CO2-expanded Solvents Research Articles

Single-step concentration of whey proteins using the pressurized gas eXpanded (PGX) liquid technology: Effect on physicochemical properties and scale-up

Pressurized Gas eXpanded (PGX) Liquid Technology precipitates and dries biopolymers using CO2-expanded organic solvents, producing open-porous materials with micro- and nanostructures. This study investigated the concentration of whey proteins from sweet whey liquid using PGX Technology as a single-step process at different scales and mass flow rate ratios (θPGX) of PGX fluid (CO2+Ethanol) to sweet whey liquid. The PGX process efficiently removed >50% dwb lactose and lipids from the feedstock, forming a whey protein concentrate (PGX-W, ≥45% protein dwb) consisting mainly of β-lactoglobulin, α-lactalbumin, and bovine serum albumin. At low θPGX, PGX-W had high protein concentrations (50% dwb), with reduced solvent effects on protein secondary structure. At high θPGX, PGX-W contained 14% dwb lactose, higher than the <5% dwb obtained at lower flow rates and had finer morphologies (tens of nm) with increased specific surface area (13–29 m2/g). Resulting PGX-W powders were free-flowing with low bulk density (35–74 g/L) and high-water solubility (≥80%).

The influence of pressure on the acoustic cavitation in saturated CO2-expanded N, N-dimethylformamide

CO2-expanded organic solvent is a kind of important fluid medium and has broad applications in chemical industry, environmental protection and other fields. Ultrasonic cavitation in gas expanded liquids (GXLs) is conducive to enhancing mass transfer and producing many exciting phenomena. In this paper, the ultrasonic cavitations and streaming in the saturated CO2-expanded liquid N, N-dimethylformamide (DMF) at 4.2 MPa and 5.2 MPa are observed by a high-speed camera. The cavitation intensity and time trace of pressure pulses are recorded using a PZT hydrophone. The influences of gas–liquid equilibrium pressure and ultrasonic power on the cluster dynamics of transient and stable cavitation are examined. The excess molar enthalpies required for CO2 dissociation from DMF are calculated by Peng-Robinson equations of state and the change of surface free energy of CO2-expanded DMF is predicted. The results show that the excess enthalpy of the mixture is one of the key factors to control ultrasonic cavitation at high pressurized conditions, while the surface tension is the key factor for low pressure. As the increase of applied ultrasonic power, the formation and collapsing frequency of bubble clusters increases, and the amplitude and cyclic frequency of pressure pulse are enhanced. The transient cavitation intensity increases as it reaches a maximum value at a certain ultrasonic power and then decreases. The change trends of stable cavitation intensity under different pressures are basically same. It can be concluded from the evidence that ultrasonic cavitation in CO2-expanded DMF is affected by the combined effect of compression and substitution: compression depresses the nucleation and growth of bubbles, while the high solubility of CO2 in DMF is conducive to the generation of bubbles in cavitation.

Measurement of relative static permittivity and solvatochromic parameters of binary and ternary CO2-expanded green solvents

CO2-expanded liquids (CXLs) is a class of solvent systems giving relatively low viscosity in comparison to neat organic solvents. The challenge is to achieve a high overall polarity of the CXL, despite the presence of compressed liquid CO2. In this study, the relative static permittivity (εr) was measured for binary and ternary one-phase mixtures of CO2 + green solvent using an in-line microfluidic device. In addition, Kamlet-Taft solvatochromic parameters were experimentally determined, allowing the characterization of the polarizability, acidity, and basicity. Novel data is shown for binary and ternary systems of CO2 expanded ethanol and ethyl lactate, with or without glycerol or water added, at moderate conditions of pressure and temperature (8 MPa and 35 °C). One-phase CXLs systems of a wide relative permittivity range (7.7–75.3) at lowered viscosity were enabled, by mixing different green solvents with CO2.

