Enantioseparation of 1-phenyl-1-propanol by supercritical fluid-simulated moving bed chromatography

The enantioseparation of 1-phenyl-1-propanol through the supercritical fluid-simulated moving bed (SF-SMB) process is studied. Non-linear isotherms were measured on an analytical column, and used together with the triangle theory for SMB design to select operating conditions for the SF-SMB. Experiments were carried out on a pilot-scale SF-SMB plant at conditions that corresponded to the non-linear range of the isotherm. Under conditions of low feed concentration, complete separation (extract purity = 99.5%; raffinate purity = 98.4%) was achieved. Under conditions of larger feed concentration, the best separation corresponded to an extract purity of 98.0% and a raffinate purity of 94.0%, and yielded a productivity of 110 g of racemate per kg stationary phase per day.     

Development of an high-performance liquid chromatographic simulated moving bed separation from an industrial perspective

A binary test mixture consisting of cyclopentanone and cycloheptanone is used for the performance evaluation of a pilot-scale simulated moving bed unit. The involved adsorption equilibria and the kinetic behavior are discussed in detail. The results of the test runs are evaluated using the recently introduced "triangle theory" which allows to account for the overload conditions prevailing under preparative chromatographic conditions and to select optimal operating conditions. Under optimized conditions the separation of 735 g test mixture/kg stationary phase per day with purities >99.9% for extract and raffinate stream has been achieved.     

Enantioseparation of 1-phenyl-1-propanol on cellulose-derived chiral stationary phase by supercritical fluid chromatography II. Non-linear isotherm

The separation of the enantiomers of 1-phenyl-1-propanol by supercritical fluid chromatography on a chiral stationary phase, which consists of cellulose tris (3,5-dimethylphenylcarbamate) coated on a silica support (Chiralcel-OD), is studied under overloaded, non-linear chromatographic conditions. Pulse experiments are performed at a temperature of 30 degrees C using supercritical CO(2) modified with methanol as a mobile phase. The parameters of the binary Langmuir adsorption isotherm are determined by the inverse method, comparing experimental and simulated peak responses. Isotherm parameters are derived for modifier concentrations between 1 and 5% (w/w) and operating pressures between 125 and 185 bar, and the dependency of the isotherm parameters, namely the Henry constant and the saturation capacity, on operating conditions is investigated.     

Model-based optimization of a preparative ion-exchange step for antibody purification

A method using a model-based approach to design and optimize an ion-exchange step in a protein purification process is proposed for the separation of IgG from a mixture containing IgG, BSA and myoglobin. The method consists of three steps. In the first step, the model is calibrated against carefully designed experiments. The chromatographic model describes the convective and dispersive flow in the column, the diffusion in the adsorbent particles, and the protein adsorption using Langmuir kinetics with mobile phase modulators (MPM). In the second step, the model is validated against a validation experiment and analyzed. In the third and final step, the operating conditions are optimized. In the optimization step, the loading volume and the elution gradient are optimized with regard to the most important costs: the fixed costs and the feed cost. The optimization is achieved by maximizing the objective functions productivity (i.e. the production rate for a given amount of stationary phase) and product yield (i.e. the fraction of IgG recovered in the product stream). All optimization is conducted under the constraint of 99% purity of the IgG. The model calibration and the analysis show that this purification step is determined mainly by the kinetics, although as large a protein as IgG is used in the study. The two different optima resulting from this study are a productivity of 2.7 g IgG/(s m3) stationary phase and a yield of 90%. This model-based approach also gives information of the robustness of the chosen operating conditions. It is shown that the bead diameter could only be increased from 15 microm to 35 microm with maximum productivity and a 99% purity constraint due to increased diffusion hindrance in larger beads.     

