title: Extraordinary radical scavengers: 4-mercaptostilbenes.
abstract: In the past decade, there was a great deal of interest and excitement in developing more active antioxidants and cancer chemoprevention agents than resveratrol, a naturally occurring stilbene. In this work, eight resveratrol-directed 4-mercaptostilbenes were constructed based on the inspiration that thiophenol should be a stronger radical scavenger than phenol, and their reaction rates with galvinoxyl (GO(.)) and 2,2-diphenyl-1-picrylhydrazyl (DPPH(.)) radicals in methanol and ethyl acetate were measured by using stopped-flow UV/Vis spectroscopy at 25 °C. Kinetic analysis demonstrates that 4-mercaptostilbenes are extraordinary radical scavengers, and the substitution of the 4-SH group for the 4-OH group in the stilbene scaffold is an important strategy to improve the radical-scavenging activity of resveratrol. Surprisingly, in methanol, some of the 4-mercaptostilbenes are 10(4)-times more active than resveratrol, dozens of times to hundreds of times more effective than known antioxidants (α-tocopherol, ascorbic acid, quercetin, and trolox). The detailed radical-scavenging mechanisms were discussed based on acidified-kinetic analysis. Addition of acetic acid remarkably reduced the GO(.) and DPPH(.) radical-scavenging rates of the 4-mercaptostilbenes in methanol, a solvent that supports ionization, suggesting that the reactions proceed mainly through a sequential proton loss electron transfer mechanism. In contrast, an interesting acid-promoted kinetics was observed for the reactions of the 4-mercaptostilbenes with DPPH(.) in ethyl acetate, a solvent that weakly supports ionization. The increased ratio in rates is closely correlated with the electron-rich environment in the molecules, suggesting that the acceleration could benefit from the contribution of the electron transfer from the 4-mercaptostilbenes and DPPH(.). However, the addition of acetic acid had no influence on the GO(.)-scavenging rates of the 4-mercaptostilbenes in ethyl acetate, due to the occurrence of the direct hydrogen atom transfer. Our results show that the radical-scavenging activity and mechanisms of 4-mercaptostilbenes depends significantly on the molecular structure and acidity, the nature of the attacking radical, and the ionizing capacity of the solvent.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou 730000, PR China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Cao
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Dai
authors.forename: De-Jun
authors.initials: DJ
authors.lastname: Ding
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Kang
authors.forename: Fu
authors.initials: F
authors.lastname: Wang
authors.forename: Xiu-Zhuang
authors.initials: XZ
authors.lastname: Li
authors.forename: Guo-Yun
authors.initials: GY
authors.lastname: Liu
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Yu
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Jin
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D001713:Biphenyl Compounds; D002839:Chromans / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry; D015394:Molecular Structure; D010851:Picrates; D000077185:Resveratrol; D012997:Solvents / Q000737:chemistry; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D024505:Tocopherols / Q000737:chemistry
chemical_list: D000975:Antioxidants; D001713:Biphenyl Compounds; D002839:Chromans; D016166:Free Radical Scavengers; D010851:Picrates; D012997:Solvents; D013267:Stilbenes; D013438:Sulfhydryl Compounds; C004931:1,1-diphenyl-2-picrylhydrazyl; D000077185:Resveratrol; D024505:Tocopherols; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000432:Methanol