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JOURNAL OF MOLECULAR LIQUIDS · 2020 · IF 5.065

Study on the solid-liquid equilibrium of l-malic acid in binary solvents

Zhicheng Gao,Ying Li,Xunqiu Wang

In this study, the solubility of l -malic acid in three binary solvents (ethyl acetate +  tetrahydrofuran , acetonitrile  + tetrahydrofuran, butyl acetate  + acetonitrile) at atmospheric pressure from T = (278.15 to 323.15) K was measured via a gravimetric method. The results show that in the temperature range studied, the solubility of l -malic acid in the selected solvent gradually increases with the increase of temperature. The solubility of l -malic acid increases with the increase of the mass fraction of tetrahydrofuran at the binary system (ethyl acetate + tetrahydrofuran, acetonitrile + tetrahydrofuran), the solubility of l -malic acid increases with The mass fraction of butyl acetate increases and decreases at the butyl acetate + acetonitrile system. In addition, the dissolution behavior of l -malic acid was explained using Hansen solubility parameter (HSP). Furthermore, the solubility data were correlated with using the modified Apelblat equation, the NRTL model and the newly proposed Apelblat-Sun model, the results have shown that the modified Apelblat equation has the best fitting effect. After research found, the hydrogen bonding force plays a key role in the solubility of l -malic acid. So solubility of l - resulted malic acid from the integrated effect of solute–solvent and solvent–solvent interactions. In addition, the van't Hoff equation was used to calculate and discuss all thermodynamic parameters of dissolution, Including standard Gibbs dissolution (Δ sol G o ), standard dissolution enthalpy (Δ sol H o ) and standard dissolution entropy (Δ sol S o ), Where Δ sol H o ,Δ sol S o ,Δ sol G o were all greater than 0, it have been shown that the dissolution process is driven by heat absorption and entropy. This study can provide basic thermodynamic data for the crystallization and industrial separation of l -malic acid.

CAS / MDL: 75-05-8 109-99-9 97-67-6
研究领域: 化学工程 · 物理化学
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COMBUSTION AND FLAME · 2024 · IF 5.8

Combustion and heat release characteristics of micron aluminum with extremely large specific surface area obtained by L-malic acid surface corrosion

Xueqin Liao,Jianzhong Liu,Zexu Li,Mengxia Sun

Aluminum (Al) particles are widely used in propellants, thermite and pyrotechnics. However, commonly used micro Al has drawbacks such as agglomeration, high ignition temperature and slow burning rate, making its energy potential not fully exploited in applications. Therefore, exploring pathways to enhance the combustion of Al particles has become the focus at present. Herein, L -malic acid (LMA) was used to corrode the surface of Al particles to obtain a sample (named LMAl) with an average specific surface area of 11.456 m 2 /g (corresponding to Al particles with a diameter of 194 nm). The particle size distribution of LMAl did not change significantly compared to pristine Al. The XPS results showed that a small amount of LMA and corrosion products remained on the surface of the LMAl particles. Thermal analysis tests showed that the thermal oxidation rate and efficiency of LMAl was dramatically higher than that of pristine Al. Compared with the pristine Al, the combustion characterization parameters of LMAl such as combustion intensity, ignition delay time, maximum combustion temperature, mass burning rate and combustion efficiency were all improved. This trend was maintained after blending the ammonium perchlorate (AP). The condensed combustion products (CCPs) of Al revealed a large number of agglomerates and unburned Al particles. While many broken particles and tentacle-like structures were found in the CCPs of LMAl. Overall, compared to Al, the combustion of LMAl is significantly enhanced. The thermal reaction and combustion behaviors of the two are quite different. This study provides new insights into improving the ignition and combustion of Al.

