Improved Production of 5-Hydroxymethylfurfural in Acidic Deep Eutectic Solvents Using Microwave-Assisted Reactions.

Hydroxymethylfurfural (5-HMF) is a key platform chemical, essential for the production of other chemicals, as well as fuels. Despite its importance, the production methods applied so far still lack in sustainability. In this work, acidic deep eutectic solvents (DES), acting both as solvent and catalyst, were studied for the conversion of fructose into 5-HMF using microwave-assisted reactions. These solvents were screened and optimized by varying the hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA). The bio-based solvent γ-valerolactone (GVL) was also applied as additive, leading to a boost in 5-HMF yield. Then, a response surface methodology was applied to further optimize operating conditions, such as reaction time, temperature and wt.% of added GVL. The highest 5-HMF yield attained, after optimization, was 82.4% at 130 °C, in 4 min of reaction time and with the addition of 10 wt.% of GVL. Moreover, a process for 5-HMF recovery and DES reuse was developed through the use of the bio-based solvent 2-methyltetrahydrofuran (2-Me-THF), allowing at least three cycles of 5-HMF production with minimal yield losses, while maintaining the purity of the isolated 5-HMF and the efficacy of the reaction media.

Enhanced Furfural Production in Deep Eutectic Solvents Comprising Alkali Metal Halides as Additives.

The addition of alkali metal halide salts to acidic deep eutectic solvents is here reported as an effective way of boosting xylan conversion into furfural. These salts promote an increase in xylose dehydration due to the cation and anion interactions with the solvent being a promising alternative to the use of harsh operational conditions. Several alkali metal halides were used as additives in the DES composed of cholinium chloride and malic acid ([Ch]Cl:Mal) in a molar ratio of 1:3, with 5 wt.% of water. These mixtures were then used as both solvent and catalyst to produce furfural directly from xylan through microwave-assisted reactions. Preliminary assays were carried out at 150 and 130 °C to gauge the effect of the different salts in furfural yields. A Response Surface Methodology was then applied to optimize the operational conditions. After an optimization of the different operating conditions, a maximum furfural yield of 89.46 ± 0.33% was achieved using 8.19% of lithium bromide in [Ch]Cl:Mal, 1:3; 5 wt.% water, at 157.3 °C and 1.74 min of reaction time. The used deep eutectic solvent and salt were recovered and reused three times, with 79.7% yield in the third cycle, and the furfural and solvent integrity confirmed.

Unveiling Modifications of Biomass Polysaccharides during Thermal Treatment in Cholinium Chloride : Lactic Acid Deep Eutectic Solvent.

A deep analysis upon the chemical modifications of the cellulose and hemicelluloses fractions that take place during biomass delignification with deep eutectic solvents (DES) is lacking in literature, being this a critical issue given the continued research on DES for this purpose. This work intends to fill this gap by disclosing a comprehensive study on the chemical modifications of cellulose (microcrystalline cellulose and bleached kraft pulp) and hemicelluloses (xylans) during thermal treatment (130 °C) with cholinium chloride/lactic acid ([Ch]Cl/LA) at molar ratio 1 : 10, one of the best reported DES for biomass delignification. The obtained data revealed that [Ch]Cl/LA (1 : 10) has a negative impact on the polysaccharides fractions at prolonged treatments (>4 h), resulting on substantial modifications including the esterification of cellulose with lactic acid, shortening of fibers length, fibers agglomeration and side reactions of the hemicelluloses fraction (e. g., humin formation, lactic acid grafting). Wood delignification trials with [Ch]Cl/LA (1 : 10) at the same conditions also corroborate these findings. Moreover, the DES suffers degradation, including the formation of lactic acid derivatives and its polymerization. Therefore, short time delignification treatments are strongly recommended when using the [Ch]Cl/LA DES, so that a sustainable fractionation of biomass into high quality cellulose fibers, isolated lignin, and xylose/furfural co-production along with solvent recyclability could be achieved.

