Dimer Of Lactic Acid Research Articles

Modulation of bacterial infection and inflammation by release of lactide from a silicone elastomer device

The aim of this project is to assess the anti-bacterial and anti-inflammation properties of a matrix-type silicone elastomer device providing sustained release of DL-lactide (a cyclic ester dimer of lactic acid). Lactide-loaded matrices were prepared by injection molding, and the devices were assessed for of in vitro release, anti-bacterial activity, and anti-inflammatory activity. The devices provided sustained release of lactide/lactic acid over five days and were effective against E. coli and S. aureus. Further, the devices reduced inflammation through activation of the GPR81 receptor via the NF-κB and JAK-STAT signalling pathway. These lactide-releasing silicone elastomer devices could improve clinical outcomes with certain short-term medical devices.

UPLC-HRMS-based Plasma Metabolomics Study of Thymoma and Thymic Hyperplasia.

Thymoma is a rare malignant tumor but it is the most common primary tumor of the anterior mediastinum. The current imaging methods for thymoma screening suffer from false positive rate problem, and thymoma pathogenesis remains elusive. Study of thymoma metabolic characteristics could provide clues for improving the diagnosis and understanding the pathogenesis of thymoma. Metabolic profiling of sera from thymoma and thymic hyperplasia patients was performed using UPLC-HRMS in both positive and negative ionization modes. After pre- and post-processing, the dataset was divided into three age groups and statistical analysis was performed to select differential metabolites of thymoma. For feature identification, experimental MS/MS spectra were matched to those of databases and available chemical standards, and also manually annotated with plausible chemical structures to ensure high identification confidence. A total of 47 differential metabolites were identified in thymoma. Significant higher levels of histidine, sphinganine 1-phosphate, lactic acid dimer, phenylacetylglutamine, LPC (18:3) and LPC (16:1), and significant lower levels of phenylalanine, indole-3-propionic acid (IPA), hippuric acid and mesobilirubinogen were associated with thymoma. Tryptophan level in thymoma-associated myasthenia gravis (TAMG) was significantly lower than that of the MG (-) group. IPA and hippuric acid abundances exhibited increasing trends from indolent to aggressive thymoma. Our study revealed aberrant aromatic amino acid metabolism and fatty acid oxidation might be associated with thymoma. The identified unique metabolic characteristics of thymoma may provide valuable information for study of the molecular mechanism of thymoma pathogenesis, and improvement of diagnosis and discovery of new therapeutic strategies for thymoma.

Characterization of Thymoma by Ultra-Performance Liquid Chromatography—High Resolution Mass Spectrometry (UPLC-HRMS) and Metabolomics of Serum

Thymoma is a rare thymic tumor but is the most common anterior mediastinal tumor. Currently, there are still limitations regarding to its screening and the pathology remains elusive. In this study, nontargeted metabolomic analysis of serum was performed to study the metabolic characteristics of thymoma using ultra-performance liquid chromatography—high resolution mass spectrometry (UPLC-HRMS) in positive and negative ionization modes. The metabolites that were differentially abundant in thymoma were identified by MS/MS and matching to chemical standards. Forty-one metabolic features differentially abundant in thymoma were identified in the corresponding age groups, including uridine, dipeptides, arachidonic acid (AA)/8,11,14,17-eicosatetraenoic acid, lactic acid and its dimer, acylcarnitines, lysophosphatidylcholines (LPCs), and ceramide 1-phosphate (Cer1P) (d18:0/3:0). Among these metabolites, lactic acid and 9-decenoylcarnitine also had significant abundance changes between thymoma patients with and without myasthenia gravis (MG). Uridine, lactic acid and Cer1P (d18:0/3:0) may also be associated with the aberrant immune status in thymoma. Orthogonal partial least squares—discriminant analysis (oPLS-DA) showed that classification between thymoma and thymic hyperplasia was possible with 94.7% sensitivity, 100% specificity and 96.8% accuracy for all patient samples. The discriminant feature panel included uridine, AA/8,11,14,17-eicosatetraenoic acid, lactic acid dimer, and N-(1-deoxy-1-fructosyl)tryptophan. The distinct serum metabolic characteristics of thymoma identified in this study may offer insights into improvement of the diagnosis and discovery of new therapeutic strategies for thymoma, in addition to providing information for study of the underlying molecular mechanism of thymoma pathogenesis.

