Integrated preparation of functional lignin nanoparticles and levulinic acid directly from the pre-hydrolysis liquor of poplar wood.

The pre-hydrolysis liquor (PHL) produced during pulp dissolution and biomass refining is mainly composed of hemicellulose and lignin, and it is a potential source for production of value-added materials and platform chemicals; however, their utilization has been a serious challenge. In this study, we proposed a green and simple strategy to simultaneously prepare size-controlled functional lignin nanoparticles (LNPs) and levulinic acid (LA) from PHL as the raw material. The as-prepared LNPs exhibited remarkable stability thanks to the presence of saccharides with abundant oxygen-containing groups and surface charges, which prevented aggregation and maintained long-term storage stability. Trace amounts of the LNPs (≤ 0.2 wt%) could stabilize various Pickering emulsions, even with oil-to-water ratios as high as 5:5 (v/v). Subsequently, the remaining PHL was directly used to produce LA without adding a catalyst; under optimal conditions (160 °C and 1 h), the yield of LA was 56.3 % based on the dry saccharide content in the raw PHL. More importantly, p-toluenesulfonic acid (p-TsOH), the only reactive reagent used during the entire preparation process, including the two preparation steps of the LNPs and LA, was reusable, and the recovery rate was >70 % after five cycles. Overall, this green and simple strategy effectively and comprehensively utilized the PHL and showed potential for producing biobased nanomaterials and platform chemicals.

Coupling process for preparing biomass-based furfural and levulinic acid from corncob: Extraction, green chemistry and techno-economic assessment.

The purpose of this study is to design and investigate two coupling processes for acid-catalyzed hydrolysis of corncob, achieving the simultaneous preparation of biomass-based furfural and levulinic acid (LA). Meanwhile, high concentration and yield of LA were obtained through a situ feeding strategy of pretreated furfural residue with high solids loading (20%, w/v). In Scenario A, 2-methyltetrahydrofuran was selected as the solvent for the LA extraction process compared with the neutralization process in Scenario B. Techno-economic assessment results show that Scenario A is technically feasible and cost-competitive, with an internal rate of return of 21.92%, a net present value of 121 million US dollars, a carbon efficiency of 72%, an environmental factor of 4.38, and a process mass intensity of 32.19. This study will provide new insights for fully utilizing lignocellulosic biomass to prepare renewable energy resources, comprehensively evaluating the economic feasibility, and promoting green and low-carbon development.

Sulfonated P-W modified nitrogen-containing carbon-based solid acid catalysts for one-pot conversion of cellulose to ethyl levulinate under water-ethanol medium.

Converting cellulose (Cel) into ethyl levulinate (EL) is one of the promising strategies for supplying liquid fuels. In this paper, the prepared sulfonated P-W-modified N-containing carbon-based solid acid catalyst (PWNCS), in which the Polyaniline (PANI) was employed as N and C precursors, successfully converted Cel into EL under the water-ethanol medium. The characterization results demonstrated that a tiny addition of P increased the Brønsted acid sites (BAS) content and defective WO3 provided the Lewis acid sites (LAS), meanwhile, the sulfonation process did not change the fundamental structure but introduced the sulfonic groups to dramatically increase the acidic content. Therefore, under optimized reaction conditions, PWNCS realized about 100% Cel conversion and 71.61% of EL yield, furthermore, the selectivity of EL reached 89.14%. In addition, the effect of water on the reaction pathway of Cel to EL over PWNCS was proposed. The addition of water generally resulted in the hydration of defective WO3 to reduce the LAS and increase BAS, which significantly inhibited the side reactions of retro-aldol condensation (RAC) and subsequent etherification reactions during Cel conversion and then improved the selectivity of EL.

The Interventions to Minimize Pain During Photodynamic Therapy With 5-Aminolevulinic Acid for the Treatment of Cutaneous Diseases.

