Malonic Acid Research Articles

Tetraparesis as an initial manifestation of biotinidase deficiency: a case report.

The authors present a case of 2.5-year-old boy complained of progressive weakness in all four limbs, with difficulties in breathing. Abdominal examination revealed hepatomegaly and splenomegaly. Also, her parents were first-degree cousins. Therefore, tandem mass spectroscopy and urine organic acid analysis were planned to exclude metabolic disorders. Urinary organic acid analysis revealed elevated levels of methylmalonic acid and 3-hydroxyisovaleric acid. Serum biotinidase activity was found to be 3.9nmol/min/ml. Oral biotin at a dose of 1mg/kg daily was initiated. A marked improvement of his neurological deficit was noted over a period of 15 days after treatment and cutaneous manifestations resolved within 3 weeks. Myelopathy due to BTD is a challenging diagnosis. Spinal cord impairment is a rare complication of this disease and is frequently unrecognized. BTD should be included in the differential diagnosis of children presenting with demyelinating spinal cord disease.

A Comprehensive Study on DES Pretreatment Application to Microalgae for Enhanced Lipid Recovery Suitable for Biodiesel Production: Combined Experimental and Theoretical Investigations

Cell wall disturbance is an important step in the downstream process of improving the efficiency of lipid extraction from microalgae. Surfactants have been proven to be efficient alternatives to organic solvents in the extraction process. In this study, an effective approach involving deep eutectic solvent (DES) (choline chloride and carboxylic acids) treatment supplemented with surfactants has been developed to disrupt the cell walls of microalgae and increase the extraction of lipids suitable for biodiesel production. A combination of polar and non-polar solvents (ethyl acetate and n-butanol) was used for the lipid extraction process. Microalgae biomass pretreated with choline chloride malonic acid supplemented with the surfactant hexadecyl trimethylammonium chloride (HTAC) showed the best results, improving lipid extraction by 12.365%. Further elucidation of the detailed mechanism behind the cell disruption of the microalga wall by DES was achieved using density functional theory (DFT) methods. The DFT calculations revealed that hydrogen bonds between the chloride ion of the DES and hydrogen bond donor (HBD) molecules are key factors dominating the destruction of the cell wall structure of Chlorella pyrenoidosa. The optimization of lipid extraction was performed through a single-factor experiment, which included the effects of different variables (time, temperature, dosage of surfactant, and ratio of n-butanol to ethyl acetate). An extraction period of 60 min at 80 °C with a surfactant concentration of 0.5% at a 1:2 ratio of n-butanol to ethyl acetate was found to produce the maximum lipid yield (16.97%). Transesterification reactions were used to obtain fatty acid methyl esters from the optimized extracted lipids. Thus, it was determined that C16:0 (20.04%), C18:2 (29.95%), and C18:3 (21.21%) were the most prevalent fatty acids. The potential for producing biodiesel from C. pyrenoidosa was validated by the high yields of C18 fatty acid methyl esters, and the properties of biodiesel are within the European and US standards.

Phosphate Solubilization and Plant Growth Promotion by Pantoea brenneri Soil Isolates.

Phosphate solubilizing microorganisms (PSMs) in soil have been shown to reduce mineral phosphate fertilizer supplementation and promote plant growth. Nevertheless, only several P-solubilizing microorganisms capable of solubilizing both organic and mineral sources of soil phosphorus have been identified up to now. The aim of this study was to evaluate the inorganic soil phosphate solubilizing activity of phytate-hydrolyzing Pantoea brenneri soil isolates. We showed that the strains efficiently solubilize a variety of inorganic phosphates. We optimized the media composition and culturing conditions to improve the solubilization efficiency of the strains and investigated the mechanisms of their phosphate solubilization. Through HPLC analysis, it was determined that P. brenneri produce oxalic, malic, formic, malonic, lactic, maleic, acetic, and citric acids as well as acid and alkaline phosphatases while growing on insoluble phosphate sources. Finally, we analyzed the influence of P. brenneri strains with multiple PGP-treats on plant growth in greenhouse experiments and showed their ability to promote growth of potato.