Prediction of solvatochromic parameters of electronic transition energy for characterizing dipolarity/polarizability and hydrogen bonding donor interactions in binary solvent systems of liquid nonpolar-polar mixtures, CO2-expanded liquids and supercritical carbon dioxide with cosolvent

Solvatochromic parameter of electronic transition energy (ET) provides information on dipolarity/polarizability and hydrogen bonding donor interactions in the solvation shell. In this work, a predictive framework is proposed for estimating ET values of phenol blue indicator in three mixed-solvent systems as (i) liquid nonpolar-polar mixtures, (ii) CO2-expanded liquid solvent and (iii) supercritical carbon dioxide (scCO2)-polar cosolvent mixtures. The equations of the ET framework for binary mixtures of nonpolar solvent with polar hydrogen bond acceptor (HBA) solvent can be directly adopted from the previous framework for Kamlet-Taft dipolarity/polarizability (KT-π*) [Ind. Eng. Chem. Res. 2020, 59, 12319–12330] because of the linearity of the homomorphism line between ET and KT-π* for pure nonpolar solvents and pure polar HBA solvents. However, due to specific hydrogen bonding interactions of the phenol blue with polar hydrogen bond donor (HBD) solvents, the ET framework for binary mixtures of nonpolar solvent with polar HBD solvent was the modification by the addition of HBD contribution factor. The HBD contribution factor can be simply estimated by a deviation of an actual ET value of pure HBD solvents from the homomorphism line. To validate the framework, the ET values of seventeen liquid nonpolar-polar mixtures, (ii) three CO2-expanded solvent mixtures and (iii) five scCO2-polar cosolvent mixtures collected from the literature were used. The framework was found to give a reliable ET value with an overall deviation of 0.26% and was also applicable to ET values of Reichardt, Nile red and HxQMBu2 indicators with an overall deviation of 1.73%, 0.36% and 0.40%, respectively. Only four properties of pure components are required for predictions as: (i) gas-phase dipole moment of polar component, (ii) CO2 density, (iii) ET and KT-π* values and (iv) homomorphism relationship between ET and KT-π* values.

Effect of graphene sheet size on exfoliation process in CO2-expanded organic solvent: A molecular dynamics simulation

CO2-expanded organic solvents are considered to be the most promising candidates for the liquid-phase exfoliation (LPE) of graphene. Understanding the effect of the initial graphite size on LPE efficiency is important for the production of higher-quality few-layer graphene. The mechanisms involved in the exfoliation process were studied in three different sizes of expanded graphene flakes (with areas of 1.05, 3.78, and 17.92 nm2) in the CO2-expanded solvent by means of molecular dynamics simulations. The simulation results verified at a molecular level that the graphene sheets obtained from small-size expanded graphene have fewer layers than those obtained from large-size expanded graphene. Faster solvent intercalation during the exfoliation process was observed with smaller-sized expanded graphene. Furthermore, an intact solvent monolayer between the graphene sheets and a larger desorption energy barrier with a small expanded graphene size ultimately leads to the rapid formation of a stable and less defective super-burger-like conformation. This enables exfoliation with a considerable yield of mono- or few-layered graphene sheets. We believe that the results reported in this work provide the guidelines for obtaining a high yield of mono- or few-layered graphene by exfoliation with a large sheet area in the CO2-expanded solvent and provide theoretical clues for controlling the size of the graphene sheets produced by exfoliation.

Enhanced distribution kinetics in liquid-liquid extraction by CO2-expanded solvents

Liquid-liquid extraction (LLE) is a useful extraction technique for highly complex samples, however, it suffers from being slow due to mass transfer limitations. Carbon dioxide expanded liquids (CXL) is a good replacement of traditional organic solvents for extraction, and for the first time, the use of CXL in LLE was evaluated. An equipment consisting of a high-pressure view cell with on-line gas chromatography analysis was built and validated, and thereafter used to obtain novel phase equilibria data of the CO2/n-octanol/water system. The system was connected on-line to HPLC to study the potential of CO2-expanded liquid-liquid extraction (CXLLE) of pharmaceutical contaminants in water. In comparison with traditional LLE performed under similar experimental conditions, the addition of CO2 as a viscosity-lowering entrainer significantly increased the speed of mass transfer. Changes in compound log D (octanol-water distribution ratio) values brought by the CO2 expansion also proved the possibility of selectivity-tuning in CXLLE.

