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Molecules (Basel, Switzerland) Jul 2022To realize the commercialization of sustainable materials, new polymers must be generated and systematically evaluated for material characteristics and end-of-life...
To realize the commercialization of sustainable materials, new polymers must be generated and systematically evaluated for material characteristics and end-of-life treatment. Polyester polyols made from renewable monomers have found limited adoption in thermoplastic polyurethane (TPU) applications, and their broad adoption in manufacturing may be possible with a more detailed understanding of their structure and properties. To this end, we prepared a series of bio-based crystalline and amorphous polyester polyols utilizing azelaic acid and varying branched or non-branched diols. The prepared polyols showed viscosities in the range of 504-781 cP at 70 °C, with resulting TPUs that displayed excellent thermal and mechanical properties. TPUs prepared from crystalline azelate polyester polyol exhibited excellent mechanical properties compared to TPUs prepared from amorphous polyols. These were used to demonstrate prototype products, such as watch bands and cup-shaped forms. Importantly, the prepared TPUs had up to 85% bio-carbon content. Studies such as these will be important for the development of renewable materials that display mechanical properties suitable for commercially viable, sustainable products.
Topics: Alcohols; Dicarboxylic Acids; Polyesters; Polyurethanes
PubMed: 35956835
DOI: 10.3390/molecules27154885 -
International Journal of Molecular... Apr 2014Poly(alkylene dicarboxylate)s constitute a family of biodegradable polymers with increasing interest for both commodity and speciality applications. Most of these... (Review)
Review
Poly(alkylene dicarboxylate)s constitute a family of biodegradable polymers with increasing interest for both commodity and speciality applications. Most of these polymers can be prepared from biobased diols and dicarboxylic acids such as 1,4-butanediol, succinic acid and carbohydrates. This review provides a current status report concerning synthesis, biodegradation and applications of a series of polymers that cover a wide range of properties, namely, materials from elastomeric to rigid characteristics that are suitable for applications such as hydrogels, soft tissue engineering, drug delivery systems and liquid crystals. Finally, the incorporation of aromatic units and α-amino acids is considered since stiffness of molecular chains and intermolecular interactions can be drastically changed. In fact, poly(ester amide)s derived from naturally occurring amino acids offer great possibilities as biodegradable materials for biomedical applications which are also extensively discussed.
Topics: Animals; Biocompatible Materials; Dicarboxylic Acids; Drug Delivery Systems; Glycols; Humans; Models, Molecular; Nylons; Polyesters; Polymerization; Tissue Engineering
PubMed: 24776758
DOI: 10.3390/ijms15057064 -
The Journal of Organic Chemistry Oct 2021photochemical addition of propellane to diacetyl allowed construction of the bicyclo[1.1.1]pentane (BCP) core in a 1 kg scale within 1 day. Haloform reaction of the...
photochemical addition of propellane to diacetyl allowed construction of the bicyclo[1.1.1]pentane (BCP) core in a 1 kg scale within 1 day. Haloform reaction of the formed diketone in batch afforded bicyclo[1.1.1]pentane-1,3-dicarboxylic acid in a multigram amount. Representative gram scale transformations of the diacid were also performed to obtain various BCP-containing building blocks-alcohols, acids, amines, trifluoroborates, amino acids, .-for medicinal chemistry.
