Deciphering alcohol dehydrogenase catalysis in glycerol-based deep eutectic solvents through experimental and computational insights

Limited research has been conducted on the exploration of chemical reactions in deep eutectic solvents (DES) using density functional theory (DFT). In this study, a comprehensive analysis of the mechanism of a cross-aldol reaction in DES through DFT calculations at the M06-2X/6-311+G(d,p)//M06-2X/6-31G(d,p) level was carried out for the first time. The aldol reaction mechanism comprised two primary stages, namely, enolization and addition, with the former identified as the rate-determining step. In this paper, an explicit explanation of the functions of catalysts, solvents and water, with results that aligned well with experimental findings, has been provided. The theoretical analysis indicated that the -COOH group of the catalyst could enhance the stability of transition states by forming a polygonal reaction center, compared to the -OH group or water, thus favoring the reaction process. The increased susceptibility of the catalyst was attributed to the enhanced ionization of the proton in the -COOH group. Findings from the IGM analysis indicated that the stability of the system was enhanced through the formation of hydrogen bonds (HBs), resulting from the interaction between DES and the substrates. It was also noted that the number of HBs did not directly correlate with the system's stability. Notably, the most stable configuration involved the disruption of the solvent structure when DES interacted with the reactants. The introduction of water compensated for the solvent's deficiency by forming new O-H⋯Cl bonds, leading to the formation of additional hydrogen bonds and thereby enhancing the system's stability. Furthermore, the impact of substituent groups was evident through the formation of an O-H⋯ONO bond, which was generated by the interaction between ethylene glycol and the -NO2 group. The substituent effect played a crucial role in the reaction and elucidated the necessity of solvent disruption. The computational analysis revealed an increase in the energy barrier when the -NO2 group was substituted with -H, -Cl and -Br. In addition, the study offered a comprehensive understanding of the influence of DES and the role of the additional third component in the reaction.

Deep eutectic solvents-based adsorbents in environmental analysis

Alkaline anion exchange membrane fuel cells (AEMFC) have gained interest due to their potential as electrochemically energy conversion devices and a competitive alternative to the more extensively studied commercialized proton exchange membrane fuel cells (PEMFCs). Nevertheless, their development impedes the limited ion conductivity, chemical and mechanical stability in an alkaline medium of anion exchange membranes (AEMs). The ionic conductivity of AEM is lower than that of a proton exchange membrane (PEM) because the mobility of hydroxide ions is inherently lower than that of protons [1]. Deep eutectic solvents (DESs) as green solvents can overcome this issue.The main idea of this research is to fabricate a deep eutectic solvent-supported polymer-based AEM for alkaline fuel cell application by electrospinning technique. Poly(vinyl alcohol) (PVA) is one of the potential polymers for the development of AEM due to its water solubility, biodegradability, high fiber forming ability, non-toxicity, and high chemical and thermal stability [2]. This work aims to achieve high ionic conductivity, chemical and mechanical stability by two methods: swelling polyvinyl alcohol (PVA)-based nanofibers into DES and encapsulating DES inside the PVA-nanofibers together with optimizing fabrication methods.In this study, polymer electrolytes as potential AEMs were first prepared using the swelling method, where electrospun PVA nanofibers were fabricated via the electrospinning technique, followed by swelling in a series of DESs. To prepare the DES solutions, choline chloride (ChCl) and ethylene glycol (EG) were mixed at different molar ratios. The cross-linking of pure PVA fibers with glutaraldehyde in ethanol (see Figure 1B) and DES uptake and the presence of voids as channels for ion conduction (see Figure 1C) were successfully confirmed with a scanning electron microscopy (SEM, Crossbeam500, Zeiss). The ionic conductivity of swelled in DES PVA-based membranes were evaluated by electrochemical impedance spectroscopy (Metrohm Autolab) at room temperature and was equal to 0.336 mS/cm. The presence of DES in the membrane was confirmed with FTIR spectroscopy (FT-IR spectrometer, Nicolet iS10): a slight C-N+ peak at 953 cm-1 from ChCl has proven interaction between PVA and DES with FTIR spectroscopy, meaning that DES is present in the fiber. In addition, the nitrogen content in the obtained membrane was determined by CHNS elemental analysis (Elemental Vario micro cube) as 3.32 wt.%.In order to overcome high weight loss in the swelling method, the encapsulation method was suggested as an alternative option, which is based on the encapsulation of DES into the PVA solution by mixing them, varying the amount of DES added, and then preparing fibers using electrospinning. Observing the morphology of DES-encapsulated PVA nanofibers with a scanning electron microscope (SEM, Crossbeam500, Zeiss), as the content of DES in the solution increased, there was an observed rise in the average diameter of the nanofibers (see Figure 1D). Encapsulation of DES in PVA nanofibers was primarily confirmed by transmission electron microscope (TEM, JEM -1400 Plus, JEOL): PVA appears lighter due to its decreased density, proving that DES is present inside the fibers. Also, the same tendency was observed with the results of FTIR spectroscopy (FT-IR spectrometer, Nicolet iS10) as for the swelling method, meaning that DES is present in the fiber. According to CHNS elemental analysis (Elemental Vario micro cube), nitrogen content was lower than for the swelling method - 0.70 wt.%. The ionic conductivity was evaluated as 0.364 mS/cm by electrochemical impedance spectroscopy (Metrohm Autolab) at room temperature, which was almost the same as for the swelling method.As a result, very flexible and visually transparent electrospun DES-supported PVA-based AEMs were obtained via the swelling and encapsulation method.