Simultaneous ozonation of ethylbenzene and fluorene in water, soil, and air

Most of the studies regarding aromatic hydrocarbon degradation by ozone focus on individual treatment. Hence, two aromatic hydrocarbons, ethylbenzene (ETB) presented in water and fluorene (FL) distributed in soil, were selected to be eliminated simultaneously in water, soil, and air using ozone. In this study, the effect of the physicochemical properties of ETB and FL, the distribution of FL on sandy and agricultural soils, and the influence of the presence of moisture in both soils were analyzed. The chemical composition of the agricultural soil (mainly metal oxides) enhanced the FL degradation by the possible catalytic ozone decomposition into reactive species, such as •OH, O2•−, H2O2, O3•−, and O•, which reduced its treatment time 4.5-fold in this solid matrix compared to the sandy soil. Moreover, the moisture liberated from water by the gas flow and adsorbed on the soil bed (up to 0.33% at 180 min) reduced the ozonation time 2-fold in the agricultural and sandy soils, due to the •OH formation. Contrary to FL, the rapid elimination of ETB (< 20 min) in both soils did not allow to observe the possible effect of reactive species generation on ETB decomposition due to the low amount of moisture accumulated during this time (<0.06%). The proposed simultaneous ozonation scheme permitted to achieve up to 96% and 100% of the ETB and FL decomposition. Some identified by-products, such as maleic, malonic, oxalic, and formic acids, suggest that ozone and possible reactive species formed on the soil surfaces reacted with both compounds, leading to non-toxic simple by-products with their partial mineralization (≈80%), which was proven by a toxicity evaluation (phytotoxicity and eco-toxicity). The rapid and efficient simultaneous ozonation of aromatic hydrocarbons in water, soil, and air (only ETB) proves the feasibility of ozone to treat different organic pollutants in more than one phase.

Route-based chemical significance and source origin of marine PM2.5 at three remote islands in East Asia: Spatiotemporal variation and long-range transport

We explored the route-based chemical significance, spatial distribution, temporal variation, and source origin of fine particles (PM2.5) in East Asia. Marine PM2.5 was sampled at three remote islands in the Taiwan Strait (TS) and the South China Sea (SCS) to identify their chemical significance. High PM2.5 concentrations concurred with LRT of northerly polluted air. Moreover, daytime PM2.5 levels were mostly greater than nighttime. Secondary inorganic aerosols (SIAs) accounted for 42.4–79.9% of water-soluble ions (WSIs) in PM2.5, which were commonly higher in spring and winter. Although crustal elements suppressed the metallic contents of PM2.5, trace elements (V, Cr, Mn, Ni, Zn, and Cd) came dominantly from anthropogenic origins. Additionally, OC/EC ratios >2.0 were observed due to higher organic carbon (OC) than elemental carbon (EC) during the Asian Northeastern Monsoons (ANMs) commonly in spring and winter. Levoglucosan and oxalic acid were, respectively, the most abundant anhydrosugars (ASs) and organic acids (OAs) in PM2.5, and both descended from the north to the south. The mass ratios of malonic and succinic acids (M/S) were in the range of 0.95–1.41, suggesting a high correlation of marine PM2.5 with secondary organic aerosols (SOAs). Source resolution of PM2.5 showed that sea salts, fugitive dust, mobile sources, secondary sulfate and nitrate were the major sources of PM2.5. In particular, anthropogenic origins and biomass burning (BB) contributed notably to PM2.5 during the ANMs. Overall, compared to natural sources (21–48%), anthropogenic sources (25–57%) contributed more to marine PM2.5 in East Asia.