Topics: Alcohols; Amines; Amino Acids; Dicarboxylic Acids; Pentanes
PubMed: 34166594
DOI: 10.1021/acs.joc.1c00977 -
FEMS Microbiology Reviews Oct 2004Soil bacteria collectively known as rhizobia are able to convert atmospheric dinitrogen to ammonia while participating in a symbiotic association with legume plants.... (Review)
Review
Soil bacteria collectively known as rhizobia are able to convert atmospheric dinitrogen to ammonia while participating in a symbiotic association with legume plants. This capability has made the bacteria an attractive research subject at many levels of investigation, especially since physiological and metabolic specialization are central to this ecological niche. Dicarboxylate transport plays an important role in the operation of an effective, nitrogen-fixing symbiosis and considerable evidence suggests that dicarboxylates are a major energy and carbon source for the nitrogen-fixing rhizobia. The dicarboxylate transport (Dct) system responsible for importing these compounds generally consists of a dicarboxylate carrier protein, DctA, and a two component kinase regulatory system, DctB/DctD. DctA and DctB/D differ in the substrates that they recognize and a model for substrate recognition by DctA and DctB is discussed. In some rhizobia, DctA expression can be induced during symbiosis in the absence of DctB/DctD by an alternative, uncharacterized, mechanism. The DctA protein belongs to a subgroup of the glutamate transporter family now thought to have an unusual structure that combines aspects of permeases and ion channels. While the structure of C(4)-dicarboxylate transporters has not been analyzed in detail, mutagenesis of S. meliloti DctA has produced results consistent with the alignment of the rhizobial protein with the more characterized bacterial and eukaryotic glutamate transporters in this family.
Topics: Adaptation, Physiological; Amino Acid Sequence; Bacterial Proteins; Biological Transport; Dicarboxylic Acid Transporters; Dicarboxylic Acids; Gene Expression Regulation, Bacterial; Glutamates; Molecular Sequence Data; Rhizobium; Transcription Factors
PubMed: 15374663
DOI: 10.1016/j.femsre.2004.04.002 -
Scientific Reports Feb 2022Fumaric, malic, and succinic acids have been selectively separated from their mixture obtained by Rhizopus oryzae fermentation using reactive extraction with Amberlite...
Fumaric, malic, and succinic acids have been selectively separated from their mixture obtained by Rhizopus oryzae fermentation using reactive extraction with Amberlite LA-2 dissolved in three solvents with different dielectric constants (n-heptane, n-butyl acetate, and dichloromethane). This technique allows recovering preferentially fumaric acid from the mixture, the raffinate containing only malic and succinic acids. The extractant concentration and organic phase polarity control the efficiency and selectivity of acids extraction. The increase of aqueous phase viscosity reduces the extraction yield for all studied acids, but exhibits a positively effect on separation selectivity. By using Amberlite LA-2 concentration equal to that stoichiometrically required for interfacial reaction with fumaric acid and mixing intensity which does not allow higher diffusion rates for larger molecules (malic and succinic acids), the maximum value of fumaric acid extraction rate exceeds 90%, while the selectivity factor value becomes 20. Regardless of the extraction system, the complete separation of fumaric acid from their mixture is possible by multi-stage extraction process, adjusting the extractant concentration in each stage. At higher values of aqueous phase viscosity, more extraction stages are required, while the increase of solvent polarity reduce the required number of stages for total recovery of fumaric acid.
Topics: Acetates; Amines; Chemical Fractionation; Dicarboxylic Acids; Fermentation; Fumarates; Heptanes; Liquid-Liquid Extraction; Methylene Chloride; Rhizopus oryzae; Solvents; Succinic Acid; Viscosity; Water
PubMed: 35132158
DOI: 10.1038/s41598-022-06069-y -
Cardiovascular Diabetology Aug 2020Bempedoic acid is an oral, once-daily, first-in-class drug being developed for the treatment of hyperlipidemia. However, evidence of bempedoic acid use for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bempedoic acid is an oral, once-daily, first-in-class drug being developed for the treatment of hyperlipidemia. However, evidence of bempedoic acid use for the prevention of cardiovascular events and diabetes is lacking. Thus, we aim to evaluate the benefit and safety of bempedoic acid use for the prevention of cardiovascular events and diabetes.
METHODS
We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials with no language restriction from inception until March 3, 2020. Pairs of reviewers independently identified randomized controlled trials comparing the use of bempedoic acid with placebo or no treatment for primary prevention of cardiovascular events in statin-intolerant patients with hypercholesterolemia. The primary outcomes were major adverse cardiac events, and percent change in LDL-C.
