Investigating Antioxidant Mechanism Of Phenolic Compounds And Exploring A Suitable Way To Synthesis Novel Antioxidant

Reactive oxygen species play an important role in the origin of life and biological evolution. However, excess mount of Reactive oxygen species can oxidate biomolecular and cause many diseases. Experimental results find that antioxidant is helpful to cure those diseases by scavenging free radical. Thus, evaluating and developing novel antioxidant is one of the hot topic recently.In this study, a simple method is built to evaluate the protection of antioxiant on DNA damage caused by hydroxyl radical. However, it is difficult for experiment methods to describe the change of antioxidant in free radical scavenging process, and the theoretical method, especial density functional theory method, is another better choice because it is a useful tool used to simulate the reaction process.The density functional theory method is used to explore the antioxidant mechanism of butein and violacein. In order to analyze their antioxidant properties, the ionization potential (IP), the bond dissociation energy (BDE), the highest occupied molecular orbital (HOMO), and the spin density have been calculated. The calculated results reveal that the antioxidant mechanism of the butein corresponds to its H-atom transfer, and that the B-ring of the butein has a strong hydrogen-donated ability and the 4-OH is the active site with the lowest BDE. The calculated results also show that the butein can serve as a powerful antioxidant against DPPH radical, and that the reaction mechanism was described in detail. On the basis of the calculated BDE, one finds that the butein is a more effective antioxidant than the a-tocopherol. For violacein, it has a strong electron donating ability, but a weak hydrogen atom transfer ability. While its coplanar isomers have a strong hydrogen atom transfer ability as well as electron donating ability. The N7-H7 band plays an important role in violacein's antioxidant activity.The geometries of M²⁺-butein complexes (M²⁺=Mg²⁺, Fe²⁺, Cu²⁺ and Cr²⁺) have been investigated by using density functional density theory to explore the interaction between metal cation and butein, and to give a insight into the chelate mechanism of butein on metal cations. The natural bond orbital (NBO) has also been calculated to analyze the charge transfer in the complexes. The results find that the oxygen atoms of 2' and 9 position are the favored coordination sites for all divalent metal cations involved in this study. The sequence of binding strength is Cu²⁺> Cr²⁺>Fe²⁺>Mg²⁺. In the lowest energy Cu²⁺-butein complex, more charge transfers from butein ligend to Cu atom. In addition, the lowest energy Cu²⁺-butein complex has the lowest HOMO-LUMO gap compared with other lowest energy M²⁺-butein complexes.Recently, some ortho hydroxy-amino coumarin derivatives have been synthesized and demonstrated to have stronger antioxidant activity than the ortho dihydroxy coumarin derivatives and a-tocopherol. Some theoretical and experimental results reveal that the amino group will decrease the BDE and IP of phenol, especially ortho amino group. Therefore, the ortho hydroxy-amino group may be another choice for synthesizing novel antioxidants because a low BDE or IP means a higher antioxidant activity. In order to testify our hypothesize, four ortho hydroxy-amino derivatives have been designed based on the structures of flavonoids to explore the effect of the ortho hydroxy-amino group on the antioxidant properties of molecules, and their bond dissociation enthalpies (BDE), ionization potentials (IP), the highest occupied molecular orbitals (HOMO), and spin densities have been calculated. The results reveal that the ortho hydroxy-amino group plays an important role in promoting the antioxidant properties of molecules because of its lowering effect on BDE and IP. The derivatives with ortho hydroxy-amino group show stronger antioxidant activity than the derivatives with mono hydroxy or ortho dihydroxy group. Thus, the ortho hydroxy-amino group can be used as another potential functional group to synthesize novel antioxidants as guessed.The promoting effect of heterocyclic ring and heteroatom on the antioxidant properties of vitamin E has been investigated systemically by using density functional theory method. The calculated results show that the heteroatom plays a more important role in promoting the antioxidant properties than the heterocyclic ring, indicating that replacing O atom by S or Se is impossible to synthesize the novel better antioxidants. Furthermore, the bond dissociation enthalpy (BDE) and ionization potential (IP) of the corresponding molecules are decreased dramatically when the O atom is replaced by NH. In addition, the calculated results reveal that reducing the atom number of heterocyclic ring is an ideal way to synthesize novel antioxidants with better antioxidant activity than vitamin E.