ROS-mediated TCA cycle is greatly related to the UV resistance of Bacillus thuringiensis

Bacillus thuringiensis (Bt) is a popular and environment-friendly biopesticide. However, similar to other microbial pesticides, Bt is limited by ultraviolet (UV) radiation during its application, which greatly reduces its toxicity and persistence. To further know the mechanism of Bt against UV radiation, metabolomic profiles between Bt LLP29 and its UV-resistant mutant LLP29-M19 were compared, analyzed, and annotated in this study, and then a total of 61 metabolites with different abundances were detected. With P < 0.05 as the standard, a total of 12 metabolic pathways were enriched, including the TCA cycle. According to the result of RT-qPCR, the expression levels of the TCA cycle key genes in Bt LL29-M19, such as icd1 citZ, citB, sdhA, sdhB, sdhC, fumA, and mdh, were found down-regulated for 85.58%, 37.02%, 70.87%, 85.97%, 76.33%, 83.15%, 87.28%, and 35.77% than those in Bt LLP29. It was consistent with the down-regulation trend of the TCA cycle key enzymes activity in Bt LLP29-M19. Consistently, the enzyme activities of ICDH, SDH, and PDH in LLP29-M19 were detected 86.28%, 43.93%, and 83.03% lower than those in Bt LLP29. It was revealed that the reduced TCA cycle was required for Bt UV radiation resistance, which was also demonstrated by the addition of inhibitors furfural and malonic acid, respectively. Based on the result of RT-qPCR, the gene transcription levels of the main reactive oxygen species (ROS) generation pathways were down-regulated, such as EMP, however, the activity of the main degrading enzymes was up-regulated, which showed the reduction of ROS generation rate was a way for the TCA cycle to regulate the anti-ultraviolet resistance of Bt. All of these provide solid evidence for reprogramming metabolomics to strengthen Bt UV radiation resistance.

Thermodynamic functions of succinic acid in acetone–water binary mixtures based on computation of KI & KII constants

Succinic acid is commonly used in various chemical, pharmaceutical, environmental and industrial activities and its reactivity is principally determined by the pK(I & II) values. Therefore, the dissociation constants of succinic acid have been determined in this study on the basis of emf measurements in both different acetone mole fractions and temperature range. The pK(I or II) values of the studied acids in acetone aqueous media were found higher than those obtained in other organic aqueous media with the same conditions (temperature and mole fraction of solvent). Moreover, (KI/KII) in 40 wt% acetone–water mixture was identified to follow succinic acid < malic acid < malonic acid < maleic acid owing to the stabilization of intramolecular hydrogen bonding. The free energy of transfer (ΔG0I or II) for succinic acid was increased with the increasing of pKI or pKII values due to the decrease in relative permittivity (εr) via increment of the acetone fraction in the aqueous medium. The trend of ΔS°I value among the studied acids were found to follow maleic < malic < succinic < malonic. ΔS°II values were characterized lower than ΔS°I due to possible solvent interactions with the acid anion (L2-). Therefore, ΔH°II values of the second dissociation process were identified lower than ΔH°I to favor an exothermic reaction.

Decarboxylative Mannich Reactions with N‐Alkyl Imines

AbstractThe use ofN‐alkyl imines in decarboxylative Mannich reaction with substituted malonic acids half oxyesters (SMAHOs) has been developed to afford a direct access to secondary β2,3‐aminoesters. The transformation occurs under very practical conditions (DABCO as a catalyst in bulk toluene and open to air) and can be performed with a broad range of each substrate in yields of 36 to 97 %. Importantly, the reaction was found to require the use of acidic additives in combination with the organocatalyst to limit the competitive olefination reaction.

Synthesis of diethyl 6-amino-1,4-diaryl-2-oxo1,2,3,4-tetrahydropyridin-3,5-dicarboxylates based on the reaction of arylmethylidenecyanoacetic esters with &lt;i&gt;N&lt;/i&gt;-arylamido esters of malonic acid

The reaction of arylmethylidenecyanoacetic esters with N -arylamides of malonic acid led to the formation of previously unknown diethyl 6-amino-1,4-diaryl-2-oxo-1,2,3,4-tetrahydropyridine-3,5-dicarboxylates in 15-83% yields. Antibacterial activity of some obtained compounds was studied.

Amorphization of Ethenzamide and Ethenzamide Cocrystals-A Case Study of Single and Binary Systems Forming Low-Melting Eutectic Phases Loaded on/in Silica Gel.

