Sven Jakobtorweihen

Molecular simulation of alkene adsorption in zeolites

The adsorption isotherms of various alkenes and their mixtures in zeolites such as silicalite-1 (MFI-type), theta-1 (TON-type), and deca-dodecasil 3R (DDR-type) were calculated using the grand canonical Monte Carlo (GCMC) approach. Additionally, the adsorption of alkene–alkane mixtures was simulated. The GCMC approach was combined with the configurational-bias Monte Carlo (CBMC) method. Effective Lennard–Jones parameters for the interaction between the oxygen atoms of all-silica zeolites and the sp2-hybridized groups of linear alkenes were determined using a united atom force field. They were adjusted to the experimental adsorption data of silicalite-1 (MFI). The inflection behaviour of the 1-heptene isotherm was investigated in detail. It is shown that, in the inflection region, the 1-heptene molecules alter their end-to-end length depending on their location. The occurrence of a maximum in the mixture adsorption isotherms is attributed to two effects: entropic effects and non-ideality effects. From the mixture simulations some general conclusions concerning the separation of hydrocarbons with silicalite-1 can be drawn. The transferability of the Lennard–Jones parameters to other zeolites was investigated. Simulations of adsorption isotherms in the zeolites theta-1 and DD3R and their comparison with experimental data indicate the possibility of transferring the parameters to other all-silica zeolites.

Prediction of Micelle/Water and Liposome/Water Partition Coefficients Based on Molecular Dynamics Simulations, COSMO-RS, and COSMOmic

Liposomes and micelles find various applications as potential solubilizers in extraction processes or in drug delivery systems. Thermodynamic and transport processes governing the interactions of different kinds of solutes in liposomes or micelles can be analyzed regarding the free energy profiles of the solutes in the system. However, free energy profiles in heterogeneous systems such as micelles are experimentally almost not accessible. Therefore, the development of predictive methods is desirable. Molecular dynamics (MD) simulations reliably simulate the structure and dynamics of lipid membranes and micelles, whereas COSMO-RS accurately reproduces solvation free energies in different solvents. For the first time, free energy profiles in micellar systems, as well as mixed lipid bilayers, are investigated, taking advantage of both methods: MD simulations and COSMO-RS, referred to as COSMOmic (Klamt, A.; Huniar, U.; Spycher, S.; Keldenich, J. COSMOmic: A Mechanistic Approach to the Calculation of Membrane-Water Partition Coefficients and Internal Distributions within Membranes and Micelles. J. Phys. Chem. B 2008, 112, 12148-12157). All-atom molecular dynamics simulations of the system SDS/water and CTAB/water have been applied in order to retrieve representative micelle structures for further analysis with COSMOmic. For the system CTAB/water, different surfactant concentrations were considered, which results in different micelle sizes. Free energy profiles of more than 200 solutes were predicted and validated by means of experimental partition coefficients. To our knowledge, these are the first quantitative predictions of micelle/water partition coefficients, which are based on whole free energy profiles from molecular methods. Further, the partitioning in lipid bilayer systems containing different hydrophobic tail groups (DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), SOPC (stearoyl-oleoylphosphatidylcholine), DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine), and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine)) as well as mixed bilayers was calculated. Experimental partition coefficients (log P) were reproduced with a root-mean-square error (RMSE) of 0.62. To determine the influence of cholesterol as an important component of cellular membranes, free energy profiles in the presence of cholesterol were calculated and shown to be in good agreement with experimental data.

Diffusion of chain molecules and mixtures in carbon nanotubes: The effect of host lattice flexibility and theory of diffusion in the Knudsen regime

A novel algorithm for modeling the influence of the host lattice flexibility in molecular dynamics simulations is extended to chain-like molecules and mixtures. This technique, based on a Lowe-Andersen thermostat, maintains the advantages of both simplicity and efficiency. The same diffusivities and other properties of the flexible framework system are reproduced. Advantageously, the computationally demanding flexible host lattice simulations can be avoided. Using this methodology we study the influence of flexibility on diffusion of n-alkanes inside single-walled carbon nanotubes. Furthermore, results are shown for diffusion of two mixtures (methane-helium and ethane-butane). Using these results we investigate the accuracy of theories describing diffusion in the Knudsen regime. For the dynamics in carbon nanotubes the Knudsen diffusivities are much too low. The Smoluchowski model gives better results. Interestingly, the extended Smoluchowski model can reproduce our simulation results obtained with a rigid host lattice. We modify this model to also treat collisions with a flexible interface correctly. As the tangential momentum accommodation coefficient is needed for the theoretical models, we introduce a simple concept to calculate it.