Metabolic Profiling Identifies Changes in the Winter Wheat Grains Following Fusarium Treatment at Two Locations in Croatia

Fusarium head blight (FHB) is one of the most dangerous diseases of winter wheat, resulting in reduced grain yield and quality, and production of mycotoxins by the Fusarium fungi. In the present study, changes in the grain metabolomics of winter wheat samples infected with Fusarium spp. and corresponding non-infected samples from two locations in Croatia were investigated by GC-MS. A Mann-Whitney test revealed that 24 metabolites detected were significantly separated between Fusarium-inoculated and non-infected samples during the variety by treatment interactions. The results confirmed that in grains of six FHB-resistant varieties, ten metabolites were identified as possible resistance-related metabolites. These metabolites included heptadecanoic acid, 9-(Z)-hexadecenoic acid, sophorose, and secolaganin in grains of FHB-resistant varieties at the Osijek location, as well as 2-methylaminomethyltartronic acid, maleamic acid, 4-hydroxyphenylacetonitrile, 1,4-lactonearabinonic acid, secolaganin, and alanine in grains of FHB-resistant varieties at the Tovarnik location. Moreover, on the PCA bi-plot, FHB-susceptible wheat varieties were closer to glycyl proline, decanoic acid, and lactic acid dimer that could have affected other metabolites, and thus, suppressed resistance to FHB. Although defense reactions were genetically conditioned and variety specific, resulting metabolomics changes may give insight into defense-related pathways that could be manipulated to engineer plants with improved resistance to the pathogen.

Controlled Synthesis of l-Lactide Using Sn-Beta Zeolite Catalysts in a One-Step Route

Polylactic acid (PLA), as a biodegradable and renewable polymer, has been widely used in biomedical and commercial applications. The energy-efficient synthesis of lactide from lactic acid (La) via a one-step route is highly desired for megaton-scale PLA production. In this work, stereo-pure l-lactide was synthesized with high yield (88.2–95.8%) via a one-step route catalyzed by Sn-beta zeolites. Sn–O–Si bonds on tin–silica catalysts are indeed important for a high l-lactide yield. The Sn4+ ions with four isolated coordinates in tetrahedral configuration of Sn-beta zeolites are more active for l-lactide synthesis than those with hexacoordinated polymeric Sn–O–Sn-type species. l-La was first converted into a lactic acid dimer (L2a) and then formed l-lactide catalyzed by a Sn-beta zeolite, and the average reaction rate in first 20 min (R20minav) increased linearly with increasing Sn content. Importantly, lactic acid trimers (L3a) formed during the reaction could also be converted to l-lactide in the later stage of the reaction, and the diffusion of L3a to the active site within the Sn-beta zeolite pore is the rate-limiting step. The lactic acid oligomer (Lna, n ≥ 4) was limited to form lactide with an R20minav of only 0.013 mmol min–1 gcat–1.

Macrocycles in dual role: ancillary ligands in metal complexes and organocatalysts for the ring-opening polymerization of lactide

AbstractIn the twenty-first century, one of the central focus of polymer research in academia and industries is directed towards the design of environmentally-benign materials produced from reagents that have minimal deleterious effects on our environment. The aliphatic polyester PLA is one such example. Due to its biodegradable, biorenewable and biocompatible nature, PLA finds diverse applications, especially in the biomedical field. PLA is exclusively synthesized by the ring-opening polymerization of lactide (cyclic dimer of lactic acid) in the presence of a catalyst. The macrocycles and macrocyclic metal moieties can act as effective catalysts for the polymerization resulting in the formation of PLA with controlled tacticity and predetermined molecular weight. This review reports metal-based catalytic systems supported by porphyrin, calixarene and bispyrrolidine- salan as ancillary ligand and metal-free organocatalyst sparteine for the ROP of LA. The variation in catalytic activity, tacticity of PLA, and PLA's molecular weight distribution by substitutional changes in the catalyst framework have been discussed in detail. Graphic abstract

Quantitative analysis of lactic acid oligomers from dimer to 15mer in poly(D,L-lactide) (PDLLA) polymers

