Study On The Molecular Design, Synthesis And Antioxidation Activity Of Ferulic Acid Derivatives

Ferulic acid has biological activity in antioxidation, anti-tumor, anti-lipoperoxidation and anti-aging. Ferulic acid exists widely in many medicinal plants with limited resources cause the content is very low, it can not meet the demands of the market, so the synthesis of ferulic acid and its derivatives has become one of research hot spots. The theoretical calculation of quantum chemistry can study the relationship between the structure and antioxidant activities, which can reduce the blindness on screening structures of antioxidant, so it can serve as theoretical guidance on researching and developing new antioxidant.The structure, infrared, raman and1H/13C-NMR spectra of ferulic acid were calculated using density functional theory (B3LYP) and Hartree-Fock method. Based on this, we designed six series(twenty-six compounds) ferulic acid derivatives whose precursor structure was ferulic acid, the optimized geometries of neutral, radical, radical cation forms of ferulic acid and its derivatives were obtained. The two main working mechanism—H atom donation and single-electron trasfer were investigated, and the O-H bond dissociation enthalpy(BDE) and ionization potential(IP) were computed in gas phase. Five compounds of the1st serie were synthetized, and their antioxidant activities were measured experimentally by DPPH. Through the combination of experimental and the theoretical research, structure-activity relationship were analysed and many important conclusions were obtained as follows:(1)The computational results of ferulic acid showed that the structure optimized by B3LYP and HF were in substantial agreement, the main atoms and benzene ring created a conjugated system. The frequencies calculated by HF were10%higher than B3LYP, the vibrational modes of ferulic acid in DFT calculation were assigned and compared with the experimental datas from SDBS database, the calculated results were in good agreement with the experimental results. The caculated and experiment chemical shift of1H/13C-NMR existed some errors, the hydrogen bonding may bring big errors of1H-NMR, and13C-NMR had smaller errors than1H-NMR. Overall, the caculated and experiment results had good consistency, this suggested that DFT(B3LYP) and HF can effectively predict the structure of ferulic acid. (2)The computational results of series of ferulic acid derivatives showed that the introduction of withdrawing groups on the moleculars increased both BDE and IP,the electron-donating groups showed the oppsite effect,however the acetyl group showed opposite qualities in two working mechanism,the order of BDE was FA一3>FA一2> FA一5>FA一1>FA一4>FA一6>FA一7>FA-11. and the order of IP was FA一2>FA一5>FA一3> FA一4>FA-1>FA-7>FA-6>FA-11. BDE and IP decreased with the extension of ester chain. the order of BDE and IP was FA一1>FA一22>FA一23>FA一24>FA一25>FA-26. The BDE and IP increased with the introduction of groups with lone pairs of electrons on benzene ring,the order of BDE was FA一1>FA-8>FA一7>FA一10>FA一9,and the order of IP was FA一1>FA一7>FA一8>FA-9>FA一10. The extended conjugate chain in molecular decreased BDE and IP. the order of BDE and IP was FA-18>FA-1>FA-17. The introduction of hydroxy group, alkyl group and ester group on the end chain decreased BDE and IP,and aldehyde group and carboxyl group increased BDE and IP,the order of BDE and IP was FA-19>FA-l>FA-22>FA-20>FA-21. The introduction of ether on the side-chain decreased BDE and IP,however the length of ether had little influence on BDE and IP. he order of BDE and IP was FA-1>FA-14>FA-15>FA-16>FA-17> FA-18>FA-19.The antioxidant activities increased as the decreasing of BDE and IP.(3)5-bromovanillin and5-nitrovanillin were syntheSized using vanilla as raw material,the knoevenagel condensation of vanilla,5一bromovanillin,5一nitrovanillin, syringaldehyde and3一Methoxybenzaldehyde with malonate acid respectively giving products of corresponding ferulic acid and its derivatives,their production rate were about55％-75％, the structure had been determined by1H-NMR.(4)Antioxidant activities of ferulic acid and its derivatives were determined by DPPH·.The IC50of scavenging DPPH pf FA-1,FA-5,FA-2and FA-11were33.15,55.24,1802,23.66μmol·L-1, their order of capability of scavenging DPPH were FA-11>FA-1>FA-5>FA-2>FA-27,which showed phenolic hydroxyl group was the most important activity groups of antioxidant,the introduction of withdrawing groups on the moleculars decreased the activities of antioxidants,while the electron-donating groups showed the oppsite effect.The experimental results were in agreement with the computational results, which showed DFT can effectively disclose the relationship between molecular structure and antioxidant activities of ferulic acid and its derivatives,and played a significant role in synthesis and perfomance analysis of antioxidant.