Structure-Antioxidant Activity Relationships in a Series of NO-Donor Phenols (original) (raw)
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Quantum chemical QSAR study of flavones and their radical-scavenging activity
Medicinal Chemistry Research, 2007
Flavonoid antioxidants act as scavengers of free radicals by rapid donation of a hydrogen atom. This quantitative structure-activity relationship (QSAR) study of flavones was carried by using selected quantum chemical descriptors. PM3 calculations performed by MOPAC 2000 associated with Cache pro. Molecular weight, dielectric energy (kcal/mole), total energy (Hartree), heat of formation (kcal/mole), highest unoccupied molecular orbital (HOMO) energy (eV), lowest unoccupied molecular orbital (LUMO) energy (eV), log P, molar refractivity (MR), hardness (g), softness (S), chemical potential (l), electrophilicity index (x), etc. were tested as descriptors, and various QSAR models were constructed. The best-fit model (r 2 CV ¼ 0:92; r 2 ¼ 0:96) involved heat of formation, log P, MR, and molecular weight. The overall study indicates that steric bulk and solvation are mainly responsible for the radical scavenging activity of flavones.
Structure-Radical Scavenging Activity Relationships of Flavonoids
Croatica Chemica Acta
The relationship between the structural characteristics of 29 flavonoids and their antiradical activity was studied. The obtained results suggest that the free radical scavenger potential of these polyphenolic compounds closely depends on the particular substitution pattern of free hydroxyl groups on the flavonoid skeleton. The possible mechanism of action of flavonoids lacking B ring OHs as free radical scavengers has been proposed.
Structure–property studies on the antioxidant activity of flavonoids present in diet
Free Radical Biology and Medicine, 2005
The screening of natural flavonoids for their bioactivity as antioxidants is usually carried out by determinination of their profile as chainbreaking antioxidants, by the evaluation of their direct free radical-scavenging activity as hydrogen-or electron-donating compounds. Since this may not be the only mechanism underlying the antioxidant activity it is important to check the ability of these compounds to act as chelators of transition metal ions. Accordingly, in the present study the acidity constants of catechin and taxifolin, as well as the formation constants of the corresponding copper (II) complexes, were investigated by potentiometry and/or spectrophotometry. Moreover, a detailed quantitative examination of the coordination species formed is presented. In addition, the partition coefficients of both catechin and taxifolin in a biomimetic system (micelles) were determined, since these properties may also contribute to the antioxidant behavior of this type of compound. The log P values determined depend on the electrostatic interactions of the compounds with the differently charged micelles (the highest values were obtained for zwitterionic and cationic micelles). The prooxidant behavior of the compounds was assessed through the oxidation of 2V-deoxyguanosine, induced by a Fenton reaction, catalyzed by copper. The data obtained reveal that the flavonoids under study did not present prooxidant activity, in this particular system. The results obtained are evidence of a clear difference among the pK a , the complexation properties, and the lipophilicity of the flavonoids studied, which can partially explain their distinct antioxidant activity. The most stable geometries of the free compounds were determined by theoretical (ab initio) methods, in order to properly account for the electron correlation effects which occur in these systems, thus allowing a better interpretation of the experimental data.
Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships
The Journal of Nutritional Biochemistry, 2002
Flavonoids are a class of secondary plant phenolics with significant antioxidant and chelating properties. In the human diet, they are most concentrated in fruits, vegetables, wines, teas and cocoa. Their cardioprotective effects stem from the ability to inhibit lipid peroxidation, chelate redox-active metals, and attenuate other processes involving reactive oxygen species. Flavonoids occur in foods primarily as glycosides and polymers that are degraded to variable extents in the digestive tract. Although metabolism of these compounds remains elusive, enteric absorption occurs sufficiently to reduce plasma indices of oxidant status. The propensity of a flavonoid to inhibit free-radical mediated events is governed by its chemical structure. Since these compounds are based on the flavan nucleus, the number, positions, and types of substitutions influence radical scavenging and chelating activity. The diversity and multiple mechanisms of flavonoid action, together with the numerous methods of initiation, detection and measurement of oxidative processes in vitro and in vivo offer plausible explanations for existing discrepancies in structure-activity relationships. Despite some inconsistent lines of evidence, several structureactivity relationships are well established in vitro. Multiple hydroxyl groups confer upon the molecule substantial antioxidant, chelating and prooxidant activity. Methoxy groups introduce unfavorable steric effects and increase lipophilicity and membrane partitioning. A double bond and carbonyl function in the heterocycle or polymerization of the nuclear structure increases activity by affording a more stable flavonoid radical through conjugation and electron delocalization. Further investigation of the metabolism of these phytochemicals is justified to extend structure-activity relationships (SAR) to preventive and therapeutic nutritional strategies. .
