Enhanced Production of Podophyllotoxin by Fed‐batch Cultivation of Podophyllum hexandrum

Podophyllum hexandrum (Indian May Apple) was successfully cultivated in a 3 L stirred tank bioreactor under low shear conditions in batch and fed‐batch modes of operation. A statistically optimized culture medium was used for the batch cultivation of Podophyllum hexandrum. Under optimum culture conditions of P. hexandrum, the batch culture showed a growth‐associated product formation with a maximum biomass of 21.4 g/L dry cell weight (DCW) basis and a podophyllotoxin production of 13.8 mg/L in 26 d. A mathematical model was developed to design the nutrient feeding strategies for a fed‐batch cultivation to prolong the productive log phase of cultivation. The fed‐batch cultivation was able to enhance the biomass and podophyllotoxin accumulation to 48 g/L (DCW basis) and 43.2 mg/L, respectively, in 60 d. The volumetric productivity of podophyllotoxin in fed‐batch cultivation was found to be 0.72 mg/(L. d) as opposed to 0.53 mg/(L. d) in batch cultivation under optimized culture conditions.     

Continuous‐Flow Di‐N‐Alkylation of 1H‐Benzimidazole in a Fixed‐Bed Reactor

A new process for a continuous‐flow di‐N‐alkylation of 1H‐benzimidazole to 1H‐benzimidazole‐3‐ium iodide by methylene iodide in the presence of potassium carbonate in a fixed‐bed reactor is presented. The synthesis was transferred from batch to continuous operation with similar yields and conversion rates. Moreover, the influence of temperature and residence time in the continuous flow setup was characterized; optimized conditions led to a doubling of yield. In addition, the continuous flow allowed for a better control of the two‐step reaction by adding an additional tube reactor after the fixed bed that further enhanced the overall performance. With this, the continuous‐flow system presented itself as superior due to higher available temperatures and a better controllability.     

A preliminary evaluation of a continuous‐flow reactor for liquid–liquid–solid phase‐transfer catalyzed synthesis of n‐butyl phenyl ether

This study evaluates the feasibility of using a continuous‐flow stirred vessel reactor (CFSVR) to synthesize n‐butyl phenyl ether (ROPh) from n‐butyl bromide (RBr) and sodium phenolate (NaOPh) by liquid–liquid–solid phase‐transfer catalysis (triphase catalysis). The factors affecting the preparation of triphase catalysts, the etherification reaction in a batch reactor, and the performance in a CFSVR were investigated. The kinetic study with a batch reactor indicated that when the initial concentration of NaOPh or RBr was high, the conversion of RBr would depend on the initial concentration of both RBr and NaOPh. The reaction can be represented by a pseudo‐first‐order kinetic model when the concentration of NaOPh is in proper excess to that of RBr, and the apparent activation energy is 87.8 kJ mol^?1. When the etherification reaction was carried out in the CFSVR, the catalyst particles did not flow out of the reactor, even at a high agitation speed. The conversion of RBr in the CFSVR was, as predicted, lower than that in the batch reactor, but was higher than the theoretical value because the dispersed phase is not completely mixed. Copyright © 2004 Society of Chemical Industry     

Study of Hydrodynamics,Mixing and Gas‐Liquid Mass Transfer in a Split‐Rectangular Airlift Reactor

Global hydrodynamic characteristics, liquid mixing and gas‐liquid mass transfer for a 63 L split‐rectangular airlift reactor were studied. Correlations for gas holdup and overall liquid circulation velocity were derived for the air‐water system as a function of the specific power input; these were compared to data and correlations for reactor volumes between 4.7 L and 4600 L. A partial recirculation of small bubbles in the riser was observed when U_gr > 0.03 m/s, which was attributed to the use of a single‐orifice nozzle as the gas phase distributor. The dimensionless mixing time and the overall axial dispersion coefficient were nearly constant for the range of gas flow rates studied. However, values of K_L/d_B were greater than those reported in previous studies and this is caused by the partial recirculation of the gas phase in the riser. While scale effects remain slight, the use of a gas distributor favouring this partial recirculation seems adequate for mass transfer in split‐rectangular airlift reactors.     