Modification of a commercial chiral stationary phase influences on enantiomer separations using simulated moving bed chromatography

Chromatographic enantiomer separations using high-performance chromatography and the simulated moving bed (SMB) principle have become a practically useful method for obtaining optical isomers. The carbamate derivatives of amylose coated onto silica particles are very effective chiral stationary phases (CSPs). Several lots of Chiralpak AS, and its successor, Chiralpak AS-V, were compared by laser diffraction, microscopic imaging and pulse injections with increasing amounts of various racemates in order to determine the loading capacity and the competitive adsorption isotherms. Software simulations allowed to assess the possible effects due to the observed variations between the CSPs on the performance of a pilot SMB unit. The obtained results were verified by two multi-kilogram separations performed under current good manufacturing principles (cGMP) guidelines employing the two CSPs. The results of the two production runs are discussed in the light of the recently introduced "triangle theory" which allows to account for the overload conditions prevailing under preparative chromatographic conditions and to predict optimal operating conditions. Under optimized conditions the enantiomer separation of 1.4 kg racemate/kg stationary phase per day with purities >99.6% for the target enantiomer have been achieved.     

Gas permeability and stability of poly(1-trimethylsilyl-1-propyne-co-1-phenyl-1-propyne) membranes

A significant reduction in the gas permeability of the poly(1-trimethylsilyl-1-propyne) (PMSP) membrane was investigated in terms of the membrane thickness and the storage environment. The effects of physical aging were observed with thinner membranes and under vacuum conditions compared with storage in air. The decrease in the permeability coefficient was dependent on the decrease in the hole saturation constant of Langmuir adsorption (C'_H), which is related to the volume of the microvoids. Physical aging in the PMSP membrane affected not only the glassy domain but also the rubbery one. To stabilize the permeability of the PMSP membrane, a poly(1-trimethylsilyl-1-propyne-co-1-phenyl-1-propyne) [poly(TMSP-co-PP)] membrane was prepared. Poly(TMSP-co-PP) has the same unit of poly(1-phenyl-1-propyne), which membrane has stable permeability. The poly(TMSP-co-PP) with less than 20 mol % PP content was estimated to be a random copolymer based on theoretical gas permeation analysis. In the poly(TMSP-co-PP) membrane, the relation between the PP content and C'_H was similar to the relation between the PP content and the gas permeability. The stability of the permeability was dependent on the PP content. The poly(TMSP-co-PP) membrane containing 10 mol % PP had both high permeability and good stability under some of the aging conditions performed in this work. © 1995 John Wiley & Sons, Inc.     

Study of the adsorption behavior of the enantiomers of 1-phenyl-1-propanol on a cellulose-based chiral stationary phase

Using single-step frontal analysis, we measured single-component and competitive adsorption isotherm data for the two enantiomers of 1-phenyl-1-propanol (PP). These experimental data were fitted to several competitive bi-Langmuir models (with 8, 6, 5 and 4 parameters) and to the competitive Langmuir model. The latter model accounted well for the behavior of both PP enantiomers on Chiracel OB (cellulose tribenzoate coated on silica gel). The parameters obtained were used in numerical calculations to predict the band profiles of the two single components and of their mixtures under overloaded conditions. The equilibrium-dispersive model provides satisfactory results, with minor differences between the calculated and the experimental profiles. These differences became negligible when a more complex kinetic model was used, with a concentration-dependent rate coefficient.     

Standing wave design of a four-zone thermal SMB fractionator and concentrator (4-zone TSMB-FC) for linear systems

For a dilute feed, a four-zone SMB with temperature gradient (4-zone TSMB-FC) can fractionate and simultaneously concentrate two solutes. Optimization of the operating parameters for this system, which include four zone flow rates and port switching time, is a major challenge because of the five variables. Initial choice of the variables using the triangle theory followed by a systematic search using rate model simulations is time-consuming. In this study, the SWD developed previously for isothermal systems is modified for the first time for a 4-zone TSMB-FC. The optimum operating parameters are determined with the new method. Only linear isotherm systems with significant mass transfer resistances are considered. For a dilute feed, a 4-zone SMB-FC can produce pure desorbent, in addition to extract and raffinate products with high purities. For the separation of p-xylene and toluene with silica gel in the temperature range from 0 to 80 °C, the enrichment factor in the linear region can be as high as 80 fold for an extract purity of 99.99 % and tenfold for raffinate purity of 99.8 %, while withdrawing the desorbent at a desorbent to feed flow rate ratio of 0.53 and 0.78, respectively.     