On the antioxidant properties of three synthetic flavonols
Die Pharmazie, 2007
The antioxidant properties of a series of synthetic and natural flavonoids towards the oxygenated species superoxide radical anion (O 2 .-) enzimatically generated, were evaluated. 7-Hydroxyflavonol, 7,3 0-dihydroxyflavonol and 3 0-hydroxyflavonol were synthesised, with a systematic variation of the OH substitution on positions C3, C7, C3 0 and C4 0 , and their respective antioxidative abilities compared to those of the already characterised natural flavonoids quercetin, kaempferol and rutin. The efficiency of O 2 .-deactivation by the flavonoids does not correlate with their respective determined oxidation potentials, suggesting that the pure one-electron-transfer-mechanism of O 2 .-quenching could not be the main scavenging process involved. Experimental evidence demonstrated that the possible inhibition of the O 2 .-generator enzymatic system by the flavonoids must be disregarded as a possible indirect cause for the inhibition of the oxidative species. One possible mechanism for the inhibition of O 2 .-, highly dependent on the substitution pattern of the flavonoid, may be the generation of hydroperoxides or dioxetanes as oxidation products, as already postulated for other biologically relevant compounds. The simultaneous OH-substitution on positions C3 and C7 of the flavonoid skeleton plays a definitive role in the enhancement of the O 2 .-inhibitory effect. The replacement of OH by a O-rutinosyl group on position C7 suppresses at all that effect, whereas the absence of an OH group in position 7 significantly reduces the antioxidative power. Finally, the presence of OH groups on positions 3 0 and 4 0 does not produce any determinant effect in the antioxidative behaviour of the flavonoids.
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences, 2015
The recent advances in the field of computational data production and analyses have made it easier to formulate the relationship involved between physiological properties of chemical compounds and their structures. Flavonoids are one such group of plant products that are known for exhibiting strong anti-oxidant properties owing to their radical scavenging nature. These properties establish them as important anti-cancer compounds along with being anti-bacterial, antifungal, anti-viral and anti-allergic molecules. This study aims at establishing a quantitative structure activity relationship between flavonoid structure and their anti-oxidant property. A number of molecular descriptors were calculated namely, SdsCHE-index, MMFF_2, MMFF_6, chi1, XcompDipole, T_O_O_6, MMFF_5, ?vePotentialSurfaceArea, and MMFF_29 which were chosen to build the model to elucidate crucial structural features that enhance or decrease this property. A statistically robust QSAR model was obtained with an r 2 value of 0.8765, cross validation coefficient, q 2 value of 0.7189 and pred_r 2 value of 0.5795, well above the threshold. The selected descriptors and their contribution to the regression model indicate towards the respective properties that they denote. A decrease in positively charged surface area, a high dipole moment, high number of aromatic carbon atom distribution signifies the importance of unsaturated rings, and hydroxyl groups etc. enhance the anti-oxidant activity. Thus, the present study and thus induce understanding of the structural properties of flavonoids that influence their physiological properties.
Structure–antioxidant activity relationships of flavonoids isolated from different plant species
Food Chemistry, 2005
Anti-DPPH radical effect as well as anti-peroxide activity of o-hydroxyl, o-methoxy, and alkyl ester derivatives of p-hydroxybenzoic acid in a bulk fish oil system and its O/W emulsion were investigated. Electronic phenomena, intra-and/or intermolecular hydrogen bonds, interfacial properties, and chemical reaction of the solvent molecules with phenolic compounds were considered to be mainly involved in the antiradical activities observed. Antioxidant activity of the phenolic acids derivatives as a function of these factors was variously affected by the environmental conditions which may occur in practice.