Use of Ionic Liquids and Deep Eutectic Solvents in Polysaccharides Dissolution and Extraction Processes towards Sustainable Biomass Valorization.

A shift to a bioeconomy development model has been evolving, conducting the scientific community to investigate new ways of producing chemicals, materials and fuels from renewable resources, i.e., biomass. Specifically, technologies that provide high performance and maximal use of biomass feedstocks into commodities with reduced environmental impact have been highly pursued. A key example comprises the extraction and/or dissolution of polysaccharides, one of the most abundant fractions of biomass, which still need to be improved regarding these processes' efficiency and selectivity parameters. In this context, the use of alternative solvents and the application of less energy-intensive processes in the extraction of polysaccharides might play an important role to reach higher efficiency and sustainability in biomass valorization. This review debates the latest achievements in sustainable processes for the extraction of polysaccharides from a myriad of biomass resources, including lignocellulosic materials and food residues. Particularly, the ability of ionic liquids (ILs) and deep eutectic solvents (DESs) to dissolve and extract the most abundant polysaccharides from natural sources, namely cellulose, chitin, starch, hemicelluloses and pectins, is scrutinized and the efficiencies between solvents are compared. The interaction mechanisms between solvent and polysaccharide are described, paving the way for the design of selective extraction processes. A detailed discussion of the work developed for each polysaccharide as well as the innovation degree and the development stage of dissolution and extraction technologies is presented. Their advantages and disadvantages are also identified, and possible synergies by integrating microwave- and ultrasound-assisted extraction (MAE and UAE) or a combination of both (UMAE) are briefly described. Overall, this review provides key information towards the design of more efficient, selective and sustainable extraction and dissolution processes of polysaccharides from biomass.

Aqueous solutions of deep eutectic systems as reaction media for the saccharification and fermentation of hardwood xylan into xylitol.

The aim of this study was to evaluate the effect of aqueous solutions of deep eutectic solvent, Cholinium Chloride:Urea ([Ch]Cl:U) at 50 wt% and 20 wt%, using different molar ratios (1:1, 2:1 and 1:2) on the enzymatic hydrolysis of xylan for xylose production and its subsequent bioconversion into xylitol using a recombinant yeast strain. The lowest xylan conversion into xylose (45%) was obtained using 1:2 [Ch]Cl:U molar ratio. On the other hand, the 1:1 [Ch]Cl:U molar ratio, at 20 wt% in water, improved this conversion, achieving the highest xylose yield (81.4%). The xylitol production was then optimized with [Ch]Cl:U (1:1) at 20 wt% by simultaneous saccharification and fermentation process, attaining 23.67 g/L, corresponding to 66.04% of xylitol yield. This study reveals the possibility of using xylan solubilized in DES aqueous solutions directly for xylitol production, thus assembling a one-step process.

Extraction of High Value Triterpenic Acids from Eucalyptus globulus Biomass Using Hydrophobic Deep Eutectic Solvents.

Triterpenic acids (TTAs), known for their promising biological properties, can be found in different biomass sources and related by-products, such as Eucalyptus globulus bark, and have been extracted using organic volatile solvents such as dichloromethane. Recently, deep eutectic solvents (DES) have been identified as promising alternatives for the extraction of value-added compounds from biomass. In the present work, several hydrophobic DES were tested for the extraction of TTAs from E. globulus bark. Initial solubility studies revealed that DES based on menthol and thymol as the most promising solvents for these compounds given the highest solubilities obtained for ursolic acid (UA) at temperatures ranging from room temperature up to 90 °C. Accordingly, an eutectic mixture of menthol:thymol (1:2) was confirmed as the best candidate for the TTAs extraction from E. globulus outer bark, leading to extraction yields (weight of TTA per weight of biomass) at room temperature of 1.8 wt% for ursolic acid, 0.84 wt% for oleanolic acid and 0.30 wt% for betulinic acid. These values are significantly higher than those obtained with conventional organic solvents under similar conditions. The results obtained using these DES are promising for the recovery of TTAs for nutraceutical and pharmacological applications, while reinforcing the potential of DES as promising solvents to be applied in biorefinery processes.

