Radiation Physics and Chemistry 60 (2001) 345–350 Reactions of reducing and oxidizing radicals with caffeic acid: a pulse radiolysis and theoretical study Xifeng Li, Zhongli Cai, Yosuke Katsumura*, Guozhong Wu, Yusa Muroya Nuclear Engineering Research Laboratory, The Graduate School of Engineering, The University of Tokyo, 2-22 Shirakata Shirane, Tokai-mura, Naka-gun, Ibaraki 319-1106, Japan Abstract Molecular calculations coupled with pulse radiolysis studies are performed to understand the reactions of radicals with caffeic acid. From molecular calculation, we find that e  aq and  OH tend to form adducts with caffeic acid, while N  3 tends to abstract H from 4-hydroxyl group in benzene ring, generating a semi-quinoid radical. Based on comparison of the heat of formation, the most favorable radical attack sites and the most stable radical structures are predicted. The calculation results suggest that the stability of the electron adducts 5semi-quinoid radicals 5  OH adducts of caffeic ions, in good agreement with their experimental second-order decay rate constants (2k¼ð1:1  0:2Þ 10 9 , (6.0  0.4)  10 7 and (2.0  0.2)  10 7 M 1 s 1 , respectively), determined by pulse radiolysis. Molecular calculations seem to be a powerful tool to predict the stability and structures of transient radicals. # 2001 Elsevier Science Ltd. All rights reserved. Keywords: Caffeic acid; Free radical; Pulse radiolysis; Molecular orbital calculation 1. Introduction Radical reactions, especially with participation of oxidative radical, have been known to be involved in many biological processes that cause damage to lipids, proteins, membranes and DNA or result in carcinogenesis (Pryor, 1987). Compounds such as phenolic acid and flavonoids can scavenge oxidative radicals, thus reduce the possible damages. Such antioxidant properties have caused a great interest on their research. Caffeic acid (3,4-dihydroxy cinnamic acid) is one of the phenolic acids that widely exists in fruits, wine, tea, coffee and olive oil, etc. (Ho, 1992). It has been demonstrated to be able to scavenge super- oxide, peroxyl and hydroxyl radicals (Kono et al., 1997; Wang et al., 1993; Facino et al., 1995), lipid alkoxyl radical (Milic et al., 1998) and nitronium ions (Pannala et al., 1998; Kerry and Rice-Evans, 1998). Some researches also demonstrated its prooxidant activities, such as enhancement of dopa oxidation (Takahama, 1997), auto-oxidization to form superoxide and direct reduction of Fe(III) to Fe(II) (Odnick et al., 1988). All the antioxidant or prooxidant activities involve radical reactions. A major concern in medicinal application of antioxidants is the possible side effects caused by products resulted from radical reactions. Thus, it is important to know the details of radical reaction as well as possible structures of final products. Recently, Lien et al. (1999) has reported a quantitative analysis of phenolic antioxidants using calculation methods. They used AM1 semi-empirical method to obtain heat of formation (H f ) and energy (E homo , E lumo ) of antioxidant radicals, and found some correlation between antioxidant activities and calculated parameters. They derived a model to calculate the redox potentials of phenolic compounds based on the parameters such as H f , E lumo and number of the OH group. *Corresponding author. Tel.: +81-3-5841-6979; fax: +81-3- 5841-8624. E-mail address: katsu@q.t.u-tokyo.ac.jp (Y. Katsumura). 0969-806X/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved. PII:S0969-806X(00)00404-7