Photosensitization with 5-aminolevulinic acid (ALA) combined with photodynamic therapy (PDT) is approved in the United States for the treatment of actinic keratosis (AK) and is used off-label for other indications including acne treatment and photo rejuvenation. However, pain, particularly during the initial illumination period, limits the utility of this highly efficacious therapy. Although modifications to conventional ALA-PDT protocols that improve tolerability without diminishing efficacy have been identified, few have been evaluated in randomized, controlled trials, and the number of variables involved in ALA incubation (eg, duration, occlusion, ALA formulation, and strength) and PDT illumination (eg, light source, fluence rate, irradiance, and duration) confounds standardization.  Perhaps the most promising modifications to date involve continuous activation of low levels of protoporphyrin IX, the photoactive metabolite of ALA, as well as using shorter incubation times (with or without prolongation of illumination), lower irradiance, and daylight or combined (daylight and conventional) PDT. However, reimbursement of PDT with alternative light sources in the US is hampered by the US Food and Drug Administration (FDA) labeling, which specifies the blue or red light devices approved for use with corresponding marketed ALA 20% solution and 10% gel, respectively. This review summarizes the existing evidence with respect to pain control in patients undergoing ALA-PDT, recommendations from clinical experience, and goals for future research. J Drugs Dermatol. 2023;22(11):1082-1087   doi:10.36849/JDD.7637.

Intraoperative Fluorophores: An Update on 5-Aminolevulinic Acid and Sodium Fluorescein in Resection of Tumors of the Central Nervous System and Metastatic Lesions-A Systematic Review and Meta-Analysis.

INTRODUCTION: Recent advances in tumor visualization have improved the extent of resection (EOR) of primary and secondary tumors of the central nervous system, while limiting the morbidity and mortality of the surgery. One area of recent interest has been the use of intraoperative fluorophores for tumor visualization such as 5-aminolevulinic acid (5-ala) and sodium fluorescein. We performed a systematic review and meta-analysis on the utility of fluorophore administration and EOR with each fluorophore to update the current literature. METHODS: We conducted a systematic review and meta-analysis on the use of intraoperative 5-ala or fluorescein between 2021 and 2023 using the PubMed, SCOPUS, and WOS databases. The initial search yielded 8688 results. After inclusion and exclusion criteria were met, 44 studies remained for review. A meta-analysis was performed to compare the EOR between studies for each fluorophore and to compare the presence of intraoperative fluorescence by tumor type. Odds ratios (OR) were calculated for gross total resection (GTR), and two-way ANOVA tests were performed to compare rates of intraoperative fluorescence by fluorophore and tumor type. RESULTS: In all groups except low-grade glioma, fluorescence was present after 5-ala administration; fluorescence was present for all groups after fluorescein administration. Two-way ANOVA analysis for both fluorophores demonstrated no statistically significant difference in presence of fluorescence between type of tumor resected. Meta-analysis of EOR did show a higher, but not significant, rate of GTR in the 5-ala group compared to controls (OR = 1.29, 95% CI = 0.49; 3.37). In the fluorescein group, there were statistically significant higher odds of GTR compared to the control group (OR = 2.10, 95% CI = 1.43; 3.10, I2 = 0%). CONCLUSIONS: Both 5-ala and sodium fluorescein demonstrated intraoperative fluorescence among various tumor types in both cranial and spinal tumors, as well as efficacy in improving EOR. Both fluorophores merit further investigation for use in surgery of CNS tumors.

Cellulose dissolution and regeneration behavior via DBU-levulinic acid solvents.

Most organic solvents are unable to dissolve carbohydrates due to the lack of hydrogen bonding ability. The development of solvent systems for dissolving cellulose is of great importance for its utilization and conversion. In this study, four new cellulose solvents were designed using inexpensive levulinic acid (LevA) and 1,8-diazabicyclo [5,4,0] undec-7-ene (DBU) as raw materials. The results showed that the prepared DBU-LevA-2 solvent was able to dissolve up to 7 wt% of bamboo cellulose (DP = 860) and 16 wt% of microcrystalline cellulose (DP = 280) at 100 °C and regenerated without derivatization. Also, the molar ratio of each component of this solvent has a significant effect on the dissolution properties of cellulose. The regenerated cellulose had the typical crystalline characteristics of cellulose II. Subsequently, the interactions and microscopic behaviors of solvent and cellulose during the dissolution process were thoroughly investigated by using NMR spectroscopy combined with density functional theory. The systematic study showed that the hydrogen bond-forming ability provided by DBU, a superbase, plays an indispensable role in the overall solvent system.

Direct and efficient conversion of cellulose to levulinic acid catalyzed by carbon foam-supported heteropolyacid with Brønsted-Lewis dual-acidic sites.

