Sumatranus lignans (SL) isolated from Cleistanthus sumatranus have demonstrated bioactivities, e.g., they were shown to exhibit immunosuppressive properties in previous research. Their structure suggests potential antioxidant activity that has not attracted any attention thus far. Consistently, a comprehensive analysis of the antioxidant activity of these compounds is highly desirable with the view of prospective medical applications. In this work, the mechanism and kinetics of the antiradical properties of SL against hydroperoxyl radicals were studied by using calculations based on density functional theory (DFT). In the lipid medium, it was discovered that SL reacted with HOO⢠through the formal hydrogen transfer mechanism with a rate constant of 101-105 M-1 s-1, whereas in aqueous media, the activity primarily occurred through the sequential proton loss electron transfer mechanism with rate constants of 102-108 M-1 s-1. In both lipidic and aqueous environments, the antiradical activity of compounds 6 and 7 exceeds that of resveratrol, ascorbic acid, and Trolox. These substances are therefore predicted to be good radical scavengers in physiological environments.
Syringic acid (SA) is a natural phenolic acid found in vegetables, fruits, and other plant-based foods. A range of biological activities were proposed for this compound including anticancer, antimicrobial, anti-inflammation, and anti-diabetic activities, as well as antioxidant and antinitrosant properties. In this study, the focus is on the latter two. The HOâ¢, HOOâ¢, NO, and NO2 scavenging activities of SA were evaluated in physiological environments by kinetic and thermodynamic calculations. The computed rate constants of the HO⢠radical scavenging of SA were 4.63 × 109 and 9.77 × 107 M-1 s-1 in polar and nonpolar solvents, respectively. A comparison with the experimentally determined rate constant in aqueous solution yields a kcalculated/kexperimental ratio of 0.3, thus the computed kinetic data are reasonably accurate. SA exhibited excellent HOO⢠and NO2 scavenging activity in water (koverall(HOOâ¢) = 1.53 × 108 M-1 s-1 and koverall(NO2) = 1.98 × 108 M-1 s-1), whereas it did not show NO scavenging activity in any of the studied environments. In lipid medium, SA exhibited weak activity. Thus, in polar environments, the HOO⢠radical scavenging of SA is 1.53 times higher than that of ascorbic acid. Consistently, SA is a promising antioxidant and antinitrosant agent in polar environments.
Antioxidants , Gallic Acid , Antioxidants/pharmacology , Free Radical Scavengers/pharmacology , Gallic Acid/analogs & derivatives , Gallic Acid/pharmacology , Kinetics
A novel coumarin derivative (5) was synthesized and used as a colorimetric and fluorescent probe for selective detection of Cu2+ ions in the presence of other metal ions, with the detection limits of 5.7 and 4.0 ppb, respectively. Cu2+ ion reacts with probe 5 to form a 1:1 stoichiometry complex, resulting in a remarkable redshift of absorption maximum from 460 to 510 nm, as well as almost completely quenching fluorescence intensity of probe 5 at the wavelength of 536 nm. These changes can be distinctly observed by naked eyes. In addition, the working pH range of probe 5 is wide and suitable for physiological conditions, thus probe 5 may be used for detection of Cu2+ ions in living cells. The stable structures of probe 5 and its 1:1 complex with Cu2+ ion were optimized at the PBE0/6-31+G(d) level of theory. The presence and characteristics of bonds in compounds were studied through atoms in a molecule and natural bond orbital analysis. The formation of the complex led to a strong transfer of electron density from probe 5 as a ligand to Cu2+ ion, resulting in breaking the π-electron conjugated system, which is the cause of fluorescence quenching and color change of 5-Cu2+ complex.