Poly(D,L-lactide) (PDLLA) polymer is widely used in biomedical applications. To control the degradation of PDLLA, as well as to ensure effective quality control of the polymer raw material, it is essential to have analytical methods capable of analyzing the PDLLA oligomer species content quantitatively. In this study, liquid chromatography-mass spectrometry (LC-MS) based analytical methods were developed to quantitate oligomer species from dimer to 15mer (total of 14 analytes) in the PDLLA polymer resin. Negative electrospray ionization was employed as the LC-MS interface. For the lactic acid dimer and trimer analysis, a SIELC Primesep SB column was used for high performance liquid chromatography (HPLC) separation and selected reaction monitoring (SRM) was used as the acquisition mode. For other lactic acid oligomer (4mer to 15mer) analysis, a Phenomenex Synergi™ 4 µm Polar-RP column was used, and selected ion monitoring (SIM) was used as the acquisition mode. Both columns demonstrated good tolerability for samples with high polymer content which is critical for method development. Analytical parameters such as calibration, correlation, accuracy, and precision were evaluated. Quadratic functions best described the correlation between response and concentration for each oligomer analyte. Excellent accuracy and precision were demonstrated with both methods. The methods developed in this study can be used to evaluate the impact of manufacturing process on polymers and can also be a good reference for oligomer analysis method development of similar polymers.

Lactic Acid Spectroscopy: Intra- and Intermolecular Interactions.

Lactic acid, a relevant molecule in biology and the environment, is an α-hydroxy acid with a high propensity to form hydrogen bonds, both internally and to other hydrogen-bond-accepting molecules. This work includes the novel recording of infrared spectra of gas-phase lactic acid using Fourier transform infrared spectroscopy, and the vibrational absorption features of lactic acid are assigned with the aid of computationally simulated vibrational spectra with anharmonic corrections. Theoretical chemistry methods are used to relate intramolecular hydrogen-bond strengths to the relative stability of lactic acid conformers. The formation of hydrogen-bonded lactic acid dimers and 1:1 water complexes is investigated by simulated vibrational spectra and calculated thermodynamic parameters for the lactic acid monomer and dimer and its water complex in the gas phase. The results of this study are discussed in the context of environmental chemistry with an emphasis on indoor environments.

A Preliminary Study on Metabolome Profiles of Buffalo Milk and Corresponding Mozzarella Cheese: Safeguarding the Authenticity and Traceability of Protected Status Buffalo Dairy Products.

The aim of this study is to combine advanced GC-MS and metabolite identification in a robust and repeatable technology platform to characterize the metabolome of buffalo milk and mozzarella cheese. The study utilized eleven dairies located in a protected designation of origin (PDO) region and nine dairies located in non-PDO region in Italy. Samples of raw milk (100 mL) and mozzarella cheese (100 g) were obtained from each dairy. A total of 185 metabolites were consistently detected in both milk and mozzarella cheese. The PLS-DA score plots clearly differentiated PDO and non-PDO milk and mozzarella samples. For milk samples, it was possible to divide metabolites into two classes according to region: those with lower concentrations in PDO samples (galactopyranoside, hydroxybuthyric acid, allose, citric acid) and those with lower concentrations in non-PDO samples (talopyranose, pantothenic acid, mannobiose, etc.,). The same was observed for mozzarella samples with the proportion of some metabolites (talopyranose, 2, 3-dihydroxypropyl icosanoate, etc.,) higher in PDO samples while others (tagatose, lactic acid dimer, ribitol, etc.,) higher in non-PDO samples. The findings establish the utility of GC-MS together with mass spectral libraries as a powerful technology platform to determine the authenticity, and create market protection, for “Mozzarella di Bufala Campana.”

Nomenclature and terminology for linear lactic acid-based polymers (IUPAC Recommendations 2019)

Abstract Lactic acid enantiomers and cyclic lactic acid dimers, the latter referred to as lactides, are sources of degradable aliphatic polymers that are composed of chiral constitutional repeating units. The different synthesis routes and the various combinations of chiral units result in a multitude of chiral structures and of corresponding properties. Distinctive structural identification is often crucial, especially for applications as degradable polymers. This document provides recommendations for the nomenclature, abbreviations, and terminology related to lactic acid-based polymers in order to allow consistent comparison between polymers of different origins and between data collected within different disciplines.

Chemistry and Photochemistry of Pyruvic Acid Adsorbed on Oxide Surfaces.