CAS / MDL: 7429-90-5
研究领域: 材料科学 · 燃烧学
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POLYMER · 2021 · IF 4.43

Functional biopolyesters based on cross-linked Poly(L-malic acid): Network engineering towards tailoring brittle-ductile transition and shape-memory performance

Qianru Wanyan,Yaxin Qiu,Wenting Zhang,Hai Yu,Defeng Wu

Crosslinking opens more possibilities of biodegradable poly ( L -malic acid) (PLMA) as functional materials , and network structure is key to its mechanical states and final applications. In this work, the diols with various chain lengths, including six types of fatty diols and four types of polyethylene glycols , were used to construct networks in PLMA, aiming at establishing network structure-mechanical state-material function correlations. As the molecular weights of diols increased from 100 to 400, the samples experienced evident transition from high-strength plastic to low-loss rubber, finally to soft elastomer . The strengths and Young's moduli varied from 71 MPa to 0.6 MPa and from 2.3 GPa to 2.7 MPa, respectively, accompanied by a broad variation of glass transition temperature ( T g , 50 o C–7 o C). This brittle-ductile transition was revealed in terms of elastoplastic and dielectric relaxations, then. Using the samples with different network structures as components, the actuators with attractive capability to complete asynchronous actions were fabricated. This work proposes promising applications of cross-linked PLMA as functional or smart materials due to its easily-tuned mechanical states and T g , together with its good antibactierial activity and shape memory effect.

研究领域: 材料科学 · 生物医学工程
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TOXICOLOGY AND APPLIED PHARMACOLOGY · 2025 · IF 3.4

Lung microbiota metabolite L-malic acid attenuates the airway inflammation in asthma by inhibiting ferroptosis

Lishan Lin,Danhui Huang,Haohua Huang,Lingyan Xie,Yi Huang,Cuiping Ye,Lanhe Chu,Yujie Qiao,Xiaojing Meng,Shaoxi Cai,Hangming Dong

Inhaled environmental allergens, such as house dust mites (HDM), have been shown to induce an inflammatory reaction, tissue injury, and increased airway sensitivity in the lungs, ultimately leading to the development of allergic asthma. The imbalance of respiratory microbiota and metabolites plays a crucial role in the progression of allergic asthma. However, there is limited knowledge available regarding the alterations in respiratory microbiota and metabolites and their impact on the host in the context of asthma. The aim of this study was to investigate the potential pathways involved in the development of asthma through the analysis of lung flora and metabolites. A mouse model of house dust mite (HDM)-induced asthma was established, and alveolar lavage samples were collected for microbiome 16S rRNA sequencing and untargeted metabolic analysis. Microbiological analyses indicated a significant alteration in the microbiota after 4 and 6 weeks of HDM nebulisation stimulation. This was characterized by a decrease in microbial diversity, as well as reductions in the relative proportion of Gallionella and Lactobacillus . Conversely, the abundance of Flavobacterium and Ralstonia increased in the HDM4W and HDM6W groups, respectively. Metabolomic analyses revealed seven distinct metabolites, among them L-malic acid, which were linked to signaling pathways in a mouse model of HDM-induced asthma. The correlation analysis demonstrated a positive association between L-malic acid and Rhodanobacter and Nocardioides . L-malic acid was discovered to be efficacious in reducing airway inflammation in mice with house dust mite-induced asthma. Further analysis revealed that this change was linked to lipid peroxidation and changes in ferroptosis markers, namely GPX4 and FTH. These findings suggest that L-malate inhibits ferroptosis. However, the introduction of ferroptosis inducers, such as Erastin, was observed to negate the beneficial effect of butyrate. In summary, this research implies that the respiratory microbiota metabolite L-malic acid lessens airway inflammation in asthma by inhibiting ferroptosis, offering a potential approach for managing asthma.