Hydralazine (HZ) and dihydralazine (DHZ) are phthalazine derivatives substituted at position 1 (HZ) or positions 1 and 4 (DHZ) by a hydrazinyl substituent. These compounds are widely used for treating hypertension and heart failure, essentially acting as vasodilators on the arteries and arterioles. In this study, the antioxidant activity of HZ and DHZ in the gas phase and in physiological environments was investigated by thermodynamic and kinetic calculations. It was found that the HOO⢠radical scavenging activity of these compounds follows the formal hydrogen transfer (FHT) mechanism. The H abstraction of the N9-H bond plays a deciding role in the HOO⢠radical scavenging of HZ-1 and DHZ-1, whereas the HOO⢠radical scavenging activities of HZ-2 and DHZ-2 are defined by the dissociation of the N10-H and N11-H bonds, respectively. The rate constants for the HOO⢠radical scavenging of the HZ and DHZ in the gas phase are in the range of 9.64 × 106 to 4.52 × 108 M-1 s-1, whereas in aqueous solutions and the lipid medium they are in the range of 2.62 × 104 to 5.13 × 107 M-1 s-1 and 5.75 × 104 to 6.66 × 106 M-1 s-1, respectively. The HOO⢠radical scavenging of DHZ-1 and DHZ-2 is thus faster than that of the reference antioxidant compound Trolox in all the studied environments. Consistently, DHZs are not only vasodilators but also potent antioxidants.
Depsidones are secondary metabolites in lichens with a range of potential health benefits. Among others, these compounds are believed to exhibit high hydroxyl radical and superoxide scavenging abilities, warranting a detailed investigation of their antioxidant properties. In this study, the radical scavenging activity of natural depsidones from Ramalina lichenized fungi was investigated in silico. Calculations of the thermodynamic parameters suggested that the main radical scavenging pathway follows the formal hydrogen transfer (FHT) mechanism; however, unexpectedly low rate constants were found in the CH3OO⢠scavenging reaction. Establishing that the depsidones are mostly ionized in an aqueous environment suggested that the single-electron transfer (SET) mechanism should not be ruled out. Consistently, depsidones were revealed to be excellent HO⢠and O2 â¢- scavengers in aqueous solutions (k = 4.60 × 105 - 8.60 × 109 M-1 s-1 and k = 2.60 × 108 - 8.30 × 109 M-1 s-1, respectively) following the sequential proton loss electron transfer (SPLET) mechanism. These results suggest that natural fungal depsidones are potent hydroxyl and superoxide radical scavengers in aqueous solutions.
The binding pose and affinity between a ligand and enzyme are very important pieces of information for computer-aided drug design. In the initial stage of a drug discovery project, this information is often obtained by using molecular docking methods. Autodock4 and Autodock Vina are two commonly used open-source and free software tools to perform this task, and each has been cited more than 6000 times in the last ten years. It is of great interest to compare the success rate of the two docking software programs for a large and diverse set of protein-ligand complexes. In this study, we selected 800 protein-ligand complexes for which both PDB structures and experimental binding affinity are available. Docking calculations were performed for these complexes using both Autodock4 and Autodock Vina with different docking options related to computing resource consumption and accuracy. Our calculation results are in good agreement with a previous study that the Vina approach converges much faster than AD4 one. However, interestingly, AD4 shows a better performance than Vina over 21 considered targets, whereas the Vina protocol is better than the AD4 package for 10 other targets. There are 16 complexes for which both the AD4 and Vina protocols fail to produce a reasonable correlation with respected experiments so both are not suitable to use to estimate binding free energies for these cases. In addition, the best docking option for performing the AD4 approach is the long option. However, the short option is the best solution for carrying out Vina docking. The obtained results probably will be useful for future docking studies in deciding which program to use.