Recent advances in extraction and food applications of natural bioactives using deep eutectic solvents.

Redox biocatalysis plays an increasingly important role in modern organic synthesis. The recent integration of novel media such as deep eutectic solvents (DESs) has significantly impacted this field of chemical biology. Alcohol dehydrogenases (ADHs) are important biocatalysts where their unique specificity is used for enantioselective synthesis.This review explores aspects of redox biocatalysis in the presence of DES both with whole cells and with isolated ADHs. In both cases, the presence of DES has a significant influence on the outcome of reactions albeit via different mechanisms. For whole cells, DES was shown to be a useful tool to direct product formation or configuration - a process of solvent engineering. Whole cells can tolerate DES as media components for the solubilization of hydrophobic substrates. In some cases, DES in the growth medium altered the enantioselectivity of whole cell transformations by solvent control. For isolated enzymes, on the other hand, the presence of DES promotes substrate solubility as well as enhancing enzyme stability and activity. DES can be employed as a smart solvent or smart cosubstrate particularly for cofactor regeneration purposes.From the literatures examined, it is suggested that DES based on choline chloride (ChCl) such as ChCl:Glycerol (Gly), ChCl:Glucose (Glu), and ChCl:1,4-butanediol (1,4-BD) are useful starting points for ADH-based redox biocatalysis. However, each specific reaction will require optimisation due to the influence of several factors on biocatalysis in DES. These include solvent composition, enzyme source, temperature, pH and ionic strength as well as the substrates and products under investigation.

This study explores the mechanisms of CO2 absorptionin two amino acid-containing deep eutectic solvents (DESs) throughmolecular dynamics (MD) simulations and density functional theory(DFT) calculations. The MD simulations, which focus mainly on physicalabsorption, reveal that alanine-based DES (Ala DES) exhibits higherCO2 solubility than l-arginine-based DES (l-arg DES), attributed to stronger physical absorption. Furthermore,the hydrogen bond donor paired with the amino acids is identifiedas a critical factor for enhancing physical absorption efficiency.DFT calculations, which account for chemical absorption, investigatetwo reaction pathways: single-molecule reactions involving intramolecularproton transfer and two-molecule reactions involving intermolecularproton exchange. While Ala DES does not exhibit spontaneous chemicalabsorption, l-arg DES demonstrates such reactions, leadingto the formation of carbamic acid or carbamate (ΔG < 0), indicative of CO2 capture through chemical interactions.Consequently, Ala DES primarily relies on physical absorption, whereas l-arg DES utilizes multiple reactive sites for chemical absorption.These results are consistent with experimental findings, which showthat l-arg DES achieves higher CO2 solubilityunder atmospheric conditions. Overall, our study highlights the interplaybetween DES components and reactivity in enhancing CO2 captureefficiency.

