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Drug candidates must undergo thermal evaluation as early as possible in the preclinical phase of drug development because undesirable changes in their structure and physicochemical properties may result in decreased pharmacological activity or enhanced toxicity. Hence, the detailed evaluation of nitrogen-rich heterocyclic esters as potential drug candidates, i.e., imidazolidinoannelated triazinylformic acid ethyl esters 1 - 3 (where R 1 = 4-CH 3 or 4-OCH 3 or 4-Cl, and R 2 = -COOC 2 H 5 ) and imidazolidinoannelated triazinylacetic acid methyl esters 4 - 6 (where R 1 = 4-CH 3 or 4-OCH 3 or 4-Cl, and R 2 = -CH 2 COOCH 3 )-in terms of their melting points, melting enthalpy values, thermal stabilities, pyrolysis, and oxidative decomposition course-has been carried out, using the simultaneous thermal analysis methods (TG/DTG/DSC) coupled with spectroscopic techniques (FTIR and QMS). It was found that the melting process (documented as one sharp peak related to the solid-liquid phase transition) of the investigated esters proceeded without their thermal decomposition. It was confirmed that the melting points of the tested compounds increased in relation to R 1 and R 2 as follows: 2 (R 1 = 4-OCH 3 ; R 2 = -COOC 2 H 5 ) < 6 (R 1 = 4-Cl; R 2 = -CH 2 COOCH 3 ) < 5 (R 1 = 4-OCH 3 ; R 2 = -CH 2 COOCH 3 ) < 3 (R 1 = 4-Cl; R 2 = -COOC 2 H 5 ) < 1 (R 1 = 4-CH 3 ; R 2 = -COOC 2 H 5 ) < 4 (R 1 = 4-CH 3 ; R 2 = -CH 2 COOCH 3 ). All polynitrogenated heterocyclic esters proved to be thermally stable up to 250 °C in inert and oxidising conditions, although 1 - 3 were characterised by higher thermal stability compared to 4 - 6 . The results confirmed that both the pyrolysis and the oxidative decomposition of heterocyclic ethyl formates/methyl acetates with para -substitutions at the phenyl moiety proceed according to the radical mechanism. In inert conditions, the pyrolysis process of the studied molecules occurred with the homolytic breaking of the C-C, C-N, and C-O bonds. This led to the emission of alcohol (ethanol in the case of 1 - 3 or methanol in the case of 4 - 6 ), NH 3 , HCN, HNCO, aldehydes, CO 2 , CH 4 , HCl, aromatics, and H 2 O. In turn, in the presence of air, cleavage of the C-C, C-N, and C-O bonds connected with some oxidation and combustion processes took place. This led to the emission of the corresponding alcohol depending on the analysed class of heterocyclic esters, NH 3 , HCN, HNCO, aldehydes, N 2 , NO/NO 2 , CO, CO 2 , HCl, aromatics, and H 2 O. Additionally, after some biological tests, it was proven that all nitrogen-rich heterocyclic esters-as potential drug candidates-are safe for erythrocytes, and some of them are able to protect red blood cells from oxidative stress-induced damage.

While organophosphorus chemistry is gaining attention in a variety of fields, the synthesis of the phosphorus derivatives of amino acids remains a challenging task. Previously reported methods require the deprotonation of the nucleophile, complex reagents or hydrolysis of the phosphonate ester. In this paper, we demonstrate how to avoid these issues by employing phosphonylaminium salts for the synthesis of novel mixed n -alkylphosphonate diesters or amino acid-derived n -alkylphosphonamidates. We successfully applied this methodology for the synthesis of novel N -acyl homoserine lactone analogues with varying alkyl chains and ester groups in the phosphorus moiety. Finally, we developed a rapid, quantitative and high-throughput bioassay to screen a selection of these compounds for their herbicidal activity. Together, these results will aid future research in phosphorus chemistry, agrochemistry and the synthesis of bioactive targets.

Arylsulfonyl group-bearing α,β-unsaturated enol esters were readily assembled via the Cs 2 CO 3 -mediated union of 2-bromoallyl sulfones and cinnamic acids. The overall transformation is equivalent to an sp 2 carbon-oxygen coupling reaction, and therefore constitutes a formal vinylic substitution. Several of the products display promising levels of antiproliferative activities higher than that of the anticancer drug carboplatin. Thiophenol reacted with 2-bromoallyl sulfones under identical conditions to afford α-thiophenyl-α'-tosyl acetone via an apparent aerial oxidation.

Severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) has infected more than 762 million people to date and has caused approximately 7 million deaths all around the world, involving more than 187 countries. Although currently available vaccines show high efficacy in preventing severe respiratory complications in infected patients, the high number of mutations in the S proteins of the current variants is responsible for the high level of immune evasion and transmissibility of the virus and the reduced effectiveness of acquired immunity. In this scenario, the development of safe and effective drugs of synthetic or natural origin to suppress viral replication and treat acute forms of COVID-19 remains a valid therapeutic challenge. Given the successful history of flavonoids-based drug discovery, we developed esters of substituted cinnamic acids with quercetin to evaluate their in vitro activity against a broad spectrum of Coronaviruses. Interestingly, two derivatives, the 3,4-methylenedioxy 6 and the ester of acid 7, have proved to be effective in reducing OC43-induced cytopathogenicity, showing interesting EC50s profiles. The ester of synaptic acid 7 in particular, which is not endowed with relevant cytotoxicity under any of the tested conditions, turned out to be active against OC43 and SARS-CoV-2, showing a promising EC 50 . Therefore, said compound was selected as the lead object of further analysis. When tested in a yield reduction, assay 7 produced a significant dose-dependent reduction in viral titer. However, the compound was not virucidal, as exposure to high concentrations of it did not affect viral infectivity, nor did it affect hCoV-OC43 penetration into pre-treated host cells. Additional studies on the action mechanism have suggested that our derivative may inhibit viral endocytosis by reducing viral attachment to host cells.

pH-sensitive amphiphilic diblock polyphosphoesters containing lactic acid units were synthesized by multistep one-pot polycondensation reactions. They comprise acid-labile P(O)-O-C and C(O)-O-C bonds, the cleavage of which depends on the pH of the medium. The structure of these copolymers was characterized by 1 H, 13 C {H}, 31 P NMR, and size exclusion chromatography (SEC). The newly synthesized polymers self-assembled into the micellar structure in an aqueous solution. The effects of the molecular weight of the copolymer and the length of the hydrophobic chain on micelle formation and stabilityand micelle size were studied via dynamic light scattering (DLS). Drug loading and encapsulation efficiency tests using doxorubicin revealed that hydrophobic drugs can be delivered by copolymers. It was established that the molecular weight of the copolymer, length of the hydrophobic chain and content of lactate units affects the size of the micelles, drug loading, and efficiency of encapsulation. A copolymer with 10.7% lactate content has drug loading (3.2 ± 0.3) and efficiency of encapsulation (57.4 ± 3.2), compared to the same copolymer with 41.8% lactate content (1.63%) and (45.8%), respectively. It was demonstrated that the poly[alkylpoly(ethylene glycol) phosphate- b -alkylpoly(ethylene glycol)lactate phosphate] DOX system has a pH-sensitive response capability in the result in which DOX was selectively accumulated into the tumor, where pH is acidic. The results obtained indicate that amphiphilic diblock polyphosphoesters have potential as drug carriers.