Separation of amino acids with simulated moving bed chromatography*

Authors have constructed an automatized four-column large laboratory scale (I.D. = 50 mm, L = 500 mm) simulated moving bed (SMB) equipment. The applied model system for separation of biomolecules is glycine, L-phenylalanine, water and Sepabeads SP825 adsorbent. The authors determined the adsorption equilibrium data and the packing characteristics. The operating conditions of SMB equipment were calculated with the help of the Morbidelli variables. During the SMB experiments, glycine and L-phenylalanine were separated in water on Sepabeads SP825 with an average particle size 0.3 mm at temperatures 20 degrees C and 60 degrees C. The measurement series were carried out on a four-column three-zone open loop SMB. Both L-phenylalanine and glycine were produced with more than 99.9% (m/m) purity and 99% yield at productivity 1.7-3.7, with productivity 3.7-8.1 mg/(g adsorbent h) in case of 2-1-1-0 column configuration. The measured and the calculated data agreed well.     

Solvent gradient operation of simulated moving beds. 2. Langmuir isotherms

Simulated Moving Bed separations of enantiomers or fine chemicals are usually carried out in the isocratic mode, i.e. by applying the same operating conditions (temperature, pressure, mobile phase composition, pH) in the whole SMB unit. However, it has been recently recognized that by properly modulating operating conditions in the SMB sections. i.e. Sections 1-4 normally, separation performance in terms of productivity and solvent consumption can be significantly improved. In this work, we study solvent gradient SMB (SG-SMB) operation, where the concentration of a modifier in the main solvent constituting the mobile phase is adjusted along the SMB unit, so as to have weaker retention of the species to be separated in the first two sections, and stronger retention in Sections 3 and 4. Overload chromatographic conditions are considered, where the adsorption behavior is characterized by a nonlinear competitive adsorption isotherm, e.g. a binary Langmuir isotherm. Design criteria to achieve complete separation are developed in the frame of the equilibrium theory of chromatography. The theoretical findings are discussed in view of typical effects of the modifier concentration on retention times and solubility of the species to be separated, and an overall assessment of the SG-SMB technology is attempted.     

Equilibrium theory based design of simulated moving bed processes for a generalized Langmuir isotherm

In the frame of the local equilibrium theory of chromatography, design criteria for complete separation of binary mixtures in simulated moving bed (SMB) separations are developed, presented and discussed. These apply to systems, whose retention behavior is characterized by a generalized Langmuir isotherm. By allowing for negative terms in the denominator of the classical Langmuir isotherm, this newly introduced adsorption model captures a broad class of competitive or synergistic adsorption, including anti-Langmuir behavior for both adsorbates, and mixed cases where one species behaves in a Lagmuirian and the other in an anti-Langmuirian manner. By extending classical equilibrium theory results for the binary Langmuir isotherm, and by generalizing the approach followed earlier to derive SMB design criteria for the binary and multi-component Langmuir isotherm, exact algebraic equations for the boundary of the complete separation region in the operating parameter space are derived for all possible generalized Langmuir isotherm. The effect of changing feed composition on the shape of the complete separation region and on the position of the optimal operating point is analyzed and discussed.     