Drug Design , Proteins/chemistry , Ligands , Molecular Docking Simulation , Protein Binding
Radical-scavenging activity of isorhamnetin (1) and its diglycosides, named isorhamnetin-3,5'-O-ß-D-diglucoside (2) and isorhamnetin-3,7-O-ß-D-diglucoside (3) extracted from Anoectochilus roxburghii, has been studied through three main antioxidant pathways: hydrogen atom transfer (HAT), single electron transfer followed by proton transfer, and sequential proton loss electron transfer (SPLET). All thermodynamic parameters related to these radical-scavenging mechanisms were computed at the B3LYP/6-311G(d,p) level of theory both in the gas phase and in solution. The results suggest that HAT is the predominant mechanism in the gas phase, while SPLET is supported in an aqueous environment. In addition, the stability of radicals has also been explored by electron spin density and intramolecular hydrogen bonding. The potential energy profiles and kinetic calculations for the reactions between the selected compounds and the CH3OO⢠radical were calculated at 298.15 K. Among all investigated, compound 2 has the highest antioxidant activity with the lowest Gibbs free energy (-4.05 kcal/mol) and the highest hydrogen atom transfer rate constant (3.61 × 105 M-1 s-1). Substitution of the OH and OMe groups by two glucoses at the 3 and 5' sites of isorhamnetin has a significant impact on its antioxidant activity.
A mercury sensor (N-(rhodamine-6G)lactam-ethylenediamine-4-dimethylamino-cinnamaldehyde-RLED) based on the Hg2+-promoted hydrolysis reaction has been designed and developed with a combination of theoretical calculations and experimental investigations. The interaction between RLED and Hg2+ goes through a fast-initial stage with formation of a 1:1 complex, followed by a slow hydrolysis process. The formation of durable intermediate complexes is due to quite a long hydrolysis reaction time. As a result, RLED can selectively detect Hg2+ in the presence of other metal ions, with a detection limit of 0.08 µM for the colorimetric method, and of 0.008 µM with the fluorescent method. In addition, the RLED sensor can work in a solution with a small amount of organic solvent, with a wide pH range from 5 to 10. The time-dependent density functional theory has been used for investigations of the excitation and de-excitation processes in RLED, intermediate complexes, and reaction products, thereby clarifying the changes in the fluorescence intensity before and after the RLED interacts with Hg2+ ions.
Oxidative stress is implicated in aging and aging-related diseases, including cancer. Prevention-focused health management approaches emphasize the importance of dietary antioxidants, which naturally draws attention to the antioxidant capacity of natural products. Several groups of plant-derived antioxidant compounds have been identified and their radical scavenging activity confirmed and measured; it has proven challenging, however, to link the experimentally determined activity quantitatively to a molecular mechanism of action. Based on our success with a computational approach, in this study, the methylperoxyl radical scavenging activity of 12 natural stilbenes was evaluated based on kinetic and thermodynamic calculations. The results suggest that for stilbenes hydrogen atom transfer (HAT) is a main mechanism for the ROOË radical scavenging in the gas. Assessing the role of substitutes on the antioxidant properties of stilbenes revealed that the presence of O-H groups in ring B can increase the antioxidant activity due to a decrease in the bond dissociation energy (BDE) of the O4'-H, while the replacement of a H atom in the O-H groups by a methyl group reduces the radical scavenging capacity. Among the studied compounds, astringin is a promising antioxidant with the low BDE(O-H) value (73.4 kcal mol-1) and the high rate constants (3.36 × 106, 4.11 × 103 and 9.31 × 108 M-1 s-1 in the gas phase, pentyl ethanoate and water, respectively) that suggest higher activity than trans-resveratrol.
Antioxidants are a diverse group of chemicals with proven health benefits and thus potential preventive medicine and therapeutic applications. While most of these compounds are natural products, determining their mechanism of radical scavenging and common motifs that contribute to antioxidant activity would allow the rational design of novel antioxidants. Here the origins of the antioxidant properties of ten natural products of the lignan family were studied in silico by calculating their thermochemical properties by using ROB3LYP/6-311++G(2df,2p)//B3LYP/6-311G(d,p) model chemistry. Three conditions were modelled: gas phase, ethanol and water solvents. The results allowed assigning the antioxidant activity to specific moieties and structural features of these compounds. It was found that the benzylic hydrogen atoms are the most likely to be abstracted to form radicals and hence define antioxidant properties in most of the studied compounds. The results also suggested that the most likely mechanism of HOO⢠radical scavenging differs by the key moiety: it is hydrogen atom transfer in case the benzylic C-H bonds, however it is proton coupled electron transfer in case of the compounds where O-H bonds are responsible for radical scavenging.