The natural pesticide phenazine-1-carboxylic acid (PCA) is known to lack phloem mobility, whereas Metalaxyl is a representative phloem systemic fungicide. In order to endow PCA with phloem mobility and also enhance its antifungal activity, thirty-two phenazine-1-carboxylic acid- N -phenylalanine esters conjugates were designed and synthesized by conjugating PCA with the active structure N -acylalanine methyl ester of Metalaxyl. All target compounds were characterized by 1 H NMR, 13 C NMR and HRMS. The antifungal evaluation results revealed that several target compounds exhibited moderate to potent antifungal activities against Sclerotinia sclerotiorum , Bipolaris sorokiniana , Phytophthora parasitica , Phytophthora citrophthora . In particular, compound F7 displayed excellent antifungal activity against S. sclerotiorum with an EC 50 value of 6.57 µg/mL, which was superior to that of Metalaxyl. Phloem mobility study in castor bean system indicated good phloem mobility for the target compounds F1 - F16 . Particularly, compound F2 exhibited excellent phloem mobility; the content of compound F2 in the phloem sap of castor bean was 19.12 μmol/L, which was six times higher than Metalaxyl (3.56 μmol/L). The phloem mobility tests under different pH culture solutions verified the phloem translocation of compounds related to the "ion trap" effect. The distribution of the compound F2 in tobacco plants further suggested its ambimobility in the phloem, exhibiting directional accumulation towards the apical growth point and the root. These results provide valuable insights for developing phloem mobility fungicides mediated by exogenous compounds.

Here we describe the application of photochemical decarboxylative arylation as a late-stage functionalization reaction for peptides. The reaction uses redox-active esters of aspartic acid and glutamic acid on the solid phase to provide analogues of aromatic amino acids. By using aryl bromides as arylation reagents, a wide variety of amino acids can be accessed without having to synthesize them individually in solution. The reaction is compatible with proteinogenic amino acids and was used to perform a structure-activity relationship study of a PRMT5 binding peptide.

Vulcanodinium rugosum is a benthic dinoflagellate known for producing pinnatoxins, pteriatoxins, portimines and kabirimine. In this study, we aimed to identify unknown analogs of these emerging toxins in mussels collected in the Ingril lagoon, France. First, untargeted data acquisitions were conducted by means of liquid chromatography coupled to hybrid quadrupole-orbitrap mass spectrometry. Data processing involved a molecular networking approach, and a workflow dedicated to the identification of biotransformed metabolites. Additionally, targeted analyses by liquid chromatography coupled to triple quadrupole mass spectrometry were also implemented to further investigate and confirm the identification of new compounds. For the first time, a series of 13-O-acyl esters of portimine-A (n = 13) were identified, with fatty acid chains ranging between C12:0 and C22:6. The profile was dominated by the palmitic acid conjugation. This discovery was supported by fractionation experiments combined with the implementation of a hydrolysis reaction, providing further evidence of the metabolite identities. Furthermore, several analogs were semi-synthesized, definitively confirming the discovery of these metabolization products. A new analog of pinnatoxin, with a molecular formula of C 42 H 65 NO 9 , was also identified across the year 2018, with the highest concentration observed in August (4.5 μg/kg). The MS/MS data collected for this compound exhibited strong structural similarities with PnTX-A and PnTX-G, likely indicating a substituent C 2 H 5 O 2 in the side chain at C33. The discovery of these new analogs will contribute to deeper knowledge of the chemodiversity of toxins produced by V. rugosum or resulting from shellfish metabolism, thereby improving our ability to characterize the risks associated with these emerging toxins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The solvent-free esterification of the free fatty acids (FFAs) obtained by the hydrolysis of castor oil (a non-edible vegetable oil) with 2-ethyl-1-hexanol (a branched fatty alcohol) was catalyzed by different free lipases. Eversa Transform 2.0 (ETL) features surpassed most commercial lipases. Some process parameters were optimized by the Taguchi method (L16'). As a result, a conversion over 95% of the FFAs of castor oil into esters with lubricants properties was achieved under optimized reaction conditions (15 wt% of biocatalyst content, 1:4 molar ratio (FFAs/alcohol), 30 °C, 180 rpm, 96 h). The substrates molar ratio had the highest influence on the dependent variable (conversion at 24 h). FFAs/2-ethyl-1-hexanol esters were characterized regarding the physicochemical and tribological properties. Interestingly, the modification of the FFAs with 2-ethyl-1-hexanol by ETL increased the oxidative stability of the FFAs feedstock from 0.18 h to 16.83 h. The biolubricants presented a lower friction coefficient than the reference commercial mineral lubricant (0.052 ± 0.07 against 0.078 ± 0.04). Under these conditions, ETL catalyzed the oligomerization of ricinoleic acid (a hydroxyl fatty acid) into estolides, reaching a conversion of 25.15% of the initial FFAs (for the first time)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The nonaqueous catalysis of lipases is significant for synthesis of high pure esters, but they usually behave low catalytic activity due to denaturation and aggregation of enzyme protein in organic phases. To improve the nonaqueous catalysis, the inexpensive copper phthalocyanine was taken as a new carrier on which Pseudomonas cepacia lipase was immobilized by physical absorption, and used for synthesis of hexyl acetate, an important flavor, via transesterification of hexanol and vinyl acetate. Results showed that the desired loading was 10-mg lipase immobilized on 10-mg copper phthalocyanine powder. When the immobilized lipase was employed in the reaction system consisted of 1.5-mL hexanol and 1.5-mL vinyl acetate at 37°C and 160 rpm, the conversion was fivefolds of that catalyzed by native lipase after 1 h, and reached 99.0% after 8 h. In six times of 8-h reuses, the immobilized lipase behaved an activity attenuation rate 1.22% h -1 , lower than 1.77% h -1 of native lipase, which meant that the immobilized lipase was more stable. Even at the room temperature and the static state without shaking or stirring, the immobilized lipase still brought conversion 42.8% after 10 h and the native lipase gave 20.1%. Obviously, the immobilized lipase is an available biocatalyst in organic phase and has great potential in food industry., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study investigated the homogeneous synthesis of cellulose acetate (CA) and propionate (CP) with varying degrees of substitution (DS) from sisal cellulose in a N, N-dimethylacetamide/lithium chloride (DMAc/LiCl) solvent system. These esters were used to prepare neat (CA DS F/CP DS F) and nanocomposite films (CA DS FFe/CP DS FFe) from prior synthesized magnetite nanoparticles (NPs, Fe 3 O 4 , 5.1 ± 0.5 nm). Among the CA and CP series, the composite CA 0.7 FFe and the neat CP 0.7 F films exhibited the highest modulus of elasticity, 2105 MPa and 2768 MPa, respectively, probably a consequence of the continuous fibrous structures present on the surface of these films. Microsphere formation on the film's surface was observed in scanning electron microscopy micrographs. This points to applications in the controlled release of targeted substances. The VSM analysis showed that the cellulosic matrices preserved the superparamagnetic characteristics of the NPs. This study suggested a reduced coupling effect between nanoparticles inside polymeric films due to magnetic saturation at low fields. CA 0.7 FFe and CA 1.3 FFe composite films reached a saturation magnetization (M SAT ) of 46 emu/g around 7 kOe field. Hosting magnetite nanoparticles in cellulose ester matrices may be an interesting way to develop new functional cellulose-based materials, which have the potential for diverse applications, including microelectromechanical systems and microsensors., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As a part of our systematic study on Castanopsis genus (Fagaceae), one new triterpene hydrolysable tannin ( 1 ) and two new phenol glucosides ( 2 and 3 ) were isolated from the leaves of Castanopsis eyrei (Champ. ex Benth.) Hutch. Compound 1 was identified as a triterpene hexahydroxydiphenoyl (HHDP) ester. This type of compounds has only been isolated from Castanopsis genus. The structures of 1 - 3 were elucidated by the combination of spectroscopic analysis (MS, 1 D and 2 D NMR) and chemical evidence.

