Complete biodiverse lignocellulosic biomass fractionation process using the green solvent γ-valerolactone

Complete biodiverse lignocellulosic biomass fractionation process using the green solvent gvalerolactone Moritz Schweiger, * a Thomas Lang, a Eva Müller, a Vojtˇ ech Jeˇ r´ abek, b Jan Heyda, b Martin Klajmon, b Didier Touraud, a Magdalena Bendov´ a, b Karel ˇ Reh´ ak b and Werner Kunz a Biomass pretreatment processes using organic solvents have historically been investigated for the separation of lignin from lignocellulosic biomass. This research explores how the pretreatment process can be expanded to fractionate all biomass components from various feedstock and waste streams and transform them into valuable bio-based molecules using green solvent mixtures and mild conditions. Using experimental and computational investigation techniques, this study further expands on the use of the green solvent g-valerolactone (GVL) in biomass fractionation processes. Combining both results, a complete biodiverse process for the fractionation of all biopolymers in lignocellulosic biomass was achieved. This process yields lignin in native quality, very high purity and very high yield after a single extraction cycle at very mild conditions. Additionally, lignin-free cellulose in very high purity and yield, and hemicellulose degradation products in very high yield and purity, mainly xylose and glucose, can be separated during the process. These properties are essential for efficient valorization of the biopolymer products. The fractionation process proved to be similarly efficient in every step for different biomasses and waste-stream biomasses. GVL could be recovered and reused in every separation step and even be prepared from hemicellulose products, enabling a sustainable biomass dissolution cycle. This cycle stands as a basis for producing valuable biopolymer molecules, from biodiverse origin, that can be further converted into quality products for the chemical industry. Sustainability spotlight To achieve the replacement of fossil-based resources in the chemical industry by renewable and sustainable materials, the biodiverse, complete fractionation of lignocellulosic biomass into high purity biopolymer products with a green process is of great importance. Our interest was to develop a biomass fractionation process that can separate lignin, hemicellulose, and cellulose in an efficient way and in high yields and purities. We also used green solvents and mild fractionation conditions compared to existing processes. Furthermore, we validated the biodiversity of this process, making it applicable not only for high value lignocellulosic biomasses, but also for waste materials like wood sawdust, nutshells, or coffee silverskin. Our process aligns with the UN goals in responsible consumption and production (UN SDG 12). 1 Introduction The primary goal of the chemical industry today is its transition towards renewable and sustainable resources. Currently, there is an enormous demand for fossil-based chemicals and their derived products, a demand that is projected to double over the next 25 years. 1,2 However, with the continuous depletion of fossil resources, future production will be unable to meet this rising demand. Therefore, it is crucial to identify and develop alternative feedstocks that can replace fossil-based materials in the chemical industry. One such promising alternative is lignocellulosic biomass, with an estimated global annual production of 181.5 billion tons. This feedstock holds great potential due to its renewability, economic viability, and carbon neutrality. 3 Lignocellulosic biomass encompasses renewable resources such as wood, plants, agricultural residues, grasses, and plantbased industrial waste streams like nutshells. 4 Despite its vast availability, only 8.2 billion tons are currently utilized, 5 primarily for livestock feed (61%), food (15%), and energy production (16%). 2 Traditionally, biomass has been used in the paper industry to produce cellulose bers. 3 However, the concept of bioreneries, which seek to fully exploit the potential of lignocellulosic biomass, is gaining attraction due to the versatility of a Faculty of Chemistry and Pharmacy, Department of Physical Chemistry II, University of Regensburg, Universit¨ atsstraße 31, 93053 Regensburg, Germany. E-mail: moritz. [email protected]ni-regensburg.de b Department of Physical Chemistry, University of Chemistry and Technology, Prague 6, CZ-16628, Czech Republic Cite this: RSC Sustainability,2025,3, 4533 Received 18th July 2025 Accepted 26th August 2025 DOI: 10.1039/d5su00600g rsc.li/rscsus © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability,2025,3, 4533–4555 | 4533 RSC Sustainability PAPER Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online View Journal | View Issue the usable rawmaterials. These components could serve as precursors for producing sustainable energy, 6 biofuels, 7 bioplastics, 8 and various biochemicals, 9 such as amino acids, 10 platform chemicals like furfural, 11 or organic solvents like gvalerolactone (GVL), 12 thereby offering a viable alternative to fossil-based chemical production. Nevertheless, several challenges must be addressed to fully realize the biorenery concept, including reducing processing costs, improving process efficiency, ensuring the complete valorization of all biomass components, scaling up to industrial levels, and competing with the established fossil-based market. 13 This study highlights the improvements to a complete separation of all components of lignocellulosic biomass using green solvents compared to existing processes. With the green solvent GVL, complete lignocellulosic biomass fractionation can be achieved through a simple, mild, and optimized process, which greatly improves upon existing biomass fractionation processes in terms of biopolymer yield, purity and quality, and process conditions. Lignocellulosic biomass consists mainly of cellulose (44%), hemicellulose (28%), and lignin (20%), with smaller fractions of proteins, other extractives (6%), and ash (2%). The overall structures of these three main biopolymers are depicted in Fig. (1). 14,15 Hemicellulose is a heterogeneous polysaccharide primarily composed of xylose and glucose backbones, with varying pentose or hexose substituents depending on the biomass type. 16–21 In this study, the degradation products of hemicellulose, particularly xylose, are being dissolved and separated from other biomass extractives. Xylose can act as a precursor for important platform chemicals in the future. 22 Cellulose, a polysaccharide from glucose, can be efficiently separated from lignin and hemicellulose and be recovered in high purity to enable further processing. Lignin is a complex, threedimensional heteropolymer. It is composed mainly of the aromatic monomers sinapyl alcohol, coniferyl alcohol, and pcoumaryl alcohol, which are interconnected by ether and carbon–carbon linkages. These monomers form the corresponding subunits syringyl (S), guaiacyl (G), and hydroxyphenyl (H). The monomers can bond through carbon–carbon linkages, including b-b0,b-10, and 5-50, or through carbon–oxygen bonds, such as b-O-40,a-O-40, and 4-O-50linkages, varying on the biomass source. 23–39 Lignin in biomass is typically present in lignin–carbohydrate complexes with hemicellulose, enabling their co-extraction. 23 While lignin is currently mostly burned to recover process energy in the paper industry, 3 it has potential for a variety of applications, such as UV-protective lms, 30–32 antioxidant additives, 33,34 fragrance monomers, 35 medical uses 36 or vanillin production. 37,38 With an effective separation of lignin in maximally natural constitution with its native ether content comes the fractionation of all biopolymers in high yields and quality. This was done through the combination of well-established extraction methods, namely organosolv processes 39,40 and aldehydeassisted processes to prohibit extensive lignin condensation reactions. 41 Since GVL/water mixtures have shown good lignin solubility already in the past, 39 we also investigated the performance of the GVL/water solvent system by means of advanced computational techniques, namely, the quantum-mechanicsaided COSMO-SAC model and atomistic molecular simulations, to provide further theoretical insights into the behavior of the proposed fractionation media. Both experimental and simulation results led to a further understanding of the potential of GVL in biomass fractionation, not only due to its nature as a green solvent, 42–44 but also its potential to be produced efficiently from biobased resources. 45–50 Given GVL's ability to dissolve lignin 51 and hemicellulose 52 in substantial quantities, and its prospect to improve cellulose dissolution, 53 it was considered an ideal solvent for this study. Additionally, GVL Fig. 1 (a) Structural excerpt of lignin. (b) Structural excerpt of cellulose chains with intermolecular and intramolecular hydrogen bonding. (c) Structural excerpt of hemicellulose. (d) Possible monomeric sugar molecules that can be part of the substituted hemicellulose backbone in place of R. 4534 |RSC Sustainability,2025,3, 4533–4555 © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability Paper Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online can be easily recycled through simple distillation techniques 54 or CO 2 extraction. 55 Summarizing all results, we designed an efficient process for complete biodiverse biomass fractionation using mainly GVL, yielding cellulose, lignin and hemicellulose products with high value for further processing, all in one efficient and mild extraction cycle. It is very important to clarify the several problems of other fractionation processes in existing literature, which our process greatly improves upon. A common approach is the use of ionic liquids (IL's) to dissolve biomass components and fractionate them. IL's are mainly organic salts with melting points <100 °C. They provide advantages such as low volatility, high thermal stability, and high adaptability to certain processes due to the large number of possible combinations of cations and anions. IL's mainly disrupt the intermolecular hydrogen bonds between biopolymers, facilitating their fractionation and dissolution. 56 Examples for IL's being developed for biomass fractionation are especially imidazolium-based IL's like 1-ethyl-3methylimidazolium acetate 57 or 1-butyl-3-methylimidazolium acetate. 58 These IL's have high cost and toxicity, and do not show complete fractionation ability of all biopolymers. 57,58 Protic IL's such as triethylammonium hydrogen sulfate dissolved up to 85% lignin and 100% hemicellulose from Miscanthus x giganteus with low production cost and high recovery. Still, the purity and quality of the extracted biopolymers was not yet efficient enough for industrial application. 59 Other general problems of using IL's for biomass fractionation are their high costs, potential toxicity, and difficult recovery. 56,60 A better alternative to IL's are deep eutectic solvents (DES). DES are mainly formed by mixing a hydrogen bond accepting and a hydrogen bond donating component, resulting in a mixture with a melting point lower than that of the individual components. DES are generally considered more biodegradable, less toxic, and more cost-efficient than IL's. 59,61 Several DES formulations have been developed to fractionate biomass. A choline chloride/oxalic acid DES showed medium delignication capabilities from wheat straw of 57.9% lignin removal. This process allows a breakdown of the lignin structure, but struggles with further processing cellulose into valuable products, while fully removing lignin and hemicellulose from the biomass. 