The surface chemistry and photochemistry of gas-phase pyruvic acid (CH3COCOOH) on two oxides, Al2O3 and TiO2, have been investigated using transmission Fourier transform infrared spectroscopy and mass spectrometry. At 298 K, the carboxylic acid group within pyruvic acid is found to react with surface hydroxyl groups (M-OH, M = Al, Ti) to yield pyruvate as a predominant adsorbed organic species. Upon broad-band UV irradiation (λ > 280 nm), there is a loss of adsorbed pyruvate with the concomitant formation of new products. The photochemical loss of pyruvate is higher on TiO2 than on Al2O3 indicating that the photochemistry is enhanced on the surface of a semiconductor oxide, TiO2, compared with an insulator oxide, Al2O3. Analysis of products extracted from the surface with mass spectrometry shows the formation of several new compounds. This includes zymonic acid, which is found to be present under both dark and light conditions, and other higher-molar-mass oligomeric species such as parapyruvic acid, acetolactic acid, and 2,4-dihydroxy-2-methyl-5-oxohexanoic acid that form only under irradiation. Although this study shows that there are some parallels between the aqueous-phase photochemistry of pyruvic acid and the photochemistry of adsorbed pyruvic acid in terms of the products that form, there are also distinct differences, with several other new photoproducts observed on these oxide surfaces, including lactic acid dimers and trimers as well as significant amounts of even larger oligomeric species not seen in the aqueous phase. Because of the role of pyruvic acid, the simplest of the α-keto acids, in the atmosphere and in metabolic pathways, these results have implications for the chemistry that occurs in both indoor and outdoor environments and under prebiotic Earth conditions. Overall, this study provides insights into the surface chemistry and photochemistry of pyruvic acid on different oxides (Al2O3 and TiO2).

Degradation of Post-consumer PLA: Hydrolysis of Polymeric Matrix and Oligomers Stabilization in Aqueous Phase

Degradation of post-consumer PLA to lactic acid was analysed in order to assess the economic feasibility of the PLA chemical recycling process. Hydrolysis of PLA, in batch reactor, was analysed in the temperature range of 443–473 K, under autogenous pressure and a constant PLA to water ratio (equal to approximately 0.11 by weight), without the use of a catalyst. The experimental results suggest that the complete degradation of PLA can be obtained using relatively low reaction-times with the production of a mixture containing the monomer and traces of the dimer of lactic acid. The overall process was modelled using a two-step process: bulk degradation of PLA (in the solid or molten phase) with the solubilisation of low molecular weight oligomers, and their subsequent hydrolysis in water (stabilization). The model describes the trend of oligomer concentrations in the aqueous phase and PLA conversion as a function of time with both high accuracy and agreement with experimental results.

Importance of Dimer Quantification for Accurate Catalytic Evaluation of Lactic Acid Dehydration to Acrylic Acid

Catalytic dehydration of lactic acid in the presence of water is a potentially green, synthetic approach for the production of acrylic acid, and development of a highly selective catalyst is a primary challenge, leading to a resurgence in catalyst exploration and discovery. However, because the complexity in the analytical assessment of the efficiency of catalysts stemming from the possible presence of dimers in lactic acid feedstocks has often been neglected in the literature, we demonstrate, without consideration of the dimer during catalyst evaluation, that they can have a substantial influence on the determination of conversion of lactic acid and selectivity to acrylic acid in aqueous solution. In one example of a modified zeolite catalyst, a true acrylic acid of selectivity of 64% was overestimated to be 80% if the dimers in the feed solution were neglected in the analytical analysis. A survey of the literature demonstrated very few researchers account for the possible presence of lactic acid dimers ...

Enhancement of Mechanical and Thermal Properties of Poly(L-lactide) Nanocomposites Filled with Synthetic Layered Compounds

