Quantitative structure activity relationships of some pyridine derivatives as corrosion inhibitors of steel in acidic medium

Quantum chemical calculations using the density functional theory (B3LYP/6-31G* DFT) and semi-empirical AM1 methods were performed on ten pyridine derivatives used as corrosion inhibitors for mild steel in acidic medium to determine the relationship between molecular structure and their inhibition efficiencies. Quantum chemical parameters such as total negative charge (TNC) on the molecule, energy of highest occupied molecular orbital (E _HOMO), energy of lowest unoccupied molecular orbital (E _LUMO) and dipole moment (μ) as well as linear solvation energy terms, molecular volume (Vi) and dipolar-polarization (π*) were correlated to corrosion inhibition efficiency of ten pyridine derivatives. A possible correlation between corrosion inhibition efficiencies and structural properties was searched to reduce the number of compounds to be selected for testing from a library of compounds. It was found that theoretical data support the experimental results. The results were used to predict the corrosion inhibition of 24 related pyridine derivatives.     

Modulation of arachidonic acid metabolism by phenols: relation to their structure and antioxidant/prooxidant properties

The effects of substituted catechols (3-methylcatechol, 4-methylcatechol, 4-nitrocatechol, and guaiacol) and trihydroxybenzenes (pyrogallol, propyl gallate, 1,2,4-trihydroxybenzene, and 1,3,5-trihydroxybenzene) on the synthesis of prostaglandin (PG)E₂ and leukotriene (LT)B₄ were tested in human A23187-stimulated polymorphonuclear leukocytes. The effects were related to their peroxyl-radical-scavenging (antioxidant), superoxide-scavenging (antioxidant), and superoxide-generating (prooxidant) properties. In general, compounds with hydroxyl groups in the ortho position increased PGE₂/LTB₄ ratio, and compounds with hydroxyl groups in the meta position decreased PGE₂/LTB₄ ratio. Catechols, which have hydroxyl groups in the ortho position, were the most potent peroxyl radical and superoxide anion scavengers. Trihydroxybenzenes (pyrogallol, 1,2,4-trihydroxybenzene, and 1,3,5-trihydroxybenzene) generated superoxide, whereas dihydroxybenzenes did not. Thus, the positions and number of hydroxyl groups seem to be the most important properties determining the action of phenolic compounds on PGE₂/LTB₄ ratio and their antioxidant/prooxidant activities.     

An assessment to evaluate the validity of different methods for the description of some corrosion inhibitors

New research and development efforts using computational chemistry in studying an assessment of the validity of different quantum chemical methods to describe the molecular and electronic structures of some corrosion inhibitors were introduced. The standard and the highly accurate CCSD method with 6-311++G(d,p), ab initio calculations using the HF/6-31G++(d,p) and MP2 with 6-311G(d,p), 6-31++G(d,p), and 6-311++G(2df,p) methods as well as DFT method at the B3LYP, BP86, B3LYP*, M06L, and M062x/6-31G++(d,p) basis set level were performed on some triazole derivatives and sulfur containing compounds used as corrosion inhibitors. Quantum chemical parameters, such as the energy of the highest occupied molecular orbital energy (E_HOMO), the energy of the lowest unoccupied molecular orbital energy (E_LUMO), energy gap (ΔE), dipole moment (μ), sum of total negative charges (TNC), chemical potential (Pi), electronegativity (χ), hardness (η), softness (σ), local softness (s), Fukui functions (f ⁺,f ^?), electrophilicity (ω), the total energy change (?E_T) and the solvation energy (S.E), were calculated. Furthermore, the accuracy and the applicability of these methods were estimated relative to the highest accuracy and standard CCSD with 6-311++G(d,p) method. Good correlations between the quantum chemical parameters and the corresponding inhibition efficiency (IE%) were found.     