Enhanced Conversion of Xylan into Furfural using Acidic Deep Eutectic Solvents with Dual Solvent and Catalyst Behavior.

An efficient process for the production of furfural from xylan by using acidic deep eutectic solvents (DESs), which act both as solvents and catalysts, is developed. DESs composed of cholinium chloride ([Ch]Cl) and malic acid or glycolic acid at different molar ratios, and the effects of water and γ-valerolactone (GVL) contents, solid/liquid (S/L) ratio, and microwave heating are investigated. The best furfural yields are obtained with the DES [Ch]Cl:malic acid (1:3 molar ratio)+5 wt % water, under microwave heating for 2.5 min at 150 °C, a S/L ratio of 0.050, and GVL at a weight ratio of 2:1. Under these conditions, a remarkable furfural yield (75 %) is obtained. Direct distillation of furfural from the DES/GVL solvent and distillation from 2-methyltetrahydrofuran (2-MeTHF) after a back-extraction step enable 89 % furfural recovery from 2-MeTHF. This strategy allows recycling of the DES/GVL for at least three times with only small losses in furfural yield (>69 %). This is the fastest and highest-yielding process reported for furfural production using bio-based DESs as solvents and catalysts, paving the way for scale-up of the process.

Polyvinylidene fluoride-Hyaluronic acid wound dressing comprised of ionic liquids for controlled drug delivery and dual therapeutic behavior.

To improve the efficacy of transdermal drug delivery systems, the physical and chemical properties of drugs need to be optimized to better penetrate into the stratum corneum and to better diffuse into the epidermis and dermis layers. Accordingly, dual-biological function ionic liquids composed of active pharmaceutical ingredients were synthesized, comprising both analgesic and anti-inflammatory properties, by combining a cation derived from lidocaine and anions derived from hydrophobic nonsteroidal anti-inflammatory drugs. Active pharmaceutical ingredient ionic liquids (API-ILs) were characterized through nuclear magnetic resonance, cytotoxicity assay, and water solubility assay. All properties were compared with those of the original drugs. By converting the analgesic and anti-inflammatory drugs into dual-function API-ILs, their water solubility increased up to 470-fold, without affecting their cytotoxic profile. These API-ILs were incorporated into a bilayer wound dressing composed of a hydrophobic polyvinylidene fluoride (PVDF) membrane to act as a drug reservoir and a biocompatible hyaluronic acid (HA) layer. The prepared bilayer wound dressing was characterized in terms of mechanical properties, membrane drug uptake and drug release behavior, and application in transdermal delivery, demonstrating to have desirable mechanical properties and improved release of API-ILs. The assessment of anti-inflammatory activity through the inhibition of LPS-induced production of nitric oxide and prostaglandin E2 by macrophages revealed that the prepared membranes containing API-ILs are as effective as those with the original drugs. Cell adhesion of fibroblasts on membrane surfaces and cell viability assay confirmed improved the viability and adhesion of fibroblasts on PVDF/HA membranes. Finally, wound healing assay performed with fibroblasts showed that the bilayer membranes containing dual-function API-ILs are not detrimental to wound healing, while displaying increased and controlled drug delivery and dual therapeutic behavior. STATEMENT OF SIGNIFICANCE: This work shows the preparation and characterization of bilayer wound dressings comprising dual-biological function active pharmaceutical ingredients based on ionic liquids with improved and controlled drug release and dual therapeutic efficiency. By converting analgesic and anti-inflammatory drugs into ionic liquids, their water solubility increases up to 470-fold. The prepared bilayer wound dressing membranes have desirable mechanical properties and improved release of drugs. The prepared membranes comprising ionic liquids display anti-inflammatory activity as effective as those with the original drugs. Cell adhesion of fibroblasts on membrane surfaces and cell viability assays show improved viability and adhesion of fibroblasts on PVDF/HA membranes, being thus of high relevance as effective transdermal drug delivery systems.