62 A DES based on choline chloride/levulinic acid could effectively fractionate cellulose (3% lignin le), lignin, and hemicellulose from acacia wood at high temperatures of 160 °C, still being very energy-intensive and the lignin being of very poor quality, meaning high condensation and low purity due to cellulose/ hemicellulose breakdown products. 63 Other DES, or natural deep eutectic solvents (NADES), based on lactic acid, 64 or three components DES, with additional protection agents like ethylene glycol, that ensure an uncondensed state of lignin 65 also yielded great results for biomass fractionation, yet still struggle with DES recovery, high temperatures up to 160 °C, recovery of the hemicellulose component, biodiversity, and long reaction times up to 24 hours. DES provide clear advantages compared to IL's in lignin separation and subsequent complete biomass fractionation but are not yet effective enough for industrial application. 56,61,65 A last possibility is the use of organosolv processes to fractionate biomass. This method has been highly developed, with the use of different organic solvents like ethanol, methanol or acetone in combination with water and other catalysts/additives to solubilize lignin and hemicellulose, leaving behind a pure cellulose residue. Core mechanisms are the disruption of lignin-hemicellulose complexes due to slightly acidic conditions, and the dissolution of lignin and hemicellulose fragments through the organic solvents. While pathways to efficiently separate lignin, hemicellulose, and cellulose have been found, problems like solvent toxicity, energy-intensive and solvent-intensive process conditions, lack of biodiversity, or unsatisfactory quality of biopolymer products still reside. 66,67 While simple mixtures of acidic organic solvent/water mostly extract lignin in high quantities, elevated temperatures are necessary due to the condensation of lignin during the process, leading to lower value products. Additionally, many organic solvents pose the risk of ammability or other safety/environmental risks due to their high volatility. 68–70 GVL has proven to be an excellent option for organosolv processes due to its advantageous properties, 67 with its large-scale availability increasing signicantly over the next few years. Due to additives that can reduce lignin condensation and thus fractionate all biopolymers at relatively low temperatures below 100 °C, GVL could be industrially used in the future. The challenge of designing a process using the advantages of GVL combined with simple solvent recovery, low process temperatures, low solvent quantities, high biopolymer yields and purities, high lignin quality, low extraction times, and especially biodiversity of the process has been developed in the frame of this work. This process improves greatly upon various problems of existing biomass fractionation processes. Through experimental and computational methods, the potential of GVL as the optimal solvent for biomass fractionation was validated. Cellulose, lignin and hemicellulose were then extracted from biomass using mild GVL extraction processes and the process efficiency was analyzed by fractionation yield and purity. The differences between a default extraction process with GVL and the improved aldehydeassisted GVL extraction process were examined qualitatively to show how efficient lignin removal enables complete biopolymer fractionation. In a concluding remark, it was shown how the process in this study greatly improves upon existing processes in literature. The extractives from all three biopolymers can be considered for further applications, as pathways for specic applications were developed, which will also be specically addressed in future research following up on this article. 2 Materials and methods 2.1 Chemicals and materials Sulfuric acid (95–98%, CAS 7664-93-9), L-cysteine (98%, CAS 5290-4), DMSO-d6 (99.8%, CAS 2206-27-1), acetaldehyde (for synthesis, CAS 75-07-0), acetone (>99.5%, CAS 67-64-1), dimethyl sulfoxide (DMSO) (for analysis, CAS 67-68-5), 1,4dioxane (for analysis, CAS 123-91-1), ethanol (for analysis, CAS 64-17-5), ethyl acetate (for analysis, CAS 141-78-6), para-formaldehyde (37% in water, CAS 50-00-0), hydrochloric acid (37%, CAS 7647-01-0), methanol (for analysis, CAS 67-56-1), toluene © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability,2025,3, 4533–4555 | 4535 Paper RSC Sustainability Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online (for analysis, CAS 108-88-3), sodium hydroxide (for analysis, CAS 1310-73-2), propionic aldehyde (>98%, CAS 123-38-6), were purchased from Merck KGaA (Darmstadt, Germany). g-Valerolactone (GVL) (anal. Grade, CAS 108-29-2) was provided by KVT-Technology/Glaconchemie (Graz, Austria). n-Hexane (>99%, CAS 110-54-3), n-heptane (>99%, CAS 14282-5), methyl-tetrahydrofuran (>99%, CAS 96-47-9 were purchased from Fisher Scientic GmbH (Schwerte, Germany). Sodium hydrogen carbonate (>99.5%, CAS 144-55-8) was purchased from Carl Roth GmbH & Co. KG (Karlsruhe, Germany). Millipore distilled water was cleaned in a Millipore puri- cation system (electrical conductivity p>18MUcm). Peanut shells and skin were removed from store bought peanuts; pistachio shells were removed from store bought pistachios; hazelnut shells were removed from store bought hazelnuts. Walnut shells were removed from home grown walnuts. Coffee silverskin was provided by Rheorik Rösterei & Feinkost GmbH (Regensburg, Germany). Birch sawdust and Beech sawdust were provided by Schreinerei Heitzner (Traitsching, Germany). Cashew shell powder was provided by Orpia-Innovation (Paris, France). Almond shells were provided by Otto A. Müller Recycling GmbH (Ahrensburg, Germany). Spruce sawdust was provided by HCR Holz Centrum Regensburg GmbH (Regensburg, Germany). 2.2 Lignin and hemicellulose extraction process The default lignin extraction follows a method established by Cheng et al. 39 Using GVL/water mixtures as extraction solvent, the optimum extraction parameters were determined through variation in temperature, solid loading, extraction time, solvent composition and pH value. Biomass samples were dried at 75 °C for 48 h to remove water residues, then milled into powder with a diameter of 2 mm. An amount of 9 g of the milled biomass powder was transferred into a 250 mL round ask. To the ask, 90 mL of a GVL/water (9/1 wt/wt) mixture were added. The mixture was subjected to ultrasonic treatment for 30 min at 60 °C to achieve optimal swelling of the lignocellulose structure, enabling a good solvent penetration for the extraction. A concentration of 0.075 mol L −1 sulfuric acid was set in the mixture. The round ask was equipped with a magnetic stirring bar and subjected into an oil bath at 120 °C for 2 h under continuous stirring. These optimum conditions for the GVLbased organosolv process were determined by variation of solid loading, acid concentration, solvent composition, extraction time, and reaction temperature to maximize yield and purity of the extracted lignin (details see SI Section S1). Aer the extraction nished, the round ask was air-cooled to room temperature before being put in an ice bath for 20 min to prohibit intense condensation reactions. Residual biomass residue, mostly cellulose, was removed through a Buchner lter from the lignin/ hemicellulose/GVL/water solution. The lter cake was washed with 15 mL of GVL and 15 mL of water three times each. The ltrate was collected in an appropriate beakerand subjected to10 times its volume of water to precipitate the lignin. The lignin was collected through centrifugation at 4000 rpm for 15 min. The residual solution was subjected to vacuum distillation at 60 °C and 0.001 bar to completely remove the solvent mixture and collect the hemicellulose residues. The solid lignin was washed with distilled water multiple times to remove GVL and hemicellulose residues (which were in the end added to the hemicellulose fraction) and then dried at 75 °C for 48 h in a drying oven, then for 24 h in a vacuum desiccator equipped with silica gel. Finally, light brown colored lignin powder was obtained. The color varied for different biomass sources. Each biomass sample underwent three separate extraction steps to ensure nearly complete lignin extraction. The lignin yield was calculated through eqn (1). Yield ¼mextracted lignin mbiomass lignin content 100 (1) Following this, the purity of the extracted lignin was assessed using a modied version of the CASA method, see Section 2.6.2. 2.3 Aldehyde assisted extraction process The modied extraction method of lignin and hemicellulose is based on the aldehyde-assisted fractionation established by Lan et al. (2018). 41 The method was optimized for our extraction process using GVL by varying temperature, extraction time, acid content, water content, and neutralization method (for details see SI Section S2). 5 g of biomass, 27.5 mL of GVL, 5.3 mL of propionaldehyde, and 0.94 mL of 37% HCl solution (instead of sulfuric acid, details see SI) were added into a 100 mL glass ask containing a 20 mm PTFE-coated stir bar. Aer connecting the ask to areux condenser, the mixture was heated to 85 °C for 3 h (heat up time included). To ensure ideal stirring during the reaction, the stirrer was turned on 15 min into the reaction and was set to approx. 400 rpm. Aer completion of the extraction, the ask was set aside until it cooled down to room temperature. The mixture was ltered using a Buchner funnel and washed with 5 ×5 mL GVL and 2 ×10 mL methanol (important for neutralization, see SI Section S2). The collected cellulose was set aside. The ltrate was neutralized by adding 1.7 g of NaHCO 3 and stirred for approx. 1 h at room temperature. Aer neutralization residual NaHCO 3 and resulting NaCl were ltered using a Buchner funnel. Neutralization was necessary to avoid deprotection and recondensation during lignin recovery. GVL from the neutralized ltrate was evaporated by using a vacuum distillation setup (1 ×10 −3 bar, 60 °C). The resulting slurry was redissolved in 10 mL ethyl acetate until it was not viscous anymore. Lignin was precipitated by slowly pipetting one part (volume) of the prepared solution to 10 parts of vigorously stirring heptane. The stirring was stopped aer the residue was disaggregated, and the yellow-colored supernatant was decanted into an Erlenmeyer ask. The remaining lignin-rich residue was solidied by adding 20 mL of distilled water to the gel-like residue. The residue was ltered using a Buchner funnel and washed with 2 ×10 mL distilled water. The 4536 |RSC Sustainability,2025,3,4533–4555 © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability Paper Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online recovered lignin was dried overnight using a desiccator. The resulting lignin powder was puried using the following procedure: 10 mL diethyl ether (see SI, Section S2) were added to the lignin powder and placed into an ultrasonic bath. The yellow-colored supernatant liquid was decanted through a fritted lter funnel (pore size: G3) and added to the hemicellulose fraction. The purication process was repeated one more time. The resulting lignin was dried at 40 °C for 1 h and stored in a closed container. The depolymerized hemicellulose from the heptane/ethyl acetate ltrate and the washing step was received by distillation using a rotary evaporator. The heptane/ethyl acetate solvent mixture was used instead of water for precipitation of the lignin to reduce the overall solvent consumption from a total of 322.5 mL of solvents in the default extraction process to 197.5 mL of solvents in the aldehyde assisted extraction process. Moreover, the high enthalpy of vaporization for water could be avoided, and easily vaporizable n-heptane could reduce the distillation energy needed. Still, aqueous precipitation can be used in this process if a complete set of green solvents is necessary. The theoretical lignin extraction yield was calculated by using eqn (1) to further calculate the actual lignin extraction yield, as the introduction of protecting groups altered the molecular weight of lignin structures. This was suggested by lan et al. (2019). 