Decomposition of the interaction energy of several flavonoids with Escherichia coli DNA Gyr using the SAPT (DFT) method: The relation between the interaction energy components,ligand structure,and biological activity

In this study, the SAPT (DFT) method is used to determine the components of the electronic interaction energies (electrostatic (E_ele), exchange (E_ex), induction (E_ind), exchange-induction (E_ex-ind), dispersion (E_disp), and exchange-dispersion (E_ex-disp)) between the several selected flavonoids and the important residues of the active site of Escherichia coli DNA Gyr determined by molecular docking. A significant linear correlation between the calculated SAPT (DFT) interaction energies of flavonoids and their experimental pIC50 values is found, which is not observed for the free binding energies (ΔG_b) of flavonoids obtained from molecular docking. The variation of the interaction energy components of flavonoids with their structural differences is investigated to find the relation between the flavonoids structures and their biological activity based on the interaction energy components.     

Quantitative elucidation of the molecular mechanisms of hydroxyl radical quenching reactivity of phenolic compounds

Reported discrepancies have confused the understanding of the molecular mechanisms of antioxidant reactivity somewhat. The consequent problems necessitate systematic investigations on the molecular orbital features of antioxidants and their correlation with antioxidant potentials. In the present work, phenolic compounds as typical antioxidants were selected to investigate their hydroxyl radical-scavenging properties, and the related mechanisms of action were studied theoretically by computational chemistry. A good correlation was observed between antioxidant activity and theoretical parameters, such as O-H bond dissociation energy (BDE), ionization potential (IP), enthalpy of electron transfer (E(a)), chemical hardness (HOMO-LUMO gap), and spin delocalization of the phenoxyl radicals (D(s)(r)). The results demonstrate that the molecular mechanisms regulating the antioxidant action were more complex than hydrogen or electron-transfer processes and explain previous contradictions. Meanwhile, a satisfactory quantitative structure-activity relationship (QSAR) model was established which should be of predictive value in evaluating or screening hydroxyl radical-scavenging antioxidants.     

Characterization of plant phenolic compounds by cyclic voltammetry

Phenolic acids and flavonoids were characterized by cyclic voltammetry and total antioxidant activity in the reaction with the ABTS cation radical. Anode peak voltages (E_ap) and their pH dependences were determined for the studied phenolic acids and flavonoids. The E_ap and Trolox equivalent antioxidant capacity (TEAC) values were found to correlate for polyphenols, which react with the ABTS cation radical in two steps. Correlation between the half-wave potential (E_1/2) and TEAC was determined for electrochemically irreversible compounds. Mechanisms of the reaction of phenolics on the electrode involving one-and two-electron oxidation are proposed.     

Hydroxyl radical scavenging activity of flavonoids

The flavonoids scavenge hydroxyl (^.OH) radicals generated by UV photolysis of hydrogen peroxide. Free ^.OH radicals were spin-trapped by 5,5-dimethyl-1-pyrroline N-oxide and the adduct was detected by high pressure liquid chromatography coupled with an electrochemical detector. The scavenging activity of flavonoids decreases in the order: myricetin > quercetin > rhamnetin > morin > diosmetin > naringenin > apigenin > catechin >5,7- dihydroxy -3′,4′,5′-trimethoxyflavone > robinin > kaempferol > flavone. The activity increases with the number of hydroxyl groups substituted in the aromatic B-ring. The presence of a hydroxyl at C-3 and its glycosylation does not further increase scavenging efficiency. It is suggested that the overall antioxidant effect of flavonoids on lipid peroxidation may be due to their ^.OH and O·⁻₂ scavenging properties and the reaction with peroxy radicals.     

Estrogen A-ring structure and antioxidative effect on lipoproteins

The oxidative modification of lipoprotein particles is an important step in atherogenesis. Estrogens are known to be powerful antioxidants independently of their binding to the estrogen receptors and the hormonal functions. We explored the structural determinants for the antioxidant activity of a large number of estrogen derivatives (n=43) in an aqueous lipoprotein solution in vitro by monitoring formation of conjugated dienes. Our results indicate that estrogen derivatives with an unsubstituted A-ring phenolic hydroxyl group with one or two adjacent methoxy groups provide strongest antioxidant protection of low density lipoprotein (LDL) and high density lipoprotein (HDL). The electron donating methoxy groups may enhance the antioxidant effect by weakening the phenolic OH bond and providing stability to the formed phenoxyl radical. With some exceptions, compounds completely lacking unsubstituted hydroxyl groups in the A-ring exhibited no antioxidant effect, e.g. the most hydrophilic "tetrol" compound with three unsubstituted A-ring hydroxyl groups had no antioxidant effect. Moreover, additional hydroxyl groups in the B-, C- or D-ring seemed to weaken the antioxidant effect. Accordingly, both the presence of unsubstituted hydroxyl groups and adjacent substituents, as well as the lipophilicity of the derivatives determine the antioxidant activity of estrogen derivatives in aqueous lipoprotein solutions.     