The purity of laboratory chemicals with regard to measurement uncertainty

The purity P of laboratory chemicals is often declared in the form P > or = xy% (e.g., P > or = 97%). With a randomly chosen set of 40 compounds we found that their purity is generally closer to 100% than to the lower limit. The distribution of the purity data as found in the laboratory depends on the analytical technique used. Whereas purities determined by chromatography do not exceed 100% (because the sum of all observed peak areas is set to 100%), the purities obtained by titration can exceed 100% (because the functionality of the compound is measured). Therefore, the data for these two groups need to be dealt with in different ways. For purities based on titration we propose to use a rectangular distribution with a range from Pmin to 101%, an expected purity value which is the mean and a standard uncertainty of the purity u(P) of 29% of the range. Purities determined by chromatography can be described with a triangular distribution (ramp function). One leg of the triangle represents the range from Pmin to 100% and the right-angle is located at 100%. The expected value is the median and the uncertainty u(P) is 24% of the range. These proposals match the experimental data well.     

High Phase‐Purity 1T‐MoS2 Ultrathin Nanosheets by a Spatially Confined Template

The crystal phase plays an important role in controlling the properties of a nanomaterial; however, it is a great challenge to obtain a nanomaterial with high purity of the metastable phase. For instance, the large‐scale synthesis of the metallic phase MoS₂ (1T‐MoS₂) is important for enhancing electrocatalytic reaction, but it can only be obtained under harsh conditions. Herein, a spatially confined template method is proposed to synthesize high phase‐purity MoS₂ with a 1T content of 83 %. Moreover, both the confined space and the structure of template will affect the purity of 1T‐MoS₂; in this case, this approach was extended to other similar spatially confined templates to obtain the high‐purity material. The obtained ultrathin nanosheets exhibit good electrocatalytic activity and excellent stability in the hydrogen evolution reaction.     

Extruder‐made TPO nanocomposites. II. Effect of maleated poly(propylene)/organoclay ratio on morphology and thermal expansion behavior

Coefficients of linear thermal expansion (CTE) for poly(propylene)/ poly(propylene)‐grafted‐maleic anhydride/montmorillonite ethylene‐co‐octene elastomer (PP/PP‐g‐MA/MMT/EOR) blend nanocomposites were determined as a function of MMT content and various PP‐g‐MA/organoclay masterbatch ratios. The nanocomposites were prepared in a twin‐screw extruder at a fixed 30 wt % elastomer, 0–7 wt % MMT content, and various PP‐g‐MA/organoclay ratio of 0, 0.5, 1.0, and 1.5. The organoclay dispersion facilitated by the maleated PP helps to reduce the size of the dispersed phase elastomer particles in the PP matrix. The elastomer particle size decreased significantly as the PP‐g‐MA/organoclay ratio and MMT content increased; the elastomer particles viewed // to flow direction (FD) are smaller and less deformed compared to those viewed // to transverse direction (TD). The elastomer particle shape based on the view along the three orthogonal directions of the injection molded sample is similar to a prolate ellipsoid. The CTE decreased significantly in the FD and TD, whereas a slight increase is observed in the normal direction in the presence of MMT and PP‐g‐MA. The Chow model based on a two population approach showed better fit to experimental CTE when the effect of MMT and elastomer are considered individually. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B Polym. Phys. 2013 , 51, 952–965     

Determination of biodiesel purity through feature mapping to the multi-dimensional space by the LS-SVM approach

Purity is one of the essential properties of biodiesel. Since the purity parameter depends on different operating conditions, its direct measurement is too hard and can only be obtained for specific ranges of conditions. Therefore, this work considers the least-squares support vector machines (LS-SVMs) that transform operating conditions to a multi-dimensional space to simulate biodiesel purity in wide ranges of operating conditions. Indeed, we develop a reliable LS-SVM approach for modeling the biodiesel purity as a function of catalyst type and its concentration, reaction time, temperature, methanol-to-oil volume ratio, frequency, and amplitude of ultrasonic waves. The designed LS-SVM’s predictive performance is compared with four available artificial intelligence (AI) techniques in reliable literature. The obtained results confirm that the LS-SVM paradigm outperforms other considered AI-based techniques regarding five different statistical criteria. Our LS-SVM model provides AARD?=?2.2%, RMSE?=?3.46, and R²?=?0.9868 for the prediction of 267 experimental data points, which includes 267 data points. This model is finally employed for investigating the effect of different influential variables on biodiesel purity.

