Phenolic Hydroxy Groups Research Articles

Antioxidant hydrogel from poly(aspartic acid) and carboxymethylcellulose with quercetin loading as burn wound dressing

Susceptibility to infection and excessive accumulation of reactive oxygen species (ROS) are the greatest obstacles for burn wound healing. In this research, the 5-aminosalicylic acid (ASA) grafted poly(aspartic hydrazide) (PASH) was synthesized by successive ploysuccinimide (PSI) ring opening reaction and reacted with oxidized carboxymethyl cellulose (DCMC) to fabricate biodegradable hydrogel through Schiff-base cross-linking. Moreover, the hydrogel was loaded with quercetin (QT) to enhance its anti-inflammatory performance. The ASA moiety endowed the hydrogel with the free radical scavenging ability and mussel inspired tissue adhesion to maintain the healing bioenvironment of the wound. The loading of QT gave the hydrogel more phenolic hydroxy group and further enhanced the antioxidant capacity of the hydrogel. The in vitro experiment revealed the grafted ASA moiety and the loaded QT greatly enhanced the ROS elimination property and antibacterial property. Moreover, the QT loaded hydrogel accelerated the burn wound repairing rate in the in vivo mice model. Based on above result, the PASH/DCMC could act as a new platform for QT loading to promote the burn wound repairing.

Kinetic Resolution of BINOLs and Biphenols by Atroposelective, Cu-H-Catalyzed Si-O Coupling with Hydrosilanes.

A nonenzymatic kinetic resolution of monoprotected BINOL and biphenol derivatives by atroposelective Si-O coupling with hydrosilanes is described. The reaction relies on a previously unprecedented Cu-H-catalyzed silylation of phenols. The catalyst system consisting of CuCl, (R,R)-Ph-BPE, and NaOtBu enables the enantioselective coupling of the phenolic hydroxy group with a hydrosilane with moderate to good selectivity factors.

Herbidomicins, two pairs of polyketide tautomers produced by an actinomycete of the genus Herbidospora.

Herbidospora is one of the underexplored actinomycete genera from which only a limited number of secondary metabolites are reported. In our continuing investigation on less explored actinomycetes, a liquid culture of Herbidospora sp. RD 11066 was found to contain unknown metabolites that had no match in our in-house UV database. Chromatographic separation and following structural analysis using NMR and MS identified these metabolites to be chromanone and chromene derivatives, which were respectively composed of an inseparable mixture of two isomeric forms. The former polyketides, designated to be herbidomicins A1 (1) and A2 (2), are positional isomers in terms of a methyl substituent on an aromatic ring that mutually interconvert by acetal exchange by two phenolic hydroxy groups. The latter pair, herbidomicins B1 (3) and B2 (4), is Z/E-isomers regarding an enol ether double bond. Herbidomicins 1-4 were weakly antifungal against a dermatophytic fungus Trichophyton rubrum and were moderately cytotoxic against murine leukemia P388 cells.

Iron-catalyzed non-directed arene C-H difluoromethylation

Practical, undirected and selective catalytic functionalization of unactivated arenes remains a challenging problem in organic synthesis. We herein report a bioinspired L-cystine-derived ligand BCPOM/Fe-enabled innate C-H difluoromethylation of unactivated arenes as limiting reagents with stable and inexpensive BrCF2CO2Et as the difluoromethylation source in high efficiency. Notably, this method uses environmentally benign H2O2 as the sole oxidant, and enables late-stage functionalization and exceptionally functional-group tolerance, even including oxidation-labile aldehyde, phenolic hydroxy, primary amine, and boronic acid groups, which is difficult to access by current means.

