Antioxidant action of deprotonated flavonoids: Thermodynamics of sequential proton-loss electron-transfer

2020 ◽  
Vol 180 ◽  
pp. 112528 ◽  
Author(s):  
Monika Biela ◽  
Ján Rimarčík ◽  
Erika Senajová ◽  
Andrea Kleinová ◽  
Erik Klein
Keyword(s):  
Electron Transfer ◽  
Antioxidant Action ◽  
Proton Loss

scholarly journals Non-Linear Quantitative Structure–Activity Relationships Modelling, Mechanistic Study and In-Silico Design of Flavonoids as Potent Antioxidants

2019 ◽  
Vol 20 (9) ◽  
pp. 2328 ◽  
Author(s):  
Petar Žuvela ◽  
Jonathan David ◽  
Xin Yang ◽  
Dejian Huang ◽  
Ming Wah Wong
Keyword(s):  
Electron Transfer ◽  
Antioxidant Activities ◽  
Qsar Model ◽  
Quantitative Structure ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Non Linear ◽  
Quantitative Structure Activity Relationships ◽  
Mean Square Errors ◽  
Proton Loss

In this work, we developed quantitative structure–activity relationships (QSAR) models for prediction of oxygen radical absorbance capacity (ORAC) of flavonoids. Both linear (partial least squares—PLS) and non-linear models (artificial neural networks—ANNs) were built using parameters of two well-established antioxidant activity mechanisms, namely, the hydrogen atom transfer (HAT) mechanism defined with the minimum bond dissociation enthalpy, and the sequential proton-loss electron transfer (SPLET) mechanism defined with proton affinity and electron transfer enthalpy. Due to pronounced solvent effects within the ORAC assay, the hydration energy was also considered. The four-parameter PLS-QSAR model yielded relatively high root mean square errors (RMSECV = 0.783, RMSEE = 0.668, RMSEP = 0.900). Conversely, the ANN-QSAR model yielded considerably lower errors (RMSEE = 0.180 ± 0.059, RMSEP1 = 0.164 ± 0.128, and RMSEP2 = 0.151 ± 0.114) due to the inherent non-linear relationships between molecular structures of flavonoids and ORAC values. Five-fold cross-validation was found to be unsuitable for the internal validation of the ANN-QSAR model with a high RMSECV of 0.999 ± 0.253; which is due to limited sample size where resampling with replacement is a considerably better alternative. Chemical domains of applicability were defined for both models confirming their reliability and robustness. Based on the PLS coefficients and partial derivatives, both models were interpreted in terms of the HAT and SPLET mechanisms. Theoretical computations based on density functional theory at ωb97XD/6-311++G(d,p) level of theory were also carried out to further shed light on the plausible mechanism of anti-peroxy radical activity. Calculated energetics for simplified models (genistein and quercetin) with peroxyl radical derived from 2,2′-azobis (2-amidino-propane) dihydrochloride suggested that both SPLET and single electron transfer followed by proton loss (SETPL) mechanisms are competitive and more favorable than HAT in aqueous medium. The finding is in good accord with the ANN-based QSAR modelling results. Finally, the strongly predictive ANN-QSAR model was used to predict antioxidant activities for a series of 115 flavonoids designed combinatorially with flavone as a template. Structural trends were analyzed, and general guidelines for synthesis of new flavonoid derivatives with potentially potent antioxidant activities were given.

scholarly journals pH Effect and Chemical Mechanisms of Antioxidant Higenamine

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2176 ◽  
Author(s):  
Yulu Xie ◽  
Xican Li ◽  
Jingyu Chen ◽  
Yuman Deng ◽  
Wenbiao Lu ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Proton Transfer ◽  
Ph Effect ◽  
Reducing Power ◽  
Chemical Mechanism ◽  
Antioxidant Action ◽  
Ic50 Values ◽  
Reducing Power Assay ◽  
Dpph Scavenging ◽  
Tof Ms

In this article, we determine the pH effect and chemical mechanism of antioxidant higenamine by using four spectrophotometric assays: (1) 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical (PTIO•)-scavenging assay (at pH 4.5, 6.0, and 7.4); (2) Fe3+-reducing power assay; (3) Cu2+-reducing power assay; and (4) 1,1-diphenyl-2-picryl-hydrazyl (DPPH•)-scavenging assay. The DPPH•-scavenging reaction product is further analyzed by ultra-performance liquid chromatography, coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) technology. In the four spectrophotometric assays, higenamine showed good dose-response curves; however, its IC50 values were always lower than those of Trolox. In UPLC-ESI-Q-TOF-MS/MS analysis, the higenamine reaction product with DPPH• displayed three chromatographic peaks (retention time = 0.969, 1.078, and 1.319 min). The first gave m/z 541.2324 and 542.2372 MS peaks; while the last two generated two similar MS peaks (m/z 663.1580 and 664.1885), and two MS/MS peaks (m/z 195.9997 and 225.9971). In the PTIO•-scavenging assays, higenamine greatly decreased its IC50 values with increasing pH. In conclusion, higenamine is a powerful antioxidant—it yields at least two types of final products (i.e., higenamine-radical adduct and higenamine-higenamine dimer). In aqueous media, higenamine may exert its antioxidant action via electron-transfer and proton-transfer pathways. However, its antioxidant action is markedly affected by pH. This is possibly because lower pH value weakens its proton-transfer pathway via ionization suppression by solution H+, and its electron-transfer pathway by withdrawing the inductive effect (-I) from protonated N-atom. These findings will aid the correct use of alkaloid antioxidants.

Antioxidants and radical damage in a hydrophilic environment: chemical reactions and concepts

2019 ◽  
Vol 64 (1) ◽  
pp. 67-74 ◽  
Author(s):  
Thomas Nauser ◽  
Janusz M. Gebicki
Keyword(s):  
Oxidative Stress ◽  
Electron Transfer ◽  
Reaction Mechanisms ◽  
Large Fraction ◽  
Radical Reaction ◽  
Antioxidant Action ◽  
Transfer Processes ◽  
Endogenous Antioxidants ◽  
Electron Transfer Processes ◽  
Radical Damage

Abstract Known endogenous antioxidants are unlikely to prevent radical damage due to oxidative stress or achieve complete repair by established reaction mechanisms. While near complete prevention seems very unrealistic, some of the initial damage can be repaired. Depending on tissue, this may be even a large fraction. Antioxidants, however, will efficiently break radical reaction chains and, therefore, certainly limit the damage caused by radicals. It is not clear if chemical antioxidant action is strictly limited to electron-transfer processes or if additional reaction mechanisms may contribute.

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