The applicability of different solvent-free approaches leading to the amorphization of active pharmaceutical ingredients (APIs) was tested. Ethenzamide (ET), an analgesic and anti-inflammatory drug, and two ethenzamide cocrystals with glutaric acid (GLU) and ethyl malonic acid (EMA) as coformers were used as pharmaceutical models. Calcinated and thermally untreated silica gel was applied as an amorphous reagent. Three methods were used to prepare the samples: manual physical mixing, melting, and grinding in a ball mill. The ET:GLU and ET:EMA cocrystals forming low-melting eutectic phases were selected as the best candidates for testing amorphization by thermal treatment. The progress and degree of amorphousness were determined using instrumental techniques: solid-state NMR spectroscopy, powder X-ray diffraction, and differential scanning calorimetry. In each case, the API amorphization was complete and the process was irreversible. A comparative analysis of the dissolution profiles showed that the dissolution kinetics for each sample are significantly different. The nature and mechanism of this distinction are discussed.

Unraveling the matching of reaction and separation for reactive distillation process based on reaction equilibrium degree (RED)

The multiplicity of matching between reaction and separation for reactive distillation (RD) process leads to a more complex design of RD column, however, the exploration of coupling problem between reaction and separation for the design of reaction section in the RD column is still a blank of RD research. In this article, a design framework for the reaction section in the RD column based on the reaction equilibrium degree (RED) is demonstrated. The interaction relationship between residence degree and separation efficiency of reaction section is established by means of spline interpolation method. Herein, the synthesis of malonic acid (MA) from dimethyl malonate (DM) hydrolysis, as a case study, was investigated to obtain coupling regularities of reaction and separation for specified design targets and further design the reaction section of RD column from principle. The results validated the effectiveness of the proposed framework and provided theoretical guidance for challenging RD process.

1H NMR-based urinary metabolic analysis of high-dose cyclophosphamide-induced toxicity in mice

Cyclophosphamide (CP) is widely used in clinical fields. Beside its therapeutic effects, CP shows toxicity depending on dose and administration schedule. In this study, the urinary metabolic profiles were investigated in mice intraperitoneally injected with high-dose CP (150 mg/kg body weight) once a week over four weeks using nuclear magnetic resonance (NMR)-based metabolomics. Twenty-six metabolites were identified as potential biomarkers by multivariate statistical analysis. A decrease in isoleucine, alanine, N-acetylglutamic acid, proline, methionine, valine, phenylacetylglulamine, dimethylamine, hippurate, acetic acid, lactate, α-oxoglutarate, citrate, malonic acid, creatinine, niacin, β-hydroxybutyrate, and betaine, whereas an increase in leucine, glutamate, glycine, taurine, phenylacetylglycine, glucose, creatine, and choline were observed in the urine of high-dose CP-treated mice. Metabolites related to amino acid metabolism, energy metabolism, and gut microbial metabolism were changed markedly in the urine. Further metabolic pathway analysis suggested that seven metabolic pathways, including alanine, aspartate, and glutamate metabolism, arginine biosynthesis, glyoxylate, and dicarboxylate metabolism, glycine, serine and threonine metabolism, d-glutamine and d-glutamate metabolism, arginine, and proline metabolism, citrate cycle, as well as the gut microbiota metabolism, were significantly involved in response to high-dose CP treatment. These findings help to predict the toxicity of CP and understand the biological mechanism of the toxicity of CP.

Binary mixtures formed between methyl malonic acid and alkyloxy benzoic acids: optical and thermal investigations

Double hydrogen bond liquid crystals (MM + nBOA) are prepared from Methyl Malonic acid (MM) and p-n alkyloxy benzoic acid (nBOA, whose carbon chain length varies from pentyl to dodecyl) treated with dimethyl form amide. MM + 7BOA and MM + 9BOA mesogenic complexes are preferred as chemical ingredients for preparing binary mixtures as they exhibit rich phase polymorphism. MM + 7BOA is treated as X component while MM + 9BOA is treated as Y component. Appropriate molar ratio (0.1X to 0.9X and 0.1Y to 0.9Y) variation leads to formation of nine binary mixtures. Chemical, optical and thermal investigations are performed for fitting the binary mixtures to applicational viability.