Synthesis, bioactivity, and molecular docking of pyrazole bearing Schiff-bases as prospective dual alpha-amylase and alpha-glucosidase inhibitors with antioxidant activity

A series of pyrazole-Schiff base derivatives, 3a-i, were synthesized by reacting arylamines 2a-i with pyrazole aldehyde 1, utilizing two catalysts: ammonium chloride (catalystA) or acetic acid (catalystB). The compounds were analyzed using spectroscopic methods, including 1H and 13C NMR, along with high-resolution mass spectrometry. Their antidiabetic and antioxidant activities were assessed through various in vitro assays, encompassing evaluation of inhibitory effects on α-glucosidase, α-amylase enzymes and determination of reducing power, free radical scavenging activity. The most promising in vitro antidiabetic results were also observed with analogs 3c (α-amylase IC50 = 19.57 ± 0.07 µM, α-glucosidase IC50 = 17.13 ± 0.28 µM) and 3h (α-amylase IC50 = 22.50 ± 0.06 µM, α-glucosidase IC50 = 20.75 ± 0.17 µM). Both products 3c and 3h revealed activity near to the standard acarbose (IC50 (α-amylase) =16.28 ± 0.24 µM, IC50 (α-glucosidase) =13.19 ± 0.26 µM). Among all compounds, 3c and 3h exhibited the highest transition metal reducing activity at levels of 75.27 ± 1.99 and 78.42 ± 0.58 µM Trolox equivalents (TE), respectively, along with the most significant free radical scavenging effects at levels of 73.79 ± 0.11 and 72.98 ± 0.33 µM TE, respectively. The antioxidant results of the current set of pyrazole-Schiff base derivatives 3a–i indicated their potential benefits as free radical scavenging and metal-reducing agents, thus proving their antioxidant capability. Their higher antidiabetic and antioxidant activities compared to other compounds might be explained by the presence of a free phenolic hydroxy group in 3c and a benzothiazole motif in 3h. These findings also lend support to the multifaceted biological functions associated with their antidiabetic activity, including their antioxidant activity. In silico molecular docking studies confirm the antihyperglycemic impact, elucidating the nature of interactions between 3c and 3h and HPA/HLAG catalytic sites.

Effect of imine-containing phenolic hardeners with different chain lengths and epoxy functionalities on thermal, mechanical, and healing properties of bio-based epoxy vitrimers

Mixtures of polyglycerol polyglycidyl ether (PGPE) and poly(ethylene glycol) diglycidyl ether (PEGDGE) with different molar ratios were cured with imine-containing phenolic hardeners prepared by the reactions of vanillin with ethylene glycol bis(3-aminopropyl) ether, diethylene glycol bis(3-aminopropyl) ether, and a polyetheramine (JEFFAMINE® ED-600) to produce bio-based epoxy cured products. Fourier-transform infrared spectroscopy (FT-IR) of the cured products revealed that the curing reaction of the epoxy and phenolic hydroxy groups was almost complete. The cross-linking density, glass transition temperature, and mechanical strength of the cured products decreased with decreasing the PGPE/PEGDGE ratio and increasing the oligoalkyleneoxy chain length of the phenolic hardeners. All cured products were healed three times at 100 °C under 2 MPa for 2 h. The healing efficiency, in terms of tensile strength, increased with decreasing PGPE/PEGDGE ratio and increasing oligoalkyleneoxy chain length. The polyetheramine-based cured product with the lowest PGPE/PEGDGE ratio exhibited the highest healing efficiency (94–97%), which only slightly decreased following repeated healing treatments.

Structural investigations on the mitochondrial uncouplers niclosamide and FCCP.

There has been renewed interest in using mitochondrial uncoupler compounds such as niclosamide and carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) for the treatment of obesity, hepatosteatosis and diseases where oxidative stress plays a role. However, both FCCP and niclosamide have undesirable effects that are not due to mitochondrial uncoupling, such as inhibition of mitochondrial oxygen consumption by FCCP and induction of DNA damage by niclosamide. Through structure-activity analysis, we identified FCCP analogues that do not inhibit mitochondrial oxygen consumption but still provided good, although less potent, uncoupling activity. We also characterized the functional role of the niclosamide 4'-nitro group, the phenolic hydroxy group and the anilide amino group in mediating uncoupling activity. Our structural investigations provide important information that will aid further drug development.