71 Yield ¼mbiomass LC 236 196 %G þ266 226 %SEC þð1ECÞ(2) In eqn (2), m means weight of biomass subjected to extraction, LC means lignin content in the biomass, %G/%S means percentage of guaiacyl/syringyl units present in lignin, and EC means the ether content. S/G-ratio and ether content are determined by 2D HSQC NMR spectroscopy. The molecular weights of the b-O-4 bonded monomeric units in native lignin are 196 g mol −1 for a G unit and 226 g mol −1 for an S unit. Following protection with propionaldehyde, these molecular weights increase to 236 g mol −1 for G and 266 g mol −1 for S. A comparison for the process parameters for both extraction processes is shown in SI Section S7. 2.4 Solvent recovery process Solvents from all mixtures containing GVL could be recovered for solvent reusability. GVL was recovered through simple vacuum distillation at 60 °C and 10 −3 bar. Water can be separated from GVL through rotary vacuum evaporation at 40 °C and 0.1 bar. Similarly, ethyl acetate (50 °C, 0.150 bar) and heptane (50 °C, 0.07 bar) can be separated and reused for lignin precipitation aer rotary vacuum evaporation. 2.5 NMR spectroscopy NMR experiments were conducted using an Avance III HD 400 spectrometer (400.13 MHz Proton, 5 mm BBO 400 SB BB-H-D sample head with Z-gradient). Lignin samples were dissolved in DMSO-d 6 at 60 mg mL −1 and transferred to NMR glass tubes aer complete dissolution. For all samples, 1H-NMR and 2DHSQC-NMR spectra were measured to evaluate the S/G-ratio and the ether content of lignin from different biomass sources to accurately calculate lignin yields through eqn (1). For lignin from the aldehyde extraction process, the protection rate can also be calculated through 2D-HSQC-NMR. SpinWorks was used to analyze the NMR spectra. The detailed NMR assignment method can be found in SI Section S3. 2.6 UV/vis spectroscopy 2.6.1 Spectroscopy. UV/vis spectroscopy experiments were conducted on a double-beam UV/vis spectrophotometer from PerkinElmer Lambda 19 UV/Vis/NIR (Dodgau, Germany). Examined samples were measured in micro-UV cuvettes with an optical path length (L) of 1 cm from brand GmbH & Co.KG (Wertheim, Germany) against a reference sample at 25 °C in a wavelength range from 200 nm to 400 nm. 2.6.2 CASA lignin content and purity determination. In all biomass samples, the lignin content was determined through the Cysteine Assisted Sulfuric Acid (CASA) method, which was rst described by Lu et al. (2021). 72 A stock solution of 0.1 g mL −1 L-cysteine in 72% sulfuric acid was prepared. In 1 mL of stock solution, 20 mg of a ground biomass sample (m) were dissolved under stirring at room temperature, before being diluted to 100 mL (V) with distilled water. The UV/vis absorbance (A 283 biomass ) was measured at 283 nm to determine the overall lignin content using eqn (3) with a molar absorption coefficient 3of 17.25 L g −1 cm −1 . The lignin content can be overestimated due to other aromatic extractives from proteins, but this is generally negligible due to their very low content. Lignin content ½%¼ A283biomass V 3Lm100 (3) Additionally, the lignin purity could be determined by using a modication of the CASA method, which was validated internally. The loss of lignin in a representative biomass sample modeled with extracted lignin was measured, which correlated to the purity of the extracted lignin sample. To this end, instead of biomass, an equivalent amount of extracted lignin to the lignin content in the respective biomass (e.g. 1 g biomass, 20% lignin content /0.2 g extracted lignin) was dissolved in 1 mL stock solution and diluted to 100 mL with distilled water. Eqn (4) was used to calculate the lignin purity by dividing the absorbance of the extracted lignin sample (A 283 ) by the absorbance of the respective biomass sample (A 283 biomass ). Since aromatic parts from proteins are also removed during extraction, the lignin purity can be underestimated. Lignin purity½%¼ A283 A283biomass 100 (4) 2.7 Carbohydrate content determination The hemicellulose and cellulose contents for different biomasses were determined using a simple acid hydrolysis method, since the lignin content was already determined © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability,2025,3,4533–4555 | 4537 Paper RSC Sustainability Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online through UV/vis spectroscopy. The biomass sample was dried in an oven at 105 °C for 15 h to remove residual moisture. Of the dried biomass, 1 g was subjected in a round ask to 100 mL of a neutral detergent solution containing sodium lauryl sulfate (30 g L −1 ) and EDTA (20 g L −1 ) to remove extractives like proteins, lipids, and other non-ber components. The gravimetric difference determined the extractive content. Aer ltering and drying, the residual biomass was subjected to 100 mL of 1 mol L −1 sulfuric acid at 100 °C for 2 h to hydrolyze hemicellulose into water-soluble sugar molecules. Aer ltering and drying the residual biomass at 105 °C for 15 h, it was weighed. The gravimetric difference determined the hemicellulose content of a certain biomass. Due to the known lignin content, the cellulose content was determined by subtracting the overall lignin content from the residual weight of the biomass aer extractive and hemicellulose removal. 2.8 Gas chromatography coupled with mass spectrometry Qualitative analysis was carried out using GC-MS with an Agilent 7890B GC system, tted with a ZB-5MSplus column, and a Jeol AccuTOF GCX mass spectrometer. Samples (1 mL) were injected using an autosampler in split mode (split ratio 75 : 1) at an injection temperature of 300 °C. The septum purge ow was maintained at 3 mL min −1 . The column temperature was initially set at 40 °C for 3 minutes, then ramped to 100 °C at 30 ° C min −1 , followed by a further increase to 300 °C at 40 ° C min −1 , where it was held for 5 minutes. Molecules were identied by comparison with the NIST MS Search 2.2 database. 2.9 Computational and simulation methods For the purposes of computational investigations conducted within this study, we developed a model organosolv lignin oligomer. It consists of ve p-coumaryl alcohol (PCA has proven to be a suitable building block for this purpose in previous research 73,74 ) units connected by three b-O-40and one b-50 linkages, reecting a typical distribution of linkages in most wood-based biomasses (determined through 2D-HSQC-NMR, details see SI Section S3). This pentamer is hereaer denoted “PCA-5mer”and its molecular topology can be found in the SI Section S6. 2.9.1 COSMO-SAC. To examine the thermodynamic behavior of PCA-5mer/solvent(s) systems, the conductor-like screening model-segment activity coefficient (COSMO-SAC) model 75–77 was employed. COSMO-SAC is an advanced, strictly predictive model that combines quantum-mechanical (QM) calculations and a statistical approach to estimate macroscopic thermodynamic properties of solutions, such as the activity coefficients (ln g i ) of individual solution components and, hence, phase equilibria including miscibility and solubility. In this framework, QM density functional theory (DFT) calculations within a continuum solvation model are used to generate the molecular surface screening charge density, s, which is then transformed into the s-prole, a histogram representing the amount of molecular surface area as a function of s. The sproles of the involved molecular species are subsequently used in a statistical model to estimate solution properties. As such, COSMO-based models rely solely on molecular structure as input and do not require auxiliary solution-specic data. Therefore, they provide an efficient tool for solvent screening and ranking (based on predicted phase equilibria or ln g i ) across various elds, including (bio)polymer systems. 73,78–80 In this work, we applied the revised, open-source COSMOSAC implementation, 77 specically the COSMO-SAC-2010 variant. 78 Although several applications of other COSMObased models and implementations to biopolymer-based systems exist, 73,74,78,81–84 to the best of our knowledge, the present study represents the rst application of this opensource COSMO-SAC implementation in this eld. The molecular s-prole database distributed with the COSMO-SAC package 77 did not cover all the compounds we intended to include. Therefore, for the sake of consistency, we determined the s-proles de novo for all solvents and lignin solutes considered in this study, not just the missing ones. This was based on QM calculations of molecular surface screening charge densities using Gaussian 16 soware 85 at the BP86/TZVP level with the conductor-like polarizable continuum model (CPCM) 86 for the solvation. The initial molecular geometries of solvents were generated from SMILES codes using the sophisticated ETKDGv3 method, 87 rened at a molecular-mechanical level 88 (both using the RDKit package 89 ), and subsequently optimized quantum-mechanically at BP86/TZVP/C-PCM in Gaussian. For the solute PCA-5mer, its geometry was taken directly from the nal snapshot (at 100 ns) of an MD simulation of the PCA-5mer/GVL system (for details, see the following section) to reect a realistic liquid-phase conformation. The geometry was used without further renement. In principle, oligomers –and even smaller oligomers –can adopt numerous conformers. However, we demonstrate in Section S4 of the SI that the specic geometry of PCA-5mer has a limited impact on qualitative solvent screening. The s-proles and corresponding geometries of all molecular species considered in this study are provided as part of the SI. In the computational study, we used the activity coefficient of the solute PCA-5mer at innite dilution in solvents (ln g N PCA5mer ), as predicted by COSMO-SAC, to assess PCA-5mer–/solvent thermodynamic affinity in the liquid phase (that is, the ability of solvents to dissolve this lignin model), following previous studies. 73,74,78 For poorly soluble species, the mole fraction solubility and the activity coefficient are interrelated by the following proportion: x isat f1/g i N , As a result, low ln g i values indicate higher solute–solvent affinity and tendency to solubilize the solute, and vice versa. Comparing predicted ln g N PCA5mer values across different solvents thus enabled an evaluation of their dissolving efficiency. 