Thomas Ingram

Comparison of different pretreatment methods for lignocellulosic materials. Part I: Conversion of rye straw to valuable products.

The conversion of lignocellulose to valuable products requires I: a fractionation of the major components hemicellulose, cellulose, and lignin, II: an efficient method to process these components to higher valued products. The present work compares liquid hot water (LHW) pretreatment to the soda pulping process and to the ethanol organosolv pretreatment using rye straw as a single lignocellulosic material. The organosolv pretreated rye straw was shown to require the lowest enzyme loading in order to achieve a complete saccharification of cellulose to glucose. At biomass loadings of up to 15% (w/w) cellulose conversion of LHW and organosolv pretreated lignocellulose was found to be almost equal. The soda pulping process shows lower carbohydrate and lignin recoveries compared to the other two processes. In combination with a detailed analysis of the different lignins obtained from the three pretreatment methods, this work gives an overview of the potential products from different pretreatment processes.

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.

Experimental Methods and Prediction with COSMO-RS to Determine Partition Coefficients in Complex Surfactant Systems

Surfactant-based separation processes are a promising alternative to conventional organic solvent processes. A crucial parameter to describe the efficiency of such processes is the partition coefficient between the surfactant aggregates (micelles) and the aqueous bulk phase. In this work, several experimental methods to determine these partition coefficients (micellar liquid chromatography, micellar enhanced ultrafiltration, and cloud point extraction) are evaluated and compared. In addition, these results are compared to predictions with the thermodynamic model COSMO-RS. In particular, systems with the nonionic surfactant TritonX-100 are studied. The partition equilibria of various solutes (pyrene, naphthalene, phenanthrene, phenol, 3-methoxyphenol, and vanillin) and the influence of different additives (alcohols) are investigated. All experimental methods show very good reproducibility. Moreover, the results from different methods are in good agreement, supplementing one another concerning the temperature ranges. Notably, the COSMO-RS model is capable of predicting partition coefficients between micelles and water in the investigated temperature range and at different alcohol concentrations. The results demonstrate the potential of the model COSMO-RS to facilitate the selection of optimized process parameters for a given separation problem. By predicting partition equilibria in multicomponent systems, the selection of surfactant, temperature, and appropriate additives can be facilitated.

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.

Kinetic investigation of a solvent-free, chemoenzymatic reaction sequence towards enantioselective synthesis of a β-amino acid ester.

A solvent‐free, chemoenzymatic reaction sequence for the enantioselective synthesis of β‐amino acid esters has been kinetically and thermodynamically characterized. The coupled sequence comprises a thermal aza‐Michael addition of cheap starting materials and a lipase catalyzed aminolysis for the kinetic resolution of the racemic ester. Excellent ee values of >99% were obtained for the β‐amino acid ester at 60% conversion. Kinetic constants for the aza‐Michael addition were obtained by straightforward numerical integration of second‐order rate equations and nonlinear fitting of the progress curves. A different strategy had to be devised for the biocatalytic reaction. Initially, a simplified Michaelis–Menten model including product inhibition was developed for the reaction running in THF as an organic solvent. Activity based parameters were used instead of concentrations in order to facilitate the transfer of the kinetic model to the solvent‐free system. Observed solvent effects not accounted for by the use of thermodynamic activities were incorporated into the kinetic model. Enzyme deactivation was observed to depend on the ratio of the applied substrates and also included in the kinetic model. The developed simple model is in very good agreement with the experimental data and allows the simulation and optimization of the solvent‐free process. Biotechnol. Bioeng. 2012; 109:1479–1489.

Partition Coefficients of Ionizable Solutes in Mixed Nonionic/Ionic Micellar Systems

Surfactant solutions in practical applications usually are mixtures of ionic and nonionic surfactants. Because of synergistic effects, the solubilization of hydrophobic compounds can be enhanced while decreasing the needed amount of surfactant at the same time. In this work, the influence of the composition of Brij 35/CTAB and Brij 35/SDS mixed micelles on the partition coefficient log D(MW) of various acids and bases over the entire pH range was investigated. Two experimental methods (MLC, micellar liquid chromatography; MEUF, micellar enhanced ultrafiltration) are evaluated for the determination of partition coefficients in mixed-micelle systems. Although MLC stands out because of its automation and easy handling, MEUF is applicable to a broader log D(MW) range. It is shown that the partitioning can be influenced dramatically by the two investigated parameters. By adjusting the pH value and the composition of the micelles, we can tailor the partition behavior of solutes for virtually any application. The thermodynamic model COSMO-RS gives valuable predictions of the partition coefficients if the composition of the micelle is available. Different approaches for the description of the micellar composition are evaluated in this work. On the basis of the cmc value of the single surfactants and the mixture only, it is shown that the regular solution approximation gives reasonable micellar compositions. The partition coefficients between water and the mixed micelles are predicted with the COSMO-RS model, in good agreement with the experimental data. Moreover, the micellar composition can be evaluated by fitting the prediction to the experimentally determined partition coefficients.