The effects of a layered double hydroxide (LDH) (Zn/Al palmitate) and two layered hydroxide salts (LHS), intercalated with the anion salicylate or palmitate, on the properties of poly(L-lactide) (PLLA) nanocomposites were investigated. PLLA and the nanocomposites were synthesized by ring opening polymerization of the cyclic dimer of lactic acid (lactide), using tin(II) 2-ethylhexanoate (stannous octanoate) as catalyst. PLLA nanocomposites containing two different fillers concentrations (1 wt% and 2 wt%) were produced. Compared to PLLA, almost all the nanocomposites exhibited an enhancement on thermal resistance. The sample containing 1 wt% of Zn/Al palmitate exhibited a decomposition temperature 51°C higher than neat polymer. Results of flexural properties demonstrated that the nanocomposites containing Zn/Al palmitate displayed the highest values of maximum flexural stress and elongation at break. The sample with 2 wt% of this filler revealed values of maximum flexural stress and strain at break, 15% and 157%, respectively, higher than PLLA. Contrary to PLLA, which only exhibited break point, this nanocomposite showed a less fragile behavior, as a yield point was observed. In this case, it was possible to promote a higher flexibility without reducing the flexural stress, revealing an advantage of the Zn/Al palmitate under the plasticizers that have been used so far for PLLA.

Lactide synthesis optimization: investigation of the temperature, catalyst and pressure effects

AbstractThe most applicable method to produce polylactic acid (PLA) is via ring opening polymerization of lactide, which involves three steps: polycondensation of low-molecular-weight PLA (LMW PLA), depolymerization or dimerization of a prepolymer into a cyclic dimer of lactic acid (lactide) and ring opening polymerization of lactide to achieve high-molecular-weight PLA. This work aimed to optimize the reaction conditions of lactide synthesis. Reactions at different temperatures and pressures were carried out in the presence of tin (II) oxide, tin (II) chloride, tin (II) octate, antimony trioxide, sulfuric acid and no catalyst in a semi-batch reactor. Different analytical techniques such as gas chromatography, gel permeation chromatography, differential scanning calorimetry, nuclear magnetic resonance and Fourier transform infrared spectroscopy have been used to evaluate the LMW PLA properties, rate of lactide synthesis and racemization. Results showed that the highest rate of conversion occurred in the presence of tin (II) chloride and octate. Synthesis rate increased with the increase in reaction temperature and the decrease in pressure. Increasing temperature also resulted in higher amounts of optical and chemical impurities in the crude lactide.

Spatial Separation of Dimers of Chiral Molecules

A method for the spatial separation of R-R and S-S homodimers from R-S heterodimers, where R and S are chiral molecules of opposite handedness ("enantiomers"), is introduced. The separation, achieved by using two spatially inhomogeneous time-delayed laser pulses, is a result of one type of dimer forming a "dark state" and experiencing no light-induced potential, while the other type of dimer, forming a "bright" state, undergoes deflection. The direction of deflection of the two types of chiral dimers may be reversed by reversing the time delay between the laser pulses. We demonstrate the feasibility of the process by simulating the separation of lactic acid dimers.

Efficient production of polylactic acid and its copolymers by metabolically engineered Escherichia coli

Polylactic acid (PLA) is one of the promising biodegradable polymers, which has been produced in a rather complicated two-step process by first producing lactic acid by fermentation followed by ring opening polymerization of lactide, a cyclic dimer of lactic acid. Recently, we reported the production of PLA and its copolymers by direct fermentation of metabolically engineered Escherichia coli equipped with the evolved propionate CoA-transferase and polyhydroxyalkanoate (PHA) synthase using glucose as a carbon source. When employing these initially constructed E. coli strains, however, it was necessary to use an inducer for the expression of the engineered genes and to feed succinate for proper cell growth. Here we report further metabolic engineering of E. coli strain to overcome these problems for more efficient production of PLA and its copolymers. This allowed efficient production of PLA and its copolymers without adding inducer and succinate. The finally constructed recombinant E. coli JLXF5 strain was able to produce P(3HB- co-39.6 mol% LA) having the molecular weight of 141,000 Da to 20 g l −1 with a polymer content of 43 wt% in a chemically defined medium by the pH-stat fed-batch culture.