Controlling Solvation and Mass Transport Properties of Biobased Solvents through CO2 Expansion: A Physicochemical and Molecular Modeling Study

Gas-expanded liquids have been studied during past years; however, the physicochemical properties of some of these fluids still need to be characterized and understood. In particular, the study of properties concerning solvation and mass transport is key for industrial applications. This work presents the characterization of eight CO2-expanded biosourced solvents: organic carbonates (dimethyl, diethyl, ethylene, and propylene carbonates), anisole, veratrole, γ-valerolactone, and 2-methyltetrahydrofuran. Two approaches have been used: spectroscopic measurements and molecular modeling. Phase equilibrium was determined for each CO2/biosourced solvent system, and then the solvatochromic probe Nile Red was used to determine changes in dipolarity/polarizability (π* Kamlet–Taft parameter) by CO2 pressure. Molecular dynamics calculations were performed to determine the density and viscosity changes with CO2 pressure. It is shown in this study that the degree of modulation of dipolarity/polarizability parameter can go from that of pure solvent (around 0.4 for linear organic carbonates) to negative values, close to that of pure CO2 at the T and P used in this study. Concerning transport properties, such as density and viscosity, a great decrease in both these properties’ values was observed after swelling of the solvent by CO2, for instance, in linear organic carbonates where density can decrease to 50% the density of pure solvent; concerning viscosity a decrease of up to 90% was measured for these compounds. It was observed that the solubility of CO2 and then modulation of properties were higher in linear organic carbonates than in the cyclic ones. This study shows once more that CO2 has a great capacity to be used as a knob for triggering changes in the physicochemical properties of green biosourced solvents that can help to implement these solvents in industrial applications.

Predictive Framework for Estimating Dipolarity/Polarizability of Binary Nonpolar–Polar Mixtures with Relative Normalized Absorption Wavelength and Gas-Phase Dipole Moment

A predictive framework is proposed for estimating the dipolarity/polarizability (π*) values of binary mixtures via the relative normalized maximum absorption wavelength (ΔλmixN) of an indicator (N,N-dimethyl-4-nitroaniline) in the pure liquids and the pure component gas-phase dipole moments (μ). New spectroscopic measurements of 13 nonpolar (1)–polar (2) liquid mixtures are reported and local composition was used to correlate variations of ΔλmixN values with mole fraction, x2. The resulting multivariate linear relationship in x2 and μ allowed data correlation and was applied to prediction of π* of (i) ten additional nonpolar–polar mixtures at temperatures of (15 to 45) °C, (ii) nine polar–polar mixtures, (iii) six CO2-expanded solvent mixtures, and (iv) five molecular solvent–ionic liquid mixtures and was found to give an overall deviation of 8.9% in π*. The predictive framework was applied to the dipolarity/polarizability scales of Effenberger–Wurthner and Catalan for 16 polar–polar liquid mixtures and w...

Synergy of in-situ formation of carbonic acid and supercritical CO2-expanded liquids: Application to extraction of andrographolide from Andrographis paniculata

The environmental impact of excessive solvent usage in the pharmaceutical industry has generated research interests in the area of green and sustainable extraction processes. In this study, solvent minimization was done by exploiting the synergistic effect of pH lowering (via in-situ H2CO3 formation) and solvent’s volume expansion (via CO2-expanded solvent) in the extraction of andrographolide from Andrographis paniculata. Conventional solid-liquid extraction (CSLE) and CO2-expanded liquid extraction (CXLE) were conducted using different solvents at a pressure range of 0.1–10 MPa and 40 °C in a batch-type extraction vessel to verify both the independent and combined effect of pH and the solvent’s volume expansion coefficient (V/V0) in the extraction recovery. Also, fresh and spent biomass were analyzed using X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) in order to assess the physical impact of the extraction scheme. The highest andrographolide recovery of 65% was obtained using CXLE with ethanol and water at pH = 3.02 and V/V0 = 4.8, owing to the synergistic effects of the two variables. Furthermore, an increase in extraction recovery with decreasing pH and increasing V/V0 was observed. Moreover, a significant morphological difference between the fresh and spent samples was observed from the results of characterizations, indicating a disruption in the cell wall associated to the expansion of the solvent as it penetrated the plant matrix. The proposed novel extraction strategy allowed a high extraction recovery of andrographolide while complying with sustainable and green practices.