Marine microalgae Schizochytrium sp. have a high content of docosahexaenoic acid (DHA), an omega-3 fatty acid that is attracting interest since it prevents certain neurodegenerative diseases. The obtention of a bioactive and purified DHA fatty acid ester using a whole-integrated process in which renewable sources and alternative methodologies are employed is the aim of this study. For this reason, lyophilized Schizochytrium biomass was used as an alternative to fish oil, and advanced extraction techniques as well as enzymatic modification were studied. Microalgal oil extraction was optimized via a surface-response method using pressurized liquid extraction (PLE) obtaining high oil yields (29.06 ± 0.12%) with a high concentration of DHA (51.15 ± 0.72%). Then, the enzymatic modification of Schizochytrium oil was developed by ethanolysis using immobilized Candida antarctica B lipase (Novozym ® 435) at two reaction temperatures and different enzymatic loads. The best condition (40 °C and 200 mg of lipase) produced the highest yield of fatty acid ethyl ester (FAEE) (100%) after 8 h of a reaction attaining a cost-effective and alternative process. Finally, an enriched and purified fraction containing DHA-FAEE was obtained using open-column chromatography with a remarkably high concentration of 93.2 ± 1.3% DHA. The purified and bioactive molecules obtained in this study can be used as nutraceutical and active pharmaceutical intermediates of marine origin.

To explore the use of nonfood plant-derived secondary metabolites for plant protection, a series of ester derivatives for controlling the major migratory agricultural pests were obtained by structural modification of andrographolide, a labdane diterpenoid isolated from Andrographis paniculata . Compound Id showed good insecticidal activity against the fall armyworm Spodoptera frugiperda Smith. Compounds IIa (LC 50 : 0.382 mg/mL) and IIIc (LC 50 : 0.563 mg/mL), the acaricidal activities of which were, respectively, 13.1 and 8.9 times that of andrographolide (LC 50 : 4.996 mg/mL), exhibited strong acaricidal and control effects against Tetranychus cinnabarinus Boisduval. Against Aphis citricola Van der Goot, compounds IIIc and IVb displayed 3.9- and 3.7-fold pronounced aphicidal activity of andrographolide. Effects of compound Id on three protective enzymes (superoxide dismutase, peroxidase, and catalase) of S. frugiperda were also observed. The obvious differences of epidermal cuticle structures of mites treated with compound IIa were determined by scanning electron microscopy. Structure-activity relationships indicated that 14-ester derivatives of andrographolide showed potential insecticidal/acaricidal activities and can be further utilized as lead compounds.

We report the first biocatalytic modification of sesquiterpene lactones (STLs) found in the chicory plants, specifically lactucin (Lc), 11β,13-dihydrolactucin (DHLc), lactucopicrin (Lp), and 11β,13-dihydrolactucopicrin (DHLp). The selective O-acylation of their primary alcohol group was carried out by the lipase B from Candida antarctica (CAL-B) using various aliphatic vinyl esters as acyl donors. Perillyl alcohol, a simpler monoterpenoid, served as a model to set up the desired O-acetylation reaction by comparing the use of acetic acid and vinyl acetate as acyl donors. Similar conditions were then applied to DHLc, where five novel ester chains were selectively introduced onto the primary alcohol group, with conversions going from >99 % (acetate and propionate) to 69 % (octanoate). The synthesis of the corresponding O-acetyl esters of Lc, Lp, and DHLp was also successfully achieved with near-quantitative conversion. Molecular docking simulations were then performed to elucidate the preferred enzyme-substrate binding modes in the acylation reactions with STLs, as well as to understand their interactions with crucial amino acid residues at the active site. Our methodology enables the selective O-acylation of the primary alcohol group in four different STLs, offering possibilities for synthesizing novel derivatives with significant potential applications in pharmaceuticals or as biocontrol agents., (© 2024 Wiley-VCH GmbH.)

Organophosphate esters (OPEs) can cause adverse biological effects through binding to integrin α v β 3 . However, few studies have focused on the binding activity and mechanism of OPEs to integrin α v β 3 . Herein, a comprehensive investigation of the mechanisms by which OPEs bind to integrin α v β 3 and determination of the binding affinity were conducted by in vitro and in silico approaches: competitive binding assay as well as pharmacophore, molecular docking and QSAR modeling. The results showed that all 18 OPEs exhibited binding activities to integrin α v β 3 ; moreover, hydrogen bonds were identified as crucial intermolecular interactions. In addition, essential factors, including the -P = O structure of OPEs, key amino acid residues and suitable cavity volume of integrin α v β 3 , were identified to contribute to the formation of hydrogen bonds. Moreover, aryl-OPEs exhibited a lower binding activity with integrin α v β 3 than halogenated- and alkyl-OPEs. Ultimately, the QSAR model constructed in this study was effectively used to predict the binding affinity of OPEs to integrin α v β 3 , and the results suggest that some OPEs might pose potential risks in aquatic environments. The results of this study comprehensively elucidated the binding mechanism of OPEs to integrin α v β 3 , and supported the environmental risk management of these emerging pollutants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fatty acid cellulose esters (FACE) are common cellulose-based thermoplastics, and their thermoplasticity is determined by both the contents and the lengths of the side chains. Herein, various FACE were synthesized by the ball-milling esterification of cellulose and fatty acyl chlorides containing 10-18 carbons, and their structures and thermoplasticity were thoroughly studied. The results showed that FACE with high degrees of substitution (DS) and low melting flow temperatures ( T f ) were achieved as the chain lengths of the fatty acyl chlorides were reduced. In particular, a cellulose decanoate with a DS of 1.85 and a T f of 186 °C was achieved by feeding 3 mol of decanoyl chloride per mole anhydroglucose units of cellulose. However, cellulose stearate (DS = 1.53) synthesized by the same protocols cannot melt even at 250 °C. More interestingly, the fatty acyl chlorides with 10 and 12 carbons resulted in FACE with superior toughness (elongation at break up to 94.4%). In contrast, due to their potential crystallization of the fatty acyl groups with 14-18 carbons, the corresponding FACE showed higher tensile strength and Young's modulus than the others. This study provides some theoretical basis for the mechanochemical synthesis of thermoplastic FACE with designated properties.