Continuous Application of Polyglycerol‐Supported Salen in a Membrane Reactor: Asymmetric Epoxidation of 6‐Cyano‐2,2‐dimethylchromene

In the current work, suitability of hyperbranched polyglycerol as a high loading catalyst support is demonstrated. A polyglycerol‐supported manganese‐salen complex (chemzyme) is applied as a homogeneous catalyst in the epoxidation of 6‐cyano‐2,2‐dimethylchromene. The recyclability of the corresponding catalyst was investigated in repetitive batch experiments as well as a continuous operation of the reaction in an ultrafiltration membrane reactor. An enhanced stability of the catalyst in repetitive batches was observed as a result of immobilization whereby the total turnover number increased from 23 in a single batch to 80 in four repetitive batches. To enable continuous operation, a continuously operated, stirred tanked reactor (CSTR) was equipped with an ultrafiltration membrane (MPF‐50) and a retention of 98% was determined. The continuous chemzyme membrane reactor was operated over the course of 20 residence times. After approximately 12 residence times, the steady state was reached yielding 70% conversion as well as an enantiomeric excess up to 92%. A space‐time yield (sty) of 458 g L ⁻¹ d⁻¹ and a turnover frequency (TOF_reaction) of up to 18 h⁻¹ was reached in the steady state. It was determined that the total turnover number (TTN) was enhanced by a factor of 10 from 24 (batch) up to 240 for 20 residence times in CSTR operation.     

Chemoselective hydrolysis of methyl 2‐acetoxybenzoate using free and entrapped esterase in K‐carrageenan beads

Porcine liver esterase was entrapped in natural polysaccharides K‐carrageenan and retention of its activity was determined using p‐nitrophenyl acetate as the substrate. The optimum pH for esterase activity of entrapped enzyme showed a little shift towards acidic side. Immobilized enzyme showed improved thermal and storage stability. The entrapped esterase retained 50% of its activity after eight repetitive cycles. Michaelis constant K_m for the free and entrapped enzymes was almost same indicting no conformational change during immobilization. Maximum velocity V_max was observed to decrease on immobilization. The free and entrapped esterase was used for selective hydrolysis of methyl 2‐acetoxybenzoate to methyl 2‐hydroxybenzoate in batch process as well as in a fixed bed reactor. The hydrolysis was observed to be 99% within 2 h for free as well as immobilized enzyme in batch process. The rate of hydrolysis was found to depend on pH. The turn over number of selective hydrolysis in batch and fixed bed reactor was 3.08 × 10⁶ and 1.19 × 10⁷, respectively. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Investigation of zinc(II) adsorption on Cladophora crispata in a two‐staged reactor

In this study, the adsorption of zinc(II) ions on Cladophora crispata, a green alga, was studied with respect to initial pH, temperature, initial metal ion and biomass concentration in order to determine the optimum adsorption conditions. Optimum initial pH values for zinc(II) ions were found to be 5.0 at optimum temperature, 25 °C. The initial adsorption rates increased with increasing initial zinc(II) ion concentration up to 100 mgdm⁻³. The Freundlich and Langmuir adsorption isotherms were developed at various initial pH and temperature values. Then, the adsorption of zinc(II) ions to C crispata was investigated in a two‐staged mixed batch reactor. The residual metal ion concentrations (C_eq) at equilibrium at each stage for a given quantity of dried algae (X_o)/volume of solution containing heavy metal ion (V_o) ratio were calculated by using Freundlich and Langmuir isotherm constants. It was observed that the experimental biosorption equilibrium data for zinc(II) ions are in good agreement with those calculated using both Freundlich and Langmuir models. The adsorbed zinc(II) ion concentration increased with increasing X_o/V_o ratios while the adsorbed metal quantities per unit mass of dried algae decreased. © 2000 Society of Chemical Industry     

