Side Chain Research Articles

Effect of lecithin on the antioxidant mechanism of action of fucoidan in stripped bulk sunflower oil and respective oil in water emulsion.

The objective of this study was to investigate the antioxidant mechanism of action of fucoidan in sunflower oil and its oil-in-water emulsion. In addition, the effect of lecithin on the antioxidant mechanism of action of fucoidan in sunflower oil was investigated. In sunflower oil, fucoidan at 0.02 % (w/w) concentration showed the highest induction period (591.02 h), while in sunflower oil-in-water emulsion, fucoidan at 0.04 % (w/w) concentration showed the highest induction period (141.57 h). In addition, the induction period of sunflower oil samples containing fucoidan with lecithin was higher than those without lecithin. Evaluating the mechanism of action of fucoidan in sunflower oil and its oil-in-water emulsion indicated that fucoidan took part in the initiation chain's side reactions and the major termination reaction. The interfacial tensions of samples containing lecithin were significantly lower than those without lecithin. In addition, the reverse micelle size of samples containing lecithin was considerably lower than those without lecithin. Therefore, lecithin enhanced fucoidan's effectiveness by decreasing interfacial activity and increasing the capacity to incorporate lipid hydroperoxides within the structure of reverse micelles. The water produced during oxidation played an essential role in the antioxidant potency of fucoidan. Taken together, lecithin significantly enhanced the antioxidant activity of fucoidan by improving its interfacial activity in sunflower oil.

Dual Responsive Emulsions Based on Amphiphilic Elastin-like Polypeptide Bioconjugates.

To achieve the desired therapeutic response, drug delivery systems must ensure the controlled release of the loaded content at the targeted site. One possible strategy relies on the improvement of conventional drug delivery systems. To do so, smart polymers, able to change their behavior upon chemical, physical, or biological stimuli, can be used. In this context, this study aims to evaluate the potential of natural amphiphilic smart elastin-like polypeptides grafted with alkyl chains (ELP-g-Bu) to stabilize conventional oil-in-water emulsions and trigger the release of loaded molecules upon dual stimuli. With butyl pendant chains and methionine residues, the macromolecular surfactant ELP-g-Bu demonstrated a modification of physicochemical properties, looking at critical aggregation concentration, upon both temperature and oxidation stimuli. The macromolecular surfactant was then able to stabilize a paraffin-oil-in-water emulsion. The ELP-g-Bu emulsion presented a droplet size of 9 ± 1 μm and stability for at least a month at 4 and 25 °C. After successful loading of a fluorescent lipophilic molecule used as a drug model, a complete destabilization of the ELP-g-Bu emulsion and burst release of the content was achieved with thermal triggering at 42 °C. In oxidative conditions, a partial release was measured, which can be improved by increasing the number of oxidable thioether groups. Overall, these dually responsive amphiphilic ELP-g-Bu demonstrated their potential for smart-polymer-based drug delivery systems that can be promising for inflammatory disease treatment as increased temperature and radical oxygen species are present in such cases.

DART isotope dilution high resolution mass spectrometry and 19F-NMR detection of fluorotelomeric alcohols in hydrolyzed food contact paper

Fluorotelomer-based acrylate polymers and surfactants used to grease-proof food contact paper (FCP) are potential sources of dietary exposure to perfluoroalkyl substances (PFAS). Food contact substances (FCS) containing polyfluorinated long-chains (≥C8) were voluntarily removed by their manufacturers from the U.S. market in 2011 due to health concerns and largely replaced with FCSs containing short-chain (≤C7) PFAS. In 2020, FDA findings of potential biopersistence of 6:2 FTOH (CF3(CF2)5CH2CH2OH) similarly prompted an additional voluntarily phase-out of FCSs containing 6:2 FTOH by their manufacturers that was completed by the end of 2023. To monitor the phase-out process, a screening method was developed to detect FCPs containing ester-linked polyfluorinated pendant chains. Direct Analysis in Real Time-Isotope Dilution-High Resolution Mass Spectrometry (DART-ID-HRMS) enabled rapid semi-quantitative detection of 6:2 FTOH in FCP saponification reaction headspace without requiring sample concentration or chromatography. 19F-NMR analysis confirmed 6:2 FTOH pendant chain identity and detection dependence on saponification. The speed and specificity of this approach arise from ester saponification in the presence of stable isotopically labeled 6:2 FTOH; high FTOH differential volatility relative to nonfluorinated matrix, and the facile production of FTOH gas-phase anions (e.g., [M + O2]·−, [M-H + CO2]−) under ambient ionization conditions. The efficiency of this simple workflow makes it well-suited for monitoring the phase-out of FCS containing ester-linked polyfluorinated chains from the U.S. marketplace.