Molecular profiling of whey permeate reveals new insights into molecular affinities related to industrial unit operations during lactose production

Lactose powder production from whey permeate generates various side-streams. Molecular profiling of these side-streams and lactose powder can help to detect minor compounds affecting lactose crystallization, lactose powder properties and document the composition of the underutilized side-streams. In this study, whey permeate, lactose powder and intermediate streams from trial lactose productions were analyzed using gas chromatography-mass spectrometry (GC–MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy. In total, 110 compounds were identified and 49 were quantified. Linking the molecular profiles to in-process steps revealed differential compositional attenuation by the unit operations. Small molecules (e.g. methanol) and a few larger molecules (e.g. fatty acids) permeated reverse osmosis membrane, while twenty-three compounds (e.g. hydroxypyruvic acid, malonic acid, gluconic acid and ribonic acid) co-crystallized with lactose and ended up in lactose power. These results help to better understand and control lactose powder production and highlights possibilities to develop new food ingredients.

Synthesis of Diethyl 6-Amino-1,4-diaryl-2-oxo-1,2,3,4-tetrahydropyridin-3,5-dicarboxylates Based on the Reaction of Arylmethylidenecyanoacetic Esters with N-Arylamidoesters of Malonic Acid

Synthesis of Diethyl 6-Amino-1,4-diaryl-2-oxo-1,2,3,4-tetrahydropyridin-3,5-dicarboxylates Based on the Reaction of Arylmethylidenecyanoacetic Esters with N-Arylamidoesters of Malonic Acid

EVALUATION OF BIOCHEMICALAND HEMATOLOGICAL PARAMETERS IN MACROCYTIC ANEMIA

Background: In the age of calibrated automatic analysers, biochemical and hematological parameter evaluation form the yardstick to dene macrocytic anemias. The size of red cells in relation to mean corpuscular volume (MCV) has been used to categorize anemia. Aim of current study was to evaluate the role of routine blood parameters and biochemical parameters in differentiating megaloblastic anemia and non megaloblastic anemia. Methods:Aretrospective study was carried out on retrieved records (laboratory parameters) of the patients who were admitted at a tertiary care hospital, this included a total of 90 cases of anaemia between January 2020 - July 2021. These included records of patients with anaemia based on Vitamin B12 levels, LDH levels. Other various parameters like mean corpuscular volume, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration were also taken into consideration for descriptive statistics. Results: Liver disease was the most common cause of macrocytosis (40%). The other causes in decreasing order of frequency were megaloblastic anaemia (27.7%), hemolytic anemia (8%), drug induced (9%).When comparisons of various complete blood count parameters between megaloblastic and non-megaloblastic group was done with LDH having signicance (p=0.001) in megaloblastic group and .011 in non-megaloblastic group. Conclusions: Evaluation of Methyl malonic acid and homocysteine levels, is sensitive, but expensive and scarcely available. The overall performance which is measured using Area under the Curve indicates that a contribution of LDH and MCV are good at differentiating megaloblastic Vs. Non megaloblastic causes of macrocytic anemias, However a larger population should be studied to nd variances between ethnicity, gender and age

Reaction of 2-R-naphtho[2,3-d][1,3,2]dioxaphosphinin-4-ones with arylidene derivatives of malonic acid esters: synthesis, molecular and crystal structures of 5-oxo-2-R-naphtho[2,3-f][1,2]oxaphosphepine 2-oxides

Reaction of 2-R-naphtho[2,3-d][1,3,2]dioxaphosphinin-4-ones with arylidene derivatives of malonic acid esters: synthesis, molecular and crystal structures of 5-oxo-2-R-naphtho[2,3-f][1,2]oxaphosphepine 2-oxides

Investigation of sustainable reactive distillation process to produce malonic acid from dimethyl malonate

