neglected, and it is quite difficult to find diffusion coefficients of small molecules of pharmaceutical relevance in the literature. The available methods to measure diffusion coefficients of drugs all suffer from limitations that range from poor sensitivity to high selectivity of the measurements or the need for dedicated instrumentation. In this work, a simple but reliable method based on time-resolved concentration measurements by UV-visible spectroscopy in an unstirred aqueous environment was developed. This method is based on spectroscopic measurement of the variation of the local concentration of a substance during spontaneous migration of molecules, followed by standard mathematical treatment of the data in order to solve Fick's law of diffusion. This method is extremely sensitive and results in highly reproducible data. The technique was also employed to verify the influence of the environmental characteristics (i.e., ionic strength and presence of complexing agents) on the diffusivity. The method can be employed in any research laboratory equipped with a standard UV-visible spectrophotometer and could become a useful and straightforward tool in order to characterize diffusion coefficients in physiological conditions and help to better understand the drug permeability process.

Taylor Dispersion of Inorganic Nanoparticles and Comparison to Dynamic Light Scattering and Transmission Electron Microscopy

Taylor dispersion analysis (TDA) is an analytical method that has so far mainly been utilized to determine the diffusion coefficient of small molecules, and proteins. Due to increasing interest in nanoscience, some research has been done on the applicability of TDA towards characterizing nanoparticles. This work aims to expand this knowledge and give insight into the range for which TDA can be used for nanoparticle characterization, focusing on various materials and sizes. The TDA setup shown in this work was successful in characterizing all engineered metallic, non-metallic nanoparticles, and proteins tested in this work. Results were compared to dynamic light scattering and electron microscopy, and were in good agreement with both methods. Taking into consideration the wide range of nanoparticle sizes that can be characterized, the minimal sample preparation, and sample volume, required and the simplicity of the method, TDA can be considered as a valuable technique for nanoparticle characterization.

Decoupling energetic modifications to diffusion from free volume in polymer/nanoparticle composites.

Diffusion coefficients of small molecules in a model composite of spherical nanoparticles and polymer with attractive interfacial interactions are reduced from that in the pure polymer, to a degree far below the level expected from geometric tortuosity arguments. We determine whether such dramatic reductions are due to modifications to the matrix polymer free volume near the nanoparticle surface, or alternatively are due to energetic attractions between the diffusants and nanoparticle surface. We performed ethyl acetate sorption experiments within the vicinity of the polymer glass transition (Tg ≤ T ≤ Tg + 25 K) for a model polymer/nanoparticle composite, silica-filled poly(methyl acrylate). By application of the Vrentas-Duda free volume theory of diffusion we have decoupled the energetic effects from those related to free-volume and segmental dynamics. While the latter is unaffected by addition of nanoparticles, the energy needed for the ethyl acetate diffusant to overcome neighboring attractive forces doubles after adding 40 vol% nanoparticles with a diameter of 14 nm. This is qualitatively consistent with hydrogen bonding interactions between the silica surface and ethyl acetate slowing its rate of diffusion. On the other hand for benzene, which does not hydrogen bond to the silica surface, diffusion coefficients that can be explained by tortuosity effects were obtained. This work provides quantitative evidence that the diffusant-filler energetic interactions and geometric blocking effects can be fully responsible for the substantially reduced diffusivity commonly observed in polymer/nanoparticle composite systems.

Investigation of Molecular Diffusivity of Photoresist Membrane using Coarse-Grained Molecular Dynamics Simulation

Biocompatible permeable membranes integrated with a microfluidic system, which allow the diffusion of biological molecules with certain molecular weight, are desirable in biomedical applications. This paper reports on a molecular level study of the molecules permeability of epoxy-based chemically-amplified photoresists in MEMS by employing a coarse-grained molecular dynamics simulation. For analyzing diffusion coefficient of molecular in photoresists, Kremer-Grest model (bead-spring model) with an extended angle bending potential was employed. The simulation results show that, with increasing the cross-linked ratio of photoresists, the diffusion coefficient of small molecules in photoresist have larger diffusion coefficient, and which suggests photoresist membrane can be used as permeable membranes with controllable permeability by varying photolithography parameters.