This study aimed to produce bio-based levulinic acid (LA) via direct and efficient conversion of cellulose catalyzed by a sustainable solid acid. A carbon foam (CF)-supported aluminotungstic acid (HAlW/CF) catalyst with Brønsted-Lewis dual-acidic sites was creatively engineered by a hydrothermal impregnation method. The activity of the HAlW/CF catalyst was determined via the hydrolysis and conversion of cellulose to prepare LA in aqueous system. The cooperative effect of Brønsted and Lewis acids in HAlW/CF resulted in high cellulose conversion (89.4%) and LA yield (60.9%) at 180 °C for 4 h, which were greater than the combined catalytic efficiencies of single HAlW and CF under the same conditions. The HAlW/CF catalyst in block form exhibited superior catalytic activity, facile separation from reaction system, and favorable reusability. This work offers novel perspectives for the development of recyclable dual-acidic catalysts to achieve one-pot catalytic conversion of biomass to value-added chemicals.

Conversion of the hydrochar recovered after levulinic acid production into activated carbon adsorbents.

Levulinic acid production by acid-catalyzed hydrothermal conversion of (ligno)cellulosic biomass generates significant amounts of carbonaceous hydrochar, which is currently considered a final waste. In this work, the hydrochar recovered after the levulinic acid production, was subjected to cascade pyrolysis and chemical activation treatments (by H3PO4 or KOH), to synthesize activated carbons. The pyrolysis post-treatment was already effective in improving the surface properties of the raw hydrochar (Specific Surface Area: 388 m2/g, VP: 0.22 cm3/g, VMESO: 0.07 cm3/g, VMICRO: 0.14 cm3/g), by removing volatile compounds. KOH activation resulted as the most appropriate for further improving the surface properties of the pyrolyzed hydrochar, showing the best surface properties (Specific Surface Area: 1421 m2/g, VP: 0.63 cm3/g, VMESO: 0.10 cm3/g, VMICRO: 0.52 cm3/g), which synergistically makes it a promising system towards adsorption of CO2 (∼90 mg/g) and methylene blue (∼248 mg/g). In addition, promising surface properties can be achieved after direct chemical activation of the raw hazelnut shells, preferably by H3PO4 (Specific Surface Area: 1918 m2/g, VP: 1.34 cm3/g, VMESO: 0.82 cm3/g, VMICRO: 0.50 cm3/g), but this choice is not the smartest, as it does not allow the valorization of the cellulose fraction to levulinic acid. Our approach paves the way for possible uses of these hydrochars originating from the levulinic acid chain for new environmental applications, thus smartly closing the biorefinery loop of the hazelnut shells.

Levulinic Acid-Based "Green" Solvents for Lignocellulose Fractionation: On the Superior Extraction Yield and Selectivity toward Lignin.

The high potential use of lignin in novel biomaterials and chemicals represents an important opportunity for the valorization of the most abundant natural resource of aromatic molecules. From an environmental perspective, it is highly desirable replacing the hazardous methods currently used to extract lignin from lignocellulosic biomass and develop more sustainable and environmentally friendly approaches. Therefore, in this work, levulinic acid (a "green" solvent obtained from biomass) was successfully used, for the first time, to selectively extract high-quality lignin from pine wood sawdust residues at 200 °C for 6 h (at atmospheric pressure). Moreover, the addition of catalytic concentrations of inorganic acids (i.e., H2SO4 or HCl) was found to substantially reduce the temperature and reaction times needed (i.e., 140 °C, 2 h) for complete lignin extraction without compromising its purity. NMR data suggests that condensed OH structures and acidic groups are present in the lignin following extraction. Levulinic acid can be easily recycled and efficiently reused several times without affecting its performance. Furthermore, excellent solvent reusability and performance of extraction of other wood residues has been successfully demonstrated, thus making the developed levulinic acid-based procedure highly appealing and promising to replace the traditional less sustainable methodologies.

Hydrothermal processing of agar waste to levulinic acid and fermentation of hydrolysate to bioethanol.