Recent Advances in the Synthesis and Analysis of Atorvastatin and its Intermediates.

Atorvastatin, a lipid-lowering drug that is widely used in the treatment of cardiovascular diseases, has significant clinical significance. This article focuses on the synthetic procedures of atorvastatin, including Paal-Knorr synthesis and several new synthetic strategies. It also outlines chemical and chemo-enzymatic methods for synthesizing optically active side chain of atorvastatin. In addition, a comprehensive overview of the analytical monitoring techniques for atorvastatin and its metabolites and impurities is reported, alongside a discussion of their strengths and limitations.

UV-curable aromatic polyurethanes from different sustainable resources: Protocatechuic and cinnamic acids

An innovative aromatic monomer, 3,4-dihydroxybenzyl cinnamate (CDHB), was synthesized from protocatechuic and cinnamic acids. These latter can be obtained from different sustainable resources, such as plastic waste or biomass, by biotechnology and/or chemistry routes. From CDHB, used as chain extender, and aromatic or aliphatic diisocyanates, various aromatic thermoplastic polyurethanes (TPU) with cinnamic pendant chains were carefully synthesized and characterized. Different techniques such as NMR, FTIR, TGA and DSC have been used. The main results show that the TPUs exhibited good phase segregation and thermal stability, due to the aromaticity of the chain extender. The pendant cinnamic chains acted as internal plasticizer with a reduction of the glass transition temperature (Tg). The cinnamic groups were also able to undergo a [2 + 2] cycloaddition under UV irradiation, leading to the crosslinking of PU with a strong evolution of the properties. This reaction was followed by UV–Vis spectroscopy. 80 % of cycloaddition was reached in 20 h, significantly increasing PU gel fraction, Tg, and thermal stability. This study highlights the potential to create modulable sustainable and aromatic PU macromolecular architectures that can be UV curable and display enhanced properties.

Thermotropic "Plumber's Nightmare"-A Tight Liquid Organic Double Framework.

Gyroid, double diamond and the body-centred "Plumber's nightmare" are the three most common bicontinuous cubic phases in lyotropic liquid crystals and block copolymers. While the first two are also present in solvent-free thermotropics, the latter had never been found. Containing six-fold junctions, it was unlikely to form in the more common phases with rod-like cores normal to the network columns, where a maximum of four branches can join at a junction. The solution has therefore been sought in side-branched mesogens that lie in axial bundles joined at their ends by flexible "hinges". But for the tightly packed double framework, geometric models predicted that the side-chains should be very short. The true Plumber's nightmare reported here, using fluorescent dithienofluorenone rod-like mesogen, has been achieved with, indeed, no side chains at all, but with 6 flexible end-chains. Such molecules normally form columnar phases, but the key to converting a complex helical column-forming mesogen into a framework-forming one was the addition of just one methyl group to each pendant chain. A geometry-based explanation is given.

Thermotropic “Plumber's Nightmare”—A Tight Liquid Organic Double Framework

AbstractGyroid, double diamond and the body‐centred “Plumber's nightmare” are the three most common bicontinuous cubic phases in lyotropic liquid crystals and block copolymers. While the first two are also present in solvent‐free thermotropics, the latter had never been found. Containing six‐fold junctions, it was unlikely to form in the more common phases with rod‐like cores normal to the network columns, where a maximum of four branches can join at a junction. The solution has therefore been sought in side‐branched mesogens that lie in axial bundles joined at their ends by flexible “hinges”. But for the tightly packed double framework, geometric models predicted that the side‐chains should be very short. The true Plumber's nightmare reported here, using fluorescent dithienofluorenone rod‐like mesogen, has been achieved with, indeed, no side chains at all, but with 6 flexible end‐chains. Such molecules normally form columnar phases, but the key to converting a complex helical column–forming mesogen into a framework‐forming one was the addition of just one methyl group to each pendant chain. A geometry‐based explanation is given.

Synergetic Effect of β-Cyclodextrin and Its Simple Carbohydrate Substituents on Complexation of Folic Acid and Its Structural Analog Methotrexate.