RESULTS
We identified 11 trials including a total of 4391 participants. Bempedoic acid use was associated with a reduction in composite cardiovascular outcome (RR 0.75, 95% CI 0.56-0.99; I = 0%). Bempedoic acid reduced LDL-C levels (MD - 22.91, 95% CI - 27.35 to - 18.47; I = 99%), and similarly reduced CRP levels (MD -24.70, 95% CI - 32.10 to - 17.30; I = 53%). Bempedoic acid was associated with a reduction in rates of new-onset or worsening diabetes (RR 0.65, 95% CI 0.44-0.96; I = 23%).
CONCLUSIONS
Bempedoic acid in patients with hypercholesterolemia was associated with a lower risk of cardiovascular events and diabetes.
Topics: Aged; Biomarkers; Cardiovascular Diseases; Cholesterol, LDL; Diabetes Mellitus; Dicarboxylic Acids; Down-Regulation; Fatty Acids; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Male; Middle Aged; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32787939
DOI: 10.1186/s12933-020-01101-9 -
Molecules (Basel, Switzerland) Dec 2022We describe the carbonylation of a series of mono and dihydroxy derivatives of polyfluorinated alkylbenzenes and benzocycloalkenes with OH groups at benzylic positions...
We describe the carbonylation of a series of mono and dihydroxy derivatives of polyfluorinated alkylbenzenes and benzocycloalkenes with OH groups at benzylic positions using carbon monoxide in the presence of a superacid (TfOH, a TfOH-SbF mixture, or a FSOH-SbF mixture). It was shown that the superacid-catalyzed addition of CO to various primary and secondary polyfluorinated alcohols and diols gives the corresponding mono- and dicarboxylic acids or lactones. The efficiency of various superacids depending on alcohol structure was evaluated, and FSOH-SbF yielded the best results in most transformations. The addition of CO to secondary 1-arylalkan-1-ols containing vicinal fluorine atoms was found to be accompanied by elimination of HF with the formation of -unsaturated aryl-carboxylic acids. In contrast to primary and secondary alcohols, conversion of tertiary perfluoro-1,1-diarylalkan-1-ols into carbonylation products is not complete, and the resulting carboxylic acids are easily decarboxylated after water treatment of the reaction mixture.
Topics: Molecular Structure; Ethanol; Dicarboxylic Acids; Carbon Monoxide
PubMed: 36557890
DOI: 10.3390/molecules27248757 -
Journal of Clinical Lipidology 2020An ongoing need exists for safe and effective lipid-lowering therapies (LLTs) for patients unable to achieve desired lipid levels with current treatment options.
BACKGROUND
An ongoing need exists for safe and effective lipid-lowering therapies (LLTs) for patients unable to achieve desired lipid levels with current treatment options.
OBJECTIVE
The objective of this study was to describe the safety profile of bempedoic acid, an oral, first-in-class, adenosine triphosphate (ATP)-citrate lyase inhibitor that significantly reduces low-density lipoprotein cholesterol (LDL-C) levels by 17.4%-28.5% vs placebo.
METHODS
This was a pooled analysis of four phase 3, randomized (2:1), double-blind, placebo-controlled studies in patients with hypercholesterolemia who required additional LDL-C lowering, despite stable maximally-tolerated LLT. Patients received 180 mg of bempedoic acid (n = 2424) or placebo (n = 1197) once daily for 12 to 52 weeks. Assessments included treatment-emergent adverse events (TEAEs) and clinical laboratory tests.
RESULTS
Of 3621 patients (the median drug exposure: 363 days), exposure-adjusted TEAE rates were 87.1/100 and 82.9/100 person-years (PY) for bempedoic acid and placebo, respectively. No single TEAE influenced the difference in rates. TEAEs leading to discontinuation occurred at rates of 13.4/100 and 8.9/100 PY for bempedoic acid vs placebo, with the most common cause being myalgia, which occurred less frequently with bempedoic acid vs placebo (1.5/100 vs 2.0/100 PY). Rates of myalgia and muscle weakness were comparable vs placebo. Bempedoic acid was associated with mild increases in blood urea nitrogen, creatinine, and uric acid and decreases in hemoglobin. These laboratory abnormalities were apparent by week 4, stable over time, and reversible after treatment cessation. Gout incidence was 1.6/100 vs 0.5/100 PY in the bempedoic acid vs placebo groups. New-onset diabetes/hyperglycemia occurred less frequently with bempedoic acid vs placebo (4.7/100 vs 6.4/100 PY). The safety profile was consistent across subgroups.