Flavonoids and Melanins: A Common Strategy across Two Kingdoms

Ultraviolet (UV) radiations alter a number of metabolic functions in vivant. They produce damages to lipids, nucleic acids and proteins, generating reactive oxygen species such as singlet oxygen (O₂), hydroxyl radical (HO) and superoxide anion (O₂^-). Plants and animals, after their water emersion, have developed biochemical mechanisms to protect themselves from that environmental threat through a common strategy. Melanins in animals and flavonoids in plants are antioxidant pigments acting as free radical scavenging mechanisms. Both are phenol compounds constitutively synthesized and enhanced after exposure to UV rays, often conferring a red-brown-dark tissue pigmentation.Noteworthy, beside anti-oxidant scavenging activity, melanins and flavonoids have acquired secondary functions that, both in plants and animals, concern reproductions and fitness. Plants highly pigmented are more resistant to biotic and abiotic stresses. Darker wild vertebrates are generally more aggressive, sexually active and resistant to stress than lighter individuals. Flavonoids have been associated with signal attraction between flowers and insects and with plant-plant interaction. Melanin pigmentation has been proposed as trait in bird communication, acting as honest signals of quality.This review shows how the molecular mechanisms leading to tissue pigmentation have many functional analogies between plants and animals and how their origin lies in simpler organisms such as Cyanobacteria. Comparative studies between plant and animal kingdoms can reveal new insight of the antioxidant strategies in vivant.     

Synthesized different derivatives of low molecular fucoidan extracted from Laminaria japonica and their potential antioxidant activity in vitro

Six low molecular fucoidan (DFPS) derivatives were synthesized successfully, and their potential antioxidant activities were investigated employing various established in vitro systems. All DFPS derivatives possessed considerable antioxidant activity, and had stronger antioxidant ability than DFPS in certain tests. The benzoylated DFPS (PHDF) showed strongest scavenging activity on superoxide, hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, however, DFPS exhibited greatest reducing power. Available data suggested that substituted groups of DFPS played an important role on antioxidant activity, and the mechanism on influence the antioxidant activity of samples of substituted group was indicated.     

Synthesis of N-benzyl substituted 1,4-imino-l-lyxitols with a basic functional group as selective inhibitors of Golgi α-mannosidase IIb

Inhibition of the biosynthesis of complex N-glycans in the Golgi apparatus is one of alternative ways to suppress growth of tumor tissue. Eight N-benzyl substituted 1,4-imino-l-lyxitols with basic functional groups (amine, amidine, guanidine), hydroxyl and fluoro groups were prepared, optimized their syntheses and tested for their ability to inhibit several α-mannosides from the GH family 38 (GMIIb, LManII and JBMan) as models for human Golgi and lysosomal α-mannoside II. All compounds were found to be selective inhibitors of GMIIb. The most potent structure bearing guanidine group, inhibited GMIIb at the micromolar level (K_i = 19 ± 2 µM) while no significant inhibition (>2 mM) of LManII and JBMan was observed. Based on molecular docking and pK_a calculations this structure may form two salt bridges with aspartate dyad of the target enzyme improving its inhibitory potency compared with other N-benzyl substituted derivatives published in this and previous studies.     