Modeling high pressure vapor–liquid equilibrium of ternary systems containing supercritical CO2 and mixed organic solvents using Peng–Robinson equation of state

High pressure vapor–liquid equilibrium (VLE) of CO2-expanded organic solvents was investigated using Peng–Robinson-LCVM-UNIFAC equation of state. Bubble pressure of several ternary mixtures was predicted using this model and correlations were developed based only on binary experimental data. A sensitivity study of the LCVM parameter numerical value was done by considering the coherence between the mathematical features of the mixing rule and the quality of the simulation. The results provided by PR-LCVM-UNIFAC were compared with those ones given by Peng–Robinson equation of state using the classical quadratic mixing rules (PR-CMR). Despite the use of two adjustable parameters for each binary system, PR-CMR is not able to provide good results when applied to ternary systems. The capability of PR-LCVM-UNIFAC model to predict liquid mixture density for ternary systems using parameters regressed only from bubble pressure experimental data was also investigated. Due to the lack of liquid density experimental data, it was possible to perform only a qualitative assessment of the density curves calculated by this equation of state.

Improvement of predictive Soave–Redlich–Kwong (PSRK) equation of state for representing volumetric properties of carbon dioxide-expanded organic solvents

In this study, the volume translation correction is applied to the predictive Soave–Redlich–Kwong (PSRK) equation of state (EOS) for improving the prediction accuracy of liquid densities of carbon dioxide (CO2)-expanded organic solvents. A total of 23 CO2-expanded organic solvents including hydrocarbons, ketones, and esters are considered in our calculation. By applying the original PSRK EOS, the prediction accuracy of liquid density is only qualitative and the average deviation is about 15%. When applying the translated volumes proposed by Péneloux and Rauzy (1982) and Lin et al. (2006), significant improvements in prediction accuracy are obtained and the average deviation is reduced to 4% and 6%, respectively. To further enhance the predictive accuracy, one attempt has been made in this study to consider the translated volume of CO2 and organic solvent separately. With Péneloux and Rauzy's translated volume for organic solvent, an alternative translated volume for CO2 is developed and adopted. With this approach, satisfactory predicted results are obtained especially at higher pressures and the average deviation can be further reduced to 3%. The volume-translated PSRK EOS discussed in this study provides a simple, empirical and totally predictive approach to accurate representation of liquid densities of CO2-expanded organic solvents.

On the optimal design of gas-expanded liquids based on process performance

Gas-expanded liquids (GXLs) are mixed solvents composed of an organic solvent and a compressible gas, usually carbon dioxide (CO2) due to its environmental and economic advantages. The best choice of GXL, as defined by the specific organic solvent and the CO2 composition, depends strongly on the process in which the solvent is to be used. Given the large range of possible choices, there is a need to predict the impact of GXL design on process performance from economic and environmental perspectives. In this work, we present a design methodology in which limited experimental data are used to build a predictive model which allows a wider design space to be assessed. The proposed methodology for the integrated design of CO2-expanded solvent and process is applied to the Diels–Alder reaction of anthracene and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). Three organic co-solvents are studied: acetonitrile, methanol and acetone. Given that the process cost is sensitive to the operating pressure and reactor volume, a trade-off between reaction rate constant and solubility is required in order to design an optimal process from a cost perspective. From a total cost perspective and in terms of energy consumption, it is found that designs with small amounts of CO2 or, in the case of acetone, without any CO2, offer the best performance. However, CO2 use is found to lead to a significant reduction in organic solvent inventory, up to 70 % in some cases. In this work the importance of taking multiple performance criteria, including process metrics, into account when designing GXLs is demonstrated.