Ionic liquids (ILs) which synthesized from bio-renewable materials have recently attracted much attention for their applications in biocatalysis. Ethyl (R)-3-hydroxybutyrate ((R)-EHB) as a versatile chiral intermediate is of great interest in pharmaceutical synthesis. This study focuses on evaluating the performances of choline chloride (ChCl)-based and tetramethylammonium (TMA)-based neoteric ILs in the efficient synthesis of (R)-EHB via the bioreduction of ethyl acetoacetate (EAA) at high substrate loading by recombinant Escherichia coli cells. It was found that choline chloride/glutathione (ChCl/GSH, molar ratio 1:1) and tetramethylammonium/cysteine ([TMA][Cys], molar ratio 1:1) as eco-friendly ILs not only enhanced the solubility of water-insoluble EAA in the aqueous buffer system, but also appropriately improved the membrane permeability of recombinant E. coli cells, thus boosting catalytic reduction efficiency of EAA to (R)-EHB. In the developed ChCl/GSH- or [TMA][Cys]-buffer systems, the space-time yields of (R)-EHB achieved 754.9g/L/d and 726.3g/L/d, respectively, which are much higher than neat aqueous buffer system (537.2g/L/d space-time yield). Meanwhile, positive results have also been demonstrated in the bioreduction of other prochiral ketones in the established IL-buffer systems. This work exhibits an efficient bioprocess for (R)-EHB synthesis under 325g/L (2.5M) substrate loading, and provides promising ChCl/GSH- and [TMA][Cys]-buffer systems employed in the biocatalysis for hydrophobic substrate.

The increased awareness of environmental and economic issues has led many researchers to seek green and low-cost solvent for the conversion of lingocellulosic biomass to bioenergy. In this context, deep eutectic solvents, a new class of ionic liquids, have been regarded as greener substitute to conventional solvents for pretreatment of biomass. This paper is concerned with the stability and synergicity action of deep eutectic solvents for the digestion of biomass. The stability was studied by incubating commercial cellulases to different concentration of ethylene glycol–choline chloride-based deep eutectic solvent. The synergistic tests were studied by performing enzymatic saccharification after pretreatment of rice husk with deep eutectic solvent at various temperatures. The stability test showed that, the commercial cellulase activity retained more than 90% of relative activity after 1 hour of incubation in 10(%,v/v) deep eutectic solvent at 30°C. The prepared deep eutectic solvent in combination with commercial cellulases study showed that the higher pretreatment temperature improved the production of simple sugar from rice husk.

The pretreatment or disruption of a cellulose I \(\beta \) crystallite by four deep eutectic solvents (DES): choline-chloride ethylene glycol, choline-chloride oxalic acid, choline-chloride urea, and choline-chloride levulinic acid, was described from the atomistic interactions observed in molecular dynamics and ab-initio (NCI-AIM) studies. The cellulose I \(\beta \) disruption was studied considering plausible correlations between the Kamlet-Taft (α and β) solvent parameters, and a series of thermodynamic, structural, and energetic properties. It was found that the Kamlet-Taft parameters correlated with the thermodynamic properties of the DES, as well as their variations after the addition of the cellulose crystallite. Structural analysis revealed that the weaker the interactions within the molecules of the solvent, the stronger the interactions between the hydroxyl group from cellulose with the chloride anion and with the hydrogen bond donor. Further analysis indicated that the \(R-CO-R\) moieties in the hydrogen bond donor within the solvent, displayed best interplaying with the cellulose. The hydrogen bond occupancies within the cellulose crystallite, evidenced that the main \(O6-H6\cdots O2/O3\) and \(O2-H2\cdots O6\) interchain hydrogen bonds in the glucan located at the edge of the solute, were replaced by weak \(O6-H6\cdots O4\) hydrogen bonds in all solvents. This effect was related to the \({O/Cl}_{DES}\cdots H-donor\) and \({O}_{DES}-{H}_{DES}\cdots acceptor\) HBs between cellulose and DES molecules, and it was confirmed by the non-covalent interactions obtained through DFT calculations. The energetic interactions and the atomistic degree of disruption of the cellulose crystallite, were not completely described by the Kamlet-Taft β or α parameters when considered separately. Surprisingly, by using the net basicity (\(\beta -\alpha \)) definition such correlations were improved, suggesting that both parameters must be considered together to develop new, green, and sustainable solvents for cellulose pretreatment process.Graphic abstract

Green solvents-based rutin extraction from Sophora japonica L.