Molecular Dynamics Simulation of SDS and CTAB Micellization and Prediction of Partition Equilibria with COSMOmic

Molecular dynamics (MD) simulations of the self-assembly of different ionic surfactants have been performed in order to obtain representative micellar structures. Subsequently, these structures were used to predict the partition behavior of various solutes in these micelles with COSMOmic, an extension of COSMO-RS. This paper includes multiple self-assembled micelles of SDS (sodium dodecyl sulfate, anionic surfactant) and CTAB (cetyltrimethylammoniumbromide, cationic surfactant) at different concentrations. Micellar size, density profiles, and shape (eccentricity) have been investigated. However, the size strongly depends on the functional definition of a micelle. For this reason, we present a method based on the free monomer concentration in aqueous solution as an optimization criterion for the micelle definition. The combination of MD with COSMOmic has the benefit of combining detailed atomistic information from MD with fast calculations of COSMOmic. For the first time the influence of micelle structure on pratition equilibria, predicted with COSMOmic, were investigated. In case of SDS more than 4600 and for CTAB more than 800 single micelles have been studied. The predictions of the partition coefficients with COSMOmic are in good agreement with experimental data. Additionally, the most favorable locations of selected molecules in the micelles as well as probable energy barriers are determined even for complex solutes such as toluene, propanolol, ephedrine, acetone, phenol, lidocaine, syringic acid, coumarin, isovanillin, ferulic acid, and vanillic acid. This method can therefore be applied as a potential screening tool for solutes (e.g., drugs) to find the optimal solute-surfactant combination.

Combining reactive and configurational-bias Monte Carlo: confinement influence on the propene metathesis reaction system in various zeolites.

In order to efficiently calculate chemical equilibria of large molecules in a confined environment the reactive Monte Carlo technique is combined with the configurational-bias Monte Carlo approach. To prove that detailed balance is fulfilled the acceptance rule for this combination of particular Monte Carlo techniques is derived in detail. Notably, by using this derivation all other acceptance rules of any Monte Carlo trial moves usually carried out in combination with the configurational-bias Monte Carlo approach can be deduced from it. As an application of the combination of reactive and configurational-bias Monte Carlo the influence of different zeolitic confinements (MFI, TON, LTL, and FER) on the reaction equilibrium and the selectivity of the propene metathesis reaction system was investigated. Compared to the bulk phase the conversion is increased significantly. The authors study this reaction system in the temperature range between 300 and 600 K, and the pressure range from 1 to 7 bars. In contrast to the bulk phase, pressure and temperature have a strong influence on the composition of the reaction mixture in confinement. At low pressures and temperatures both conversion and selectivity are highest. Furthermore, the equilibrium composition is strongly dependent on the type of zeolite. This demonstrates the important role of the host structure in catalytic systems.

Reactive Monte Carlo and grand-canonical Monte Carlo simulations of the propene metathesis reaction system

The influence of silicalite-1 pores on the reaction equilibria and the selectivity of the propene metathesis reaction system in the temperature range between 300 and 600 K and the pressure range from 0.5 to 7 bars has been investigated with molecular simulations. The reactive Monte Carlo (RxMC) technique was applied for bulk-phase simulations in the isobaric-isothermal ensemble and for two phase systems in the Gibbs ensemble. Additionally, Monte Carlo simulations in the grand-canonical ensemble (GCMC) have been carried out with and without using the RxMC technique. The various simulation procedures were combined with the configurational-bias Monte Carlo approach. It was found that the GCMC simulations are superior to the Gibbs ensemble simulations for reactions where the bulk-phase equilibrium can be calculated in advance and does not have to be simulated simultaneously with the molecules inside the pore. The confined environment can increase the conversion significantly. A large change in selectivity between the bulk phase and the pore phase is observed. Pressure and temperature have strong influences on both conversion and selectivity. At low pressure and temperature both conversion and selectivity have the highest values. The effect of confinement decreases as the temperature increases.

Combination of COSMOmic and molecular dynamics simulations for the calculation of membrane–water partition coefficients

The importance of membrane‐water partition coefficients led to the recent extension of the conductor‐like screening model for realistic solvation (COSMO‐RS) to micelles and biomembranes termed COSMOmic. Compared to COSMO‐RS, this new approach needs structural information to account for the anisotropy of colloidal systems. This information can be obtained from molecular dynamics (MD) simulations. In this work, we show that this combination of molecular methods can efficiently be used to predict partition coefficients with good agreement to experimental data and enables screening studies. However, there is a discrepancy between the amount of data generated by MD simulations and the structural information needed for COSMOmic. Therefore, a new scheme is presented to extract data from MD trajectories for COSMOmic calculations. In particular, we show how to calculate the system structure from MD, the influence of lipid conformers, the relation to the COSMOmic layer size, and the water/lipid ratio impact. For a 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine (DMPC) bilayer, 66 partition coefficients for various solutes were calculated. Further, 52 partition coefficients for a 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (POPC) bilayer system were calculated. All these calculations were compared to experimental data.

