Hydroxyl Group In Ortho Position Research Articles

Selecting phenolics by means of thermodynamics for scavenging free radicals in camellia oil induced by heating

Phenolics have been employing as promising scavengers for free radicals, theoretical calculation is a convenient method for selecting excellent phenolics. In this study, the efficiencies of 33 phenolics scavenging free radicals were confirmed by means of Bond Dissociation Enthalpy (BDE) of active group and Gibbs Free Energy Change (ΔG) of scavenging reaction computed by Quantum Chemical Calculations. Ultimately, the preferable phenolics were picked out for scavenging free radicals in camellia oil induced by heating. These phenolics scavenged free radicals via Hydrogen Atom Transfer (HAT) mechanism. Specifically, (−)-epigallocatechin gallate (EGCG), myricetin and piceatannol performed the top-ranking efficiencies in camellia oil under 120 °C for 50 min, with the inhibition ratios of 75.7 ± 4.1%, 72.9 ± 5.4% and 69.4 ± 11.0%, respectively. The results indicated that the efficiencies of phenolics were predominantly affected by the amount of hydroxyl groups attached to aromatic ring and the BDE of O−H bond. In phenolic acids, the hydroxyl group in ortho-position of the active site was in favor of reinforcing the efficiency. In flavonoids, the hydroxyl group in B-ring and the functional groups of C2=C3 and 4-carbonyl in C-ring were prone to elevating the efficiency.

Lipid peroxidation inhibition study: A promising case of 1,3-di([1,1′-biphenyl]-3-yl)urea

In the present study eighteen inhibitors of the hydrolytic enzymes of the endocannabinoid system were investigated for antioxidant activity using lipid peroxidation (LP) method. Among the assayed compounds ten belong to carbamates with phenyl [1,1′-biphenyl]-3-ylcarbamate (6), reported for the first time, and eight are retro-amide derivatives of palmitamine. Interestingly, results indicated that most of the tested compounds have good antioxidant properties. In particular, 1,3-di([1,1′-biphenyl]-3-yl)urea (3) shows IC50 = 26 ± 6 μM comparable to ones obtained for standard antioxidants trolox and quercetin (IC50 = 22 ± 6 μM and 23 ± 6 μM, respectively). Compound 3 was investigated further by means of DFT calculations, to clarify a possible mechanism of the antioxidant action. In order to estimate the capability of 3 to act as radical scavenger the structure was optimized at B3LYP/6–311++G** level and the respective bond dissociation enthalpies were calculated. The calculations in non-polar medium predicted as favorable mechanism a donation of a hydrogen atom to the free radical and formation of N-centered radical, while in polar solvents the mechanism of free radical scavenging by SPLET dominates over HAT H-abstraction. The possible radical scavenging mechanisms of another compound with potent antioxidant properties (IC50 = 53 ± 12 μM), the retro-amide derivative of palmitamine (compound 18), was estimated computationally based on the reaction enthalpies of a model compound (structural analogue to 18). The computations indicated that the most favorable mechanisms are hydrogen atom transfer from the hydroxyl group in meta-position of the benzamide fragment in nonpolar medium, and proton transfer from the hydroxyl group in ortho-position of the benzamide fragment in polar medium.

Synthesis of selected 3- and 4-arylcoumarin derivatives and evaluation as potent antioxidants

A series of hydroxyl-, methoxy-, and acetoxy-substituted 3- and 4-arylcoumarins were synthesized. All title compounds were screened for their antioxidant capacity, ability to scavenge the 1,1-diphenyl-1-picrylhydrazyl (DPPH) radical, and ability to chelate iron ions. Furthermore, all derivatives were assessed using molecular properties prediction and drug likeness using Molinspiration. It was found that all studied derivatives were potential candidates for further research, as they complied with Lipinski’s rule of five for drug likeness. 3- or 4-arylcoumarins that possess two hydroxyl groups in ortho position, such as 4h, 5b, h, and 6a, had remarkable half-maximal effective concentration (EC50) for radical scavenging, with better performance than known antioxidants in DPPH and metal-chelating assays. In addition, the cupric-reducing antioxidant capacity and ferric-reducing antioxidant power of the synthesized compounds were investigated for antioxidant activity. Among them, 5g, h and 6a, b showed significantly better Trolox equivalent antioxidant capacity (TEAC) than standard compounds. The results demonstrate that the compounds with dihydroxyl groups at 6- and 7-positions of the benzopyrone ring of the arylcoumarin structure are the most active of the series as antioxidants. On the basis of these findings, these new coumarin derivatives are potential therapeutic candidates for pathogenesis of many diseases characterized by free-radical overproduction.