Melanoma, one of the most devastating forms of skin cancer, currently lacks effective clinical treatments. Delivery of functional genes to modulate specific protein expression to induce melanoma cell apoptosis could be a promising therapeutic approach. However, transfecting melanoma cells using non-viral methods, particularly with cationic polymers, presents significant challenges. In this study, we synthesized three branched poly(β-amino ester)s (HPAEs) with evenly distributed branching units but varying space lengths through a two-step "oligomer combination" strategy. The unique topological structure enables HPAEs to condense DNA to form nano-sized polyplexes with favorable physiochemical properties. Notably, HPAEs, especially HPAE-2 with intermediate branching unit space length, demonstrated significantly higher gene transfection efficiency than the leading commercial gene transfection reagent, jetPRIME, in human melanoma cells. Furthermore, HPAE-2 efficiently delivered the Bax-encoding plasmid into melanoma cells, leading to a pronounced pro-apoptotic effect without causing noticeable cytotoxicity. This study establishes a potent non-viral platform for gene transfection of melanoma cells by harnessing the distribution of branching units, paving the way for potential clinical applications of gene therapy in melanoma treatment., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Electrochemical transformations are a subject of increasing interest in early drug discovery due to its ability to assemble complex scaffolds under rather mild reaction conditions. In this context, we became interested in electrochemical decarboxylative cross-coupling (DCC) protocols of redox-active esters (RAEs) and halo(hetero)arenes. Starting with the one-step electrochemical synthesis of novel methylamino-substituted heterocycles we recognized the potential of this methodology to deliver a novel approach to β- and γ- amino acids by starting from the corresponding RAEs. Our work finally resulted in the delivery of novel and highly valuable trifunctional building blocks based on ß- and γ-amino-acid scaffolds., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. María Méndez, Dr. Sven Ruf, Dr. Michel Kurz and Dr. Christoph Heubel are Sanofi employees and may hold shares and/or stock options in the company. Barbara Pavlovic, Elisabeth Oehl and Prof. Dr. Siegfried Waldvogel have nothing to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Methyl branching on the carbon chains of fatty acids and fatty esters is among the structural variations encountered with fatty acids and fatty esters. Branching in fatty acid/ester chains is particularly prominent in bacterial species and, for example, in vernix caseosa and sebum. The distinction of branched chains from isomeric straight-chain species and the localization of branching can be challenging to determine by mass spectrometry (MS). Condensed-phase derivatization strategies, often used in conjunction with separations, are most commonly used to address the identification and characterization of branched fatty acids. In this work, a gas-phase ion/ion strategy is presented that obviates condensed-phase derivatization and introduces a radical site into fatty acid ions to facilitate radical-directed dissociation (RDD). The gas-phase approach is also directly amenable to fatty acid anions generated via collision-induced dissociation from lipid classes that contain fatty esters. Specifically, divalent magnesium complexes bound to two terpyridine ligands that each incorporate a ((2,2,6,6-tetramethyl-1-piperidine-1-yl)oxy) (TEMPO) moiety are used to charge-invert fatty acid anions. Following the facile loss of one of the ligands and the TEMPO group of the remaining ligand, a radical site is introduced into the complex. Subsequent collision-induced dissociation (CID) of the complex exhibits preferred cleavages that localize the site(s) of branching. The approach is illustrated with iso- , anteiso- , and isoprenoid branched-chain fatty acids and an intact glycerophospholipid and is applied to a mixture of branched- and straight-chain fatty acids derived from Bacillus subtilis .

Synthetic ester oils are widely used in many applications due to their ideal cleaning properties, lubricating performance and assured polarity. The majority of esters oils are more biodegradable. than any other base stock. For instance, oil soluble polyalkyleneglycols (PAGs) or polyalphaolephins (PAOs), are only biodegradable in the lower viscosity grades. The goal of this study is to create some synthetic base oils by two major protocols; the first is esterifying valeric acid with various glycols (ethylene glycol, propylene glycol, butylene glycol and poly (ethylene glycol 400). The second involves esterification of propanoic acid, heptanoic acid, or octanoic acid with ethylene glycol. The reaction yield varies between 85 and 94%. The chemical composition of the prepared esters was examined using various spectroscopic methods (Fourier-transform infrared (FT-IR) and proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy. The thermal properties investigation by thermo gravimetric analysis (TGA) showed pronounced thermal stability of the prepared esters. The biodegradability was verified versus two bacterial isolates (B1, B2). The results showed that percentage of degradation of the lube oil was in the range of 34% to 84% after 3 days of incubation. Moreover, the rheological study revealed that the prepared esters exhibited Newtonian rheological behaviours. Viscosity examination displayed that the esters based on ethylene glycol, such as (A), had the highest VI: 179 values when compared to those based on higher glycols. Viscosity and viscosity index results showed slight increase as the number of carbon atoms in the acid chain increases. At last, most of the synthesized esters possessed pour points ≤ - 32 °C: ≤ - 40 except in case of using higher acids like heptanoic acid and octanoic acid in preparation the pour point increases to - 9 °C and - 15 °C., (© 2024. The Author(s).)

Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis 1,2 , we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn's disease. Several of these compounds and related structures affected pathways associated with IBD, such as interferon-γ production in CD4 + T cells 3 and agonism of the pregnane X receptor 4 . Culture of bacteria belonging to the Bifidobacterium, Clostridium and Enterococcus genera produced these bile amidates. Because searching repositories with tandem mass spectrometry spectra has only recently become possible, this reverse metabolomics approach can now be used as a general strategy to discover other molecules from human and animal ecosystems., (© 2023. The Author(s).)

The low percentage of recyclability of the polymeric materials obtained by olefin transition metal (TM) polymerization catalysis has increased the interest in their substitution with more eco-friendly materials with reliable physical and mechanical properties. Among the variety of known biodegradable polymers, linear aliphatic polyesters produced by ring-opening polymerization (ROP) of cyclic esters occupy a prominent position. The polymer properties are highly dependent on the macromolecule microstructure, and the control of stereoselectivity is necessary for providing materials with precise and finely tuned properties. In this review, we aim to outline the main synthetic routes, the physical properties and also the applications of three commercially available biodegradable materials: Polylactic acid (PLA), Poly(Lactic- co -Glycolic Acid) (PLGA), and Poly(3-hydroxybutyrate) (P3HB), all of three easily accessible via ROP. In this framework, understanding the origin of enantioselectivity and the factors that determine it is then crucial for the development of materials with suitable thermal and mechanical properties.