Increasing global energy consumption and depleting fossil-fuel reserves prompted the search for green alternatives. This study focuses on conversion of waste agar using different acids/alkalis (0.5% and 1%) as catalysts under varied temperature and time towards galactose (Gal), 5-hydroxymethylfurfural (HMF) and levulinic acid (LA) production in sequential reactions. The optimized process for agar depolymerisation was achieved using 1% acid (H2SO4/HCl) catalysed conditions with a maximum of 11 g/L Gal yield (121 °C; 15 min). Increase in temperature (150 °C) and time (180 min) with 1% HCl/H2SO4 catalyst resulted in improved LA production along with Gal and HMF. The hydrolysis process was optimised for the selective production of LA (10 g/L at 175 °C; 180 min). Further, galactose-rich hydrolysates were assessed for bioethanol production using Saccharomyces cerevisiae that resulted in 3 g/L ethanol. Thus, the study comprehensively demonstrates waste agar utilization to yield biochemicals/fuels in a circular bio-based economy approach.

Catalytic hydrogenation of levulinic acid to γ-valerolactone over lignin-metal coordinated carbon nanospheres in water.

The hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) has attracted much attention, as GVL can be used as biofuel, green solvent, and platform chemical. Inspired by Stöber method, various lignin-metal coordinated colloidal nanospheres (LCS) from lignin and cetyltrimethylammonium bromide (CTAB) were synthesized in which the metal ions (Co2+) replace formaldehyde as the crosslinker. The characterization of the catalyst revealed that alkali lignin was first self-assembled with CTAB through electrostatic attraction to form a lignin polymer, the subsequent addition of metal ions (Co2+) promoted the aggregation of lignin polymers and generated the LCS. Increasing calcination temperature for LCS resulted in the Co2+ being reduced to metallic Co. The lignin-metal coordinated colloidal nanospheres calcined at 500 °C possess both CoO and metallic Co active sites, which effectively accelerated the hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) than simplex metallic Co active sites. A 99.8 % yield of GVL with 100 % LA conversion was obtained after 60 min reaction time at 200 °C and 2 MPa H2.

Microwave radiation-assisted synthesis of levulinic acid from microcrystalline cellulose: Application to a melon rind residue.

The circular economy considers waste to be a new raw material for the development of value-added products. In this context, agroindustrial lignocellulosic waste represents an outstanding source of new materials and platform chemicals, such as levulinic acid (LA). Herein we study the microwave (MW)-assisted acidic conversion of microcrystalline cellulose (MCC) into LA. The influence of acidic catalysts, inorganic salt addition and ball-milling pre-treatment of MCC on LA yield was assessed. Depolymerization and disruption of cellulose was monitored by FTIR, TGA and SEM, whereas the products formed were analyzed by HPLC and NMR spectroscopy. The parameters that afforded the highest LA yield (48 %, 100 % selectivity) were: ball-milling pre-treatment of MCC for 16 min at 600 rpm, followed by MW-assisted thermochemical treatment for 20 min at 190 °C, aqueous p-toluenesulfonic acid (p-TSA) 0.25 M as catalyst and saturation with KBr. These optimal conditions were further applied to a lignocellulosic feedstock, namely melon rind, to afford a 51 % yield of LA. These results corroborate the suitability of this method to obtain LA from agroindustrial wastes, in line with a circular economy-based approach.

Preparation and In Vitro Evaluation of W/O Nanoemulsions for the Skin Permeation of 5-Aminolevulinic Acid.

We investigated the skin permeation of 5-aminolevulinic acid (ALA) through Yucatan micropig full-thickness skin by using ALA-loaded W/O nanoemulsions composed of Span/Tween/ethanol (EtOH)/isopropyl palmitate (IPP)/10 wt% aqueous ALA solution. The nanoemulsions were prepared using Span 20/Tween 20 (S20/T20), Span 80/Tween 80 (S80/T80), and Span 20/Tween 80 (S20/T80) mixed surfactant systems. Based on the results of the phase diagram study and hydrodynamic diameter measurement of the nanoemulsions, we decided that the optimal weight ratio of Span/Tween/EtOH/IPP/10 wt% aqueous ALA solution in the nanoemulsion was 0.8/0.2/14/19/1.4. The permeability coefficient of ALA in the S20/T80 system was approximately five times larger than those in the S20/T20 and S80/T80 systems. The high skin permeation of ALA afforded by the ALA-loaded W/O nanoemulsion in the S20/T80 system is attributable to a significant enhancement in the partitioning of ALA to the stratum corneum.

