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Molecular Pharmaceutics Aug 2022Acid-base multicomponent systems have become a popular choice as a strategy to fine-tune the physicochemical properties of active pharmaceutical ingredients. Current...
Acid-base multicomponent systems have become a popular choice as a strategy to fine-tune the physicochemical properties of active pharmaceutical ingredients. Current prediction tools based on the principles of anticrystal engineering cannot always accurately predict the nature of intermolecular interactions within a multicomponent system. Even small changes in the physicochemical parameters of parent components can result in unexpected outcomes, and many salt, cocrystal, and ionic liquid forms are still being discovered empirically. In this work, we aimed to establish structural consistency in a series of mixtures comprising lidocaine (LID) with decanedioic, undecanedioic, dodecanedioic, and tridecanedioic acids and to explore how length and flexibility of the acid carbon backbone affect the molecular recognition, crystallization, and thermal behavior of the expected binary systems. We found that neat grinding of LID with dicarboxylic acids results in the formation of eutectic phases. The observed eutectic melting points deviated from the ideal eutectic temperatures predicted by the Schroeder van Laar model because of hydrogen bonding between the reacting components within the mixtures. Furthermore, thermal and infrared analysis provided evidence for the possible formation of new phases stemming from partial ionization of the counterions. Besides, the structure of a previously undetermined form I of the tridecanedioic acid was solved by single crystal X-ray diffraction.
Topics: Crystallization; Dicarboxylic Acids; Hydrogen Bonding; Ionic Liquids; Lidocaine
PubMed: 35850530
DOI: 10.1021/acs.molpharmaceut.2c00381 -
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 -
Molecules (Basel, Switzerland) Jan 2019New enantiomerically pure C-alkyl diamides derived from trihydroxy cyclohexane-1,2-dicarboxylic acid have been synthesized from (-)-shikimic acid. The hydroxyl groups in...
New enantiomerically pure C-alkyl diamides derived from trihydroxy cyclohexane-1,2-dicarboxylic acid have been synthesized from (-)-shikimic acid. The hydroxyl groups in these compounds are free or, alternatively, they present full or partial protection. Their gelling abilities towards several solvents have been tested and rationalized by means of the combined use of Hansen solubility parameters, scanning electron microscopy (SEM), and circular dichroism (CD), as well as computational calculations. All the results allowed us to account for the capability of each type of organogelator to interact with different solvents and for the main mode of aggregation. Thus, compounds with fully protected hydroxyl groups are good organogelators for methanol and ethanol. In contrast, a related compound bearing three free hydroxyl groups is insoluble in water and polar solvents including alcohols but it is able to gelate some low-polarity solvents. This last behavior can be justified by strong hydrogen bonding between molecules of organogelator, which competes advantageously with polar solvent interactions. As an intermediate case, an organogelator with two free hydroxyl groups presents an ambivalent ability to gelate both apolar and polar solvents by means of two aggregation patterns. These involve hydrogen bonding interactions of the unprotected hydroxyl groups in apolar solvents and intermolecular interactions between amide groups in polar ones.
Topics: Cyclohexanecarboxylic Acids; Dicarboxylic Acids; Furans; Gels; Hydrogen Bonding; Models, Molecular; Solubility; Solvents; Stereoisomerism; Water
PubMed: 30669453
DOI: 10.3390/molecules24020352 -
Skin Therapy Letter 2015The etiology of papulopustular rosacea (PPR) is not well understood yet appears to involve both the innate and adaptive immune response in addition to possible... (Review)
Review
The etiology of papulopustular rosacea (PPR) is not well understood yet appears to involve both the innate and adaptive immune response in addition to possible infestation with Demodex mites. Current treatments for PPR consist mainly of antibiotics. Ivermectin cream 1%, a new topical treatment for PPR, possesses both anti-inflammatory and anti-parasitic properties. After 12 weeks of treatment, subjects treated with ivermectin cream 1% had significantly greater reductions in PPR symptoms and enhanced diseaserelated quality of life improvements compared to subjects who received vehicle. Furthermore, PPR symptoms continued to improve with prolonged treatment (40 weeks). Ivermectin cream 1% offers a multi-pronged approach to combat the complex pathophysiology of rosacea.
Topics: Administration, Topical; Anti-Infective Agents; Antiparasitic Agents; Clinical Trials, Phase III as Topic; Dermatologic Agents; Dicarboxylic Acids; Female; Humans; Ivermectin; Male; Metronidazole; Middle Aged; Rosacea; Skin Cream
PubMed: 26382711
DOI: No ID Found -
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 -
Scientific Reports Jul 2022Dicarboxylic acids are one of the important water-soluble organic compounds in atmospheric aerosols, causing adverse effects to both climate and human health. More...