Folic acid (FA) and its structural analog, anticancer medicine methotrexate (MTX), are known to form host/guest complexes with native cyclodextrins, of which the most stable are formed with the medium-sized β-cyclodextrin. Based on our research, proving that simple sugars (D-glucose, D-galactose, and D-mannose) can form adducts with folic acid, we envisioned that combining these two types of molecular receptors (cyclodextrin and simple carbohydrates) into one may be beneficial for the complexation of FA and MTX. We designed and obtained host/guest inclusion complexes of FA and MTX with two monoderivatives of β-cyclodextrin-substituted at position 6 with monosaccharide (glucose, G-β-CD) and disaccharide (maltose, Ma-β-CD). The complexation was proved by experimental (NMR, UV-vis, IR, TG, DSC) and theoretical methods. We proved that derivatization of β-cyclodextrin with glucose and maltose has a significant impact on the complexation with FA and MTX, as the addition of one glucose subunit to the structure of the receptor significantly increases the value of association constant for both FA/G-β-CD and MTX/G-β-CD, while further extending a pendant chain (incorporation of maltose subunit) results in no additional changes.

Synthesis and Biological Evaluations of Granulatamide B and its Structural Analogues.

While granulatamides A and B have been previously isolated, their biological activities have been only partially examined. The aim of this study was to synthesize granulatamide B (4b), a tryptamine-derivative naturally occurring in Eunicella coral species, using the well-known procedure of Sun and Fürstner and its 12 structural analogues by modifying the side chain, which differs in length, degree of saturation as well as number and conjugation of double bonds. The prepared library of compounds underwent comprehensive assessment for their biological activities, encompassing antioxidative, antiproliferative, and antibacterial properties, in addition to in vivo toxicity evaluation using a Zebrafish model. Compound 4i, which consists of a retinoic acid moiety, exhibited the strongest scavenging activity against ABTS radicals (IC50 = 36 ± 2 μM). In addition, 4b and some of the analogues (4a, 4c and 4i), mostly containing an unsaturated chain and conjugated double bonds, showed moderate but non-selective activity with certain IC50 values in the range of 20-40 μM. In contrast, the analogue 4l, a derivative of alpha-linolenic acid, was the least toxic towards normal cell lines. Moreover, 4b was also highly active against Gram-positive Bacillus subtilis with an MIC of 125 μM. Nevertheless, both 4b and 4i, known for the best-observed effects, caused remarkable developmental abnormalities in the zebrafish model Danio rerio. Since modification of the side chain did not significantly alter the change in biological activities compared to the parent compound, granulatamide B (4b), the substitution of the indole ring needs to be considered. Our group is currently carrying out new syntheses focusing on the functionalization of the indole core.

Scalable Total Synthesis of Acremolactone B.

Acremolactone B is a pyridine-containing azaphilone-type polyketide. The first total synthesis of this molecule was achieved on a gram scale, based on an aza-6π electrocyclization-aromatization strategy for construction of the tetra-substituted pyridine ring. A bicyclic intermediate was expeditiously prepared by using [2+2] photocycloaddition and chemoselective Baeyer-Villiger oxidation, which was further elaborated to a densely substituted aza-triene. An electrocyclization-aromatization cascade was utilized to forge the tetracyclic core of this natural product, and the side chain was introduced through diastereoselective acylation and reduction.

Scalable Total Synthesis of Acremolactone B

AbstractAcremolactone B is a pyridine‐containing azaphilone‐type polyketide. The first total synthesis of this molecule was achieved on a gram scale, based on an aza‐6π electrocyclization–aromatization strategy for construction of the tetra‐substituted pyridine ring. A bicyclic intermediate was expeditiously prepared by using [2+2] photocycloaddition and chemoselective Baeyer–Villiger oxidation, which was further elaborated to a densely substituted aza‐triene. An electrocyclization–aromatization cascade was utilized to forge the tetracyclic core of this natural product, and the side chain was introduced through diastereoselective acylation and reduction.

Hyperbranched Vitrimer for Ultrahigh Energy Dissipation.

Polymers are ideally utilized as damping materials due to the high internal friction of molecular chains, enabling effective suppression of vibrations and noises in various fields. Current strategies rely on broadening the glass transition region or introducing additional relaxation components to enhance the energy dissipation capacity of polymeric damping materials. However, it remains a significant challenge to achieve high damping efficiency through structural control while maintaining dynamic characteristics. In this work, we propose a new strategy to develop hyperbranched vitrimers (HBVs) containing dense pendant chains and loose dynamic crosslinked networks. A novel yet weak dynamic transesterification between the carboxyl and boronic acid ester was confirmed and used to prepare HBVs based on poly (hexyl methacrylate-2-(4-ethenylphenyl)-5,5-dimethyl-1,3,2-dioxaborinane) P(HMA-co-ViCL) copolymers. The -type of macromonomers, the crosslinking points formed by the dynamic covalent connection via the associative exchange, and the weak yet dynamic exchange reaction are the three keys to developing high-performance HBV damping materials. We found that P(HMA-co-ViCL) 20k-40-60 HBV exhibited ultrahigh energy-dissipation performance over a broad frequency and temperature range, attributed to the synergistic effect of dense pendant chains and weak dynamic covalent crosslinks. This unique design concept will provide a general approach to developing advanced damping materials.