Molecular dynamics simulation on diffusion of 13 kinds of small molecules in polyethylene terephthalate

AbstractUnderstanding the diffusion of migrants in polyethylene terephthalate (PET) and calculating the diffusion coefficients are very important for migration research. In this study, the diffusion coefficients of 13 kinds of small molecules with molecular weights ranging from 32 to 339 g/mol in amorphous PET are calculated based on molecular dynamics (MD) simulation. By comparison of diffusion coefficients simulated by MD simulation techniques, predicted by the Piringer model and by experiments, the accuracy of the Piringer model and MD simulation techniques for the estimation of diffusion coefficients of migrants in PET is evaluated. The MD simulation shows that Dsimu is very close to Dexp, within one order of magnitude of the experimental diffusion coefficients except for a few samples. The possible reasons for the differences among Dsimu, Dpred and Dexp are analysed from the molecular weight and temperature. The results show that the Piringer‐model‐predicted values at high temperatures overestimate significantly higher than that at lower temperatures. The activation energy is calculated by the Arrhenius equation, which shows the relationship between diffusion coefficient and temperature. It is shown that the MD simulation yields acceptable activation energy. The study suggests that MD simulation may be a useful approach to calculate the diffusion coefficients of small molecules in PET. Copyright © 2010 John Wiley & Sons, Ltd.

Rapid determination of partition and diffusion properties for salt and aroma compounds in complex food matrices

The measurement of physicochemical properties, such as partition or diffusion coefficients of small molecules like salt and aroma compounds, represents an important challenge to better understanding stimuli release and perception. Owing to the lack of simple and fast methods, we developed three methods for practical and rapid determination of partition and diffusion coefficients respectively of salt and aroma compounds. Our approach is based on the combination of on-line measurements with mechanistic modelling leading to accurate determination of these two parameters. Validation was performed by comparing the values obtained with agar gel and model cheeses to those available in the literature.

Using Fluorescence Correlation Spectroscopy to Study Conformational Changes in Denatured Proteins

Fluorescence correlation spectroscopy (FCS) is a sensitive analytical tool that allows dynamics and hydrodynamics of biomolecules to be studied under a broad range of experimental conditions. One application of FCS of current interest is the determination of the size of protein molecules in the various states they sample along their folding reaction coordinate, which can be accessed through the measurement of diffusion coefficients. It has been pointed out that the analysis of FCS curves is prone to artifacts that may lead to erroneous size determination. To set the stage for FCS studies of unfolded proteins, we first show that the diffusion coefficients of small molecules as well as proteins can be determined accurately even in the presence of high concentrations of co-solutes that change the solution refractive index significantly. Indeed, it is found that the Stokes-Einstein relation between the measured diffusion coefficient and solution viscosity holds even in highly concentrated glycerol or guanidinium hydrochloride (GuHCl) solutions. These measurements form the basis for an investigation of the structure of the denatured state of two proteins, the small protein L and the larger, three-domain protein adenylate kinase (AK). FCS is found useful for probing expansion in the denatured state beyond the unfolding transition. It is shown that the denatured state of protein L expands as the denaturant concentration increases, in a process akin to the transition from a globule to a coil in polymers. This process continues at least up to 5M GuHCl. On the other hand, the denatured state of AK does not seem to expand much beyond 2M GuHCl, a result that is in qualitative accord with single-molecule fluorescence histograms. Because both the unfolding transition and the coil-globule transition of AK occur at a much lower denaturant concentration than those of protein L, a possible correlation between the two phenomena is suggested.

Gas Diffusion in Glassy Polymers by a Chain Relaxation Approach

Plasticization of glassy polymers by small molecules was approached by the “concentration−temperature superposition” principle. The major effect of the plasticization by small molecules is on the reduction of the glass transition temperature. The present study suggests that the dependence of diffusion coefficients of small molecules on the penetrant concentration can be affected by the reduction of the glass transition of the penetrant/polymer system caused by a plasticization effect of the penetrant. With a WLF type shift factor, the concentration-dependent diffusion coefficient can be predicted. It is found that the calculated diffusion coefficient correlates very well to the experimental data. This study also proposes a prediction of time-lag values from the solubility and permeability measurements. Moreover, the diffusion coefficients for gases in glassy polymers can also be predicted using the time-lag values alone. The proposed diffusion model represents satisfactorily experimental data reported in ...

Effect of Thin Film Confinement on the Transport Properties of Ultra-Thin Polymer Films

ABSTRACTThe influence of film thickness and polymer molecular weight on the diffusion coefficient of a series of small molecule penetrants (including water, benzene, and trifluoroacetic acid) in thin films of two different model photoresist polymers (poly(p-hydroxystyrene) and bis-triflouromethyl carbinol substituted poly(norbornene)) has been studied using vapor sorption experiments via quartz crystal microbalance (QCM) methods. Diffusion coefficients for films ranging in thickness from approximately 1 μm to 50 nm were determined. It is observed that the diffusion coefficient of small molecules in a thin polymer film is a strong function of film thickness, and that the diffusion coefficient decreases drastically as film thickness is reduced below a critical thickness value. This critical thickness value is found to be a function of both the type of polymer used and the polymer molecular weight.