     

Determination of chemical purity and isotopic composition of natural and carbon-13-labeled arsenobetaine bromide standards by quantitative1H-NMR

In this study, we report the characterization of three arsenobetaine-certified reference materials by quantitative NMR. We have synthesized an arsenobetaine bromide high-purity standard of natural isotopic composition (ABET-1) and two carbon-13-labeled isotopic standards (BBET-1 and CBET-1). Assignments of the chemical purity and isotopic composition are not trivial in the case of arsenobetaine, and in this study we utilized quantitative¹H-NMR techniques for the determination of the mass fractions (chemical purity). The isotopic purity of all three standards was also assessed by NMR from the carbon-13 satellite signals. The standards are non-hygroscopic, high-purity (ca. 0.99 g/g), and the carbon-13 enrichment for both isotopic standards is x(¹³C)≈0.99. These standards are designed for use as primary calibrators for mass spectrometric determination of arsenobetaine in environmental samples.     

Effect of experimental conditions on the in vitro stability of99mTc (Sn)-pyrophosphate

The in vitro stability of^99mTc (Sn)-PyP as a function of experimental conditions of the preparation of the kit and time elapsed after labeling has been tested. The preparation was protected by using nitrogen-purged reactant solutions and kit vials and by ascorbic acid. The samples under nitrogen are stable for 6 h when the content of^99mTc-pertechnetate raises to 5%. The best stability was achieved by addition of 5 g of ascorbic acid per ml of the kit (content of^99mTc-pertechnetate about 0.5%). To accelerate the decomposition, exogenous hydrogen peroxide was used. In this case it was found that the presence of 10 g of ascorbic acid inhibits the effect both of oxygen and peroxide (6 g H₂O₂/ml of the kit). Radiochemical purity of^99mTc (Sn)-PyP remains practically unchanged for 6 h (content of^99mTc-pertechnetate about 0.5%).     

Experimental tests of chirality algebra

Most chiral molecules can be dissected into a collection of ligands attached to an underlying skeleton. Application of permutation group theory and group representation theory to such a model can lead to chirality functions which can be used to approximate pseudoscalar measurements such as optical rotation or circular dichroism. Such chirality functions have been tested experimentally for the following skeletons: (1) The polarized triangle of phosphines and phosphine oxides; (2) the tetrahedron of methane derivatives; (3) the disphenoid of allene and 2, 2-spirobiindane derivatives; (4) the polarized rectangle of [2, 2]-metacyclophanes; (5) the polarized pentagon of heterodisubstituted ferrocenes. The success of this method is fair to good for the polarized triangle, tetrahedron, and disphenoid skeletons but deteriorates rapidly for the polarized rectangle and polarized pentagon skeletons, in accord with the greater group-theoretical complexity of the latter skeletons.     

Constrained optimization of a preparative ion-exchange step for antibody purification

Today, the optimization of chromatographic separation is usually based on experimental work and rule of thumb. The process and analytical technology (PAT) initiative, of the US Food and Drug Administration, has provided the opportunity of using model-based approach when designing downstream processing of pharmaceutical substances. A nonlinear chromatography model was used in this study to optimize a preparative ion-exchange separation step involving two components. Separation was simulated with the general rate model employing Langmuir kinetics. Optimization was performed with an indirect method allowing constraints on the purity, thus avoiding sub-optimization, which can lead to noisy objective functions. The six decision variables used in the optimizations were flow rate, loading volume, initial salt concentration in the elution, final salt concentration in the linear elution gradient and the two cut points. A graphical representation of the effect of the decision variables on the objective function was used to verify that the optimization had converged to the true optimum. The optimal operating points, using productivity and yield separately as objective functions, were found and compared with the product of productivity and yield as objective function. The optimum obtained with this objective function had a lower productivity, than the productivity function, but much higher yield, which makes it a good substitute for a cost function.