Controlling polymer degradation by addition of plant aromatic polymer, lignin

This study examined the accelerated degradation of poly(caprolactone) films using two types of lignin derivatives. The degradation of poly(caprolactone) films was unaffected by the lignin derivative capped hydroxy groups, indicating the participation of radicals from phenolic hydroxy groups in lignin derivatives for accelerating the degradation of films. Furthermore, the role of lignin radicals in relation to polymer degradation changed as per the mechanism of polymer decomposition, e.g., the degradation of poly(ethylene carbonate) films was suppressed by feeding lignin derivatives because of the back biting type decomposition nature of poly(ethylene carbonate), which differs from the radical-mediated addition/cleavage type decomposition nature of poly(caprolactone). These results provide an approach of designing bio-degradative materials from lignin, a natural phenolic polymer.

Comparing the crystal structures and spectroscopic properties of a p-hydroxy styrylquinolinium dye with those of its p-dimethylamino analogue

Two previously synthesized styrylquinolinium dyes, namely (E)-1-butyl-4-(4-(dimethylamino)styryl)quinolinium iodide (D36) and (E)-1-butyl-4-(4-hydroxystyryl)quinolinium iodide (D34), were compared in terms of their properties by single-crystal X-ray diffraction (XRD), Hirshfeld surface analysis, Fourier transform Raman (FT-Raman), Fourier transform infrared (FT-IR), fluorescence, and ultraviolet–visible (UV–Vis) spectroscopy, and 1H- and 13C-NMR methods. Both dyes D36 and D34 crystallized in the triclinic and monoclinic systems in the centrosymmetric space groups P-1 and P21/n, respectively. The unit cell of D36 contains two molecules of the dye, participating in weak intermolecular interactions, whereas that of D34 contains four formula units. The phenolic hydroxy group of D34 participates in the formation of a hydrogen bond with the iodide anion. The 4-styrylquinolinium moieties of the cationic dye molecules are nearly planar. The dihedral angle between the mean planes through the ten-membered quinolinium system and the benzene ring is 7.5° in D36 and 5.9(1)° in D34. The structural parameters planarity and bond length alternation (BLA) are discussed, which are important for the evaluation of the first hyperpolarizability β at the molecular level, even in a centrosymmetric crystal. The UV–visible spectra of the dyes in 14 solvents of different polarities were investigated. The reversible solvatochromic behavior of the dyes is demonstrated experimentally and compared with known “binuclear dyes” by evaluating the Rezende model. Dye D36 does not fluoresce, and D34 has a very low emission in the solvents tested.

Alginate-based water-soluble adhesives: effect of incorporated phenolic hydroxy groups on adhesiveness

Abstract Alginic acid (Alg) was modified with tyramine (TA), homoveratrylamine (HVTA), and 2-phenylethylamine (PA) to obtain Alg-based adhesives, AlgTA, AlgHVTA, and AlgPA. The adhesiveness of the modified Algs were evaluated and compared with previously reported catechol-modified alginate, AlgDA. AlgTA showed adhesion tendency differently from AlgDA, depending on the incorporation ratios of TA. AlgHVTA with protected phenolic hydroxy groups showed lower adhesiveness than AlgDA for mica surfaces, but higher for polymethyl methacrylate surfaces. AlgPA without a phenolic hydroxy group also exhibited moderate adhesiveness for mica.

Cross-linking lignin and cellulose with polymers using siloxane compounds

Siloxanes are a group of substances characterized by Si-O-Si functional group. Siloxanes can react with alcohols to form Si-O-C bond. Siloxanes have been widely used as crossing linking agents and graft copolymers as well as additives for plastics. Lignin contains both phenolic and aliphatic hydroxy groups which have the potential to instigate bonding with siloxane compounds. However, there has not been any attempt to apply siloxanes as crosslinking agents for biobased composite formation. This manuscript presents the first study of applying siloxanes compounds to lignin and Cellulose nanofibers (CNF) with respective PLA, PETG, and HDPE to prepare biocomposites. Both Tetramethyl Tetraphenyl Trisiloxane (TTT) and Tetraethoxysilane (TEOS) were used as cross-linking agents. We have successfully incorporated 20 wt% lignin and 10 wt% CNF into the biocomposite filaments. The tensile properties of ensuing biocomposite were investigated. The objective of this work is to demonstrate the potential of lignin and CNF as a sustainable co-polymer to improve the properties of PLA/PETG/HDPE-based materials for 3D printing. This paper will also discuss the challenges and opportunities associated with the use of lignin in 3D printing, including the effect of lignin and CNF content on the mechanical and thermal properties, the compatibility of lignin and CNF with PLA/PETG/HDPE, and the potential for further optimization of the cross-linking chemistry using TTT and TEOS.