Action of ellagic acid on the melanin biosynthesis pathway

BackgroundTyrosinase is an enzyme involved in the first steps of the melanogenesis process. It catalyzes the hydroxylation of monophenols to o-diphenols and the oxidation of the latter to o-quinones. Ellagic acid (EA) is a phenolic compound which has been described as a tyrosinase inhibitor and is used in the cosmetic industry as a whitening agent. However, it has hydroxyl groups in ortho position and could act as a substrate rather than inhibitor. This aspect should be taken into consideration when using this compound as a cosmetic ingredient due to the reactive character of o-quinones. ObjectiveTo determine whether ellagic acid is a substrate or an inhibitor of tyrosinase, to characterize it kinetically and interpret its role in the melanogenesis process. MethodsUV–vis spectrophotometry was used to follow the action of tyrosinase on typical substrates and ellagic acid. A chronometric method was chosen for the kinetic characterization of ellagic acid. ResultsEllagic acid is not an inhibitor per se but an alternative substrate of tyrosinase. It is oxidized by the enzyme to an unstable o-quinone. Its kinetic characterization provided low Michaelis and catalytic constants (KMEA=138±13μM and kcatEA=0.47±0.02s−1). Furthermore, ellagic acid, which is a powerful antioxidant, may chemically reduce the o-quinones (o-dopaquinone) and semiquinones, in this way inhibiting the melanogenesis. ConclusionEllagic acid is oxidized by tyrosinase, producing reactive o-quinones. As an antioxidant it can inhibit the melanogenesis process. This first aspect should be taken into consideration in its application as a cosmetic ingredient due to the toxicity of o-quinones and its ability to modify the redox status of the cell.

Antioxidant and antitumor activities of 4-arylcoumarins and 4-aryl-3,4-dihydrocoumarins

Five 4-arylcoumarins (1c-g) and twelve 3,4-dihydro-4-arylcoumarins (2a-l) were synthesized and tested for antioxidant activity, antitumor activity, toxicity and structure-activity relationships analysis. 4-Arylcoumarins and 3,4-dihydro-4-arylcoumarins that possess two hydroxyl groups in ortho position, such as 1d, 1f, 2a, 2f, 2g and 2h had stronger radical scavenging properties than that of vitamin C (Vit C) in ABTS(+) assay. Kinetic traces of scavenging ABTS(+) and DPPH radicals showed that all the reaction could reached endpoint in 1min, which was similar with Vit C. 4-Arylcoumarins with 3'-hydroxyl-4'-methylphenyl structural show more efficient NO radical scavenging activity. Three compounds 2e, 1f and 2a, in particular had superior EC50 for NO scavenging than did Vit C. MTT assay indicated that one compound in particular had a potential antitumor effect, inhibiting proliferation of BGC-823 cells and almost completely killing them at a concentration 62.5mg/L. With same concentration 100μg/mL, hemolytic analysis in rabbit red blood cells showed that only two compounds had hemolytic activity with a little more than 5% hemolysis. Injection and oral toxicity tests on Galleria mellonella larvae showed that none of the tested 4-arylcoumarins significantly affected their appetite, viability and mortality.

Enhanced electrochemical response of structurally related antioxidant at nanostructured hybrid films

In this work, the redox behaviour of structurally related antioxidants, such as catechol, hydroxycinnamic acid and flavonoid derivatives, has been investigated at electrode surfaces modified with different gold nanoparticles (AuNPs)–chitosan films. Our findings demonstrate that the chemical structural features of the antioxidants play a key role in the interaction with modified electrodes that strongly affect the electrochemical response. In particular, a better response was observed for molecules with two hydroxyl groups in ortho position of the catechol ring and with a low steric hindrance. However, the redox behaviour cannot be explained only on these bases, since the nanostructure and surface functional groups of AuNPs–chitosan modified electrodes have also to be considered. The presence of interconnected metal nanoparticles into chitosan film strongly affects the electron transfer properties, whereas the surface functional groups can promote the interaction with selected antioxidants acting as scavenger. The understanding of the key factors that affect the electrochemical response of antioxidants at electrode surface modified with nanostructured hybrid films is a key issue and could significantly contribute to the development of highly efficient electrochemical sensors.

