DFT study of the mechanisms of nonenzymatic DNA repair by phytophenolic antioxidants.

Reactive oxygen species (ROS) can oxidize and thus damage DNA. Exposure to high levels of ROS is therefore linked with the development of severe illnesses such as cancer, diabetes, and coronary heart disease. Effective treatments for these diseases are yet to be found, despite intensive research. However, it is known that the natural nonenzymatic repair of DNA damage using phytophenols occurs more rapidly than the corresponding enzymatic repair process. Carvacrol, thymol, thymohydroquinone, and p-cymene-2,3-diol are strong natural antioxidant phytophenols that are found in medicinal plants. Their antioxidant activities, which involve reacting with and eliminating ROS before they reach and damage DNA, were studied in this work. Homolytic and heterolytic antioxidant mechanisms that allow these phytophenol antioxidants to eliminate the ROS .OH and .O2- in both vacuum and water (physiological environment) were investigated using density functional theory (DFT). The results showed that the homolytic mechanism is preferred in vacuum, whereas the heterolytic mechanisms are more probable in polar environments. In addition, the electronic properties of these phytophenols were studied and correlated with their antioxidant activities. It appears that these phytophenols can be used as antioxidants in vitro and in vivo to protect living systems from dangerous ROS. Graphical abstract Antioxidant reaction of carvacrol with OH. and .O-2 radicals.