Influence of ash agglomerating fluidized bed reactor scale‐up on coal gasification characteristics

To study the influence of fluidized‐bed reactor scale‐up on coal gasification characteristics, a model of the ash agglomerating fluidized‐bed reactor has been developed using an equivalent reactor network method. With the reactor network model, the scale‐up effects of a gasifier were studied in terms of the characteristics of the chemical reactions in the jet zone, the annulus dense‐phase zone and the freeboard zone. Results showed that the changes occurred in the inequality proportion of the volume of the jet zone during the reactor scale‐up. Taking into consideration the utilization of a portion of the backflow gas, the expansion of the jet zone volume and the coal particle residence time, the temperature of the jet zone was increased from 1592 to 1662 K. Also, both the annulus dense‐phase zone temperature and the freeboard zone temperature decreased, causing subsequent decrease in the carbon conversion efficiency. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1821–1829, 2014     

Effective biosynthesis of poly(3‐hydoxy‐ butyrate‐co‐4‐hydroxybutyrate) with high 4‐hydroxybutyrate fractions by Wautersia eutropha in the presence of α‐amino acids

BACKGROUND: Biopolymers produced by microbes are in demand as their biodegradable and biocompatible properties make them suitable for disposable products and for potential use as biomaterials for medical applications. The effective microbial production of copolyesters of 3‐hydroxybutyrate (3HB) and 4‐hydroxybutyrate(4HB) with high molar fractions of 4HB unit by a wild‐type Wautersia eutropha H16 was investigated in culture media containing 4‐hydroxybutyric acid (4HBA) and different carbon substrates in the presence of various α‐amino acids. RESULTS: The addition of carbon sources such as glucose, fructose and acetic acid to the culture medium containing 4HBA in the presence of α‐amino acids resulted in the production of random poly(3HB‐co‐4HB) with compositions of up to 77 mol% 4HB unit, but the yields of copolyesters with 60–77 mol% 4HB units were less than 15 wt% of dried cell weights. In contrast, when carbon sources such as propionic acid and butyric acid were used as the co‐substrates of 4HBA in the presence of α‐amino acids, poly(3HB‐co‐4HB) copolyesters with compositions of 72–86 mol% 4HB were produced at maximally 47.2 wt% of dried cell weight (11.3 g L^?1) and the molar conversion yield of 4HBA to 4HB fraction in copolyesters was as high as 31.4 mol%. Further, poly(3HB‐co‐4HB) copolyesters with compositions of 93–96 mol% 4HB were isolated at up to 35.2 wt% of dried cell weights by fractionation of the above copolymers with chloroform/n‐hexane. CONCLUSION: The productivity of copolyesters with over 80 mol% 4HB fractions was as high as 0.146 g L^?1 h^?1 (3.51 g L^?1 for 24 h) by flask batch cultivation. Copyright © 2007 Society of Chemical Industry     

Kinetics of homogeneous 5‐hydroxymethylfurfural oxidation to 2,5‐furandicarboxylic acid with Co/Mn/Br catalyst

2,5‐furandicarboxylic acid (FDCA) is a potential non‐phthalate based bio‐renewable substitute for terephthalic acid‐based plastics. Herein, we present an investigation of the oxidation rate of 5‐hydroxymethylfurfural (HMF) to FDCA in acetic acid medium using Co/Mn/Br catalyst. Transient concentration profiles of the reactant (HMF), intermediates [2,5‐diformylfuran (DFF), 5‐formyl‐2‐furancarboxylic acid (FFCA)], and the desired product (FDCA) were obtained for this relatively fast reaction in a stirred semi‐batch reactor using rapid in‐line sampling. Comparison of the effective rate constants for the series oxidation steps with predicted gas–liquid mass transfer coefficients reveals that except for the FFCA → FDCA step, the first two oxidation steps are subject to gas–liquid mass transfer limitations even at high stirrer speeds. Novel reactor configurations, such as a reactor in which the reaction mixture is dispersed as fine droplets into a gas phase containing oxygen, are required to overcome oxygen starvation in the liquid phase and further intensify FDCA production. © 2016 American Institute of Chemical Engineers AIChE J, 63: 162–171, 2017     