Dicarboxylic acids are one of the important water-soluble organic compounds in atmospheric aerosols, causing adverse effects to both climate and human health. More attention has therefore been paid to organic acids in aerosols. In this study, the molecular distribution and diurnal variations of wintertime dicarboxylic acids in a rural site of Guanzhong Plain, Northwest China, were explored. Oxalic acid (C, day: 438.9 ± 346.8 ng m, night: 398.8 ± 392.3 ng m) is the most abundant compound followed by methylglyoxal (mGly, day: 207.8 ± 281.1 ng m, night: 222.9 ± 231.0 ng m) and azelaic (C, day: 212.8 ± 269.1 ng m, night: 211.4 ± 136.7 ng m) acid. The ratios of C/C and C/Ph indicating that atmospheric dicarboxylic acids in winter in the region mainly come from biomass burning. Furthermore, secondary inorganic ions (NO, SO, and NH), relative humidity, liquid water content, and in-situ pH of aerosols are highly linearly correlated with C, suggesting that liquid phase oxidation is an important pathway for the formation of dicarboxylic acids. The δC analysis of C suggested that lighter carbon isotope compositions tend to be oxidized to form aqueous-phase secondary organic aerosols (aqSOA), leading to the decay of C in aqSOA products rather than aerosol aging. This study provides a theoretical basis for the mechanism of formation of dicarboxylic acid.
Topics: Aerosols; Carbon; Carbon Isotopes; China; Dicarboxylic Acids; Humans; Oxalic Acid; Water
PubMed: 35789176
DOI: 10.1038/s41598-022-15222-6 -
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 -
Chemical & Pharmaceutical Bulletin 2017Teneraic acid (piperidine-2,6-dicarboxylic acid) is a naturally occurring imino acid that comprises three stereoisomers due to its two asymmetric centers at C2 and C6....
Teneraic acid (piperidine-2,6-dicarboxylic acid) is a naturally occurring imino acid that comprises three stereoisomers due to its two asymmetric centers at C2 and C6. The configuration of natural teneraic acid is reported to correspond to trans-(2S,6S). However, a few studies are focused on the stereospecific synthesis of trans-(2S,6S)-teneraic acid. The present study investigates a convenient synthetic method that includes regiospecific anodic oxidation and stereospecific cobalt-catalyzed carbonylation to obtain trans-(2S,6S)-teneraic acid. Methyl (S)-N-benzoyl-α-methoxypipecolate, the key intermediate that displays a structure that corresponds to an intermediate (N-α-hydroxyalkyl amide) of intramolecular amidocarbonylation, was obtained via an anodic oxidation of methyl (S)-N-benzoylpipecolate. Subsequently, cobalt-catalyzed carbonylation converted the methyl (S)-N-benzoyl-α-methoxypipecolate to trans-(2S,6S)-N-benzoyl-teneraic acid dimethyl ester in good optical purity (>95% enantiomeric excess (ee)) and modest yield (63%). Finally, de-protection occurred via acidic hydrolysis to obtain trans-(2S,6S)-teneraic acid. The stereochemistry of synthesized teneraic acid was confirmed as corresponding to trans-(2S,6S) by comparing its physical properties with those of a cis-meso-isomer and those of a trans-(2S,6S)-isomer that were reported in previous studies.
Topics: Aldehydes; Amides; Catalysis; Circular Dichroism; Cobalt; Dicarboxylic Acids; Oxidation-Reduction; Piperidines; Stereoisomerism
PubMed: 28867713
DOI: 10.1248/cpb.c17-00391 -
The Journal of Biological Chemistry 2021Metabolic reprogramming provides transformed cells with proliferative and/or survival advantages. Capitalizing on this therapeutically, however, has been only moderately...
Metabolic reprogramming provides transformed cells with proliferative and/or survival advantages. Capitalizing on this therapeutically, however, has been only moderately successful because of the relatively small magnitude of these differences and because cancers may further adapt their metabolism to evade metabolic pathway inhibition. Mice lacking the peroxisomal bifunctional enzyme enoyl-CoA hydratase/3-hydroxyacyl CoA dehydrogenase (Ehhadh) and supplemented with the 12-carbon fatty acid lauric acid (C12) accumulate the toxic metabolite dodecanedioic acid (DDDA), which causes acute hepatocyte necrosis and liver failure. We noted that, in a murine model of pediatric hepatoblastoma (HB) and in primary human HBs, downregulation of Ehhadh occurs in association with the suppression of mitochondrial β- and endosomal/peroxisomal ω-fatty acid oxidation pathways. This suggested that HBs might be more susceptible than normal liver tissue to C12 dietary intervention. Indeed, HB-bearing mice provided with C12- and/or DDDA-supplemented diets survived significantly longer than those on standard diets. In addition, larger tumors developed massive necrosis following short-term DDDA administration. In some HBs, the eventual development of DDDA resistance was associated with 129 transcript differences, ∼90% of which were downregulated, and approximately two-thirds of which correlated with survival in numerous human cancers. These transcripts often encoded extracellular matrix components, suggesting that DDDA resistance arises from reduced Ehhadh uptake. Lower Ehhadh expression was also noted in murine hepatocellular carcinomas and in subsets of certain human cancers, supporting the likely generality of these results. Our results demonstrate the feasibility of C12 or DDDA dietary supplementation that is nontoxic, inexpensive, and likely compatible with more standard chemotherapies.
Topics: Animals; Dicarboxylic Acids; Fatty Acids; Hepatoblastoma; Humans; Liver; Liver Neoplasms; Metabolism; Mice; Mice, Knockout; Mitochondria; Oxidation-Reduction; Peroxisomal Bifunctional Enzyme; Peroxisomes
PubMed: 33450224
DOI: 10.1016/j.jbc.2021.100283