Deep eutectic solvents (DES), a class of novel green solvents, offer a promising alternative for the extraction of bioactive compounds from traditional Chinese medicinal herbs, addressing both environmental and efficiency limitations associated with conventional organic solvents. Their advantages include straightforward synthesis, low toxicity, biodegradability, and tunable physicochemical properties. This article systematically summarizes recent advances in the application of DES for extracting various active ingredients of traditional Chinese medicine, including flavonoids, saponins, alkaloids, polysaccharides, polyphenols, and volatile oils. It focuses on analyzing the structural characteristics of these compound classes and the underlying principles guiding DES selection, categorizes DES systems suitable for each class of active ingredient, and outlines the corresponding optimized process conditions. Building upon this foundation, the extraction mechanisms—particularly hydrogen bonding interactions and polarity matching between DES and target components—were investigated, and the influencing factors and underlying patterns governing DES extraction efficiency were systematically summarized. In response to current research challenges—including high viscosity, difficult separation and recovery, and the absence of a targeted design theory—future research directions were proposed to support the continued advancement of green extraction processes for traditional Chinese medicine.

Widely known as “green solvents,” ionic liquids (ILs) and deep eutectic solvents (DESs) have been used as substitutes for traditional organic solvents in separation science. To achieve better separations using ILs and DESs, this work aimed to predict the infinite dilution activity coefficients (IDACs) of molecular solutes in these solvents with the state-of-the-art factorization-machine-based neural network (DeepFM). DeepFM combines the benefits of factorization machines and deep neural networks to learn both low-order and high-order interactions among features. The IDAC prediction model was established with 52,372 experimental IDAC datapoints including 260 solvents (252 ILs and 8 DESs) and 112 molecular solutes collected at various temperatures from 288.15 to 428.15 K. Chemical information describing the ILs, DESs, and molecular solutes was included in the IDAC prediction model, including chemical functional groups, molecular weights, and Abraham solvation parameters. The IDAC prediction model showed an improved accuracy compared with alternative models; additionally, DESs were included in the IDAC prediction model for the first time. Here, the model will reduce the energy and resources needed to optimize the selection of ILs and DESs for specific separations, which will promote the development of these green solvents for sustainable chemical processes.

Deep eutectic solvents (DESs) are gaining recognition as environmentally friendly solvent alternatives for diverse chemical processes. Yet, designing DESs tailored to specific applications is a resource-intensive task, which requires an accurate estimation of their physicochemical properties. Among them, viscosity is crucial, as it often dictates a DES's suitability as a solvent. In this study, an artificial neural network (ANN) is introduced to accurately describe the viscosity of DESs and their mixtures with cosolvents. The ANN utilizes molecular parameters derived from σ-profiles, computed using the conductor-like screening model for the real solvent segment activity coefficient (COSMO-SAC). The data set comprises 1891 experimental viscosity measurements for 48 DESs based on choline chloride, encompassing 279 different compositions, along with 1618 data points of DES mixtures with cosolvents as water, methanol, isopropanol, and dimethyl sulfoxide, covering a wide range of viscosity measurements from 0.3862 to 4722 mPa s. The optimal ANN structure for describing the logarithmic viscosity of DESs is configured as 9-19-16-1, achieving an overall average absolute relative deviation of 1.6031%. More importantly, the ANN shows a remarkable extrapolation capacity, as it is capable of predicting the viscosity of systems including solvents (ethanol) and hydrogen bond donors (2,3-butanediol) not considered in the training. The ANN model also demonstrates an extensive applicability domain, covering 94.17% of the entire database. These achievements represent a significant step forward in developing robust, open source, and highly accurate models for DESs using molecular descriptors.

Deep eutectic solvents (DES) are an emerging type of green solvents that have been used in aqueous two-phase systems (ATPS). However, its application in ATPS can present some limitations, due to the nonstoichiometric partition between the two aqueous phases of the hydrogen-bond acceptor (HBA) and the hydrogen-bond donor (HBD) that compose the DES. In this context, pseudoternary DES-based ATPS, in which DES' components stoichiometry is maintained, appear as potential liquid–liquid systems to the extraction and separation of biomolecules. Here the pH influence on the phase equilibrium and DES' components partition on ATPS composed of DES, constituted by tetrabutylammonium chloride + ethanol/ n-propanol, and potassium citrate/citrate buffer was evaluated at 298 K and pH 9, 7, and 5. In addition the partition coefficients of gallic acid, caffeine, and L-tryptophan were also determined, allowing inferences to be made on the potential application of these systems. The results suggest that the change on the pH impacts the chemical speciation of the potassium citrate salt, and consequently its ability to form an ATPS, allowing the stoichiometric partition of DES' components and the formation of a pseudoternary system and the tuning of biomolecules partition behavior to be controled.

Redox and emission characteristics of Eu3+ in deep eutectic solvent: Unraveling the hidden potential of DES as luminescent media