Facile green synthesis of wasted hop-based zinc oxide nanozymes as peroxidase-like catalysts for colorimetric analysis.

Hops are a common ingredient in beer production, and a considerable quantity of hops is usually discarded as a waste material once the brewing process is completed. Transforming this waste material into valuable nanomaterials offers a sustainable approach that has the potential to significantly mitigate environmental impact. Herein, a facile and green protocol for the production of zinc oxide nanozymes (ZnO NZs) using wasted hop extract (WHE) as a natural precursor was demonstrated. The process involved a hydrothermal synthesis method followed by a calcination step to form the final ZnO NZs. The results revealed that lupulon, the main β-acid in hops, particularly the phenolic hydroxy group, is primarily responsible for the biosynthesis of ZnO NZs. The WHE-ZnO NZs exhibited exceptional peroxidase-like (POD-like) activity and served as effective catalysts for the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2). Analysis of the catalytic mechanism revealed that the POD-like activity of these WHE-ZnO NZs originated from their ability to expedite the transfer of electrons between TMB and H2O2, resulting in the enzymatic kinetics following the standard Michaelis-Menten mechanism. Furthermore, we developed a straightforward and user-friendly colorimetric technique for detecting both H2O2 and glucose. By utilizing the WHE-ZnO NZs as POD-like catalysts, we achieved a linear detection range of 1-1000 μM and a limit of detection of 0.24 μM (S/N = 3) for H2O2 detection and a linear range of 0-100 mM and a detection limit of 16.73 μM (S/N = 3) for glucose detection. These results highlighted the potential applications of our waste-to-resource approach for nanozyme synthesis in the field of analytical chemistry.

Emerging polymeric materials for treatment of oral diseases: design strategy towards a unique oral environment.

Oral diseases are prevalent but challenging diseases owing to the highly movable and wet, microbial and inflammatory environment. Polymeric materials are regarded as one of the most promising biomaterials due to their good compatibility, facile preparation, and flexible design to obtain multifunctionality. Therefore, a variety of strategies have been employed to develop materials with improved therapeutic efficacy by overcoming physicobiological barriers in oral diseases. In this review, we summarize the design strategies of polymeric biomaterials for the treatment of oral diseases. First, we present the unique oral environment including highly movable and wet, microbial and inflammatory environment, which hinders the effective treatment of oral diseases. Second, a series of strategies for designing polymeric materials towards such a unique oral environment are highlighted. For example, multifunctional polymeric materials are armed with wet-adhesive, antimicrobial, and anti-inflammatory functions through advanced chemistry and nanotechnology to effectively treat oral diseases. These are achieved by designing wet-adhesive polymers modified with hydroxy, amine, quinone, and aldehyde groups to provide strong wet-adhesion through hydrogen and covalent bonding, and electrostatic and hydrophobic interactions, by developing antimicrobial polymers including cationic polymers, antimicrobial peptides, and antibiotic-conjugated polymers, and by synthesizing anti-inflammatory polymers with phenolic hydroxy and cysteine groups that function as immunomodulators and electron donors to reactive oxygen species to reduce inflammation. Third, various delivery systems with strong wet-adhesion and enhanced mucosa and biofilm penetration capabilities, such as nanoparticles, hydrogels, patches, and microneedles, are constructed for delivery of antibiotics, immunomodulators, and antioxidants to achieve therapeutic efficacy. Finally, we provide insights into challenges and future development of polymeric materials for oral diseases with promise for clinical translation.