Effect of liquid volume in the gas‐separator on the hydrodynamics of airlift reactors

Gas hold‐up and liquid circulation velocity measurements were made using a 167 dm³ external loop airlift reactor. The gas‐separator was of the open channel configuration. The reactor height was 2.5 m with riser and downcomer diameters of 0.19 m and 0.14 m respectively. The systems investigated were Newtonian air–water and air–glycerol with the superficial air velocity varying between 0.02 and 0.12 m s⁻¹. The ratio of the liquid volume in the gas‐separator to the liquid volume in the reactor (volume‐ratio) was varied from 0.0% to 37%, to find its minimum critical value for optimum operation of the airlift reactor. For the air–water system, discernible effects of the volume‐ratio on riser and, downcomer gas hold‐ups and liquid circulation velocity were observed at volume ratios ≤7%. Beyond this value, the volume‐ratio had no effect. For a viscous and foaming air–glycerol system the critical volume‐ratio was increased to 19%. New and simple correlations for predicting gas hold‐up in the riser, gas hold‐up in the downcomer, and liquid circulation velocity were developed with reasonable accuracy. © 1999 Society of Chemical Industry     

Membrane reactor immobilized with palladium‐loaded polymer nanogel for continuous‐flow Suzuki coupling reaction

A catalytic membrane reactor, which was immobilized with palladium‐loaded nanogel particles (NPs), was developed for continuous‐flow Suzuki coupling reaction. Palladium‐loaded membranes were prepared by immobilization of NPs, adsorption of palladium ions, and reduction into palladium(0). The presence of palladium in the membrane was confirmed by the scanning electron microscopy; palladium aggregation was not observed. The catalytic activity of the membrane reactor in continuous‐flow Suzuki coupling reaction was approximately double that of a comparable reactor in which palladium ions were directly adsorbed onto an aminated membrane. This was attributed to the formation of small palladium particles. The reusability in the continuous‐flow system was higher than that in a batch system, and the palladium‐loaded membrane reactor had high long‐term stability. © 2014 American Institute of Chemical Engineers AIChE J, 61: 582–589, 2015     

High‐throughput microporous tube‐in‐tube microreactor as novel gas–liquid contactor: Mass transfer study

High‐throughput microporous tube‐in‐tube microchannel reactor (MTMCR) was first designed and developed as a novel gas–liquid contactor. Experimentally measured k_Lα in MTMCR is at least one or two orders of magnitude higher than those in the conventional gas–liquid contactors. A high throughput of 500 L/h for gas and 43.31 L/h for liquid is over 60 times higher than that of T‐type microchannel. An increase of the gas or liquid flow rate, as well as a reduction of the micropore size and annular channel width of MTMCR, could greatly intensify the gas–liquid mass transfer. The interfacial area, α, in MTMCR was measured to be as high as 2.2 × 10⁵ m²/m³, which is much higher than those of microchannels (3400–9000 m²/m³) and traditional contactors (50–2050 m²/m³). The artificial neural network model was proposed for predicting α, revealing only an average absolute relative error of <5%. © 2010 American Institute of Chemical Engineers AIChE J, 2011     

Measurement of mass transfer coefficient in an airlift reactor with internal loop using coalescent and non‐coalescent liquid media