Multifunctional Nanovesicle-Bioactive Conjugates Prepared by a One-Step Scalable Method Using CO2-Expanded Solvents

The integration of therapeutic biomolecules, such as proteins and peptides, in nanovesicles is a widely used strategy to improve their stability and efficacy. However, the translation of these promising nanotherapeutics to clinical tests is still challenged by the complexity involved in the preparation of functional nanovesicles and their reproducibility, scalability, and cost production. Here we introduce a simple one-step methodology based on the use of CO2-expanded solvents to prepare multifunctional nanovesicle-bioactive conjugates. We demonstrate high vesicle-to-vesicle homogeneity in terms of size and lamellarity, batch-to-batch consistency, and reproducibility upon scaling-up. Importantly, the procedure is readily amenable to the integration/encapsulation of multiple components into the nanovesicles in a single step and yields sufficient quantities for clinical research. The simplicity, reproducibility, and scalability render this one-step fabrication process ideal for the rapid and low-cost translation of nanomedicine candidates from the bench to the clinic.

Prediction of solubilities of solid solutes in carbon dioxide-expanded organic solvents using the predictive Soave–Redlich–Kwong (PSRK) equation of state

In this study, the solubilities of solid solutes in carbon dioxide (CO2)-expanded organic solvents are predicted using the predictive Soave–Redlich–Kwong (PSRK) equation of state (EOS). The liquid-phase compositions and volume expansion ratios of CO2-expanded organic solvents are predicted prior to the solubility predictions. With predicted liquid-phase compositions and volumetric properties, the solubilities of cholesterol in CO2-expanded acetone, naphthalene in CO2-expanded toluene, stearic acid in CO2 expanded ethyl acetate and tetradecanoic acid in CO2-expanded ethyl acetate are predicted according to their reference solubilities in pure organic solvents. In addition to satisfactory predictions of liquid-phase composition and volume expansion ratios, the PSRK EOS also provides qualitative prediction ability for solubilities of solid solutes in CO2-expanded organic solvent. This study demonstrated that the PSRK EOS was a simple model with predictive ability for solubility evaluation in preliminary process design and development for supercritical fluid technology using CO2-expanded organic solvents.

Prediction of volumetric properties of carbon dioxide-expanded organic solvents using the Predictive Soave–Redlich–Kwong (PSRK) equation of state

In this study, the Predictive Soave–Redlich–Kwong (PSRK) EOS is adopted for predicting the volumetric properties of carbon dioxide (CO2)-expanded organic solvents including the volume expansions, molar volume fractions and partial molar volumes of the solvent. The solvent systems considered in this study include hydrocarbons, alcohols, esters, ketones and other organic solvents. In addition to acceptable prediction of the volumetric properties, the PSRK EOS also provides the ability to predict solubilities of a solid solute in a CO2-expanded organic solvent. This study demonstrates that the PSRK EOS is a simple model with sufficient accuracy and predictive ability for evaluation of the volumetric properties and solubilities of solid solutes in CO2-expanded organic solvents. In addition, analysis of predicted results by molecular parameters and improvement of volumetric property calculations using a translated-volume are also discussed.

Crystallization of Microparticulate Pure Polymorphs of Active Pharmaceutical Ingredients Using CO2-Expanded Solvents

The feasibility of the Depressurization of an Expanded Liquid Organic Solution (DELOS) method to process different active pharmaceutical ingredients (APIs) as finely divided powders with narrow particle size distribution, high crystallinity degree, high polymorphic purity, and free from residual solvent has been demonstrated. Cholesterol, acetylsalicylic acid (aspirin), naproxen, acetaminophen, and ibuprofen were chosen as model drugs. It has been demonstrated that the supersaturation ratio attained during crystallization from CO2-expanded solvents can be modulated through appropriate variations of process parameters — CO2 content and concentration of the initial solution. In view of the potential application that compressed fluids-based technologies have in the pharmaceutical industry, a preliminary scalability study of the process in compliance with the constraints imposed by the Good Manufacturing Practices (GMP) specifications is presented herein.