Fatty acid esters of hydroxy fatty acids (FAHFAs), a newly discovered class of human endogenous complex lipids showing great promise for treating diabetes and inflammatory diseases, exist naturally in extremely low concentrations. This work reports a chemo-enzymatic approach for the comprehensive synthesis of phospholipids containing FAHFAs via sequential steps: hydratase-catalyzed hydration of unsaturated fatty acids to generate structurally diverse hydroxy fatty acids (HFAs), followed by the selective esterification of these HFAs with fatty acids mediated by secondary alcohol-specific Candida antarctica lipase A (CALA), resulting in the formation of a series of diverse FAHFA analogs. The final synthesis is completed through carbodiimide-based coupling of FAHFAs with glycerophosphatidylcholine. Optimal reaction conditions are identified for each step, and the substrate affinity of CALA, responsible for the catalytic mechanisms during FAHFA production, is evaluated through molecular docking. Compared to multistep lab-tedious chemical synthesis, this route, relying on natural building blocks and natural biocatalysts, is significantly facile, scalable, and highly selective, affording high yields (74-98 mol %) in each step for the construction of higher FAHFA-PC series (10/12/13-FAHFAs). The developed strategy aims to increase the availability of naturally occurring FAHFA species and provide the tools for the construction of versatile and novel analogs of FAHFA conjugates.

Aim: To achieve colon-targeted release of mefenamic acid from its ester-linked amylose prodrugs. Materials & methods: The prodrug was characterized by 1H NMR and IR spectroscopy. Drug activation and release profile was studied in enzyme enriched simulated physiological media via UV-vis spectroscopy and was validated with HPLC analysis. ELISA assay was employed for evaluating the % inhibition of COX-1 and COX-2 inhibition at different concentrations of the prodrug preincubated with ester and/ or amylose hydrolyzing enzymes. SEM studies further validated the performance of the prodrug under simulated physiological conditions. Results: Pancreatin was essential for the prodrug activation in SIM to make the ester bonds in prodrug vulnerable to hydrolysis by esterase. This evidence was confirmed by drug release studies, HPLC analysis, ELISA assay and SEM investigation where the ester conjugated prodrug showed marked stability in physiological media only to get activated in the presence of amylose degrading enzyme. Conclusion: Ester linked amylose-mefenamic acid conjugate showed both enzyme responsive activation and release in SIM.

Chemical modifications to proteins have wide applications. They may be used in, for example, the production of biopharmaceuticals and fluorescent probes. Despite their importance, highly regioselective chemical protein modifications are often challenging to achieve. We have developed two highly selective methods for protein acylation using poly-His tags inserted either at the N-terminus or in combination with a specific Lys residue. For this, we used an N-terminal Gly-His 6 (Gly-His tag) or the sequence His m -Lys-His n (Lys-His tag), respectively. The Gly-His tag directed the acylation to the N-terminal N α -amine when reacted with 4-methoxyphenyl esters to yield stable conjugates. Next, the Lys-His tag was developed to allow modifications at the C-terminus or in loop regions of proteins. This gave a high selectivity of acylation of the designated Lys N ε -amine in the tag over native Lys residues in the protein under mild conditions. Here, we describe the synthesis of aromatic esters carrying different functionalities and reactivity tuning substituents on the phenol. The expression of poly-His tagged proteins, and the procedure for the highly selective peptide and protein acylations are detailed in this contribution. The versatility of these methods has been demonstrated by the attachment of different functionalities such as fluorophores, biotin, and azides to different proteins and an antibody., (Copyright © 2024. Published by Elsevier Inc.)

We report two methods for the preparation of peptide thioesters containing Tyr(SO 3 H) residue(s), without use of a protecting group for the sulfate moiety. The first was based on direct thioesterification using carbodiimide on a fully protected peptide acid, prepared on a 2-chlorotrityl (Clt) resin with fluoren-9-ylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis (Fmoc-SPPS). Subsequent deprotection of the protecting groups with trifluoroacetic acid (TFA) (0 °C, 4 h) yielded peptide thioesters containing Tyr(SO 3 H) residue(s). Peptide thioesters containing one to three Tyr(SO 3 H) residue(s), prepared by this method, were used as building blocks for the synthesis of the N α -Fmoc-protected N-terminal part of P-selectin glycoprotein ligand 1 (PSGL-1) (Fmoc-PSGL-1(43-74)) via silver-ion mediated thioester segment condensation. The other method was based on the thioesterification of peptide azide, derived from a peptide hydrazide prepared on a NH 2 NH-Clt-resin with Fmoc-SPPS. Peptide thioester containing two Tyr(SO 3 H) residues, prepared via this alternative method, was used as a building block for the one-pot synthesis of the N-terminal extracellular portion of CC-chemokine receptor 5 (CCR5(9-26)) by native chemical ligation (NCL). The two methods for the preparation of peptide thioesters containing Tyr(SO 3 H) residue(s) described herein are applicable to the synthesis of various types of sulfopeptides.

Docosahexaenoic acid plays a crucial role in infant brain function, and the market demand of high-purity docosahexaenoic acid is continuously increasing. The availability of docosahexaenoic acid in natural fish oil is limited, prompting the exploration of alternative sources like microalgae. For algal oil, enzymatic ethanolysis is preferred to chemical methods because the former is milder and can avoid docosahexaenoic acid oxidation. However, enzymatic methods have generally low yield due to the poor substrate-specificity of lipase to long-chain polyunsaturated fatty acids, affecting the yield and purity of docosahexaenoic acid. Therefore, we developed an efficient process to produce high-purity docosahexaenoic acid ethyl ester from algal oil, by screening lipases, optimizing enzymatic ethanolysis and applying molecular distillation. Lipase UM1 was the best lipase to produce ethyl ester from algal oil with the highest ethyl ester yield (95.41%). Meanwhile, it was a catalyst for the reaction of long-chain polyunsaturated fatty acids with ethanol. The fatty acid docosahexaenoic acid conversion rates exceeded 90%. After molecular distillation, a final product containing 96.52% ethyl ester was obtained with a docosahexaenoic acid content up to 80.11%. Our findings provide an highly effective enzymatic method for the production of high-purity docosahexaenoic acid ethyl esters, with potential commercial applications.