Hyperbranched Vitrimer for Ultrahigh Energy Dissipation

AbstractPolymers are ideally utilized as damping materials due to the high internal friction of molecular chains, enabling effective suppression of vibrations and noises in various fields. Current strategies rely on broadening the glass transition region or introducing additional relaxation components to enhance the energy dissipation capacity of polymeric damping materials. However, it remains a significant challenge to achieve high damping efficiency through structural control while maintaining dynamic characteristics. In this work, we propose a new strategy to develop hyperbranched vitrimers (HBVs) containing dense pendant chains and loose dynamic crosslinked networks. A novel yet weak dynamic transesterification between the carboxyl and boronic acid ester was confirmed and used to prepare HBVs based on poly (hexyl methacrylate‐2‐(4‐ethenylphenyl)‐5,5‐dimethyl‐1,3,2‐dioxaborinane) P(HMA‐co‐ViCL) copolymers. The ‐type of macromonomers, the crosslinking points formed by the dynamic covalent connection via the associative exchange, and the weak yet dynamic exchange reaction are the three keys to developing high‐performance HBV damping materials. We found that P(HMA‐co‐ViCL) 20k‐40‐60 HBV exhibited ultrahigh energy‐dissipation performance over a broad frequency and temperature range, attributed to the synergistic effect of dense pendant chains and weak dynamic covalent crosslinks. This unique design concept will provide a general approach to developing advanced damping materials.

Role of acrylate terpolymers in flow assurance studies of crude oil

Paraffinic crude oil causes deposition in the pipeline at low temperatures which hinders the flow during pipeline transportation. The primary technique for mitigation of paraffin deposition is chemical treatment. Polymeric chemical additives have gained considerable attention as flow improvers for waxy crude oil. Terpolymer application for flow assurance is a novel approach since terpolymers are seldom used as chemical additives for crude oil. Current research aims to synthesize four acrylate terpolymers with different alkyl pendant chains and study their effect on the rheological behavior of crude oil. The structure of additives was validated and their depression effect was investigated. The results of the investigation revealed that the additives showed significant decrease in pour point (ΔPP = 21 °C for CO-1 and 15 °C for CO-2) at a dose of 1000 ppm for CO-1 and 2000 ppm for CO-2. These results were also supported by rheological data which exhibited a significant reduction in viscosity (>75%) of both the crude oils which showed the efficiency of additives as flow improvers. Moreover, the cold finger test displayed excellent paraffin inhibition efficiency of synthesized additives (66 and 52% for CO-1 and CO-2, respectively). The investigation demonstrated a promising role of terpolymers as flow improvers for waxy crude oil.

Cyclic Peptides from Graspetide Biosynthesis and Native Chemical Ligation.

The ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily of natural products includes many examples of cyclic peptides with diverse macrocyclization chemistries. The graspetides, one family of macrocyclized RiPPs, harbor side chain-side chain ester or amide linkages. We recently reported the structure and biosynthesis of the graspetide pre-fuscimiditide, a 22-amino-acid (aa) peptide with two ester cross-links forming a stem-loop structure. These cross-links are introduced by a single graspetide synthetase, the ATP-grasp enzyme ThfB. Here we show that ThfB can also catalyze the formation of amide or thioester cross-links in prefuscimiditide, with thioester formation being especially efficient. We further show that upon proteolysis to reveal an N-terminal cysteine residue, the thioester-linked peptide rapidly and quantitatively rearranges via native chemical ligation into an isopeptide-bonded head-to-tail cyclic peptide. The solution structure of this rearranged peptide was determined by using 2D NMR spectroscopy experiments. Our methodology offers a straightforward recombinant route to head-to-tail cyclic peptides.