Poly(vinyl acetate), poly((1- O-(vinyloxy) ethyl-2,3,4,6-tetra- O-acetyl-β- d-glucopyranoside) and amorphous poly(lactic acid) are the most CO 2-soluble oxygenated hydrocarbon-based polymers

Poly(vinyl acetate), PVAc, remains the most CO 2-soluble non-fluorous polymer identified to date. Small sugar acetates are known to be extraordinarily CO 2-philic, but cellulose triacetate, a crystalline high molecule weight polymer is CO 2 insoluble. Therefore, an amorphous high molecular weight polymer with pendant sugar acetates was synthesized. This polymer, poly(1- O-(vinyloxy) ethyl-2,3,4,6-tetra- O-acetyl-β- d-glucopyranoside, P(AcGIcVE), was indeed CO 2-soluble, however cloud point pressures of P(AcGIcVE) at 5 wt% polymer and 298 K were greater than that required for the dissolution of PVAc. Finally, the solubility of amorphous poly(lactic acid), PLA, was determined over a wide range of molecular weight. The corresponding cloud point pressures were much greater than either PVAc or P(AcGIcVE). Ab initio calculations for the CO 2/PVAc dimer and CO 2/PLA dimer mixtures were conducted in an attempt to elucidate the dramatic differences in the cloud point values of PVAc and PLA. Our calculations indicate that there is little difference in the average interaction energies for the CO 2/PLA and the CO 2/IPA systems. The only indication that PVAc would be expected to be more CO 2-soluble that PLA was that the vinyl acetate dimer has binding modes that will readily accept multiple CO 2 molecules, whereas the binding modes for the lactic acid dimer can apparently only accommodate a single CO 2 molecule at a time.

Gene cloning and molecular characterization of an extracellular poly(L-lactic acid) depolymerase from Amycolatopsis sp. strain K104-1.

We have isolated a polylactide or poly(L-lactic acid) (PLA)-degrading bacterium, Amycolatopsis sp. strain K104-1, and purified PLA depolymerase (PLD) from the culture fluid of the bacterium. Here, we cloned and expressed the pld gene encoding PLD in Streptomyces lividans 1326 and characterized a recombinant PLD (rPLD) preparation. We also describe the processing mechanism from nascent PLD to mature PLD. The pld gene encodes PLD as a 24,225-Da polypeptide consisting of 238 amino acids. Biochemical and Western immunoblot analyses of PLD and its precursors revealed that PLD is synthesized as a precursor (prepro-type), requiring proteolytic cleavage of the N-terminal 35-amino-acid extension including the 26-amino-acid signal sequence and 9-residue prosequence to generate the mature enzyme of 20,904 Da. The cleavage of the prosequence was found to be autocatalytic. PLD showed about 45% similarity to many eukaryotic serine proteases. In addition, three amino acid residues, H57, D102, and S195 (chymotrypsin numbering), which are implicated in forming the catalytic triad necessary for cleavage of amide bond of substrates in eukaryotic serine proteases, were conserved in PLD as residues H74, D111, and S197. The G193 residue (chymotrypsin numbering), which is implicated in forming an oxyanion hole with residue S195 and forms an important hydrogen bond for interaction with the carbonyl group of the scissile peptide bond, was also conserved in PLD. The functional analysis of the PLD mutants H74A, D111A, and S197A revealed that residues H74, D111, and S197 are important for the depolymerase and caseinolytic activities of PLD and for cleavage of the prosequence from pro-type PLD to form the mature one. The PLD preparation had elastase activity which was not inhibited by 1 mM elastatinal, which is 10 times higher than needed for complete inhibition of porcine pancreatic elastase. The rPLD preparation degraded PLA with an average molecular mass of 220 kDa into lactic acid dimers through lactic acid oligomers and finally into lactic acid. The PLD preparation bound to high polymers of 3-hydoxybutyrate, epsilon-caprolacton, and butylene succinate as well as PLA, but it degraded only PLA.

Unambiguous Determination of the 13C and 1H NMR Stereosequence Assignments of Polylactide Using High-Resolution Solution NMR Spectroscopy

Polylactide (PLA) is a biodegradable polyester formed by the ring-opening polymerization of lactide, the cyclic dimer of lactic acid. Many of the physical properties of PLA are influenced by the amount and distribution of the R and S stereocenters in the polymer chain. NMR spectroscopy is the most common technique used to determine the stereosequence distribution of the polymer. The correct determination of the stereosequence distribution is contingent upon the assignment of the peaks in the NMR spectrum to specific stereosequences. Recently, alternative assignments to the commonly accepted stereosequence assignments have been proposed. If any of these alternative assignments are found to be correct, it would invalidate the conclusions of much of the previous work in understanding the kinetics of lactide polymerization and determining the stereoselectivity of new catalysts. The most significant problem is reconciling the commonly accepted peak assignments, which were based upon statistical probabilities, ...