The production of hydrophobic and oil resistant cellulosic fibers usually requires severe chemical treatments and generates toxic by-products. Alternative approaches such as biocatalysis use milder conditions; lipase-catalyzed methods for grafting nanocellulose with hydrophobic ester moieties have been reported. Here, we investigate the lipase-catalyzed esterification of cellulose fibers, in native form or pretreated with 1,4-β-glucanases, and cellulose nanocrystals (CNC) in solvent-free conditions. The fibers were compared for degree of ester formation after incubation with methyl myristate and lipase at 50 °C. After washing, the grafting of fatty esters on cellulose was confirmed by ATR-FTIR and the degree of substitution determined by 13 C CP/MAS NMR (from 0.04 up to DS 0.1) confirming successful esterification. Optical photothermal infrared (O-PTIR) spectroscopy showed strongly localized presence of ester moieties on cellulose. Functional properties mirrored the degree of substitution of the cellulose materials whereby cellulose esters made with glucanase-pretreatment produced the highest water contact angle of 117° ± 9 and esterified cellulose blended at 10 % w/w content in paper composites showed significant differences in hydrophobicity and lipophilicity compared to plain paper. The esterification of cellulose was completely reversed by lipase treatment in aqueous media. These ester-functionalized fibers show potential in a wide range of packaging applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors have no competing financial or personal interests to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Polyglycerol fatty acid esters (PGFEs) are common food additives. PGFE-based formulations exhibit high structural stability, however, the stability mechanism of the micellar structures has not been yet elucidated. In this study, nanostructural analysis was performed using small-angle neutron and X-ray scattering (SANS and SAXS) measurements to reveal the mechanism of the structural stability of PGFE-coenzyme Q10 (CoQ10) mixtures as a CoQ10 formulation. Pure PGFE formed multilamellar vesicles, whereas PGFE-CoQ10 formed spherical micelles. Furthermore, when the amount of added water increased, the PGFE-CoQ10 micellar size and the amount of water in the micelles remained unchanged. A model-fitting analysis of the SANS results suggested that the CoQ10 molecules were introduced between the surfactants, forming a palisade-type structure. The high structural stability of the PGFE-CoQ10 micelles was attributed to two factors: proper spreading of the hydrophilic head chains and inhibition of the change of the amount of water inside the micelles by the PGFE heads and quinone ring of CoQ10. This indicates that PGFE-CoQ10 can function in water while maintaining the micellar structure formed in the storage solution. The findings of this study are important for the safety and nano-hazard aspects of PGFE-CoQ10 formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A diazo-, metal-, and base-free multi-substituted hydrazone synthesis via a formal reductive N-H bond insertion reactions of hydrazones to α-keto esters has been developed. The protocol features a broad substrate scope and good functional group tolerance, providing N-H bond insertion products in moderate to excellent yields. Moreover, P(III)-mediated N-H functionalization of pharmaceutical containing hydrazone moiety was also successfully achieved.

Phthalate esters (PAEs), accompanied by phthalate monoesters as hydrolysis metabolites in humans, have been widely used as plasticizers and exhibited disruptive effects on the endocrine and metabolic systems. The present study aims to investigate the inhibition behavior of PAEs and phthalate monoesters on the activity of the important hydrolytic enzymes, carboxylesterases (CESs), to elucidate the toxicity mechanism from a new perspective. The results showed significant inhibition on CES1 and CES2 by most PAEs, but not by phthalate monoesters, above which the activity of CES1 was strongly inhibited by DCHP, DEHP, DiOP, DiPP, DNP, DPP and BBZP, with inhibition ratios exceeding 80%. Kinetic analyses and in vitro-in vivo extrapolation were conducted, revealing that PAEs have the potential to disrupt the metabolism of endogenous substances catalyzed by CES1 in vivo. Molecular docking results revealed that hydrogen bonds and hydrophobic contacts formed by ester bonds contributed to the interaction of PAEs towards CES1. These findings will be beneficial for understanding the adverse effect of PAEs and phthalate monoesters., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sucrose esters have been deployed as surfactants in many food products since the 1950s. In addition to their useful physical characteristics, sucrose esters also have interesting biological properties that enhance their utility. This review critically examines the broad suite of biological activities that has been attributed to both synthetically-derived and naturally-occurring sucrose esters. These include insecticidal, molluscicidal, plant growth-regulating, anti-microbial, anti-tumor, anti-oxidant, anti-depressive, neuro-protective, anti-inflammatory and anti-plasmodial effects. In addition to providing a summary of the structure-activity profiles of sucrose esters, the various known mechanisms-of action of these compounds are also discussed. Furthermore, since sucrose esters are well-known surfactants, the potential to advantageously apply their industrially desirable physical characteristics in combination with their biological properties is considered. Recent advances in synthetic chemistry that have facilitated the deployment of biologically active sucrose esters as food additives are also described.

Amide-to-ester substitutions are used to study the role of the amide bonds of the protein backbone in protein structure, function, and folding. An amber suppressor tRNA/synthetase pair has been reported for incorporation of p-hydroxy-phenyl-L-lactic acid (HPLA), thereby introducing ester substitution at tyrosine residues. However, the application of this approach was limited due to the low yields of the modified proteins and the high cost of HPLA. Here we report the in vivo generation of HPLA from the significantly cheaper phenyl-L-lactic acid. We also construct an optimized plasmid with the HPLA suppressor tRNA/synthetase pair that provides higher yields of the modified proteins. The combination of the new plasmid and the in-situ generation of HPLA provides a facile and economical approach for introducing tyrosine ester substitutions. We demonstrate the utility of this approach by introducing tyrosine ester substitutions into the K + channel KcsA and the integral membrane enzyme GlpG. We introduce the tyrosine ester in the selectivity filter of the M96V mutant of the KcsA to probe the role of the second ion binding site in the conformation of the selectivity filter and the process of inactivation. We use tyrosine ester substitutions in GlpG to perturb backbone H-bonds to investigate the contribution of these H-bonds to membrane protein stability. We anticipate that the approach developed in this study will facilitate further investigations using tyrosine ester substitutions., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Synthetic polymers with additives are used in the manufacturing of face masks (FMs); hence, FMs could be a potential source of exposure to phthalic acid esters (PAEs). India stands second in the world in terms of the FMs usage since the beginning of Covid-19 pandemic. However, little is known about the PAEs content of FMs used in India. Some PAEs, such as DEHP and DBP are suspected endocrine disrupting chemicals (EDCs); hence, wearing FM may increase the risk of exposure to these EDCs. In this study, we collected 91 samples of FMs from eight Indian cities and analyzed for five PAEs viz . DMP, DEP, DBP, BBP, and DEHP. The PAEs contents in FMs ranged from 101.79 to 27,948.64 ng/g. The carcinogenic risk of N 95 with filter, N -95, and cloth masks was higher than the threshold levels. The findings indicate the need to control PAEs in FMs through regulatory actions.

Surface functionalization with biological macromolecules is an important task for the development of sensor materials, whereby the interaction with other biological materials should be suppressed. In this work, we developed a novel multifunctional poly(2-ethyl-2-oxazoline)-dithiolane conjugate as a versatile linker for gold surface immobilization of amine-containing biomolecules, containing poly(2-ethyl-2-oxazoline) as antifouling polymer, dithiolane for surface immobilization, and activated esters for protein conjugation. First, a well-defined carboxylic acid containing copoly(2-ethyl-2-oxazoline) was synthesized by cationic ring-opening copolymerization of 2-ethyl-2-oxazoline with a methyl ester-containing 2-oxazoline monomer, followed by postpolymerization modifications. The side-chain carboxylic groups were then converted to amine-reactive pentafluorophenyl (PFP) ester groups. Part of the PFP groups was used for the attachment of the dithiolane moiety, which can efficiently bind to gold surfaces. The final copolymer contained 1.4 mol% of dithiolane groups and 4.5 mol% of PFP groups. The copolymer structure was confirmed by several analytical techniques, including NMR spectroscopy and size-exclusion chromatography. The kinetics of the PFP ester aminolysis and hydrolysis demonstrated significantly faster amidation compared to hydrolysis, which is essential for subsequent protein conjugation. Successful coating of gold surfaces with the polymer was confirmed by spectroscopic ellipsometry, showing a polymer brush thickness of 4.77 nm. Subsequent modification of the coated surfaces was achieved using bovine serum albumin as a model protein. This study introduces a novel reactive polymer linker for gold surface functionalization and offers a versatile polymer platform for various applications including biosensing and surface functionalization.