Encapsulation, Permeability, and Cellular Uptake Characteristics of Hollow Nanometer-Sized Conductive Polymer Capsules

The use of nanometer-sized gold particles as templates for the synthesis of hollow poly(pyrrole), poly(N-methylpyrrole), and poly(3-methylthiophene) is described in this paper. Diffusion coefficients of small molecules through the capsule shell were found to vary by almost 3 orders of magnitude depending on the polymer, polymer oxidation state, and counteranion incorporated during polymer synthesis. A small molecule (anthraquinone) and an enzyme (horseradish peroxidase) were trapped inside hollow capsules by attaching them to the template particle prior to polymerization and particle etching. A thin poly(pyrrole) shell protected the enzyme 2 times longer in neat toluene compared to unencapsulated enzyme. Finally, the potential for using conductive polymer nanoparticles for intracellular delivery or diagnostics was examined by administering partice suspensions to 3T3 murine fibroblasts. Particles ranging in size from 25 to 100 nm were engulfed by fibroblasts without compromising cell viability.

Diffusion Coefficients of Small Molecules as Guests in Various Phases of Pluronic L64 Measured by One-Dimensional Electron Spin Resonance Imaging

The diffusion coefficients of small nitroxide probes as guests in aqueous solutions of the triblock copolymer poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) EO13PO30EO13 (Pluronic L64) were measured at 300 K by one-dimensional electron spin resonance imaging (1D ESRI). The method is based on encoding the spatial distribution of the probes as a function of time in ESR spectra recorded in the presence of magnetic field gradients and simulation of these spectra in order to extract the diffusion coefficient, D. The rate of transport of each probe as a function of polymer content in the various phases (micellar, hexagonal, lamellar, and reverse micellar) of aqueous L64 depends on the probe location in the self-assembled system. The probe site was deduced from the analysis of the ESR spectra; the isotropic hyperfine splitting, aN, from the 14N nucleus of the >NO fragment in the probes was the polarity sensitive parameter. D values for the cationic probe 4-(N,N,N-trimethyl)ammonium-2,2,6,6-tetramethyl-piperidine-1-oxyl iodide that is known to reside in the water domains follow the expression D = D0 exp(−aw2), where D0 is the diffusion coefficient in the neat solvent and w2 is the weight fraction of the polymer. For the hydrophobic probe 5DSE, the methyl ester of doxylstearic acid where 5 indicates the carbon atom to which the doxyl group is attached, D is significantly lower and almost constant for w2 in the range 0.20−0.80. For the probe perdeuterio-2,2‘,6,6‘-tetramethyl-piperidone-N-oxide that is located at the interface between water and the EO domains, D decreases with increase in the polymer content, but the decrease is more prominent for w2 in the range 0.10−0.30; at w2 = 0.90, D is similar to that of the polymer chains. The method of 1D ESRI enables the measurement of D values for guests present in small concentrations, typically ≤2 × 10-3 mol/L. This method and the results obtained in this study are relevant for assessing both the rate of transport of drugs in drug delivery systems and the partitioning of various guests in complex systems, for instance in biological membranes.

Computer simulation of molecular diffusion in amorphous polymers

Diffusion of small molecules in amorphous polymers has been examined by computer simulation. Diffusion coefficients of small molecules with molecular weights ranging from 16.04 (methane) to 452.50 (fluocinolone acetonide) Da in four amorphous polymers were calculated using the QUANTA, CHARMM and Cerius 2 programs. The four amorphous polymers used in our calculation were polyethylene (PE), poly(dimethyl siloxane) (PDMS), poly(methyl methacrylate-co-hydroxyethyl methacrylate) (P(MMA-co-HEMA)), and ethyl and benzyl esters of hyaluronic acid (HA-E, HA-B). The calculated diffusion coefficients ( D c) were compared with the experimentally obtained values ( D e) found in the literature. The ratio of D c/ D e varied from 0.04 to 24 000. In general, the close values of D c to D e were obtained when the system dealt with hydrophobic molecules diffusing through hydrophobic polymers. The D c/ D e ratio became either very high or very low when the experimental system included hydrophilic diffusants and/or a hydrophilic polymer. The simulation time and the size of molecular models also played key roles in determining the consistency of calculations and the correlation with experimental values. Our study suggests that the current computer simulation of molecular diffusion may be useful in obtaining relative values rather than absolute diffusion coefficient values.

Generating an Intracellular Diffusion Map by Two-Photon Fluorescence Correlation Spectroscopy

AbstractA new technique for determining cellular viscosity has been developed based on two-photon excitation and fluorescence correlation spectroscopy. We have applied this method to map intracellular diffusion coefficient of small molecules at selected cytoplasmic locations of mouse fibroblast cells. The cytoplasmic diffusion rate is one tenth of that in an aqueous environment.