CAS / MDL: 571203-78-6
研究领域: 免疫学 · 微生物学 · 呼吸病学
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ACS Applied Polymer Materials · 2020 · IF 0

Selectively Sensing Capacities of Biocompatible Shape Memory Materials Based on Cross-Linked Poly(l-malic acid): Visual Discrimination of the Solvents with Similar Structures

Yaxin Qiu,Juqun Xi,Qianru Wanyan,Defeng Wu

A biomass-derived and biocompatible poly(l-malic acid) (PMA) based material with shape memory effect (SME) was developed in this work. 1,8-Octanediol was used as the cross-linker to construct cross-linking networks with hydrophilic backbone chain of PMA, tuning the density of networks and their swelling capacities by controlling −COOH/–OH ratios. The solvent-induced SME of as-obtained cross-linked PMAs was activated under mild conditions in this way. Using the shape recovery levels of U-shaped samples as the probes, the mixed methanol/ethanol/water systems with various ratios could be easily discriminated because the cross-linked PMAs show different sensing capacities to different components. The mechanisms were then studied in terms of the solvent molecule–polymer interactions. This work provides an interesting approach of visible discrimination of the solvents with similar structures, or their mixtures with various ratios, and also opens applications of biocompatible shape memory polymers in biomedical and chemical industries.

CAS / MDL: 97-67-6 629-41-4
研究领域: 材料科学 · 生物医学工程 · 高分子化学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Fractionation and characterization of poly(β-L-malic acid) produced by Aureobasidium melanogenum ipe-1

Changsheng Qiao,Guohang Sun,Hongbao Li,Weifeng Cao,Fei Shen,Rong Fan,Yinhua Wan

Poly (β-L-malic acid) (PMLA) is attracting industrial interest for its potential application in medicine and other industries, whose functions primarily depend upon its molecular size and chemical structure. Up to now, the fractionation and characterization of PMLA produced by Aureobasidium spp. were still unclear. In this study, the product from A. melanogenum ipe-1 was effectively fractionated using 300 and 50 kDa membranes. During the filtration, the mechanisms of membrane fouling were illegible since the PMLA can both reject and permeate the membrane, while the main fouling mechanism varied between standard blocking and complete blocking during the diafiltration . After fractionation, 14.0, 8.4 and 77.6 % of the PMLAs with M w s of 75,134, 21,344 and 10,056 Da were distributed in the 300 kDa retentate after diafiltrating, 50 kDa retentate after diafiltrating, and the 50 kDa permeate, respectively. The M w /M n s of the PMLAs were 4.12, 1.92, and 1.12 in the three fractions. Based on characteristic spectra of NMR, HPLC and FTIR, the product was not usual L-malic acid monomers, but glucose-terminated PMLA. The glucose was located at the terminal hydroxyl of PMLA. These results would serve as a valuable guide for process design and practical operation in subsequent industrial application.

CAS / MDL: 9057-02-7
研究领域: 生物化学 · 工业微生物学 · 材料科学
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FLUID PHASE EQUILIBRIA · 2013 · IF 2.379

Measurement and correlation solubility and mixing properties of l-malic acid in pure and mixed organic solvents

Yumei Kai,Yonghong Hu,Zheng Cao,Xiang Liu,Yan Liu,Wenge Yang

The solubilities of l -malic acid in pure and mixture organic solvents were measured from 278.15 to 323.15   K using the laser monitoring observation system. The modified Apelblat equation, the semi-empirical Buchowski–Ksiazczak λh equation and the Combined Nearly Ideal Binary Solvent/Redlich (CNIBS/R-K) equation were proposed to correlate the experimental data. In pure and mixed solvents, the 100RD (relative deviation) <3.61 and 7.58, respectively, the 10 4 RMSD (root-mean-square deviations) <3.07 and 2.28, respectively, so the equations selected in this work fit the data very well. Van’t Hoff equation was used to predict the dissolution enthalpy and entropy of l -malic acid in the corresponding solvents.

研究领域: 药物化学 · 物理化学 · 溶液热力学 · 药物结晶 · 分子药剂学
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Bioresources and Bioprocessing · 2021 ·Vol. 8 ·期 1 ·1-16 · IF 4.578

Engineering Escherichia coli biofilm to increase contact surface for shikimate and L-malate production

Ding Qiang,Liu Yadi,Hu Guipeng,Guo Liang,Gao Cong,Chen Xiulai,Chen Wei,Chen Jian,Liu Liming