2.9.2 MD simulations. Simulations of PCA-5mer in water, GVL, and their 50 mol% mixture were performed in GROMACS simulation package, utilizing TIP4P/2005 water model and GAFF parameterizations (with ESP partial charges) of GVL and PCA-5mer derived according to recommended protocol. 90–94 We note that GVL dipole on carbonyl group was increased by ca 10% and sigma of atoms adjusted to quantitatively reproduce water-GVL miscibility and experimental density of pure GVL and 50 mol% mixture. Simulations were performed in 4538 |RSC Sustainability,2025,3,4533–4555 © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability Paper Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online isothermal-isobaric (NpT) ensemble at standard temperature (298 K) and pressure (1 bar), which were controlled by V-rescale thermostat (s T =0.5 ps) and C-rescale barostat (s p =2.0 ps). 95,96 LINCS algorithm was used to constrain all bonds involving hydrogen atoms. 97 1 nm cut-offwas used for short range Lennard-Jones and electrostatics. The Particle mesh Ewald (PME) method on a 0.16 nm grid accounted for long-range electrostatics. 98 Studied systems consisted of a single PCA5mer molecule, 4181 water, 800 GVL (pure solvents), or 664 water and 664 GVL molecules (equimolar mixture), which were randomly distributed in the simulation box by PACKMOL so- ware. 99 Aer minimization and short equilibration, the system reached equilibrium size of ca 5×5×5nm 3 and was propagated with 2 fs time-step (leap-frog integrator) and 1 ps sampling frequency for 100 ns, resulting in 100 000 congurations for data analysis. Solution structure in the vicinity of a fully exible PCA-5mer molecule was analyzed with groupspecic proximal (1D) resolution. The spatial (3D) resolution was applied to rigid compact and extended conformations, which represent dominant structures as sampled in water and in GVL respectively. In-house codes were utilized, and the results are compared between neat solvents and solvent mixture. 100 3 Results and discussion 3.1 GVL-water system as optimal solvent mixture for lignin extraction The effective extraction of lignin from lignocellulosic biomass is a core step in achieving high quality fractionation in our process. Multiple experimental observations indicate that GVL/ water mixed solvent exhibits remarkably efficient behavior in terms of lignin dissolution. 39,40,51 Together with the green and renewable nature of GVL, this solvent mixture appears to be optimal for the fractionation of lignocellulosic biomass. Therefore, we applied the COSMO-SAC thermodynamic model and MD simulations to support understanding of and provide insight into the behavior of the GVL/water mixture, also in the context of other (not necessarily green) solvents. Additionally, the interaction of the solvent mixture with PCA-5mer, a lignin model molecule, was investigated. This should underline the mechanistic effectiveness of GVL in GVL/water mixtures at the solubilization of lignin, while proting from the green properties of the solvent. Overall, this chapter gives arguments supporting our selection of GVL as the main solvent for our biomass fractionation process. 3.1.1 COSMO-SAC screening calculations. First, COSMOSAC was applied to a priori predict the limiting activity coefficients of the solute PCA-5mer in a range of pure solvents, including conventional, toxic, hazardous, and novel green alternatives, with the goal of assessing the relative performance of GVL compared to other pure solvents. The results are presented in Fig. 2(a) as bar charts (abbreviations and identiers of the solvents can be found in SI, Section 4). We remind the reader that the lower the ln g N PCA-5mer value, the higher the PCA5mer-/solvent thermodynamic affinity; therefore, the solvent efficiency increases from right to lein Fig. 2(a). Although some highly dipolar, toxic solvents, such as NMP and DMSO, are predicted by COSMO-SAC to exhibit better affinity with PCA5mer than GVL, GVL is among the most effective solvents and ranks second among green alternatives, following DMI. Interestingly, GVL is predicted to be more efficient than the toxic and dipolar acetonitrile. The predicted negative ln g N PCA-5mer value in GVL indicates negative deviations from ideal mixture behavior, which is a favorable factor in terms of the dissolution and solubility of PCA-5mer or lignin. Next, the COSMO-SAC analysis was extended to water/solvent binary mixtures. Fig. 2(b) shows the predicted course of ln g N PCA-5mer as a function of water mole percent in aqueous mixtures of ve selected solvents: DMI, GVL, THF, 1,4-dioxane, and BHGBL. Interestingly, in each considered system, ln g N PCA5mer does not follow a simple, monotonic trend between its Fig. 2 Activity coefficients of PCA-5mer at infinite dilution in (a) various neat solvents and (b) five selected water/solvent binary mixtures as a function of water mol%, as predicted by the open-source COSMO-SAC model. All results correspond to a temperature of 298 K. Solvent abbreviations are provided in SI Section S4. (a) also includes electrostatic potential maps of the solute PCA-5mer and solvent GVL, calculated using QM at the DFT/BVP86/TZVP/C-PCM level as part of their s-profile determination. The triangles in (b) indicate the minima on the respective curves. © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability,2025,3,4533–4555 | 4539 Paper RSC Sustainability Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online values in the pure organic solvent and pure water but instead exhibits a (favorable) minimum. This suggests that adding water (from small amounts up to 30–70 mol% water, depending on the specic solvent/water system) enhances the solvent efficiency for PCA-5mer, compared to the neat solvent, despite water itself having very poor affinity for hydrophobic PCA-5mer, as shown in Fig. 2(a). This indicates a strong cooperative effect between the considered solvents and water and highlights the importance of excess thermodynamic properties in the case of non-additive solution behavior. The only exception where the cooperative effect is not as signicant is the aqueous solution of BHGBL. This can be explained by the fact that, while the other four organic solvents exhibit only hydrogen bond acceptor ability, BHGBL contains a hydroxyl group, making it both a hydrogen bond donor and acceptor. This dual character may increase the “similarity”between water and BHGBL, rendering their mixture more thermodynamically ideal and thus lacking a signicant extremum in ln g N PCA-5mer. The position and “depth”of the ln g N PCA-5mer minimum, corresponding to maximum solubility enhancement, vary between systems. For GVL/water, the minimum was predicted to occur at 70 mol% GVL, which corresponds to 93 wt% GVL. This fully supports the 9/1 (wt/wt) GVL/water ratio used in experiments in this and previous research 39 and aligns perfectly with the optimal GVL weight percent (92–96%) estimated by L´ e et al. 51 using Hildebrand solubility parameters. Another interesting observation concerns the two green solvents: DMI and GVL. While pure DMI was predicted to be slightly more efficient than pure GVL (see Fig. 2(a)), mixing with water reverses their relative order. The decrease in g N PCA-5mer values is more pronounced for the GVL/water system, resulting in a lower minimum g N PCA-5mer than that observed for DMI/water, as shown in Fig. 2(b). The observations made in this section align with experimental ndings of lignin solubility in GVL/water mixtures at different compositions. GVL/water mixtures dissolved default organosolv lignin in different amounts, leading to the ternary phase diagram depicted in SI Section S5. In contrast to recent ndings from L´ eet al., 101 who predicted the highest solubility of lignin to be in pure GVL, our solvent mixture of GVL/water showed a clear increase in lignin solubility at mixtures of GVL with low weight percentages of water. The lignin solubility was 45 wt% in a GVL/water 9/1 wt/wt mixture, and 40 wt% in pure GVL. The full ternary phase diagram can be seen in SI Section S5. These experimental ndings correlate with the simulation ndings and also add to the suggestion of a synergistic effect of water and GVL at high GVL weight percentages. At low GVL percentages, lignin begins to show only minimal solubility, which is used when precipitating the extracted lignin from the extraction solvent via the addition of large amounts of water. The predictive thermodynamic analysis performed in this section with COSMO-SAC also identied the GVL/water system with ca. 9/1 (wt/wt) ratio as an optimal solvent medium candidate for lignin, balancing efficiency with sustainability. However, COSMO-SAC provides only limited insight into the behavior of systems at the molecular and atomic levels. Therefore, the following section presents the results of MD simulations conducted to elucidate ner interactional and structural aspects of the GVL/water system with PCA-5mer as the solute. 3.1.2 MD simulations. In order to rationalize the microscopic origin of lignin, atomistic MD simulations of PCA-5mer in neat solvents and in the equimolar GVL/water mixture were performed. For a detailed insight into PCA-5mer-/solvent interactions, spatial distribution functions were used to visualize locations of signicantly increased density of solvent molecules (opaque clouds indicate regions with 5×higherthan-average density, while transparent clouds indicate 3×). The distributions of water oxygen, carbonyl oxygen of GVL (representing the polar part) and ring carbon of GVL (representing the non-polar part) around the PCA-5mer molecule are presented in Fig. 3. These results demonstrate that pure water (lepanel, red clouds) interacts primarily with the polar hydroxyl (OH) groups of PCA-5mer, to much lesser extent affinity with the faces of aromatic ring, but the non-polar part of Fig. 3 Synergy in hydration and solvation of a swollen configuration (R g ∼0.85 nm) of PCA-5mer in pure solvents (left) and in their 50 mol% (ca. 85 w%) mixture (right). Spatial distribution of water (oxygen in red), polar carbonyl oxygen of GVL (in gold), and non-polar carbon atom of GVL (in cyan) are shown at two isocontour levels; 3×and 5×increased probabilities are denoted as transparent and opaque clouds (as illustrated by red arrows on water oxygen distributions). Compared to pure solvents, both water hydration of hydroxyl groups and hydrophobic interaction of GVL with hydrophobic moieties are significantly strengthened, with mild decrease of GVL carbonyl H-bonding interaction with hydroxyl groups. Impact of solvent quality (water vs. GVL) on a PCA-5mer conformation is captured in distribution of polymer size (radius of gyration), in the most right panel. Visualization of the regions of increased density of solvent molecules, analysis for collapsed configuration of PCA-5mer and comparison of solvation of rigid structures to flexible ensembles are provided in detail in the SI Section S6. 