Enzyme-assisted modification of flavonoids from Matricaria chamomilla: antioxidant activity and inhibitory effect on digestive enzymes

Abstract

Matricaria chamomilla L. contains antioxidant flavonoids that can have their bioactivity enhanced by enzymatic hydrolysis of specific glycosyl groups. This study implements an untargeted metabolomics approach based on ultra-performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry technique operating in MS^E mode (UPLC-QTOF-MS^E) and spectrophotometric analysis of chamomile aqueous infusions, before and after hydrolysis by hesperidinase and β-galactosidase. Several phenolic compounds were altered in the enzymatically treated infusion, with the majority being flavonoid derivatives of apigenin, esculetin, and quercetin. Although enzymatically modifying the infusion only led to a small increase in antioxidant activity (DPPH? method), its inhibitory effect on pancreatic lipase was of particular interest. The enzymatically treated infusion exhibited a greater inhibitory effect (EC₅₀ of 35.6?µM) than unmodified infusion and kinetic analysis suggested mixed inhibition of pancreatic lipase. These results are of great relevance due to the potential of enzymatically treated functional foods in human health.     

Effect of structure on antibiotic action of new 9-(ethylthio)acridines

Six new 9-(ethylthio)acridine derivatives were examined for antibacterial and antifungal activities with 10 bacterial and 8 yeast strains. The only active compounds were 2-and 3-amino derivatives. The observed MICs (mg/L) for 2-amino-9-(ethylthio)acridine (possessing the highest biological activity) were 12 (P. mirabilis), 30 (B. subtillis), 60 (C. freundii), 90 (E. coli), 128 (E. vulneris) and 500 (S. marcescens andS. aureus). Both amino derivatives have also lowest half-wave potential (E _1/2) and field Swain-Lupton constants (describing oxidoreduction behavior) what supports the importance of acridine ion formation in the mechanism of antimicrobial action.     

Antioxidant properties of Aloe vera components: a DFT theoretical evaluation

Prediction of the antioxidant activity of three Aloe vera components (aloesone, aloe-emodin, and isoeleutheol) was performed based on density functional theory calculations using the B3LYP hybrid functional and the 6–311++ G** basis set. Calculation of highest occupied molecular orbital (HOMO), lowest occupied molecular orbital (LUMO), and E_gap revealed that aloe-emodin has the lowest E_gap value, indicating good antioxidant activity. Also in terms of electron affinity, softness, electrophilicity, and chemical potential, aloe-emodin is a potent structure with potential high radical scavenging activity. Calculation of the ionisation potential revealed that isoeleutherol likely also possesses a high degree of antiradical scavenging. To study the conjugating system of the radicals, density plots of HOMO, natural bond orbital analyses, and spin density plots were used. According to calculations, the isoeleutherol radical is more delocalised and the most stable radical. Calculated proton affinity values revealed that the most probable antioxidant mechanism is sequential proton loss-electron transfer. Our results were compared with available experimental data. Published experimental data were found to correlate well with our theoretical predictions. These results support the usefulness of theoretical calculations not only for identifying potentially useful structures of studied compounds but also for predicting their relative activity.     

Potential therapeutic antioxidants that combine the radical scavenging ability of myricetin and the lipophilic chain of vitamin E to effectively inhibit microsomal lipid peroxidation

The flavonol myricetin, reacts with oxygen-centred galvinoxyl radicals 28 times faster than d-alpha-tocopherol (vitamin E), the main lipid-soluble antioxidant in biological membranes. Moreover, each myricetin molecule reduces twice as many such radicals as vitamin E. However, myricetin fails to protect vitamin E-deficient microsomes from lipid peroxidation as assessed by the formation of thiobarbituric acid reactive substances (TBARS). Novel and potentially therapeutic antioxidants have been prepared that combine the radical-scavenging ability of a myricetin-like head group with a lipophilic chain similar to that of vitamin E. C(6)-C(12) alkyl chains are attached to the A-ring of either a 3,3',4',5'-tetrahydroxyflavone or a 3,2',4',5'-tetrahydroxyflavone head group to give lipophilic flavonoids (C log P = 4 to 10) that markedly inhibit iron-ADP catalysed oxidation of microsomal preparations. Orientation of the head group as well as total lipophilicity are important determinants of antioxidant efficacy. MM2 models indicate that our best straight chain 7-alkylflavonoids embed to the same depth in the membrane as vitamin E. The flavonoid head groups are prepared by aldol condensation followed by Algar-Flynn-Oyamada (AFO) oxidation or by Baker-Venkataraman rearrangement. The alkyl tails are introduced by Suzuki or Negishi palladium-catalysed cross-coupling or by cross-metathesis catalysed by first generation Grubbs catalyst, which tolerate phenolic hydroxyl and ketone groups.     