Expression pattern and substrate specificity of Clonorchis sinensis tyrosinases

Tyrosinase (TYR) is a copper-containing glycoenzyme that mediates hydroxylation of tyrosine into dihydroxyphenylalanine and oxidation of dihydroxyphenylalanine into dihydroxyphenylalanine quinone. TYRs play pivotal roles in eggshell sclerotisation of trematode parasites, while their comprehensive biochemical properties remain elusive. We characterised genes encoding four TYRs (CsTYR1–4) of Clonorchis sinensis, a causative agent of human hepatobiliary disease. These genes shared tightly conserved amino acid residues, two copper binding catalytic motifs and a cysteine-rich epidermal growth factor-like domain. The native and recombinant CsTYRs showed high reactivity against diphenol compounds, especially those with hydroxyl groups in ortho-positions (catechol and l-dihydroxyphenylalanine), but showed minimal activity toward monophenol compounds. Diphenolase activity was enhanced by increased pH of the reaction buffer from 5.0 to 7.0. The temporal induction of CsTYR expression coordinated with the sexual maturation of the worm; enzyme activity was mainly in the vitelline glands and intrauterine immature eggs proximal to the ovary. The primary structures and functional domains of CsTYRs showed significant similarities to those of the vertebrate orthologs, whereas the amino acids shared with the nematode and insect proteins were largely restricted in the bicopper active center. Unlike highly diverged TYR homologs in vertebrates, multiple paralogs have not yet evolved into the separate lineages in trematode genomes, suggesting that duplication of TYR genes might relate to increased genic dosage/redundancy in trematodes. In vitro treatment of copper chelator, diethyldithiocarbamic acid, inhibited generation of phenotypically normal egg. TYR proteins are essential for C. sinensis reproduction, thus might be targeted for therapeutic and vaccine strategies against clonorchiasis, which is prevalent in several Asian countries and is one of the most important predisposing factors for human cholangiocarcinoma. The close phylogenetic relationships between trematode and vertebrate homologs also provide a molecular clue to understand the multifaceted evolutionary pathway of TYR homologs across animal taxa.

Blue color, metal content, and substrate binding in 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. strain P. J. 874.

Purified preparations of 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. strain P. J. 874 are blue, epsilon 595-850 approximately 2.6 +/- 0.5 (n = 6) mM-1 cm-1. Iron and zinc were the only metals detected by x-ray fluorescence of an enzyme preparation and the mean content in different preparation as determined by atomic absorption spectroscopy was determined by atomic absorption spectroscopy was 0.95 +/- 0.17 (n = 6) and 0.68 +/- 0.27 (n = 7) mol/mol 150-kilodalton tetramer, respectively. It is yet unclear if zinc is a contaminant or may be given a structural role. Results with iron chelators and reductants showed that the 595-nm absorbance is linked to enzyme-bound Fe3+ and that reduction of iron, which occurs concomitantly with disappearance of the color, is required for enzyme activity. The enol tautomer of 4-hydroxyphenylpyruvate appeared to form 2:1 a complex with enzyme-bound Fe3+, which may be the cause of the long known substrate inhibition of the enzyme. Iron chelation also seemed to be involved in the inhibition by other substrate analogues, i.e. substituted catechols and those with one phenolic hydroxyl group in ortho position to short carboxylic acid side chains. Together, substrate analogue, pH, and modification studies indicated that the tautomerizable keto group with a double bond in 3-4 position favors productive substrate binding to Fe2+ and a base with a pK alpha of approximately 6.4.

Studies on the hydrazone derivatives in fluorometric analysis. III. Relationships between fluorescence development of hydrazone derivatives, formation of its fluorescent metal complexes and their structures (author's transl)

Examination of a relationship between chemical structure and fluorescence characteristics in 37 hydrazones showed that the presence of a carbonyl group of >CONH- and hydroxyl group in ortho-position of -N=CH- are necessary for the strong fluorescence. With some of 2-hydroxy-1-naphthaldehyde hydrazones derived from various acid hydrazides, formation of a fluorescent complex with metal ions was examined by a spot test. Complexes of Al3+, Sc3+, Ga3+, and Zr4+ exhibited fluorescence in acetic acid solutions. In Al or Sc complexes of 2-hydrbxy-1-naphthaldehyde benzoic acid hydrazone, carbonyl group, hydroxyl group, and nitrogen atom of -N=CH- were considered to be concerned in chelate formation.