4540 |RSC Sustainability,2025,3,4533–4555 © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability Paper Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online PCA-5mer remains poorly hydrated. In contrast, the overall attractive GVL-PCA-5mer interactions arise favorable interaction between carbonyl oxygen of GVL (gold clouds) with polar OH groups combined with favorable interactions between the non-polar moieties of GVL (cyan clouds) and the aromatic ring and attached aliphatic group of PCA-5mer. The amphiphilic nature of GVL thus rationalizes its efficiency in the lignin dissolution since both polar and non-polar parts of PCA-5mer are well solvated in GVL. Since both experimental results and COSMO-SAC analysis indicate that the ca. 9/1 (wt/wt) GVL/water mixture is optimal for efficient PCA-5mer/lignin dissolution, we decided to investigate the intermolecular interactions occurring in the equimolar mixture of GVL and water. Note that equimolar composition of GVL/water mixture corresponds to approximately 85 wt% GVL which is close to the optimal mixture composition used in the experimental part of this paper. The analysis of the equimolar GVL/water mixture reveals that interactions of carbonyl oxygens of GVL with OH groups of PCA-5mer are partially replaced by stronger hydrogen bonds with water. This enhanced selective hydration of PCA-5mer hydroxyls is complemented by the stabilizing interaction between non-polar domain of PCA-5mer and non-polar part of GVL molecule, as water only poorly hydrates the hydrophobic regions of PCA-5mer. These concerted interactions between water, GVL and the PCA-5mer surface are visually documented in Fig. 3, where growing clouds indicate regions of increased solvent density. These structural changes are quantied in SI Section S6. Major changes occur within the rst solvation shell (∼4 Å) around the polar and non-polar regions of PCA-5mer. There is a shi towards better PCA-5mer solvation when transitioning from pure solvent to the equimolar mixture. Therefore, the presence of GVL in the solvent mixture allows water to selectively interact with the polar parts of PCA-5mer, while the non-polar part of GVL provides stabilizing interactions with the aromatic ring of PCA-5mer. This synergistic effect results in a more efficient solubilization of PCA-5mer compared to pure solvents. This effect is conditioned by the complete miscibility of GVL and water. These results suggest that the intermolecular interactions occurring in the GVL/water mixture with PCA are not merely a trivial combination of effects occurring in pure solvents. This insight opens a new pathway for future theoretical studies focused on aqueous mixtures of GVL (or similar solvents) with the aim to systematically and more thoroughly examine the nature of these interactions and their impact on biomass component dissolution. More importantly, these insights also support the effectiveness of the GVL/water mixture, and herein the green solvent GVL, in lignocellulosic biomass fractionation, as the solvent can effectively dissolve and thus separate lignin from biomass. 3.2 GVL-assisted biomass fractionation 3.2.1 Lignin extraction using acidic GVL/water mixtures. In this main part of the study, the focus was on experimentally determining whether the chosen extraction process, which is Table 1 Analysis of the lignin content for different types of biomasses, including wood and different waste streams, using the CASA method described in chapter 2.7.2. The lignin was extracted through the GVL-assisted organosolv process described in chapter 2.2. The extractions were conducted in triplicates, meaning each biomass sample was used as a substrate three subsequent times to remove most of the lignin from the biomass. The yield is given as a percentage of the determined lignin content in the respective type of biomass. Additionally, the purity of the extracted lignin was determined through the CASA method, as certain extractives (degraded sugars, proteins, ash) might be co-extracted and reside in the lignin samples Type of biomass Lignin content [wt%] Step 1 extraction yield [% of lignin content] Step 1 lignin purity [%] Step 2 extraction yield [% of lignin content] Step 2 lignin purity [%] Step 3 extraction yield [% of lignin content] Step 3 lignin purity [%] Triplicate extraction yield [% of lignin content] Purity of extracted lignin [%] Spruce sawdust 22 1572941281931121931973931 Coffee silverskin 21 161296121296151961876961 Walnut shell 28 1531941271931100931902931 Hazelnut shell 29 1511951280931130931921931 Peanut skin 26 1461941340901150901951901 Peanut shell 33 1411871340831141832892832 Pistachio shell 15 1431911331893140893902893 Almond shell 29 1502911301901120901923901 Cashew shell 27 1454952321933151964926964 Beech sawdust 22 1511941281941150931942931 Birch sawdust 23 1531941270941150931951931 © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability,2025,3,4533–4555 | 4541 Paper RSC Sustainability Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online xylose, glucose, and smaller amounts of different hexoses and pentoses, as hemicellulose composition varies depending on the origin biomass. Depending on the need for certain applications, other protected sugars can be isolated for biomasses that have a low xylose content and higher contents of other sugar monomers. For protected xylose and glucose, applications can be found by varying the protecting agent and performing modication reactions, introducing functional groups into the xylose/glucose structure that can, e.g., induce curing reactions in resin formulations. Additionally, xylose can always be deprotected in a slightly acidic environment and used to produce the solvent GVL. 117 The isolated cellulose was analyzed on its yield and purity, which was compared for a default extraction process using only an acidic mixture of GVL/water, and a modied extraction process introducing a protecting agent for lignin and hemicellulose extraction. The latter yielded a purer cellulose aer one extraction step at milder conditions compared to three extraction steps at harsher conditions for the default extraction process. The purer cellulose can be used for further valorization, which involves nding a green and efficient solvent for cellulose dissolution. Lowering the dissolution temperature and increasing the soluble amount of cellulose while maintaining the fast dissolution times and low viscosities are all challenges on cellulose solubilization that will be addressed in future work. The detailed, stepwise overview of the fractionation and decomposition of lignocellulosic biomass is nally shown in Fig. 8. Our process of complete biomass fractionation tackles different problems of many other solvent systems that have been developed for this purpose. Most organosolv processes use highly ammable or hazardous solvent mixtures in large amounts, resulting in high costs for emissions and solvent consumption. 56,68–70 The problem of using hazardous solvents and having high solvent production costs is also a problem of processes based on IL's, including their difficult recovery. 57,58,60 Using acidic mixtures of GVL/aldehyde with small amounts of water signicantly lowers the solvent consumption of the extraction to a minimum of 1 mL solvent per 0.15 g of biomass in our process. The solvent consumption of the lignin separation through precipitation could be more than halved by using a nonpolar precipitation route. Moreover, GVL and water, forming 97% of the solvent mixture, are considered green solvents due to low vapor pressure, low ammability, and general non-toxicity. However, the aldehyde used can pose minimal risks, as some aldehydes we used are classied as hazardous (propionic aldehyde, acetaldehyde). These could and should be used stoichiometrically and be replaced with less hazardous alternatives, like benzaldehyde. Also, the washing step and the precipitation system include solvents like heptane, ethyl acetate, methanol, and diethyl ether, which should all be replaced by greener alternatives in the future. For now, their use Fig. 7 Visualization of the complete lignocellulosic biomass separation, dissolution, and degradation using the green solvent GVL. Zero waste is left from the initial biomass. This process can be used for every lignocellulosic biomass, be it wood, nutshells, or different lignocellulosic wastestreams. 4548 |RSC Sustainability,2025,3,4533–4555 © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability Paper Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online reduces the solvent consumption for precipitation and the efficiency of the lignin workup. The solvent mixture itself is also fully reusable and achieves similar results aer a reuse in the extraction process. Aer separation of the biopolymers, pure GVL, water, and residual aldehyde could be regained through simple evaporation. With the regeneration of the original composition, the solvent mixture can be fully reused. To increase solvent availability, GVL can even be produced from hemicellulose fractionation products. 117 To further reduce energy consumption of the recycling process, ways have to be found to separate the solvents from the biopolymers through liquid–liquid extraction or similar methods. A bigger problem in suggested biomass fractionation processes, including organosolv, DES, and IL's, is the high process energy consumption, 57,58,64,65 coupled to a medium efficiency with not necessarily all biopolymers being accessible in high quality. 59,62,63,66,67 While some processes achieve complete fractionation with high yields, their product quality is not sufficient enough for every biopolymer, and their process energy consumption is very high, usually using temperatures of >160 °C, long reaction times >24 h and high pressures. 56 Our process combines a comparably mild method, only using 85 °C and 3 h of full processing time under slightly acidic conditions (pH ∼2). Still, our process can fractionate all biopolymers in very high yields with very high purities. Additionally, the quality of the biopolymers is not altered signicantly from their appearance in lignocellulosic biomass. Lignin structures are broken down into large oligomers, preserving their native structure through acetal-protection, which can be lied in acidic medium. Many other pulping processes alter the structure of the lignin or introduce condensation, which blocks certain ways of valorization. 23–29 Hemicellulose is regained in monomeric form as mainly protected xylose and protected glucose, leaving room for different valorization options. Cellulose is regained lignin-free and can be used for different processes like the production of cellulosic bers or enzymatic hydrolysis towards sugars. Possible improvements to our process could of course include the further reduction of process energy consumption, retaining the achieved quality of the fractionated biopolymers. Another huge advantage of our process is its biodiversity. While other processes specically mention their use on one specic type of biomass, 59,62,63 our process has been adapted to serve the fractionation of many different types of biomasses. This includes typical woods, but also more or less waste streams like nutshells or coffee silverskin. Also, the only pretreatment is their drying to remove extensive moisture contents. However, a future challenge will be the scalability of this process, as this process will have to be integrated with existing biorenery infrastructure, especially the further use of extracted biopolymer products. Lignin can be used in many applications, such as antioxidant formulations, 33,34,118 UV-protection lms or coatings for food or Fig. 8 Detailed overview of the fractionation of lignocellulosic biomass and conversion towards monomeric lignin and hemicellulose units. © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability,2025,3, 4533–4555 | 4549 Paper RSC Sustainability Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online human skin, 30–32 as occulants aer chemical modication, 119 or in bio-based phenolic resins. 