The new energy battery is currently a hot research topic, leading to an increase in the demand for malonic acid (MA) as a raw material. The objective of the present work is to find a potential reactive distillation (RD) process to solve the problem of low conversion and high energy consumption in hydrolytic system. In the meantime, the RD technology still faces the problem of how to distribute water in the RD column. Aiming at the problem, four different RD processes are proposed: RD combined water separation process (RDWS), RD combined with MA concentration process (RDMC), RD combined methanol separation process (RDMS), and single RD process (SRD). Beforehand, reaction kinetic of dimethyl malonate (DM) hydrolysis was investigated using the ion exchange resin catalysts, and the developed RD model was verified via pilot-scale RD experiments. Finally, the proposed RD process is analyzed from the aspects of economic and environmental and compared with the traditional reaction + distillation (R + D) process. Consequently, the proposed SRD process is a better economy-saving and environment-friendly technology, and has certain directive significance for the industrial production of MA.

Role of aerosol liquid water content on the production of dicarboxylic acids in the dust-laden air masses over the Arabian Sea: Implications for heterogeneous chemistry

Oxalic acid and the related organics are ubiquitous water-soluble constituents of ambient organic aerosols (OA). Their molecular distributions and relative abundances provide crucial insights on the secondary OA formation processes in the marine atmosphere and are important for understanding the cloud-aerosol interactions. Here, we measured the concentrations of dicarboxylic acids, pyruvic acid, ω-oxocarboxylic acids and α-dicarbonyls alongside aerosol chemical composition in the South Asian outflow to the Arabian Sea. Oxalic acid (C2) was the most abundant dicarboxylic acid followed by succinic (C4) and malonic (C3) acids; this distribution is typical of “less aged OA”. Oxalic acid levels correlated well with aerosol liquid water content (ALWC) and non-sea-salt (nss)-SO42− (a tracer of coal combustion influence), suggesting an important aqueous phase oxidation of successive higher homologs. This was inferred based on the prevailing inverse relationships between the relative abundances of oxalic acid in total aliphatic dicarboxylic acids and those of malonic, succinic, glutaric, adipic, and azelaic acids. Likewise, the concentrations of glyoxal (Gly: a major compound emitted from vehicular exhaust) and glyoxylic acid (ωC2) correlated strongly with C4, nss-Ca2+ (dust tracer) and elemental carbon (EC: a combustion tracer from biomass/fossil-fuels). These observations suggest gas/particle partitioning and subsequent aqueous phase oxidation of Gly to ωC2 and then elongation (oligomerization) to succinic acid associated with the mineral dust particles. This means relative abundances of anthropogenic SO42− in the dust-laden air masses govern the secondary OA formation over the Arabian Sea.

Rheological and Thermal Behavior of Choline-based Deep Eutectic Ionic Liquid and its Impact on a Poorly Soluble Drug Model

Objective: This study was conducted to prepare a deep eutectic ionic liquid based on choline chloride and malonic acid (Maline) in diff erent molar ratios and evaluate the maline properties to designate the best ratio for solubilizing risperidone, a poorly soluble drug model. Method: Malines were prepared using choline chloride and malonic acid in 1:0.8, 1:0.9 and 1:1 molar ratios. The characterization of malines involved pH rating, rheological test and thermal behavior using DSC. In addition to estimating the interactions that occur between the choline chloride and malonic acid to form the malines theoretically using the computational prediction program Mercury and experimentally by 1H-NMR and FTIR. Results: This study shows that all malines (M1-M3) represents an acidic pH and high viscosity with a non-newtonian behavior (shear thinning property ) at low temperature while a Newtonian behavior (shear rate-independent) at high temperatures. In malines (M1-M3) thermograms, the absence of pure compounds melting point peaks with a glass transition temperature at -14○C that confi rms the DES property. FTIR and 1H-NMR results represent a hydrogen bond formation between choline chloride and malonic acid and further between maline and risperidone which is similar to the computational prediction. Maline (M1) with molar ratio of 1:1 had a preferable solubilizing eff ect on risperidone reaching 20.5 mg/mL, while in (M2) (1:0.9) reaches 13.6 mg/mL, and in (M3) reaches 11.9 mg/mL. Conclusion: Maline (M1) was chosen as the optimum molar ratio to form a deep eutectic ionic liquid that successfully enhances risperidone solubility and boosts its bioavailability.