Abnormal solvent effects on hydrogen atom abstraction. 2. Resolution of the curcumin antioxidant controversy. The role of sequential proton loss electron transfer.
The rates of reaction of 1,1-diphenyl-2-picrylhydrazyl (dpph*) radicals with curcumin (CU, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), dehydrozingerone (DHZ, "half-curcumin"), and isoeugenol (IE) have been measured in methanol and ethanol and in two non-hydroxylic solvents, dioxane and ethyl acetate, which have about the same hydrogen-bond-accepting abilities as the alcohols. The reactions of all three substrates are orders of magnitude faster in the alcohols, but these high rates can be suppressed to values essentially equal to those in the two non-hydroxylic solvents by the addition of acetic acid. The fast reactions in alcohols are attributed to the reaction of dpph* with the CU, DHZ, and IE anions (see J. Org. Chem. 2003, 68, 3433), a process which we herein name sequential proton loss electron transfer (SPLET). The most acidic group in CU is the central keto-enol moiety. Following CU's ionization to a monoanion, ET from the [-(O)CCHC(O)-](-) moiety to dpph* yields the neutral [-(O)CCHC(O)-]* radical moiety which will be strongly electron withdrawing. Consequently, a phenolic proton is quickly lost into the alcohol solvent. The phenoxide anion so formed undergoes charge migration to produce a neutral phenoxyl radical and the keto-enol anion, i.e., the same product as would be formed by a hydrogen atom transfer (HAT) from the phenolic group of the CU monoanion. The SPLET process cannot occur in a nonionizing solvent. The controversy as to whether the central keto-enol moiety or the peripheral phenolic hydroxyl groups of CU are involved in its radical trapping (antioxidant) activity is therefore resolved. In ionizing solvents, electron-deficient radicals will react with CU by a rapid SPLET process but in nonionizing solvents, or in the presence of acid, they will react by a slower HAT process involving one of the phenolic hydroxyl groups.
Litwinienko
Grzegorz
G
National Research Council, Ottawa, Ontario, Canada K1A 0R6. litwin@chem.uw.edu.pl
Ingold
K U
KU
D000975:Antioxidants / Q000737:chemistry* / Q000493:pharmacokinetics; D001713:Biphenyl Compounds; D003474:Curcumin / Q000737:chemistry* / Q000493:pharmacokinetics; D004579:Electron Transport; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010851:Picrates / Q000737:chemistry / Q000493:pharmacokinetics; D011522:Protons
D000975:Antioxidants; D001713:Biphenyl Compounds; D010851:Picrates; D011522:Protons; C004931:1,1-diphenyl-2-picrylhydrazyl; D003474:Curcumin