Hydrogenation of polystyrene in CO 2-expanded liquids: The effect of catalyst composition on deactivation

The effect of catalyst composition on the hydrogenation of the aromatic rings of polystyrene dissolved in carbon dioxide-expanded decahydronaphthalene (CO 2-DHN) was studied using a slurry reactor at 150 °C. Catalyst deactivation occurred within 15 min of the addition of CO 2 to the reactor when 5% Pd/SiO 2 or 5% Pd/Al 2O 3 was used as the catalyst. The deactivation is believed to be a consequence of CO formation via the reverse water-gas shift reaction, as CO was observed at the end of each hydrogenation reaction. In an effort to convert CO to CH 4 before the poisoning of Pd sites occurred, a methanation catalyst such as 5% Ru/Al 2O 3 or 65% Ni/SiO 2–Al 2O 3 was physically mixed with 5% Pd/SiO 2 or 5% Pd/Al 2O 3 and used to hydrogenate PS. Carbon monoxide concentrations decreased, but no significant improvements in aromatic ring hydrogenation were observed. When a catalyst containing both a hydrogenation and methanation function in a single catalyst particle (1.6% Ru/4.2% Pd/SiO 2) was used, the degrees of hydrogenation in CO 2-DHN matched those obtained when neat DHN was the solvent. Furthermore, no CO was detected when the reaction was catalyzed by the bimetallic catalyst. These results suggest that the methanation function must be proximate to the hydrogenation (reverse water-gas shift) function in order for aromatic ring hydrogenation to proceed as rapidly in a CO 2-expanded solvent as in the unexpanded solvent.

Kinetically Driven Crystallization of a Pure Polymorphic Phase of Stearic Acid from CO2-Expanded Solutions

The polymorphic nature of microcrystalline solids of stearic acid prepared by the Depressurization of an Expanded Liquid Organic Solution (DELOS) and Gas Antisolvent (GAS) crystallization techniques, both based on CO2-expanded solvents as solvent media, has been studied. The crystalline solids produced by those techniques from “CO2-expanded ethyl acetate” with different contents of CO2 have been analyzed in detail and compared with those prepared by conventional cooling crystallizations, either from pure liquid ethyl acetate solutions or from the melt. It is shown that the monoclinic E form of stearic acid is more favored when using kinetically controlled crystallizations, like the DELOS one, in which a high supersaturation level is rapidly achieved. Remarkably, the DELOS process provides for the first time a pure polymorphic monoclinic E form, without the presence of traces from other polymorphs that always are present when using other kinetically driven methods, such as the conventional fast cooling. On the contrary, the C polymorph is preferentially obtained by the thermodynamically controlled GAS technique in which the increase of the solution supersaturation is slower and/or low supersaturation levels are attained.

Liquid phase oxidation of p-xylene to terephthalic acid at medium-high temperatures: multiple benefits of CO2-expanded liquids

The Co/Mn/Br catalyzed oxidation of p-xylene to terephthalic acid (TPA) is demonstrated in CO2-expanded solvents at temperatures lower than those of the traditional Mid-Century (MC) process. As compared with the traditional air (N2/O2) oxidation system, the reaction with CO2/O2 mixture at 160 °C and using an additional inert gas (N2 or CO2) pressure of 100 bar increases both the yield of TPA and the purity of solid TPA via a more efficient conversion of the intermediates, 4-carboxybenzaldehyde and p-toluic acid. At the same time, the amount of yellow colored by-products in the solid TPA product is also lessened, as determined by spectroscopic analysis. Equally important, the decomposition or burning of the solvent, acetic acid, monitored in terms of the yield of the gaseous products, CO and CO2, is reduced by ca. 20% based on labeled CO2 experiments. These findings broaden the versatility of this new class of reaction media in homogeneous catalytic oxidations by maximizing the utilization of feedstock carbon for desired products while simultaneously reducing carbon emissions.

Pd-catalyzed C–H bond activation of benzene in the CO2-expanded solvent

Abstract In the CO 2 -expanded trifluoroacetic acid, the catalytic activation and functionalization of the C–H bond in benzene to synthesize biphenyl and phenol was investigated by using palladium catalyst and dioxygen. It was found that an extra 40% improvement of catalytic efficiency could be achieved by charging 30 atm of CO 2 . Meanwhile, the presence of the small amount of water would apparently promote the catalytic oxidation. The solvent and substrate isotope effect were also investigated to provide the mechanistic information.