In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones—Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles

The 1,2,4‐triazole and its derivatives were reported to exhibit various pharmacological activities such as antimicrobial, analgesic, anti‐inflammatory, antitumoural, cytotoxic, and antioxidant properties. In this study, a series of triazole compounds (M1‐M10) were evaluated for some biological activities. In vitro qualifications of these compounds on acetylcholinesterase (AChE) and human carbonic anhydrase enzyme activities were performed. Also, their antitumoral activities in human colon cancer (HT29) cell line cultures were examined. In addition, colon cancer experimentation was induced in rats by an in vivo method, and the in vivo anticancer effects of triazole derivatives were investigated. Also, the effects of these derivatives in levels of antioxidant vitamin A, vitamin E, and MDA were studied in rat liver and blood samples. Most of the compounds were found to exhibit significant antioxidant and antitumoral activities. All the compounds had cytotoxic activities on HT29 cell lines with their IC₅₀ values lower than 10 µM concentrations. The low IC ₅₀ values of the compounds are M1 (3.88 µM), M2 (2.18 µM), M3 (4.2 µM), M4 (2.58 µM), M5 (2.88 µM), M6 (2.37 µM), M7 (3.49 µM), M8 (4.01 µM), M9 (8.90 µM), and M10 (3.12 µM).     

Structure–Activity Relationships for Antioxidant Activities of a Series of Flavonoids in a Liposomal System

Structurally diverse plant phenolics were examined for their abilities to inhibit lipid peroxidation induced either by Fe(II) and Fe(III) metal ions or by azo-derived peroxyl radicals in a liposomal membrane system. The antioxidant abilities of flavonoids were compared with those of coumarin and tert-butylhydroquinone (TBHQ). The antioxidant efficacies of these compounds were evaluated on the basis of their abilities to inhibit the fluorescence intensity decay of an extrinsic probe, 3-(p-(6-phenyl)-1,3,5-hexatrienyl)phenylpropionic acid (DPH-PA), caused by the free radicals generated during lipid peroxidation. All the flavonoids tested exhibited higher antioxidant efficacies against metal-ion-induced peroxidations than peroxyl-radical-induced peroxidation, suggesting that metal chelation may play a larger role in determining the antioxidant activities of these compounds than has previously been believed. Distinct structure–activity relationships were also revealed for the antioxidant abilities of the flavonoids. Presence of hydroxyl substituents on the flavonoid nucleus enhanced activity, whereas substitution by methoxy groups diminished antioxidant activity. Substitution patterns on the B-ring especially affected antioxidant potencies of the flavonoids. In cases where the B-ring could not contribute to the antioxidant activities of flavonoids, hydroxyl substituents in an catechol structure on the A-ring were able to compensate and become a larger determinant of flavonoid antioxidant activity.     

Effect of Vitamin E and Its Analogues Having Various Molecular Structures on the Growth and Lipid Composition of Pythium debaryanum

The effect of exogenously added vitamin E and its synthetic analogues (the hydrophilic form of vitamin E and chromans C₁₃and C₁) at a concentration of 9.86 × 10^–5M on the growth, lipogenic activity, and the fatty acid composition of the eicosapolyenoic acid–synthesizing oomycete Pythium debaryanumwas studied. The effect was found to depend on the molecular structure of particular compounds. For instance, vitamin E and chroman C₁₃stimulated fungal growth, whereas chroman C₁inhibited it. The hydrophilic form of vitamin E enhanced the lipogenic activity of the oomycete. The studied compounds, which possess antioxidant activity, did not exert any noticeable effect on the content of eicosapolyenoic acids and the degree of the unsaturation of fungal lipids.