CONCLUSIONS
Bempedoic acid is generally safe and well tolerated among patients with hypercholesterolemia who require additional LLT.
Topics: Aged; Clinical Trials, Phase III as Topic; Dicarboxylic Acids; Double-Blind Method; Fatty Acids; Female; Humans; Hypercholesterolemia; Hypolipidemic Agents; Male; Patient Safety; Prognosis; Randomized Controlled Trials as Topic
PubMed: 32980290
DOI: 10.1016/j.jacl.2020.08.009 -
Journal of Bacteriology Apr 2022The C-dicarboxylates (C4-DC) l-aspartate and l-malate have been identified as playing an important role in the colonization of mammalian intestine by enteric bacteria,... (Review)
Review
The C-dicarboxylates (C4-DC) l-aspartate and l-malate have been identified as playing an important role in the colonization of mammalian intestine by enteric bacteria, such as Escherichia coli and Salmonella enterica serovar Typhimurium, and succinate as a signaling molecule for host-enteric bacterium interaction. Thus, endogenous and exogenous fumarate respiration and related functions are required for efficient initial growth of the bacteria. l-Aspartate represents a major substrate for fumarate respiration in the intestine and a high-quality substrate for nitrogen assimilation. During nitrogen assimilation, DcuA catalyzes an l-aspartate/fumarate antiport and serves as a nitrogen shuttle for the net uptake of ammonium only, whereas DcuB acts as a redox shuttle that catalyzes the l-malate/succinate antiport during fumarate respiration. The C4-DC two-component system DcuS-DcuR is active in the intestine and responds to intestinal C4-DC levels. Moreover, in macrophages and in mice, succinate is a signal that promotes virulence and survival of . Typhimurium and pathogenic E. coli. On the other hand, intestinal succinate is an important signaling molecule for the host and activates response and protective programs. Therefore, C4-DCs play a major role in supporting colonization of enteric bacteria and as signaling molecules for the adaptation of host physiology.
Topics: Animals; Aspartic Acid; DNA-Binding Proteins; Dicarboxylic Acid Transporters; Dicarboxylic Acids; Escherichia coli; Escherichia coli Proteins; Fumarates; Gastrointestinal Microbiome; Gene Expression Regulation, Bacterial; Intestines; Mammals; Mice; Nitrogen; Protein Kinases; Salmonella typhimurium; Succinic Acid; Transcription Factors
PubMed: 34978458
DOI: 10.1128/JB.00545-21 -
Bioresource Technology May 2022Lignin valorization depends on microbial upcycling of various aromatic compounds in the form of a complex mixture, including p-coumaric acid and ferulic acid. In this...
Microbial production of 2-pyrone-4,6-dicarboxylic acid from lignin derivatives in an engineered Pseudomonas putida and its application for the synthesis of bio-based polyester.
Lignin valorization depends on microbial upcycling of various aromatic compounds in the form of a complex mixture, including p-coumaric acid and ferulic acid. In this study, an engineered Pseudomonas putida strain utilizing lignin-derived monomeric compounds via biological funneling was developed to produce 2-pyrone-4,6-dicarboxylic acid (PDC), which has been considered a promising building block for bioplastics. The biosynthetic pathway for PDC production was established by introducing the heterologous ligABC genes under the promoter P in a strain lacking pcaGH genes to accumulate a precursor of PDC, i.e., protocatechuic acid. Based on the culture optimization, fed-batch fermentation of the final strain resulted in 22.7 g/L PDC with a molar yield of 1.0 mol/mol and productivity of 0.21 g/L/h. Subsequent purification of PDC at high purity was successfully implemented, which was consequently applied for the novel polyester.
Topics: Dicarboxylic Acids; Lignin; Polyesters; Pseudomonas putida; Pyrones
PubMed: 35378283
DOI: 10.1016/j.biortech.2022.127106