120,121 Specically, lignin monomers can be produced, which can have further valuable applications. This includes uses as avor or fragrance ingredients, as monolignols like 4-propyl-syringol or 4-propy-guaiacol are already considered as such. 35,122,123 They can also be regarded as antioxidants. 124 A very important application can be the use of lignin and hemicellulose monomers in various bio-based resin formulations. This topic is currently researched by our group and will be regarded in the future in a separate publication. Lignin monomers can therefore act as bisphenol A substitutes in epoxy resins, as curing agents aer chemical modication, or as monomeric units in other resin types. A similar application can be found for degraded hemicellulose products, specically protected xylose and glucose molecules. By varying the protecting agent, different functional groups can be introduced that can induce an application as resin monomers. To round out the process of green dissolution of lignocellulosic biomass, xylose, specically aer deprotection in lightly acidic medium, can always be used to produce GVL for further extractions. 46–48 Both biopolymers show valuable applications aer considering their molecular structure aer extraction and selecting the optimal biomass for a certain application. While cellulose was regained lignin-free and must be dissolved for further use. The dissolution of cellulose is a big problem nowadays, as existing processes are neither green enough (they use too much energy or produce hazardous byproducts) nor efficient enough. Process alternatives or improvements have to be found in order to dissolve and regenerate cellulose bers to produce many valuable bio-based products. 125–130 This topic will be addressed in the future in an upcoming project. What separates our process from existing literature on GVLbased organosolv processes is the overall yield of uncondensed lignin. While existing literature nds mostly up to 60% of lignin yield at typical organosolv conditions, 39 which is then very condensed and prohibits a further use in several applications or degradation processes, and disregards other biopolymers present in biomass, our process combines the GVL organosolv process with the aldehyde-assisted process, yielding then up to 99% uncondensed lignin aer a single extraction step under milder conditions. Additionally, the biopolymers cellulose and hemicellulose can be retained in very high purity up to 99%. This shows that our process can be the next step in realizing GVL-based biorenery, producing all components of lignocellulosic biomass in high yields and purities with green solvents and mild conditions. An important note is that our process uses biodiverse starting material, from lignocellulosic waste materials such as nutshells to different types of wood, with no clear setback in process efficiency. While this article describes the basis of a scalable process for sustainable biomass fractionation, follow-up articles will describe the detailed extraction and characterization of lignin with different properties depending on the extraction conditions, making a tailoring of lignin products for specic applications possible. 131 Additionally, we will follow-up on the cellulose fractionation by introducing novel cellulose dissolution strategies involving our lignin-free cellulose from biomass. Regarding the hemicellulose degradation products, we are currently working on the valorization options for the protected sugars in resin formulations or solvent applications, which will also be addressed in future works. 4 Conclusion and outlook GVL, especially in combination with water at 9/1 wt/wt, can dissolve lignin in an effective way to facilitate biomass fractionation. This was underlined through the use of COSMO-SAC and MD simulations, which showed that the presence of GVL in the solvent allows water to interact with polar parts of lignin more efficiently, while GVL itself interacts with the aromatic core of lignin structures in a stabilizing manner. This makes for a synergistic effect between GVL and small amounts of water compared to the pure solvents. Thorough systematic computational investigations of dissolution capabilities of pure and mixed solvents on biomass components by means of both COSMO-SAC and MD simulations will be conducted as separate studies. Experimentally, starting from source-independent lignocellulosic biomass, the theoretical considerations on the simpli- ed lignin system were proven to be right as it was shown that the green solvent GVL can efficiently fractionate all its main ber components, lignin, hemicellulose, and cellulose. The process of using GVL with lignin protection-agents greatly improves biopolymer fractionation, leading to native lignin structures with high yields and purities, acetalized hemicellulose monomers, and lignin-free cellulose. The process uses mild conditions of 85 °C and 3 h reaction time, while also providing complete reusability of the solvents. This completes a full biodiverse fractionation process of lignocellulosic biomass, improving on existing processes in literature and leading to three valuable and pure biopolymer products that can be further studied for their valorization. This work will be continued in our future research on lignin and hemicellulose valorization, tailoring their properties during extraction for specic applications, and on cellulose dissolution for industrial ber production using novel approaches to replace existing processes. Overall, this work provides clear insights into the green, mild, and biodiverse fractionation of lignocellulosic biomass with GVL and its possible ways of improvement and further valorization of the high quality biopolymer products. Our process of biomass fractionation combines signicant advantages of previously developed processes, while improving on their problems. Still, improvements to parts of the process, such as solvent consumption or replacement of the protection agents with greener alternatives have to be made to achieve full implementation of this process in biorenery. Author contributions Moritz Schweiger: conceptualization, data curation, investigation, formal analysis, visualization, methodology, writing – original dra. Thomas Lang: investigation, formal analysis, 4550 |RSC Sustainability,2025,3, 4533–4555 © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability Paper Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online validation. Eva Müller: writing –review & editing, supervision, conceptualization. Didier Touraud: conceptualization, writing – review & editing. Werner Kunz: writing –review & editing, supervision, resources, project administration, funding acquisition. Vojtˇ ech Jeˇ r´ abek: investigation, formal analysis, visualization, writing –original dra. Martin Klajmon: investigation, formal analysis, data curation, visualization, writing-original dra, methodology, funding acquisition. Jan Heyda: investigation, formal analysis, data curation, visualization, writing – original dra. Magdalena Bendova: writing –review & editing, resources. Karel ˇ Reh´ ak: writing –review & editing, resources. Conflicts of interest There are no conicts to declare. Data availability Should any data les be needed in another format, they are available from the corresponding author upon reasonable request. The data supporting this article have been included in the text and as part of the SI. See DOI: https://doi.org/10.1039/ d5su00600g. Acknowledgements The German authors acknowledge the nancial support of KVTTechnology (Graz, Austria) and their cooperation with our department of physical chemistry II at the University of Regensburg. We also acknowledge the support of the project “AI-supported search for environmentally acceptable solvents for the dissolution and stabilization of biopolymers for their utilization as sustainable materials”, funded by the BayerischTschechische Hochschulagentur (BTHA) as project BTHA-JC2024-57. The Czech authors acknowledge the nancial support from the LUABA24070 joint project of The Ministry of Education, Youth and Sports of the Czech Republic and The Bavarian-Czech Academic Agency. This work was also supported by the project “The Energy Conversion and Storage”, funded as project No. CZ.02.01.01/00/22_008/0004617 by Programme Johannes Amos Comenius, call Excellent Research and by the Ministry of Education, Youth and Sports of the Czech Republic through the e-INFRA CZ (ID:90254). V. J. acknowledges the support of the grants of Specic university research –grants No. A1_FCHI_2025_001 and No. A2_FCHI_2025_009. References 1 A. Lorenz, When will we run out of fossil fuels?. Fairplanet: Sustainable Consumption; 2023, cited 2024 Jan 20, available from, https://www.fairplanet.org/story/when-will-we-runout-of-fossil-fuels/. 2F.K ¨ ahler, O. Porc and M. Carus, RCI Carbon Flows Report: Compilation of Supply and Demand of Fossil and Renewable Carbon on a Global and European Level, Nova Institute, 2023. 3 C. Ververis, K. Georghiou, N. Christodoulakis, P. Santas and R. Santas, Fiber dimensions, lignin and cellulose content of various plant materials and their suitability for paper production, Ind. Crops Prod., 2004, 19(3), 245–254. 4 B. O. Abo, M. Gao, Y. Wang, C. Wu, H. Ma and Q. Wang, Lignocellulosic biomass for bioethanol: an overview on pretreatment, hydrolysis and fermentation processes, Rev. Environ. Health, 2019, 34(1), 57–68. 5 B. Singh, J. Korstad, A. Guldhe and R. Kothari, Editorial: Emerging Feedstocks & Clean Technologies for Lignocellulosic Biofuel, Front. Energy Res., 2022, 10, 917081. 6 M. Mujtaba, L. F. Fraceto, M. Fazeli, S. Mukherjee, S. M. Savassa, G. A. de Medeiros, et al., Lignocellulosic biomass from agricultural waste to the circular economy: a review with focus on biofuels, biocomposites and bioplastics, J. Cleaner Prod., 2023, 402, 136815. 7 E. Kocaturk, T. Salan, O. Ozcelik, M. H. Alma and Z. Cancan, Recent Advances in lignin-Based Biofuel Production, Energies, 2023, 16(8), 3382. 8 V. Ashokkumar, K. Ramaswamy, M. Popat, M. Asokan, S. Devendran, K. Arutselvan, et al., Recent advances in lignocellulosic biomass for biofuels and value-added bioproducts –a critical review, Bioresour. Technol., 2022, 344B, 126195. 9 H. Li, S. Saravanamurugan, A. Pandev and S. Elumalai, Biochemicals and materials production: an introduction, in Biomass, Biofuels, Biochemicals: Biochemicals and Materials Production from Sustainable Biomass Resources, Elsevier Inc., 2022, pp. 1–8. 10 B. Xu, J. Dai, Z. Du, F. Li, H. Liu, X. Gu, et al., Catalytic conversion of biomass-derived compounds to various amino acids: status and perspectives, Front. Chem. Sci. Eng., 2023, 17, 817–829. 11 A. Jaswal, P. P. Sing and T. Mondal, Furfural –a versatile, biomass-derived platform chemical for the production of renewable chemicals, Green Chem., 2022, 24(2), 510–551. 12 P. A. Son, S. Nishimura and K. Ebitani, Production of gvalerolactone from biomass-derived compounds using formic acid as a hydrogen source over supported metal catalysts in water solvent, RSC Adv., 2014, 4(21), 10525– 10530. 13 N. Singh, R. R. Singhania, P. S. Nigam, C. Dong, A. K. Patel and M. Puri, Global status of lignocellulosic biorenery: Challenges and perspectives, Bioresour. Technol., 2022, 344B, 126415. 