Microbial organelles are a promising model to promote cellular functions for the production of high-value chemicals. However, the concentrations of enzymes and nanoparticles are limited by the contact surface in single Escherichia coli cells. Herein, the definition of contact surface is to improve the amylase and CdS nanoparticles concentration for enhancing the substrate starch and cofactor NADH utilization. In this study, two biofilm-based strategies were developed to improve the contact surface for the production of shikimate and L-malate. First, the contact surface of E. coli was improved by amylase self-assembly with a blue light-inducible biofilm-based SpyTag/SpyCatcher system. This system increased the glucose concentration by 20.7% and the starch-based shikimate titer to 50.96 g L−1, which showed the highest titer with starch as substrate. Then, the contact surface of E. coli was improved using a biofilm-based CdS-biohybrid system by light-driven system, which improved the NADH concentration by 83.3% and increased the NADH-dependent L-malate titer to 45.93 g L−1. Thus, the biofilm-based strategies can regulate cellular functions to increase the efficiency of microbial cell factories based on the optogenetics, light-driven, and metabolic engineering.

CAS / MDL: 1306-23-6 573-58-0
研究领域: 合成生物学 · 微生物工程
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Brazilian Journal of Pharmaceutical Sciences · 2023 · IF 1.3

Separation and determination of D-malic acid enantiomer by reversed-phase liquid chromatography after derivatization with (R)-1-(1-naphthyl) ethylamine

Mei Xuejiao,Lu Dingqiang,Yan Xiangping

L-Malic acid is the Active Pharmaceutical Ingredient of the latest generation of compound electrolyte injection (STEROFUNDIN ISO, Germany) and plays a very important role in the rescue of critically ill patients. The optical purity of L-malic acid is a Critical Quality Attributes. A new reversed-phase high performance liquid chromatography (RP-HPLC) method for pre-column derivatization of D-malic acid enantiomer impurity in L-malic acid bulk drug was established. The derivatization reaction was carried out using (R)-1-(1-naphthyl)ethylamine ((R)-NEA) as a chiral derivatization reagent. The Kromasil C18 column was used with a detection wavelength of 225 nm, a flow rate of 1.0 mL·min-1, and a column temperature of 30 °C. The mobile phase was acetonitrile-0.01 mol·L-1 potassium dihydrogen phosphate solution (containing 20 mmol·L-1 sodium heptanesulfonate, adjusted to pH 2.80 with phosphoric acid) (at a ratio of 45:55) and the resolution of D-malic acid and L-malic acid derivatization products reached 1.7. The proposed method possesses the advantages of simple operation, mild conditions, stable derivatization products and low cost. Also it gave better separation and was more accurate than previous methods.

CAS / MDL: 636-61-3
研究领域: 药物分析 · 分析化学
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CELLULOSE · 2025 · IF 4.8

Co-substrate fermentation of lignocellulose with added glucose and xylose to increase production of poly (β-l-malic acid)

Zhang Yutian,Zeng Dongdong,Li Jianing,Ma Xiaojun,Li Dongna,Li Yachao

Co-substrate fermentation has become an essential approach to achieving high-efficiency and low-cost production of poly (β- l -malic acid) (PMA). Herein, sustainable rubberwood ( Hevea brasiliensis ) hydrolysate (RWH) was co-fermented by A. pullulans to synthesize PMA using glucose and xylose as co-substrate carbon sources. Moreover, vitamin B was explored as nutrient supplementation in this study. Results showed that compared with the single RWH substrate, the PMA production of co-substrate fermentation increased by 38–52%. Furthermore, the addition of VB 6 promoted the utilization of substrates and shortened the fermentation cycle of PMA. During the scale-up fermentation, the PMA yield reached 0.50–0.54 g/g. Compared with traditional glucose culture medium, co-substrate fermentation improved the conversion rate of carbon sources and reduced PMA production cost by 14.9–36.6%. This work provides a new path for high-efficiency and economical industrial fermentation technology of PMA.