In this work the sulfite oxidation (SOM), dynamic pressure‐step (DPM) and gassing‐out (GOM) methods were compared for volumetric mass transfer coefficient measurement in an airlift reactor with internal loop. As a liquid phase both, non‐coalescent and coalescent media were used. Among the methods discussed here, the mass transfer coefficient (k_La) values obtained by the DPM appear as the most reliable as they were found to be independent of oxygen concentration in the inlet gas, which confirmed the physical correctness of this method. The difference between data measured using air and oxygen was not higher than 10%, which was comparable to the scatter of experimental data. It has been found that the sulfite oxidation method yielded k_La values only a little higher than those obtained by the DPM and the difference did not exceed 10%. Up to an inlet gas velocity (U_GC) of ?0.03 m s^?1 the GOM using oxygen as a gas medium gave k_La values in fact identical with those obtained by the DPM. At higher flows of the inlet gas, the GOM yielded k_La values as much as 15% lower. The enhancement in oxygen mass transfer rate determined in non‐coalescent media was estimated to be up to +15%, when compared with a coalescent batch. The experimental dependence of k_La vs the overall gas hold‐up was described by an empirical correlation. 1 Copyright © 2004 Society of Chemical Industry     

New development in flow‐through pressure‐swing frequency response method for mass‐transfer study: Ethane in ZIF‐8

A new pressure‐swing frequency response (PSFR) method has been developed to study mass transfer in adsorption systems as a function of temperature and pressure, from ?70 to 180°C, and up to 7 bar. New in‐phase and out‐of‐phase functions have been derived for the PSFR in a general way to allow information extracted from it independent of whether the system is operated in a batch volume swing or a flow‐through pressure swing mode. A new mathematical model that considers distribution of diffusion rates has been introduced to account for diffusive transport in heterogeneous samples. Numerical simulation results have shown that a single rate diffusion model works well when heterogeneity can be described by a normal distribution, but not for asymmetrically bimodal distributions. As a test reference system, the transport of ethane in ZIF‐8 was investigated at different pressures and temperatures using the new PSFR method. The mass transfer was found to be dominated by micropore diffusion. Diffusivity was found to be weakly dependent on pressure or loading, but quite strongly dependent on temperature. The results agree very well with our independent batch volume frequency response technique experiments. © 2016 American Institute of Chemical Engineers AIChE J, 63: 1077–1090, 2017     

Multistage rotor‐stator spinning disc reactor

The scale up of a rotor‐stator spinning disc reactor by stacking single stage rotor‐stator units in series is demonstrated. The gas‐liquid mass transfer per stage is equal to the mass transfer in a single stage spinning disc reactor. The pressure drop per stage increases with increasing rotational disc speed and liquid flow rate. The pressure drop is more than a factor 2 higher for gas‐liquid flow than for liquid flow only, and is up to 0.64 bar at 459 rad s^?1. The high mass and heat transfer coefficients in the (multistage) rotor‐stator spinning disc reactor make it especially suitable for reactions with dangerous reactants, highly exothermic reactions and reactions where selectivity issues can be solved by high mass transfer rates. Additionally, the multistage rotor‐stator spinning disc reactor mimics plug flow behavior, which is beneficial for most processes. © 2011 American Institute of Chemical Engineers AIChE J, 2012     

Dehydrogenation of 11α‐hydroxy‐16α, 17‐epoxyprogesterone by encapsulated Arthrobacter simplex cells in an aqueous/organic solvent two‐liquid‐phase system

BACKGROUND: Arthrobacter simplex cells immobilised in sodium cellulose sulfate/poly‐dimethyl‐diallyl‐ammonium chloride microcapsules were used for the microbial dehydrogenation of 11α‐hydroxy‐16α,17‐epoxyprogesterone to 11α‐hydroxy‐16α,17α‐epoxypregn‐1,4‐diene‐3,20‐dione in an aqueous/organic solvent two‐liquid‐phase system, which is a key reaction in the production of glucocorticoid pharmaceuticals. The aim of the study was to establish a suitable aqueous/organic solvent two‐liquid‐phase system for performing semi‐continuous production in an airlift loop reactor by encapsulated A. simplex cells with the addition of suitable surfactants to achieve a higher yield of the product. RESULTS: n‐Hexane was selected as the most suitable organic solvent. In optimised Tween‐80 emulsion feed mode the conversion in the airlift loop reactor was as high as 97.54% when the time of reaction was 2 h, and the reaction time was greatly shortened. In semi‐continuous production the cultivation with immobilised cells was carried out for five batches in total. The conversion in each batch was above 95% and the enzymatic activity still remained quite high after five batches of biotransformation. CONCLUSION: The results showed that performing the conversion by this method shortened the reaction time and increased the productivity, thus demonstrating the great potential of the method for the dehydrogenation of 11α‐hydroxy‐16α,17‐epoxyprogesterone. Copyright © 2008 Society of Chemical Industry     