14 X. Zhou, L. J. Broadbelt and R. Vinu, Mechanistic Understanding of Thermochemical Conversion of Polymers and Lignocellulosic Biomass, Adv. Chem. Eng., 2016, 49,95–198. 15 E. Jamet, H. Canut, G. Boudart and R. F. Pont-Lezica, Cell wall proteins: a new insight through proteomics, Trends Plant Sci., 2006, 11(1), 0–39. 16 J. Berglund, K. Svedström, M. Khayyami and P. Gatenholm, Wood hemicelluloses exert distinct biomechanical contributions to cellulose brillar networks, Nat. Commun., 2020, 11, 4692. © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability,2025,3,4533–4555 | 4551 Paper RSC Sustainability Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online 17 H. V. Scheller and P. Ulvskov, Hemicelluloses, Annu. Rev. Plant Biol., 2010, 61, 263–289. 18 R. W. Detroy, M. E. Himmel, J. O. Baker, W. S. Adney, S. R. Thomas, R. A. Nieves, et al., Bioconversion of wheat straw cellulose/hemicellulose to ethanol by Saccharomyces uvarum and Pachysolen tannophilus, Biotechnol. Bioeng., 1982, 24(5), 1105–1113. 19 P. H. F. Pereira, W. R. Waldman, J. M. Marconcini and L. H. C. Mattoso, Wheat straw hemicellulose added with cellulose nanocrystals and citric acid: Effect on lm physical properties, Carbohydr. Polym., 2017, 164, 317–324. 20 X. Liu, J. Ren, J. Song, X. Fu, S. Wang, Y. Zhou, et al., Hemicellulose from plant biomass in medical and pharmaceutical application: A critical review, Curr. Med. Chem., 2019, 26(14), 2430–2455. 21 P. Nechita, R. Mirela and F. Ciolacu, Xylan Hemicellulose: a renewable material with potential properties for food packaging applications, Sustainability, 2021, 13(24), 13504. 22 P. Kalita, P. Datta and P. K. Baruah, Conversion of fructose and xylose into platform chemicals using organofunctionalized mesoporous material, ChemistrySelect, 2018, 3, 10971–10976. 23 M. Graglia, Lignin Valorization [PhD Thesis], University of Potsdam, 2017. 24 C. Chio, M. Sain and W. Qin, Lignin utilization: a review of lignin depolymerization from various aspects, Renewable Sustainable Energy Rev., 2019, 107, 232–249. 25 S. H. Ghaffar and M. Fan, Lignin in straw and its applications as an adhesive, Int. J. Adhes. Adhes., 2014, 48, 92–101. 26 R. M. Trevorah and M. Z. Othman, Alkali Pretreatment and Enzymatic Hydrolysis of Australian Timber Mill Sawdust for Biofuel Production, J. Renewable Energy, 2015, 2015, 284250. 27 D. S. Bajwa, G. Pourhashem, A. H. Ullah and S. G. Bajwa, A concise review of current lignin production, applications, products and their environmental impact, Ind. Crops Prod., 2019, 139, 111526. 28 S. Jampa, A. Puente-Urbina, Z. Ma, S. Wongkasemjit, J. S. Luterbacher and J. A. van Bokhoven, Optimization of Lignin Extraction from Pine Wood for Fast Pyrolysis by Using a g-Valerolactone-Based Binary Solvent System, ACS Sustain. Chem. Eng., 2019, 7(4), 4058–4068. 29 D. Watkins, M. Nuruddin, M. Hosur, A. Tcherbi-Narteh and S. Jeelani, Extraction and characterization of lignin from different biomass resources, J. Mater. Res. Technol., 2015, 4(1), 26–32. 30 G. K. K. Anushikha, Lignin as a UV blocking, antioxidant, and antimicrobial agent for food packaging applications, Biomass Convers. Bioren., 2023, 14, 16755–16767. 31 A. Halloub, M. Raji, H. Essabir, H. Chackchak, R. Boussen, M. Bensalah, et al., Intelligent food packaging lm containing lignin and cellulose nanocrystals for shelf life extension of food, Carbohydr. Polym., 2022, 296, 119972. 32 M. H. Tran, D. Phan and E. Y. Lee, Review on lignin modications toward natural UV protection ingredient for lignin-based sunscreens, Green Chem., 2021, 23(13), 4633– 4646. 33 X. Lu, X. Gu and Y. Shi, A review on lignin antioxidants: their sources, isolations, antioxidant activities and various applications, Int. J. Biol. Macromol., 2022, 210, 716–741. 34 S. Kang, J. Chang and J. Fan, Phenolic Antioxidant Production by Hydrothermal Liquefaction of Lignin. Energy Sources A: Recovery Util, Environ. Eff., 2015, 37(5), 494–500. 35 T. Ren, Z. Zhang, S. You, W. Qi, R. Su and Z. He, Isolation and purication of 4-propylguaiacol and 4-propylsyringol by extraction and crystallization from the products of reductive catalytic fractionation processes, Green Chem., 2022, 24(19), 7355–7361. 36 Y. Li, J. Zhu, Z. Zhang and Y. Qu, Preparation of Syringaldehyde from Lignin by Catalytic Oxidation of Perovskite-Type Oxides, ACS Omega, 2020, 5(5), 2107–2113. 37 M. Fache, B. Boutevin and S. Caillol, Vanillin Production from Lignin and its Use as a Renewable Chemical, ACS Sustain. Chem. Eng., 2016, 4(1), 35–46. 38 C. Isola, H. L. Sieverding, A. M. Numan-Al-Mobin, R. Rajappagowda, E. A. Boakye, D. E. Raynie, et al., Vanillin derived from lignin liquefaction: a sustainability evaluation, Int. J. Life Cycle Assess., 2018, 23, 1761–1772. 39 F. Cheng, S. Liu, S. D. Karlen, H. Kim, F. Lu, J. Ralph, et al., Poplar lignin structural changes during extraction in gvalerolactone (GVL), Green Chem., 2023, 25(1), 336–347. 40 C. Gioia, M. Colonna, A. Tagami, L. Medina, O. Sevastyanova, L. A. Berglund, et al., Lignin-Based Epoxy Resins: Unravelling the Relationship between Structure and Material Properties, Biomacromolecules, 2020, 21(5), 1920–1928. 41 W. Lan, M. T. Amiri, C. M. Hunston and J. S. Luterbacher, Protection Group Effects During a,g-Diol Lignin Stabilization Promote High-Selectivity Monomer Production, Angew. Chem., Int. Ed., 2018, 57(5), 1356–1360. 42 J. H. Clark and J. Duncan, Handbook of Green Chemistry and Technology, Blackwell Science Ltd, 2002. 43 P. T. Anastas and J. C. Warner, Green Chemistry: Theory and Practice, Oxford University Press, 1998, p. 30. 44 C. Y. Y. Wong, A. W. Choi, M. Y. Lui, B. Fridrich, A. K. Horv´ ath, L. T. Mika, et al., Stability of gammavalerolactone under neutral, acidic, and basic conditions, Struct. Chem., 2017, 28, 423–429. 45 C. Ortiz-Cervantes, M. Flores-Alamo and J. J. Garcia, Hydrogenation of biomass-derived levulinic acid into gvalerolactone catalyzed by palladium complexes, ACS Catal., 2015, 5(3), 1424–1431. 46 B. Liu, X. Chen, Y. Xu, C. Qiao, Z. Lu and Y. Tian, A combo Zr-zeolite and Zr(OH) 4 mixture composition for one-pot production of g-valerolactone from furfural, Renewable Energy, 2024, 229, 120751. 47 B. Qiu, J. Shi, W. Hu, Y. Wang, D. Zhang and H. Chu, Efficient and selective conversion of xylose to furfural over carbon-based solid acid catalyst in water-g-valerolactone, Energy, 2024, 294, 130774. 4552 |RSC Sustainability,2025,3,4533–4555 © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability Paper Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online 48 J. Qiu, Y. Liu, J. Zhang, B. Zhou, Q. Yang, L. Zhang, et al., One-pot cascade process for efficient upgrading of furfural to g-valerolactone over adjustable Lewis-Bronsted bi-acidic catalyst, Ind. Crops Prod., 2024, 214, 118474. 49 D. di Menno di Bucchianico, G. E. Scarponi, J.-C. Buvat, S. Leveneur and V. C. Moreno, From biomass-derived fructose to g-valerolactone: process design and technoeconomic assessment, Bioresour. Technol., 2024, 401, 130753. 50 J. S. Luterbacher, J. M. Rand, D. M. Alonso, J. Han, J. T. Youngquist, C. T. Maravelias, et al., Nonenzymatic sugar production from biomass using biomass-derived gvalerolactone, Science, 2014, 343(6168), 277–280. 51 H. Q. Le, A. Zaitseva, J.-P. Pokki, M. Stahl, V. Alopaeus and H. Sixta, Solubility of organosolv lignin in g-valerolactone/ water binary mixtures, ChemSusChem, 2016, 9, 2939–2947. 52 B. Yang, S. Zhang, H. Hu, C. Duan, Z. He and Y. Ni, Separation of hemicellulose and cellulose from wood pulp using a g-valerolactone (GVL)/water mixture, Sep. Purif. Technol., 2020, 248, 117071. 53 A. Freyburger, Novel Bio-Based Materials from Cellulose and Chitin dissertation, University of, Regensburg, 2018. 54 H. Q. Lˆ e, J. Pokki, M. Borrega, P. Uusi-Kyyny, V. Alopaeus and H. Sixta, Chemical Recovery of g-Valerolactone/Water Biorenery, Ind. Eng. Chem. Res., 2018, 57(44), 15147– 15158. 55 M. Granatier, H. Q. Le, Y. Ma, M. Rissanen, I. SchlappHackls, D. Diment, et al.,g-Valerolactone biorenery: catalyzed birch fractionation and valorization of pulping streams with solvent recovery, Heliyon, 2023, 9, e17423. 56 D. J. G. P. Van Osch, L. J. B. M. Kollau, A. Van den Bruinhorst, S. Asikainen, M. A. A. Rocha and M. C. Kroon, Ionic liquids and deep eutectic solvents for lignocellulosic biomass fractionation, Phys. Chem. Chem. Phys., 2017, 19, 2636–2655. 57 A. M. Da Costa Lopes, K. G. Jo˜ ao, A. R. Morais, E. BogelLukasik and R. Bogel-Lukasik, Ionic liquids as a tool for lignocellulosic biomass fractionation, Sustainable Chem. Processes, 2013, 1,3. 58 M. Smuga-Kogut, D. Szymanowska-Powalowska, R. Markiewicz, T. Piskier and T. Kogut, Ionic liquid pretreatment of stinging nettle stems and giant miscanthus for bioethanol production, Sci. Rep., 2021, 11, 184565. 59 A. Brandt-Talbot, F. J. V. Gschwend, P. S. Fennell, T. M. Lammens, B. Tan, J. Weale, et al., An economically viable ionic liquid for the fractionation of lignocellulosic biomass, Green Chem., 2017, 19, 3078–3102. 60 E. Husanu, A. Mero, J. G. Rivera, A. Mezzetta, J. C. Ruiz, F. D'Andrea, et al., Exploiting deep eutectic solvents and ionic liquids for the valorization of chestnut shell waste, ACS Sustain. Chem. Eng., 2020, 8, 18386–18399. 61 M. Gholami, Regeneration of Deep Eutectic Solvent Post Biomass Delignication [dissertation], University of Twente, 2024. 62 M. Jablonsky, A. Skulcova, L. Kamenska, M. Vrska and J. Sima, Deep eutectic solvents: fractionation of wheat straw, Bioresearch, 2015, 10(4), 8039–8047. 63 S. Magalhaes, A. Moreira, R. Almeida, P. F. Cruz, L. Alves, C. Costa, et al., Acacia wood fractionation using deep eutectic solvents: extraction, recovery, and characterization of the different fractions, ACS Omega, 2022, 7, 26005–26014. 64 A. Mero, N. R. Moody, E. Husanu, A. Mezzetta, F. D'Andrea, C. S. Pomelli, et al., Challenging DES and ILs in the valorization of food waste: a case study, Front. Chem., 2023, 11, 1270221. 65 Y. Liu, N. Deak, Z. Wang, H. Yu, L. Harneleers, E. Jurak, et al., Tunable and functional deep eutectic solvents for lignocellulose valorization, Nat. Commun., 2021, 12, 5424. 66 J. L. Espinoza-Acosta, B. Ramirez-Wong, E. Carvajal-Millan, P. I. Torres-Chaves, B. Montano-Leyva and L. A. Bello-Perez, Ionic liquids and organic solvents for recovering lignin from lignocellulosic biomass, Bioresearch, 2014, 9(2), 3660–3687. 67 L. G. Nair, K. Agrawal and P. Verma, Organosolv pretreatment: an in-depth purview of mechanics of the system, Bioresour. Bioprocess., 2023, 10, 50. 68 D. W. K. Chin, S. Lim, Y. L. Pang and M. K. Lam, Fundamental review of organosolv pretreatment and its challenges in emerging consolidated bioprocessing, Biofuels, Bioprod. Bioren., 2020, 14, 808–829. 69 M. Chen, F. Malaret, A. E. J. Firth, P. Verdia, A. R. Abouelela, Y. Chen, et al., Design of a combined ionosolv-organosolv biomass fractionation process for biofuel production and high value-added lignin valorization, Green Chem., 2020, 22, 5161–5180. 70 D. W. K. Chin, S. Lim, Y. L. Pang, C. H. Lim, S. H. Shuit, K. M. Lee, et al.,Effects of organic solvents on the organosolv pretreatment of degraded empty fruit bunch for fractionation and lignin removal, Sustainability, 2021, 13, 6757. 71 W. Lan, J. B. de Bueren and J. S. Luterbacher, Highly selective oxidation and depolymerization of a,g-diolprotected lignin, Angew. Chem., Int. Ed., 2019, 58, 2649– 2654. 72 F. Lu, C. Wang, M. Chen, F. Yue and J. Ralph, A facile spectroscopic method for measuring lignin content in lignocellulosic biomass, Green Chem., 2021, 23, 5106–5112. 