Protection of Flavonoids Against Lipid Peroxidation: The Structure Activity Relationship Revisited
Free Radical Research, 2014
The inhibition of the lipid peroxidation, induced by iron and ascorbate in rat liver microsomes, by phenols and flavones was studied. The activity of phenol was enhanced by electron donating substituents, denoted by the Hammett sigma (s ). The concentration of the substituted phenols giving 50% inhibition (IC 50 ) of lipid peroxidation gave a good correlation with the s of the substituent ðlnð1=IC 50 Þ ¼ 28:92s þ 5:80 ðR ¼ 0:94; p , 0:05ÞÞ: In flavones two pharmacophores for the protection against lipid peroxidation were pinpointed: (i) a catechol moiety as ring B and (ii) an OH-group at the 3 position with electron donating groups at the 5 and/or 7 position in the AC-ring. An example of a flavone with the latter pharmacophore is galangin (3,5,7-trihydroxyflavone) where the reactivity of the 3-OH-group is enhanced by the electron donating effect of the 5-and 7-OH-groups. This is comparable to the effect of electron donating substituents on the activity of phenol.
Journal of Molecular Modeling, 2015
Radical scavenging potential is the key to antioxidation of hydroxyflavones which generally found in fruits and vegetables. The objective of this work was to investigate the influence of hydroxyl group on the O-H bond dissociation enthalpies (BDE) from a series of mono-and dihydroxyflavones. Calculation at the B3LYP/6-31G(d,p) level reveals the important roles of an additional one hydroxyl group to boost the BDE of hydroxyflavones that were a stabilization of the generated radicals through attractive H-bond interactions, an orthoand paradihydroxyl effect, and a presence of the 3-OH in dihydroxyflavones. On the other hand, the meta-dihydroxyl effect and range-hydroxyl effect especially associated with the either 5-OH or 8-OH promoted greater BDE. Results did not only confirm that dihydroxyflavones had lower BDE than monohydroxyflavones but also suggest the selective potent hydroxyflavone molecules that are the 6′-hydroxyflavone (for monohydroxyflavone) and the 5′,6′-, 7,8-and 3′,4′dihydroxyflavone which the corresponding radical preferable generated at C6′-O•, C8-O• and C4′-O•, respectively. Electron distribution was limited only over the two connected rings of hydroxyflavones while the expansion distribution into C-ring could be enhanced if the radical was formed especially for the 2′,3′-and 5′,6′dihydroxyflavone radicals. The delocalized bonds were strengthened after radical was generated. However the 5-O• in 5,6-dihydroxyflavone and the 3-O• in 3,6′-dihydroxyflavone increased the bond order at C4-O11 which might interrupt the conjugated delocalized bonds at the keto group.
Analysis of Conformational, Structural, Magnetic, and Electronic Properties Related to Antioxidant Activity: Revisiting Flavan, Anthocyanidin, Flavanone, Flavonol, Isoflavone, Flavone, and Flavan-3-ol, 2021
Understanding the antioxidant activity of flavonoids is important to investigate their biological activities as well as to design novel molecules with low toxicity and high activity. Aromaticity is a chemical property found in cyclic structures that plays an important role in their stability and reactivity, and its investigation can help us to understand the antioxidant activity of some heterocyclic compounds. In the present study, we applied the density functional theory (DFT) to investigate the properties of seven flavonoid structures with well-reported antioxidant activity: flavan, anthocyanidin, flavanone, flavonol, isoflavone, flavone, and flavan-3-ol. Conformational, structural, magnetic, and electronic analyses were performed using nuclear magnetic resonance, ionization potentials, electron affinity, bond dissociation energy, proton affinity, frontier molecular orbitals (highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO)), and aromaticity through nucleusindependent chemical shifts to analyze these seven flavonoid structures. We revised the influence of hydroxyl groups on the properties of flavonoids and also investigated the influence of the aromaticity of these seven flavonoids on the antioxidant activity.