The first examples of a practical procedure for a lipase-catalyzed dynamic kinetic resolution of PEGylated N -alkyl amino esters is reported. This method allows for the preparation of a broad range of aromatic and aliphatic enantiomerically enriched N -alkyl unnatural amino acids in up to 98% yield and 99% ee. We have found that PEGylated esters have a significant solubility advantage and improved reactivity over traditional hydrophobic lipase substrates, thereby allowing for efficient and scalable dynamic kinetic resolution (DKR) under aqueous conditions.

Herein, we present a novel method for the N -arylation of amino acid esters using α-bromoacetaldehyde acetal and acetoacetate via an I 2 -mediated metal-free benzannulation strategy, which disclosed the first synthetic application of N -arylation of amino acids using nonaromatic building blocks. The synthesized N -arylated amino acid derivatives were found to possess promising selective inhibition against human hepatocellular liver carcinoma cells, human melanoma cells, and human normal liver cells, with an IC 50 value as low as 16.79 μg·mL -1 .

Boronic acids/esters have recently emerged in the field of medicinal and pharmaceutical research due to their exceptional oxophilicity, low toxicity, and unique structure. They are known as potent enzyme inhibitors, cancer therapy capture agents, and can mimic certain types of antibodies to fight infections. They have been designed and developed into drugs, and this approach has emerged in the last 20 years. Five boronic acid drugs have been approved by the FDA and Health Canada, two of which are used to treat cancer, specifically multiple myeloma. The purpose of this review is to investigate boronic acid/ester derivatives as potential pharmaceutical agents as well as the mechanism of action. It will concentrate on six types of cancer: multiple myeloma, prostate cancer, breast cancer, lung cancer, cervical cancer, and colon cancer. Some newly developed boron-containing compounds have already demonstrated highly promising activities, but further investigation is required before final conclusions can be drawn.

Phthalate esters (PAEs) are widely distributed in the environment, and this has caused serious health and safety concerns. Development of rapid and ultrasensitive identification and analysis methods for phthalate esters is urgent and highly desirable. In this work, a novel nitrogen-rich covalent organic framework (N-TTI) derived quinoline bridging covalent organic framework (N-QTTI) was fabricated and used as a solid-phase microextraction (SPME) coating for the ultrasensitive determination of phthalate esters in water samples. The physical and chemical properties of N-QTTI were investigated sufficiently. The N-QTTI-coated fiber demonstrates a superior enrichment performance than either the N-TTI-coated fiber or commercial fibers under the optimized SPME conditions. For the first time, we propose a semi-immersion strategy for the extraction of PAEs from water samples based on N-QTTI-coated SPME fibers. Combined with gas chromatography-mass spectrometry (GC-MS), the developed method N-QTTI-SPME-GC-MS exhibits a wide linear range with a satisfactory linearity ( R 2 ≥ 0.995). The limits of detection (LOD, S/N = 3) and the limits of quantification (LOQs, S/N = 10) were 0.17-1.70 and 0.57-5.60 ng L -1 , respectively. The repeatability of the new method was examined using relative standard deviations (RSDs) between intraday and interday data, which were 0.38-7.98% and 1.22-6.60%, respectively. The spiked recoveries at three levels of 10, 100, and 1000 ng L -1 were in the range of 90.0-106.2% with RSDs of less than 7.48%. The enrichment factors ranged from 291 to 17180. When compared to previously published works, the LODs of the newly established method were improved 5-5400 times, and the enrichment factors were increased by at least 8 times. The absorption mechanism was investigated by X-ray photoelectron spectroscopy and noncovalent interaction force analysis. The technique was successfully employed for detecting PAEs in water samples.

Phthalic acid esters (PAEs) are a class of chemicals widely used as plasticizers. These compounds, considered toxic, do not bond to the polymeric matrix of plastic and can, therefore, migrate into the surrounding environment, posing a risk to human health. The primary source of human exposure is food, which can become contaminated during cultivation, production, and packaging. Therefore, it is imperative to control and regulate this exposure. This review covers the analytical methods used for their determination in two economically significant products: olive oil and wine. Additionally, it provides a summary and analysis of information regarding the characteristics, toxicity, effects on human health, and current regulations pertaining to PAEs in food. Various approaches for the extraction, purification, and quantification of these analytes are highlighted. Solvent and sorbent-based extraction techniques are reviewed, as are the chromatographic separation and other methods currently applied in the analysis of PAEs in wines and olive oils. The analysis of these contaminants is challenging due to the complexities of the matrices and the widespread presence of PAEs in analytical laboratories, demanding the implementation of appropriate strategies.

Increasing environmental pollution and petroleum resource depletion are important indicators for the necessary and inevitable replacement of fossil-based polymeric materials with more sustainable counterparts. Hence, the development of bio-based materials from renewable resources, such as cellulose, is of great importance. Herein, we introduce a rapid and homogeneous microwave assisted synthesis of high molecular weight (59 kDa ≤ M n ≤ 116 kDa) short chain (mixed) cellulose esters (CEs) with variable acyl side chain length (2 ≤ C ≤ 8) by using a DMSO/TMG/CO 2 switchable solvent system. Accordingly, (mixed) CEs were synthesized by implementing tetramethylguanidine (TMG) into a switchable solvent system (DMSO/TMG/CO 2 ), followed by in-depth structural characterization via IR, 1 H NMR, 13 C NMR, and SEC. Examination of the structure-property relationships revealed a decrease in the glass transition temperature (177 °C ≤ T g ≤ 204 °C), an increase in surface hydrophobicity, i.e., water contact angle (WCA) (65° ≤ WCA ≤ 98°), and a decrease of Young's modulus (7.51 MPa ≤ E ≤ 13.6 MPa), with longer alkyl side chains.