Predicting solute partitioning in lipid bilayers: Free energies and partition coefficients from molecular dynamics simulations and COSMOmic

Quantitative predictions of biomembrane/water partition coefficients are important, as they are a key property in pharmaceutical applications and toxicological studies. Molecular dynamics (MD) simulations are used to calculate free energy profiles for different solutes in lipid bilayers. How to calculate partition coefficients from these profiles is discussed in detail and different definitions of partition coefficients are compared. Importantly, it is shown that the calculated coefficients are in quantitative agreement with experimental results. Furthermore, we compare free energy profiles from MD simulations to profiles obtained by the recent method COSMOmic, which is an extension of the conductor-like screening model for realistic solvation to micelles and biomembranes. The free energy profiles from these molecular methods are in good agreement. Additionally, solute orientations calculated with MD and COSMOmic are compared and again a good agreement is found. Four different solutes are investigated in detail: 4-ethylphenol, propanol, 5-phenylvaleric acid, and dibenz[a,h]anthracene, whereby the latter belongs to the class of polycyclic aromatic hydrocarbons. The convergence of the free energy profiles from biased MD simulations is discussed and the results are shown to be comparable to equilibrium MD simulations. For 5-phenylvaleric acid the influence of the carboxyl group dihedral angle on free energy profiles is analyzed with MD simulations.

Solubilization in mixed micelles studied by molecular dynamics simulations and COSMOmic.

Up to now, micelles composed of different surfactants (mixed micelles) are rarely studied with molecular methods. This is in contrast to their importance for pharmaceutical or industrial applications, where it is of great interest to predict the partition behavior for a large set of solutes (screening) within mixed micelles. This work is focused on molecular simulations of phase equilibria in mixed surfactant systems, because mixtures of different types of surfactants (nonionic or ionic) in aqueous solution can change the partition behavior of solutes tremendously. The extension of COSMO-RS for anisotropic phases, named COSMOmic, is computationally efficient and can be used as a screening tool for finding adequate surfactant systems for a specific extraction task. However, it needs micellar structures as an input. Therefore, molecular dynamics (MD) simulations of the self-assembly of pure Brij35 (polyethylene glycol dodecyl ether) and mixtures either with CTAB (cetyltrimethyl ammonium bromide) or SDS (sodium dodecyl sulfate) at different concentrations are performed. The micelles from the self-assembly MD simulations are used to predict the partition behavior of various solutes between micelle and bulk water with COSMOmic. In this way, various micelles of different size and composition are investigated and structural influences on partition equilibria of solute molecules like ephedrine, acetone, toluene, coumarin, isovanillin, ferulic acid, vanillic acid, syringic acid, and phenol are analyzed. For the first time, the self-assembly of pure Brij35 and the mixtures of Brij35/CTAB and Brij35/SDS is studied on an atomistic scale. Significant influences of atomic structure and composition of mixed micelles on partition equilibria are elucidated. The findings of this detailed analysis are in good agreement with experimental data and likely to improve the knowledge and understanding of mixed micellar extraction processes and can pave the way for more practical applications in the future.

Molecular Modeling of Triton X Micelles: Force Field Parameters, Self-Assembly, and Partition Equilibria.

Nonionic surfactants of the Triton X-series find various applications in extraction processes and as solubilizing agents for the purification of membrane proteins. However, so far no optimized parameters are available to perform molecular simulations with a biomolecular force field. Therefore, we have determined the first optimized set of CHARMM parameters for the Triton X-series, enabling all-atom molecular dynamics (MD) simulations. In order to validate the new parameters, micellar sizes (aggregation numbers) of Triton X-114 and Triton X-100 have been investigated as a function of temperature and surfactant concentration. These results are comparable with experimental results. Furthermore, we have introduced a new algorithm to obtain micelle structures from self-assembly MD simulations for the COSMOmic method. This model allows efficient partition behavior predictions once a representative micelle structure is available. The predicted partition coefficients for the systems Triton X-114/water and Triton X-100/water are in excellent agreement with experimental results. Therefore, this method can be applied as a screening tool to find optimal solute-surfactant combinations or suitable surfactant systems for a specific application.