The Role of Copper in the Hydrogenation of Furfural and Levulinic Acid.

Currently, there is a great interest in the development of sustainable and green technologies for production of biofuels and chemicals. In this sense, much attention is being paid to lignocellulosic biomass as feedstock, as alternative to fossil-based resources, inasmuch as its fractions can be transformed into value-added chemicals. Two important platform molecules derived from lignocellulosic sugars are furfural and levulinic acid, which can be transformed into a large spectrum of chemicals, by hydrogenation, oxidation, or condensation, with applications as solvents, agrochemicals, fragrances, pharmaceuticals, among others. However, in many cases, noble metal-based catalysts, scarce and expensive, are used. Therefore, an important effort is performed to search the most abundant, readily available, and cheap transition-metal-based catalysts. Among these, copper-based catalysts have been proposed, and the present review deals with the hydrogenation of furfural and levulinic acid, with Cu-based catalysts, into several relevant chemicals: furfuryl alcohol, 2-methylfuran, and cyclopentanone from FUR, and γ-valerolactone and 2-methyltetrahydrofuran from LA. Special emphasis has been placed on catalytic processes used (gas- and liquid-phase, catalytic transfer hydrogenation), under heterogeneous catalysis. Moreover, the effect of addition of other metal to Cu-based catalysts has been considered, as well as the issue related to catalyst stability in reusing studies.

Development of bioprocess for corncob-derived levulinic acid production.

Levulinic acid is a significant platform chemical obtained from biomass and can potentially be used to produce value-added biofuels, biopolymers, and biopharmaceuticals. This study aims at statistically optimizing levulinic acid production from agrowastes. Based on the total carbohydrate content (71.93 %), corncob was selected as the target feedstock. A Box-Behnken design with four factors, such as feedstock concentration, reaction time, reaction temperature, and catalyst concentration, was used to optimize the hydrothermal conversion of corncob to levulinic acid at 180 °C for 30 min using 1 M H2SO4 as the acid catalyst and 120 g/L corncob. The maximum yield of 19.9 % was obtained. Additionally, 8.1 g/L formic acid was co-produced. The results of this study can contribute toward valorization of levulinic acid. Moreover, our results can be useful in developing strategies to utilize agrowastes as a renewable feedstock for recent biorefineries to cope with the climate crisis.

Production of 5-aminolevulinic acid from hydrolysates of cassava residue and fish waste by engineered Bacillus cereus PT1.

The economical production of 5-aminolevulinic acid (ALA) has recently received increasing attention for its extensive use in agriculture. In this study, a strain of Bacillus cereus PT1 could initially produce ALA at a titre of 251.72 mg/L by using a hydrolysate mixture of low-cost cassava residue and fish waste. The integration of endogenous hemA encoding glutamyl-tRNA reductase led to a 39.30% increase in ALA production. Moreover, improving cell permeability by deletion of the LytR-CpsA-Psr (LCP) family gene tagU led to a further increase of 59.73% in ALA production. Finally, the engineered strain B. cereus PT1-hemA-ΔtagU produced 2.62 g/L of ALA from the previously mentioned hydrolysate mixture in a 7-L bioreactor. In a pot experiment, foliar spray of the ALA produced by B. cereus PT1-hemA-ΔtagU from the hydrolysates increased salt tolerance of cucumber by improving chlorophyll content and catalase activity, while decreasing malondialdehyde content. Overall, this study demonstrated an economic way to produce ALA using a microbial platform and evidenced the potential of ALA in agricultural application.

Perspective of reactive separation of levulinic acid in conceptual mixer settler reactor.