73 Y. Chu and X. He, MoDoop: an automated computational approach for COSMO-RS prediction of biopolymers in ionic liquids, ACS Omega, 2019, 4(1), 1–12. 74 A. Casas, S. Omar, J. Palomar, M. Oliet, M. V. Alonso and F. Rodriguez, Relation between differential solubility of cellulose and lignin in ionic liquids and activity coefficients, RSC Adv., 2013, 3(10), 3453–3460. 75 S.-T. Lin and S. I. Sandler, A priori phase equilibrium prediction from a segment contribution solvation model, Ind. Eng. Chem. Res., 2002, 41(5), 899–913. 76 C.-M. Hsieh, S. I. Sandler and S.-T. Lin, Improvements of COSMO-SAC for vapor-liquid and liquid-liquid © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability,2025,3, 4533–4555 | 4553 Paper RSC Sustainability Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online equilibrium predictions, Fluid Phase Equilib., 2010, 297(1), 90–97. 77 I. H. Bell, E. Mickoleit, C.-M. Hsieh, S.-T. Lin, J. Vrabec, C. Breitkopf, et al.,J. Chem. Theory Comput., 2020, 16(4), 2635–2646. 78 M. Mohan, B. A. Simmons, K. L. Sale and S. Singh, Multiscale molecular simulations for the solvation of lignin in ionic liquids, Sci. Rep., 2023, 13, 271. 79 I. Antolovic, J. Vrabec and M. Klajmon, COSMOPharm: Drug-polymer compatibility of pharmaceutical amorphous solid dispersions from COSMO-SAC, Mol. Pharmaceutics, 2024, 21(9), 4395–4415. 80 M. Klajmon, Purely predicting the pharmaceutical solubility: what to expect from PC-SAFT and COSMO-RS?, Mol. Pharmaceutics, 2022, 19(11), 4212–4232. 81 M. Mohan, K. L. Sale, R. S. Kalb, B. A. Simmons, J. M. Gladden and S. Singh, Multiscale molecular simulation strategies for understanding the delignication mechanism of biomass in cyrene, ACS Sustain. Chem. Eng., 2022, 10(33), 11016–11029. 82 N. Kumar, B. R. Taylor, V. Chourasia, A. Rodriguez, J. M. Gladden, B. A. Simmons, H. Choudhary and K. L. Sale, Multi-scale computational screening and mechanistic insights of cyclic amines as solvents for improved lignocellulosic biomass processing, Green Chem., 2025, 27, 5482–5497. 83 S. Wang, Y. Li, X. Wen, Z. Fang, X. Zheng, J. Di, H. Li, C. Li and J. Fang, Experimental and theoretical study on the catalytic degradation of lignin by temperature-responsive deep eutectic solvents, Ind. Crops Prod., 2022, 177, 114430. 84 L. Zhou, X. Liu, J. Zhang, Q. Li, M. Yuan and Z. Kang, Ionic liquid screening for lignocellulosic biomass fractionation: COSMO-RS prediction and experimental verication, J. Mol. Liq., 2024, 407, 125214. 85 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb and J. R. Cheeseman, et al.,Gaussian 16 (Revision C.01), Gaussian, Inc., Pittsburgh, PA, 2016. 86 M. Cossi, N. Rega, G. Scalmani and V. Barone, Energies, structures, and electronic properties of molecules in solution with the C-PCM solvation model, J. Comput. Chem., 2003, 24(6), 669–681. 87 S. Riniker and G. A. Landrum, Better informed distance geometry: using what we know to improve conformation generation, J. Chem. Inf. Model., 2015, 55(12), 2562–2574. 88 T. A. Halgren, Merck molecular force eld. I. Basis, form, scope, parameterization, and performance of MMFF94, J. Comput. Chem., 1996, 17(5–6), 490–519. 89 RDKit: Open-source cheminformatics (release 2024_09_6), https://www.rdkit.org. 90 M. J. Abraham, T. Murtola, R. Schulz, S. P´ all, J. C. Smith, B. Hess, et al., GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers, SowareX, 2015, 1–2,19–25. 91 J. Wang, R. M. Wolf, J. W. Caldwell, P. A. Kollman and D. A. Case, Development and testing of a general amber force eld, J. Comput. Chem., 2004, 25(9), 1157–1174. 92 W. D. Cornell, P. Cieplak, C. I. Bayly, I. R. Gould, K. M. Merz, D. M. Ferguson, et al., A second generation force eld for the simulation of proteins, nucleic acids, and organic molecules, J. Am. Chem. Soc., 1995, 117(19), 5179–5197. 93 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb and J. R. Cheeseman et al.,Gaussian 09 (Revision A.02), Gaussian, Inc., Pittsburgh, PA, 2016. 94 J. L. F. Abascal and C. Vega, A general purpose model for the condensed phases of water: TIP4P/2005, J. Chem. Phys., 2005, 123(23), 234505. 95 G. Bussi, D. Donadio and M. Parrinello, Canonical sampling through velocity rescaling, J. Chem. Phys., 2007, 126(1), 014101. 96 M. Bernetti and G. Bussi, Pressure control using stochastic cell rescaling, J. Chem. Phys., 2020, 153(11), 114107. 97 B. Hess, P-LINCS: a parallel linear constraint solver for molecular simulation, J. Chem. Theory Comput., 2008, 4(1), 116–122. 98 U. Essmann, L. Perera, M. L. Berkowitz, T. Darden, H. Lee and L. G. Pedersen, A smooth particle mesh Ewald method, J. Chem. Phys., 1995, 103(19), 8577–8593. 99 L. Martinez, R. Andrade, E. G. Birgin and J. M. Martinez, PACKMOL: A package for building initial congurations for molecular dynamics simulations, J. Comput. Chem., 2009, 30(13), 2157–2164. 100 J. Pol´ ak, D. Ondo and J. Heyda, Thermodynamics of NIsopropylacrylamide in water: insights from experiments, simulations, and Kirkwood-Buffanalysis teamwork, J. Phys. Chem. B, 2020, 124(12), 2495–2504. 101 H. Q. L´ e, A. Zaitseva, J.-P. Pokki, M. Stahl, V. Alopaeus and H. Sixta, Solubility of organosolv lignin in g-valerolactone/ water binary mixtures, ChemSusChem, 2016, 9(20), 2939– 2947. 102 M. C. Barbu, T. Sepperer, E. M. Tudor and A. Petutschnigg, Walnut and hazelnut shells: untapped industrial resources and their suitability in lignocellulosic composites, Appl. Sci., 2020, 10, 6340. 103 S. Zhao, J. Nia, L. Yun, K. Liu, S. Wang, J. Wen, et al., The relationship among the structural, cellular, and physical properties of walnut shells, HortScience, 2019, 54(2), 275– 281. 104 P. Sannigrahi, A. J. Ragauskas and S. J. Miller, Lignin structural modications resulting from ethanol organosolv treatment of loblolly pine, Energy Fuels, 2010, 24, 683–689. 105 J. S. Luterbacher, J. M. Rand, D. M. Alonso, J. Han, J. T. Youngquist, C. T. Maravelias, et al., Nonenzymatic sugar production from biomass using biomass-derived gvalerolactone, Science, 2014, 343(6168), 277–280. 106 D. M. Alonso, S. H. Hakim, S. Zhou, W. Won, O. Hosseinaei, J. Tao, et al., Increasing the revenue from lignocellulosic biomass: maximizing feedstock utilization, Sci. Adv., 2017, 3, e1603301. 107 I. T. Horvath, H. Mehdi, V. Fabos, L. Boda and L. T. Mika, gValerolactone –a sustainable liquid for energy and carbonbased chemicals, Green Chem., 2008, 10, 238–242. 4554 |RSC Sustainability,2025,3, 4533–4555 © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability Paper Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online 108 Y.-H. P. Zhang and L. R. Lynd, Toward an aggregated understanding of enzymatic hydrolysis of cellulose: noncomplexed cellulase systems, Biotechnol. Bioeng., 2004, 88(7), 797–824. 109 Y. Pu, F. Hu, B. H. Davison and A. J. Ragauskas, Assessing the molecular structure basis for biomass recalcitrance during dilute acid and hydrothermal pretreatments, Biotechnol. Biofuels, 2013, 6, 15. 110 F. A. Carey and R. J. Sundberg, Advanced Organic Chemistry, Part A: Structure and Mechanisms, 5th edn, Springer, 2007. 111 J. L. L. N'Guessan, B. F. Niamk´ e, N. J. C. Yao and N. Amusant, Wood extractives: Main families, functional properties, elds of application and interest of wood waste, For. Prod. J., 2023, 73(3), 194–208. 112 A. Chemat, M. Schweiger, D. Touraud, R. Müller, L. Lajoie, J. B. Mazzitelli, et al., Cascade extractions of coffee silverskin: towards zero solid waste valorization of a byproduct, Sustainable Chem. Pharm., 2024, 42, 101779. 113 L. Dehne, C. V. Babarro, B. Saake and K. U. Schwarz, Inuence of lignin source and esterication on properties of lignin-polyethylene blends, Ind. Crops Prod., 2016, 86, 320–328. 114 R. N. Nishide, J. H. Truong and M. M. Abu-Omar, Organosolv fractionation of walnut shell biomass to isolate lignocellulosic components for chemical upgrading of lignin to aromatics, ACS Omega, 2021, 6, 8142–8150. 115 R. Protz, A. Lehmann, J. Ganster and H. Pink, Solubility and spinnability of cellulose-lignin blends in aqueous NMMO, Carbohydr. Polym., 2021, 251, 117027. 116 H. Nawaz, A. He, Z. Wu, X. Wang, Y. Jiang, A. Ullah, et al., Revisiting various mechanistic approaches for cellulose dissolution in different solvent systems: a comprehensive review, Int. J. Biol. Macromol., 2024, 273, 133012. 117 X. Li, X. Yuan, G. Xia, J. Liang, C. Liu, Z. Wang, et al., Catalytic production of g-valerolactone from xylose over delaminated Zr-Al-SCM-1 zeolite via a cascade process, J. Catal., 2020, 392, 175–185. 118 L. Xiao, W. Liu, J. Huang, H. Lou and X. Qiu, Study on the antioxidant activity of lignin and its application performance in SBS elastomer, Ind. Eng. Chem. Res., 2020, 60(1), 1–12. 119 B. Wang, S.-F. Wang, S. S. Lam, C. Sonne, T.-Q. Yuan, G.-Y. Song, et al., A review on production of lignin-based occulants: sustainable feedstock and low carbon footprint applications, Renewable Sustainable Energy Rev., 2020, 134, 110384. 120 G. Foyer, B.-H. Chen, B. Boutevin, S. Caillol and G. David, New method for the synthesis of formaldehyde-free phenolic resins from lignin-based aldehyde precursors, Eur. Polym. J., 2016, 74, 296–309. 121 Y. Meng, Y. Cheng, J. Lu and H. Wang, A review on ligninbased phenolic resin adhesive, Macromol. Chem. Phys., 2022, 223, 2100434. 122 T. Ren, Z. Zhang, S. You, W. Qi, R. Su and Z. He, Isolation and purication of 4-propylguaiacol and 4-propylsyringol by extraction and crystallization from the products of reductive catalytic fractionation processes, Green Chem., 2022, 24(19), 7355–7361. 123 Y. Li, J. Zhu, Z. Zhang and Y. Qu, Preparation of syringaldehyde from lignin by catalytic oxidation of perovskite-type oxides, ACS Omega, 2020, 5(5), 2107–2113. 124 K. Li, W. Zhong, P. Li, J. Ren, K. Jiang and W. Wu, Recent advances in lignin antioxidant: antioxidant mechanism, evaluation methods, inuence factors and various applications, Int. J. Biol. Macromol., 2023, 251, 125992. 125 T. Heinze and T. Liebert, 10.05 –Cellulose and Polyoses/ Hemicelluloses, in Polymer Science: A Comprehensive Reference, vol. 10, 2012, pp. 83–152. 126 T. Heinze and A. Koschella, Solvents applied in the eld of cellulose chemistry: a mini review, Polimeros, 2005, 15(2), 84–90. 127 S. Zhang, C. Chen, C. Duan, H. Hu, H. Li, J. Li, et al., Regenerated cellulose by the Lyocell process, a brief review of the process and properties, Bioresearch, 2018, 13(2), 4577–4592. 128 C. Michels and B. Kosan, Lyocell process –material and technological restrictions, Chem. Fibers Int., 2000, 50, 556–561. 129 T. Rosenau and A. D. French, N-Methylmorpholine-N-oxide (NMMO): hazards in practice and pitfalls in theory, Cellulose, 2021, 28, 5985–5990. 130 E. Hytönen, L. Sorsam¨ aki, E. Kolehmainen, M. Sturm and N. V. Weymarn, Lyocell bre production using NMMO – a simulation-based techno-economic analysis, Bioresearch, 2023, 18(3), 6384–6411. 131 M. Schweiger, T. Lang, E. Mueller, D. Touraud and W. Kunz, Inuence of the biomass-source and the extraction process on lignin properties and gvalerolactone induced conversion of biomass towards valuable lignin monomers, RSC Sustainability, 2025, DOI: 10.1039/d5su00324e. © 2025 The Author(s). Published by the Royal Society of Chemistry RSC Sustainability,2025,3, 4533–4555 | 4555 Paper RSC Sustainability Open Access Article. Published on 17 September 2025. Downloaded on 10/23/2025 12:55:17 PM. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. View Article Online