Dynamic modeling and simulations of the behavior of a fixed‐bed reactor‐exchanger used for CO2 methanation

A multidimensional heterogeneous and dynamic model of a fixed‐bed heat exchanger reactor used for CO₂ methanation has been developed in this work that is based on mass, energy and momentum balances in the gas phase and mass and energy balances for the catalyst phase. The dynamic behavior of this reactor is simulated for transient variations in inlet gas temperature, cooling temperature, gas inlet flow rate, and outlet pressure. Simulation results showed that wrong‐way behaviors can occur for any abrupt temperature changes. Conversely, temperature ramp changes enable to attenuate and even fade the wrong‐way behavior. Traveling hot spots appear only when the change of an operating condition shifts the reactor from an ignited steady state to a non‐ignited one. Inlet gas flow rate variations reveal overshoots and undershoots of the reactor maximum temperature. © 2017 American Institute of Chemical Engineers AIChE J, 64: 468–480, 2018     

Changes to bacterial community make‐up in a two‐phase anaerobic digestion system

Changes to microbial populations in a two‐phase anaerobic digestion system were studied over 34 weeks. Numbers of autofluorescent methanogenic and non‐methanogenic bacteria decreased significantly during start‐up, but did not change markedly either in the acid reactor or the upflow anaerobic filter for the remainder of the study. Although the proportion of autofluorescent methanogens increased in the acid reactor, the numbers of viable methanogens decreased 590‐fold. The numbers of viable methanogens increased 10‐fold in the port, decreased 10‐fold in the effluent and there was almost no change in the drain of the upflow anaerobic filter. The data indicated that bacterial attachment in the upflow anaerobic filter gave a 90% COD removal and a methane yield of 0.33 m³ CH₄ kg⁻¹ COD removed at an organic loading rate of 7 kg COD m⁻³day⁻¹. Epifluorescence microscopy of the seed sludge revealed a diverse methanogenic population of equally dominant groups of medium rods and filaments with Methanococcus, short rods, long rods and Methanosarcina also present. The medium rod‐shaped species remained the most dominant group in the acid reactor. As the volatile fatty acid concentration increased in the acid reactor the number of Methanosarcina and filament species decreased, becoming the least dominant groups. At the end of the operation, Methanococcus species were the dominant group in the upflow anaerobic filter having been washed from the biofilm. © 2000 Society of Chemical Industry     

Performance analysis of an integrated tangential microfilter‐fermenter

A specially designed bioreactor including an axial microfilter for cell retention was evaluated for continuous‐flow operation with selected liquid media as controls and in aerobic cultivations of Saccharomyces yeasts. In the initial tests, performance characteristics such as filtration rates and cell accumulation were assessed as a function of filter rotational speed, operating pressure, cultivation time and microfilter type (i.e. membrane or porous metal). The bioreactor did not perform satisfactorily when viscous extracellular polymer was present in the liquid. In the continuous‐flow culture enabling cell retention, Saccharomyces cerevisiae yeast cell concentrations were enhanced by as much as 16‐fold over ordinary batch growth. Concomitant filtration rates were stable over operating times of up to 130 h and hence were independent of the cell concentration. The maximum steady‐state flux was enhanced at rotational speeds up to 400‐700 rpm ranging from 22 to 42 L m^?2 h^?1. Higher rotation rates offered no further improvements. The maximum stabilized flux was independent of operating pressure. Pressure increases caused momentary flux improvements, which rapidly declined and eventually restabilized. Copyright © 2006 Society of Chemical Industry