This research presents novel ibuprofen derivatives in the form of alkyl ester salts of L-amino acids with potential analgesic, anti-inflammatory, and antipyretic properties for potential use in transdermal therapeutic systems. New derivatives of ( RS )-2-[4-(2-methylpropyl)phenyl]propionic acid were synthesized using hydrochlorides of alkyl esters (ethyl, propyl, isopropyl, butyl, sec -butyl, tert -butyl, and pentyl) of L-glutamine. These were further transformed into alkyl esters of L-amino acid ibuprofenates through neutralization and protonation reactions. Characterization involved spectroscopic methods, including nuclear magnetic resonance and Fourier-transform infrared spectroscopy. Various physicochemical properties were investigated, such as UV-Vis spectroscopy, polarimetric analysis, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, water solubility, octanol/water partition coefficient, and permeability through pig skin using Franz diffusion cells. The research confirmed the ionic structure of the obtained hydrochlorides of alkyl esters of L-amino acids and ibuprofenates of alkyl esters of L-glutamic acid. It revealed significant correlations between ester chain length and thermal stability, crystallinity, phase transition temperatures, lipophilicity, water solubility, skin permeability, and skin accumulation of these compounds. Compared to the parent ibuprofen, the synthesized derivatives exhibited higher water solubility, lower lipophilicity, and enhanced skin permeability. This study introduces promising ibuprofen derivatives with improved physicochemical properties, highlighting their potential for transdermal therapeutic applications. The findings shed light on the structure-activity relationships of these derivatives, offering insights into their enhanced solubility and skin permeation, which could lead to more effective topical treatments for pain and inflammation.

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a class of bioactive lipids that show therapeutic potential for diabetes, anti-cancer and inflammation. These FAHFAs can be obtained through dietary intake, potentially improving human health. However, there is currently inadequate knowledge regarding the presence and variety of FAHFAs in different foods. Herein, we profile FAHFAs from 12 typical food samples and 4 medicinal food samples with the aid of our previous established chemical isotope labeling-assisted liquid chromatography-mass spectrometry method and build a comprehensive dataset of FAHFA diversity. The dataset comprised a total of 1207 regioisomers belonging to 298 different families, with over 100 families being newly discovered for the first time. Therefore, our findings contribute valuable insights into the molecular diversity and presence of FAHFA in a range of foods. This dataset serves as a foundation for further exploration of the nutritional and medicinal functions of FAHFAs., (© 2023. The Author(s).)

Cell-surface proteins known as adhesins enable bacteria to colonize particular environments, and in Gram-positive bacteria often contain autocatalytically formed covalent intramolecular cross-links. While investigating the prevalence of such cross-links, a remarkable example was discovered in Mobiluncus mulieris, a pathogen associated with bacterial vaginosis. This organism encodes a putative adhesin of 7651 residues. Crystallography and mass spectrometry of two selected domains, and AlphaFold structure prediction of the remainder of the protein, were used to show that this adhesin belongs to the family of thioester, isopeptide and ester-bond-containing proteins (TIE proteins). It has an N-terminal domain homologous to thioester adhesion domains, followed by 51 immunoglobulin (Ig)-like domains containing ester- or isopeptide-bond cross-links. The energetic cost to the M. mulieris bacterium in retaining such a large adhesin as a single gene or protein construct suggests a critical role in pathogenicity and/or persistence., (open access.)

The practical and facile Mn(OAc) 2 -promoted [3+2] cycloaddition reaction of enaminones with isocyanoacetate was developed, that delivered a diversity of 3-aroyl pyrrole-2-carboxylic esters with broad substrates scope. The most of the newly synthesized compounds exhibit moderate antiproliferative activity against four cancer cells. Notably, compound 2n demonstrate the most potent activity with average IC 50 values of 5.61 μM against four distinct cancer cell lines. Moreover, 2n exhibit favorable anti-migration activity and drug-like properties. The further investigation suggests that compound 2n possesses the ability to inhibit ERK5 activity and exhibits effective binding with the ERK5 protein, making it a promising candidate as a lead compound for a new class of ERK5 inhibitors discovery., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiaopeng Peng reports financial support was provided by Gannan Medical University. Xiaopeng Peng reports a relationship with Gannan Medical University that includes: employment. Xiaopeng Peng has patent pending to No patent. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The intricate mechanisms of oil thermooxidation and their accurate prediction have long been hampered by the combinatory nature of propagation and termination reactions involving randomly generated radicals. To unravel this complexity, we suggest a two-scale mechanistic description that connects the chemical functions (scale 1) with the molecular carriers of these functions (scale 2). Our method underscores the importance of accounting for cross-reactions between radicals in order to fully comprehend the reactivities in blends. We rigorously tested and validated the proposed two-scale scheme on binary and ternary mixtures of fatty acid methyl esters (FAMEs), yielding three key insights: (1) The abstraction of labile protons hinges on the carrier, defying the conventional focus on hydroperoxyl radical types. (2) Termination reactions between radicals adhere to the geometric mean law, exhibiting symmetric collision ratios. (3) The decomposition of hydroperoxides emerges as a monomolecular process above 80 °C, challenging the established combinatorial paradigm. Applicable across a wide temperature range (80 °C to 200 °C), our findings unlock the production of blends with controlled thermooxidation stability, optimizing the use of vegetable oils across applications: food science, biofuels, and lubricants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

ABSTRACT This study aims to investigate the optimized lipase-catalysed esterification reaction from novel feedstock microalgae ( Chlorella protothecoides ) oil-free fatty acids (FFAs) for biolubricant (Trimethylolpropane (TMP)-triesters) synthesis. FFAs were obtained from microalgae oil by enzymatic hydrolysis. Response surface methodology (RSM) with the central composite design was performed to investigate the effect of experimental factors (lipase amount, TMP/FFAs molar ratio, reaction temperature) on the FFAs conversion and also investigated to resolve the optimum design points. After the experimental studies, the highest FFAs conversion of 93% with 92% triester and 8% mono, di esters contents were found when the lipase amount was 5.5%. TMP/FFAs molar ratio was 0.33 and the reaction temperature value was 60°C. The model fitted with the experimental values with R 2  = 0.97. It was also supported by gas chromatography and FTIR analyses that the product obtained was a lubricant.

Far-red BODIPY-based oxime esters for photo-uncaging were designed to release molecules of interest with carboxylic acids. The low power red LED light breaks the N-O oxime ester bond and frees the caged molecules. We studied the mechanism and kinetics of the uncaging procedure using a 1 H NMR spectrometer. Moreover, the drug delivery strategy to release valproic acid (VPA) on demand was tested in vitro using this far-red BODIPY photo-uncaging strategy to induce apoptosis in tumor cells.

Background: Antioxidant polyphenols like gallic acid (GA) and its esters called "gallates", which have health advantages for humans, have grown in significance in maintaining a healthy lifestyle and eating a significant amount of secondary plant phytochemicals. Here, for the first time, we suggest a green synthesis of a brand-new, all-natural diester based on gallic acid and polyethylene glycol., Methods: This di-gallate is created in a single step without the use of a solvent (solid-solid reaction). This reaction has a potential yield of up to 90%. The bathochromic shift of the absorption bands from 277 nm to 295 nm in the UV-VIS spectra was caused by the addition of PEG to gallic acid. To confirm the structure of this di-gallate; Fourier-transform infrared (FTIR) spectroscopy, proton and carbon nuclear magnetic resonance ( 1 H and 13 C NMR), the thermal stability identified by thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were all used to thoroughly analyze the manufactured product., Results and Conclusions: The acquired results, when compared to the literature spectrums, supported the establishment of the di-ester structure and created new opportunities for a large number of applications., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Zerigui H et al.)