Anti-inflammatory and antioxidant nanostructured cellulose membranes loaded with phenolic-based ionic liquids for cutaneous application.

The utilization of natural compounds, such as phenolic acids and biopolymers, in the healthcare domain is gaining increasing attention. In this study, bacterial nanocellulose (BC) membranes were loaded with ionic liquids (ILs) based on phenolic acids. These ionic compounds, with improved solubility and bioavailability, were prepared by combining the cholinium cation with anions derived from caffeic, ellagic and gallic acids. The obtained BC-ILs membranes were homogeneous, conformable and their swelling ability agreed with the solubility of each IL. These membranes revealed a controlled ILs dissolution rate in the wet state and high antioxidant activity. In vitro assays performed with Raw 264.7 macrophages and HaCaT keratinocytes revealed that these novel BC-ILs membranes are non-cytotoxic and present relevant anti-inflammatory properties. Diffusion studies with Hanson vertical diffusion cells showed a prolonged release profile of the ILs from the BC membranes. Thus, this work, successfully demonstrates the potential of BC-ILs membranes for skin treatment.

Cloud point extraction of chlorophylls from spinach leaves using aqueous solutions of non-ionic surfactants.

Chlorophylls and their derivatives are currently used in a wide range of applications. To replace the volatile organic solvents commonly applied for their extraction from biomass, aqueous solutions of non-ionic surfactants are studied herein in the extraction of chlorophylls from spinach leaves. Aqueous solutions of several surfactants were screened, demonstrating that their hydrophilic-lipophilic balance (HLB) plays the pivotal role on the extraction performance, with the best results obtained for surfactants with a HLB ranging between 10 and 13. A response surface methodology (RSM) was then used to optimize operational conditions (surfactant concentration, solid-liquid ratio and temperature), leading to a maximum extraction yield of chlorophylls of 0.94 mg/g. After the extraction step, the chlorophylls-rich extract was concentrated by heating above the surfactant-water cloud point, leading to the separation into two-phases, and to a concentration factor of 9 and a recovery of 97% of chlorophylls in the surfactant-rich phase. The antioxidant activity of the extracts was finally appraised, showing that the antioxidant activity of the aqueous chlorophylls-rich extracts is higher than that obtained with volatile organic solvents. The obtained results show the potential of aqueous solutions of non-ionic surfactants to extract highly hydrophobic compounds from biomass and their possible direct use in cosmetic and nutraceutical applications, without requiring an additional recovery or purification step.

Deep Eutectic Solvent Aqueous Solutions as Efficient Media for the Solubilization of Hardwood Xylans.

This work contributes to the development of integrated lignocellulosic-based biorefineries by the pioneering exploitation of hardwood xylans by solubilization and extraction in deep eutectic solvents (DES). DES formed by choline chloride and urea or acetic acid were initially evaluated as solvents for commercial xylan as a model compound. The effects of temperature, molar ratio, and concentration of the DES aqueous solutions were evaluated and optimized by using a response surface methodology. The results obtained demonstrated the potential of these solvents, with 328.23 g L-1 of xylan solubilization using 66.7 wt % DES in water at 80 °C. Furthermore, xylans could be recovered by precipitation from the DES aqueous media in yields above 90 %. The detailed characterization of the xylans recovered after solubilization in aqueous DES demonstrated that 4-O-methyl groups were eliminated from the 4-O-methylglucuronic acids moieties and uronic acids (15 %) were cleaved from the xylan backbone during this process. The similar Mw values of both pristine and recovered xylans confirmed the success of the reported procedure. DES recovery in four additional extraction cycles was also demonstrated. Finally, the successful extraction of xylans from Eucalyptus globulus wood by using aqueous solutions of DES was demonstrated.