Levulinic acid is a carboxylic acid present in industrial downstream. It is an important chemical and can be transformed into various important chemicals such as 1,4-pentanediol, aminolevulinic acid, succinic acid, gamma valarolactone, hydoxyvaleric acid, and diphenolic acid. It is considered one of the top ten most important building block chemicals and bio-derived acids. Levulinic acid can be directly produced using biomass, chemical synthesis, and fermentation processes at industrial and laboratory scales. The biomass process produces the char, whereas the fermentation process generates waste during the production of levulinic acid, leading to an increase in the production cost and waste streams. The separation of levulinic acid from the waste is expensive and challenging. In the present study, reactive extraction was employed using trioctylamine in i-octanol for the separation of levulinic acid. The experimental results were expressed in terms of performance parameters like distribution coefficient (0.099-6.14), extraction efficiency (9-86%), loading ratio (0.09-0.7), and equilibrium complexation constant (11.34-1.05). The mass action law model was also applied and found the predicted values were in close agreement with the experimental results. The mixer settler extraction in series was used to achieve more than 98% separations of acid. Furthermore, the conceptual approach for separation of levulinic acid using a mixer settler reactor scheme was discussed and presented various design parameters including extraction efficiency, diffusion coefficient, equilibrium complexation constant, and loading ratio. The study is helpful in recovering the valuable chemicals present in industrial downstream and reducing their environmental impacts if any.

ICl-Mediated Functional Group Interconversion from Methyl Homopropargyl Ether to α-Iodo-γ-chloroketone.

An ICl-mediated highly chemo- and regioselective functional group interconversion from methyl homopropargyl ether to α-iodo-γ-chloro-ketone is reported. Density functional theory (DFT)-calculated reaction coordinate and potential energy surface support the high chemo-selectivity observed for the formation of α-iodo-γ-chloroketone over furan. The five-membered oxonium ring formation-ring opening mechanism is a potential template for the preparation of polyfunctionalized carbonyl compounds.

Hydrodeoxygenation of Levulinic Acid to γ-Valerolactone over Mesoporous Silica-Supported Cu-Ni Composite Catalysts.

Monometallic (Cu, Ni) and bimetallic (Cu-Ni) catalysts supported on KIT-6 based mesoporous silica/zeolite composites were prepared using the wet impregnation method. The catalysts were characterized using X-ray powder diffraction, N2 physisorption, SEM, solid state NMR and H2-TPR methods. Finely dispersed NiO and CuO were detected after the decomposition of impregnating salt on the silica carrier. The formation of small fractions of ionic Ni2+ and/or Cu2+ species, interacting strongly with the silica supports, was found. The catalysts were studied in the gas-phase upgrading of lignocellulosic biomass-derived levulinic acid (LA) to γ-valerolactone (GVL). The bimetallic, CuNi-KIT-6 catalyst showed 100% LA conversion at 250 °C and atmospheric pressure. The high LA conversion and GVL yield can be attributed to the high specific surface area and finely dispersed Cu-Ni species in the catalyst. Furthermore, the catalyst also exhibited high stability after 24 h of reaction time with a GVL yield above 80% without any significant change in metal dispersion.

The Characteristic of Light Sources and Fluorescence in the 3-Dimensional Digital Exoscope "ORBEYE" for 5-Aminolevulinic Acid-Induced Fluorescence-Guided Surgery Compared with a Conventional Microscope.

BACKGROUND: The ORBEYE (ORB), an innovative 3-dimensional digital exoscope, is an equipped system for fluorescence-guided surgery with 5-aminolevulinic acid. Therefore, this study aimed to verify the characteristics of fluorescence-guided surgery with 5-aminolevulinic acid and excitation light source with ORB. METHODS: The same operative field of glioblastoma was recorded under blue light (BL) excitation using a conventional microscope (MS) and ORB. For in vitro studies, the energy of 405-nm wavelength light in white light and BL modes of each scope was examined in various focal lengths. To examine the degree of photobleaching with BL for each scope, protoporphyrin IX-soaked filter papers were continuously exposed with BL of an MS and ORB, and the video-recorded red fluorescence intensity was analyzed. RESULTS: The color tone of tumor-induced red fluorescence was remarkably different under each scope. Furthermore, nonfluorescent normal structures without red fluorescence were well recognized under ORB. The energy of 405-nm wavelength light in BL was significantly higher in ORB than that in an MS, especially in the short focal length. With continuous BL excitation to filter papers, the relative red fluorescence intensity of filter papers was significantly decreased over time in ORB than in an MS. In low protoporphyrin IX concentration, the difference was more significant. CONCLUSIONS: With ORB, the good visibility due to BL energy as compared with an MS might improve the surgical manipulation even in BL mode. However, the weak fluorescent tissue and short focal length should be carefully considered because photobleaching might be critical for FGS.