Homogeneous-strengthened SPEEK membrane with ultrahigh conductivity regulated by main/side-chain bisulfonated PEEK for vanadium flow battery

A comblike polymer (SPOS) with a main/side-chain bisulfonated structure has been synthesized with 1,3-propane sulfonate as the pendant chains and poly (ether ketone) (PEEK) as the reactant by the combined post-sulfonation and ring-opening grafting reaction. Taking sulfonated PEEK as a membrane matrix, the composite membranes (S/SPOS) are prepared by the solution-blending method with varied contents of bisulfonic SPOS polymer from 10 to 25 wt%. The S/SPOS composite membranes display superior conductivity owing to synergistic enhancement in the intermolecular chain interactions and the homogeneous strengthened transportation channels from main/side-chain bisulfonic acid interconnected networks. S/SPOS-15 shows better CE (96.5–98.5 %) and EE (84.7–69.9 %) than that of Nafion 212 (CE: 92.3–95.0 %, EE: 76.1–63.7 %) at 100–200 mA cm−2. Moreover, 600-cycled durability and 77.3 % EE at 150 mA cm−2, and 71.8 h self-discharge time demonstrate its improved reliable structure and cyclic stability. This provides a promising method to prepare high-performance and low-cost membranes with desirable conductivity by homogeneous structural regulation and molecular chain synergistic interactions.

Dual‐Strategy Tailoring Molecular Structures of Dopant‐Free Hole Transport Materials for Efficient and Stable Perovskite Solar Cells

AbstractDopant‐free hole transport materials (HTMs) are ideal materials for highly efficient and stable n‐i‐p perovskite solar cells (PSCs), but most current design strategies for tailoring the molecular structures of HTMs are limited to single strategy. Herein, four HTMs based on dithienothiophenepyrrole (DTTP) core are devised through dual‐strategy methods combining conjugate engineering and side chain engineering. DTTP‐ThSO with ester alkyl chain that can form six‐membered ring by the S⋅⋅⋅O noncovalent conformation lock with thiophene in the backbone shows good planarity, high‐quality film, matching energy level and high hole mobility, as well as strong defect passivation ability. Consequently, a remarkable power conversion efficiency (PCE) of 23.3 % with a nice long‐term stability is achieved by dopant‐free DTTP‐ThSO‐based PSCs, representing one of the highest values for un‐doped organic HTMs based PSCs. Especially, the fill factor (FF) of 82.3 % is the highest value for dopant‐free small molecular HTMs‐based n‐i‐p PSCs to date. Moreover, DTTP‐ThSO‐based devices have achieved an excellent PCE of 20.9 % in large‐area (1.01 cm2) devices. This work clearly elucidates the structure‐performance relationships of HTMs and offers a practical dual‐strategy approach to designing dopant‐free HTMs for high‐performance PSCs.

Azobenzene-Based Conjugated Polymers: Synthesis, Properties, and Biological Applications.

Conjugated polymers (CPs) have been developed quickly as an emerging functional material with applications in optical and electronic devices, owing to their highly electron-delocalized backbones and versatile side groups for facile processibility, high mechanical strength, and environmental stability. CPs exhibit multistimuli responsive behavior and fluorescence quenching properties by incorporating azobenzene functionality into their molecular structures. Over the past few decades, significant progress has been made in developing functional azobenzene-based conjugated polymers (azo-CPs), utilizing diverse molecular design strategies and synthetic pathways. This article comprehensively reviews the rapidly evolving research field of azo-CPs, focusing on the structural characteristics and synthesis methods of general azo-CPs, as well as the applications of charged azo-CPs, specifically azobenzene-based conjugated polyelectrolytes (azo-CPEs). Based on their molecular structures, azo-CPs can be broadly categorized into three primary types: linear CPs with azobenzene incorporated into the side chain, linear CPs with azobenzene integrated into the main chain, and branched CPs containing azobenzene moieties. These systems are promising for biomedical applications in biosensing, bioimaging, targeted protein degradation, and cellular apoptosis.

Socialane, a Nonaprenyl Terpene Hydrocarbon Surface Lipid from the Collembola Hypogastrura socialis.

Springtails use unique compounds for their outermost epicuticular wax layer, often of terpenoid origin. We report here the structure and synthesis of socialane, the major cuticular constituent of the Collembola Hypogastrura socialis. Socialane is also the first regular nonaprenyl terpene with a cyclic head group. The saturated side chain has seven stereogenic centers, making the determination of the configuration difficult. We describe here the identification of socialane and a synthetic approach using the building blocks farnesol and phytol, enantioselective hydrogenation, and α-alkylation of sulfones for the synthesis of various stereoisomers. NMR experiments showed the presence of an anti-configuration of the methyl groups closest to the benzene ring and that the other methyl groups of the polyprenyl side-chain are not uniformly configured. Furthermore, socialane is structurally different from [6+2]-terpene viaticene of the closely related H. viatica, showing species specificity of the epicuticular lipids of this genus and hinting at a possible role of surface lipids in the communication of these gregarious arthropods.

Discovery of a series of portimine-A fatty acid esters in mussels

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 C42H65NO9, 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 C2H5O2 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.