CAS / MDL: 9012-54-8
研究领域: 生物工程 · 微生物学
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Journal of Materials Chemistry B · 2024 ·Vol. 12 ·期 45 ·11696-11707 · IF 6.1

Enzyme/pH-sensitive nanoparticles based on poly(β-L-malic acid) for drug delivery with enhanced endocytosis

Songyan Guo,Youbei Qiao,Chaoli Wang,Yuming Zhang,Tiehong Yang,Hong Wu

Nanoparticles (NPs) derived from branched copolymers of poly (β-L-malic acid) (PMLA) have been extensively investigated for drug delivery due to their high density of pendant carboxyl groups. This abundant functional group availability enhances their potential as effective drug delivery systems; however, the strong negative charge of PMLA poses a challenge in its uptake by cancer cells due to electrostatic repulsion. In this study, we developed novel enzyme- and pH-sensitive nanoparticles (EP-NPs) based on PMLA, demonstrating tumor-specific behavior and selective activation within tumor tissues. To enhance the cellular internalization of the nanoparticles, we incorporated transactivator of transcription (TAT). In summary, long-chain polyethylene glycol (PEG) was conjugated to PMLA to confer specificity to the TAT peptide. This was achieved using a tetrapeptide linker: alanine–alanine–asparagine–leucine (AANL), which serves as a substrate for legumain. Legumain is a highly conserved cysteine protease primarily found in lysosomes and blood vessels, initially discovered in legumes. It is markedly overexpressed in numerous solid tumors, as well as in endothelial cells and tumor-associated macrophages. The release of doxorubicin in tumor cells was sustained due to the low pH (5.0–5.5) and degradation of PMLA. The PEG modification optimized the particle size and shielded the nanoparticles from plasma proteins and detection by the reticuloendothelial system, thereby prolonging their long circulation time. Once the nanoparticles reached the tumor microenvironment, the AANL was cleaved by legumain, exposing the TAT peptide on the surface, which enhances cellular internalization. Both in vitro and in vivo efficacy studies demonstrated that these EP-NPs significantly inhibited tumor growth while exhibiting negligible systemic toxicity, thereby suggesting that the developed enzyme/pH-sensitive PMLA-based nanoparticle holds great promise as an anti-tumor drug delivery system.

CAS / MDL: 25316-40-9 6318-55-4
研究领域: 药学 · 生物医学工程 · 肿瘤学
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JOURNAL OF APPLIED POLYMER SCIENCE · 2017 ·Vol. 135 ·期 11 ·45984 · IF 1.86

Synthesis and properties of non-cytotoxic poly(l-malic acid acetate-co-l-lysine ester)s with thermo-sensitivity as hydrophobic drug nanocarrier

Ying Yue,Zhihui Fan,Chang Zheng,Lan Ding,Huiying Wang,Miao Zhang,Kuilin Deng

In this investigation, a group of poly( l -malic acid acetate- co - l -lysine ester)s (PMALs) with excellent thermo-sensitivity and non-cytotoxicity were prepared by an optimized synthetic route from natural l -malic acid and l -lysine. The structure and properties of PMALs including monomers were systematically characterized by FTIR, 1 H NMR, UV, gel permeation chromatograph, scanning electron microscope, contact angle measurement, cell counting kit assess (CCK-8), and confocal laser scanning microscopy (CLSM). Three PMALs show a reversible lower critical solution temperature of 8–36 °C depending on their chemical structure. The contact angle measurement revealed a considerable discrepancy in the hydrophilicity/hydrophobicity of PMALs and further influence on their thermo-sensitivity. The viability of HeLa cells exposed to 0.2–100 μg/mL PMALs solution was found to be in a range 80–103% after 24, 48, and 72 h of incubation, indicating no cytotoxicity. Moreover, a spherical nanocarrier with core-shell structure was facilely fabricated via the thermo-sensitivity of PMALs and hydrophobicity of drug. CLSM observations manifested that the hydrophobic-curcumin-enwrapped nanocarriers can clearly internalize into the cellular inside. The sustained release of curcumin from nanocarriers in vitro provided a possibility of depressing fast hydrolytic degradation at physiological pH or other side-effects. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135 , 45984.

研究领域: 生物材料学 · 药物递送系统 · 高分子化学
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