Ru-catalyzed activation of free phenols in a one-step Suzuki-Miyaura cross-coupling under mechanochemical conditions.

Activation of phenols by a Ru-catalyst allows for the resulting η5-phenoxo complex to selectively react with a variety of nucleophiles under mechanochemical conditions. Conversion of phenolic hydroxy groups without derivatization is important for late-stage modifications of pharmaceuticals and in the context of lignin-material processing. We present a one-step, Ru-catalyzed cross-coupling of phenols with boronic acids, aryl trialkoxysilanes and potassium benzoyltrifluoroborates under mechano-chemical conditions. The protocol accepts a wide scope of starting materials and allows for gram-scale synthesis in excellent yields. The developed approach constitutes a very interesting and waste-limiting alternative to the known methods.

Enhancing O2 resistance during storage and 2, 4-dichlorophenol degradation reaction of nano zero-valent iron by in-situ formation on the partially delignified stalk

Nano zero-valent iron (NZVI) as reductants for pollutant removal is commonly studied. Nevertheless, its poor resistance to O2 restricts its applicability, especially for polluted surface water bodies treatment. Here we proposed a method to enhance the O2 resistance of NZVI by in-situ synthesis on a partially delignified stalk (SS/Fe). Compared to NZVI, SS/Fe did not ignite when exposed to air pulse during preparation, possessed a 56.1 % higher remaining 2, 4-dichlorophenol degradation performance after 28-day air exposure, and degraded 2, 4-dichlorophenol in the presence of O2 with an equal efficiency to that under N2. The characterization and DFT results indicated that the residual lignin in the stalk played a key role in controlling the structure and O2 resistance of NZVI. Lignin in the stalk wrapped and anchored ∼ 2 nm NZVI forming a spherical particle of size 49 ± 21 nm which further aggregated forming a tertiary structure of size 790 ± 280 nm. During air exposure, the phenolic hydroxy and methoxy groups in lignin changed the reaction equilibrium among Fe0, Fe2+, and Fe3+ by reducing Fe3+ and acting as electron donors for Fe0 and Fe2+. During 2, 4-dichlorophenol degradation, the lignin wrapping resulted in superior adsorption of 2, 4-dichlorophenol on SS/Fe and a lower electron transfer path between 2, 4-dichlorophenol and SS/Fe compared with that of interaction between O2 and SS/Fe. This work provided a feasible method to facilitate the application of NZVI in treating polluted surface water bodies.

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups.

N-Acylhydrazones are a versatile class of organic compounds with a diversity of potential applications. In this study, two new structure-related 3,4,5-trimethoxybenzoyl-containing N-acylhydrazones were synthesized and fully characterized, both in solution and in the solid state. The compounds differ with respect to the carbonyl precursors, i.e., 3-substituted salicylaldehydes with either a methyl or a nitro group. Single crystals of both compounds were isolated from the respective mother liquors and, in both cases, XRD confirmed the obtention of the (E)-isomer, in an anti-conformation. Computational calculations (gas and water phases) were performed in order to confirm some of the structural and vibrational aspects of the compounds. An important intramolecular H bond involving the phenolic hydroxy group and the azomethine nitrogen was identified in the solid state and seems to be maintained in solution. Moreover, the presence of the electron-withdrawing nitro substituent makes this interaction stronger. However, the contact should probably not subsist for the nitro compound under physiological conditions since the presence of this substituent significantly affects the pKa of the phenol: an apparent value of 5.68 ± 0.02 was obtained. This also impacts the basicity of the azomethine nitrogen and, as a consequence, increases the hydrazone's susceptibility to hydrolysis. Nevertheless, both compounds are stable at physiological-like conditions, especially the methyl-derived one, which qualifies them for further toxicological and activity studies, such as those involving trivalent metal ions sequestering in the context of neurodegenerative diseases.

Insight into structure-activity relationships of hydroxycinnamic acids modified porous starch: The effect of phenolic hydroxy groups.

Antioxidant capacity of hydroxycinnamic acids-modified starch mainly depends on their chemical structure. Herein, cinnamic acid as well as meta-substituted and para-substituted cinnamic acid were selected for esterification with porous starch (labelled as CA@PS, m-CA@PS and p-CA@PS), with the successful formation of porous starch (labelled as PS) esters then confirmed by 1H NMR, 13C solid-state NMR and FT-IR spectroscopy. Three PS esters with almost same degrees of substitution (DS) were obtained, and antioxidant assays, including DPPH radical scavenging, reducing power and hydroxyl radical scavenging tests, were subsequently used to evaluate the antioxidant activity of the esterified PS. Overall, CA@PS showed weak antioxidant activity because of the absence of phenolic hydroxy, while p-CA@PS displayed better antioxidant capacity. Because its conjugated structure offered the stronger electron-donating effect, that could enhance antioxidant capacity. Therefore, antioxidant capacity depended significantly on overall chemical structure, including numbers and substitution positions of phenolic hydroxy groups.

Electrochemistry of Flavonoids: A Comprehensive Review.

Flavonoids represent a large group of aromatic amino acids that are extensively disseminated in plants. More than six thousand different flavonoids have been isolated and identified. They are important components of the human diet, presenting a broad spectrum of health benefits, including antibacterial, antiviral, antimicrobial, antineoplastic, anti-mutagenic, anti-inflammatory, anti-allergic, immunomodulatory, vasodilatory and cardioprotective properties. They are now considered indispensable compounds in the healthcare, food, pharmaceutical, cosmetic and biotechnology industries. All flavonoids are electroactive, and a relationship between their electron-transfer properties and radical-scavenging activity has been highlighted. This review seeks to provide a comprehensive overview concerning the electron-transfer reactions in flavonoids, from the point of view of their in-vitro antioxidant mode of action. Flavonoid redox behavior is related to the oxidation of the phenolic hydroxy groups present in their structures. The fundamental principles concerning the redox behavior of flavonoids will be described, and the phenol moiety oxidation pathways and the effect of substituents and experimental conditions on flavonoid electrochemical behavior will be discussed. The final sections will focus on the electroanalysis of flavonoids in natural products and their identification in highly complex matrixes, such as fruits, vegetables, beverages, food supplements, pharmaceutical compounds and human body fluids, relevant for food quality control, nutrition, and healthcare research.

Scandium-Catalyzed Phenol-Directed Construction of 5-Carbonyl-4-hydroxybenzofurans via Intramolecular Friedel-Crafts Reaction.

Herein we report a scandium-catalyzed regioselective synthesis of 5-carbonyl-4-hydroxybenzofurans via a phenol-directed intramolecular Friedel-Crafts reaction. This synthetic method was applied for the total synthesis of furanoflavones. Experimental studies and density functional theory calculations suggest that hydrogen bond interactions between the phenolic hydroxy group and the scandium complex realize regioselective intramolecular cyclization.

Phenolic Substitution in Fidaxomicin: A Semisynthetic Approach to Antibiotic Activity Across Species.

Fidaxomicin (Fdx) is a natural product antibiotic with potent activity against Clostridioides difficile and other Gram-positive bacteria such as Mycobacterium tuberculosis. Only a few Fdx derivatives have been synthesized and examined for their biological activity in the 50 years since its discovery. Fdx has a well-studied mechanism of action, namely inhibition of the bacterial RNA polymerase. Yet, the targeted organisms harbor different target protein sequences, which poses a challenge for the rational development of new semisynthetic Fdx derivatives. We introduced substituents on the two phenolic hydroxy groups of Fdx and evaluated the resulting trends in antibiotic activity against M. tuberculosis, C. difficile, and the Gram-negative model organism Caulobacter crescentus. As suggested by the target protein structures, we identified the preferable derivatisation site for each organism. The derivative ortho-methyl Fdx also exhibited activity against the Gram-negative C. crescentus wild type, a first for fidaxomicin antibiotics. These insights will guide the synthesis of next-generation fidaxomicin antibiotics.