Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin

K.I. Priyadarsini, D.K. Maity, G.H. Naik, M.S. Kumar, M.K. Unnikrishnan, J.G. Satav, H. Mohan

Research output: Contribution to journalArticle

371 Citations (Scopus)

Abstract

To understand the relative importance of phenolic O-H and the CH-H hydrogen on the antioxidant activity and the free radical reactions of Curcumin, (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione), biochemical, physicochemical, and density functional theory (DFT) studies were carried out with curcumin and dimethoxy curcumin (1,7-bis[3, 4-dimethoxy phenyl]-1,6-heptadiene-3,5-dione). The antioxidant activity of these compounds was tested by following radiation-induced lipid peroxidation in rat liver microsomes, and the results suggested that at equal concentration, the efficiency to inhibit lipid peroxidation is changed from 82% with curcumin to 24% with dimethoxy curcumin. Kinetics of reaction of (2,2′-diphenyl-1- picrylhydrazyl) DPPH, a stable hydrogen abstracting free radical was tested with these two compounds using stopped-flow spectrometer and steady state spectrophotometer. The bimolecular rate constant for curcumin was found to be ∼1800 times greater than that for the dimethoxy derivative. Cyclic voltammetry studies of these two systems indicated two closely lying oxidation peaks at 0.84 and 1.0 V vs. SCE for curcumin, while only one peak at 1.0 V vs. SCE was observed for dimethoxy curcumin. Pulse radiolysis induced one-electron oxidation of curcumin and dimethoxy curcumin was studied at neutral pH using •N3 radicals. This reaction with curcumin produced phenoxyl radicals absorbing at 500 nm, while in the case of dimethoxy curcumin a very weak signal in the UV region was observed. These results suggest that, although the energetics to remove hydrogen from both phenolic OH and the CH 2 group of the β-diketo structure are very close, the phenolic OH is essential for both antioxidant activity and free radical kinetics. This is further confirmed by DFT calculations where it is shown that the -OH hydrogen is more labile for abstraction compared to the -CH2 hydrogen in curcumin. Based on various experimental and theoretical results it is definitely concluded that the phenolic OH plays a major role in the activity of curcumin. © 2003 Elsevier Inc.
Original languageEnglish
Pages (from-to)475-484
Number of pages10
JournalFree Radical Biology and Medicine
Volume35
Issue number5
DOIs
Publication statusPublished - 2003

Fingerprint

Free radical reactions
Curcumin
Free Radicals
Hydrogen
Antioxidants
Lipid Peroxidation
Density functional theory
Pulse Radiolysis
Lipids
Oxidation
Radiolysis
Kinetics
Spectrophotometers
Liver Microsomes

Cite this

Priyadarsini, K. I., Maity, D. K., Naik, G. H., Kumar, M. S., Unnikrishnan, M. K., Satav, J. G., & Mohan, H. (2003). Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin. Free Radical Biology and Medicine, 35(5), 475-484. https://doi.org/10.1016/S0891-5849(03)00325-3
Priyadarsini, K.I. ; Maity, D.K. ; Naik, G.H. ; Kumar, M.S. ; Unnikrishnan, M.K. ; Satav, J.G. ; Mohan, H. / Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin. In: Free Radical Biology and Medicine. 2003 ; Vol. 35, No. 5. pp. 475-484.
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title = "Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin",
abstract = "To understand the relative importance of phenolic O-H and the CH-H hydrogen on the antioxidant activity and the free radical reactions of Curcumin, (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione), biochemical, physicochemical, and density functional theory (DFT) studies were carried out with curcumin and dimethoxy curcumin (1,7-bis[3, 4-dimethoxy phenyl]-1,6-heptadiene-3,5-dione). The antioxidant activity of these compounds was tested by following radiation-induced lipid peroxidation in rat liver microsomes, and the results suggested that at equal concentration, the efficiency to inhibit lipid peroxidation is changed from 82{\%} with curcumin to 24{\%} with dimethoxy curcumin. Kinetics of reaction of (2,2′-diphenyl-1- picrylhydrazyl) DPPH, a stable hydrogen abstracting free radical was tested with these two compounds using stopped-flow spectrometer and steady state spectrophotometer. The bimolecular rate constant for curcumin was found to be ∼1800 times greater than that for the dimethoxy derivative. Cyclic voltammetry studies of these two systems indicated two closely lying oxidation peaks at 0.84 and 1.0 V vs. SCE for curcumin, while only one peak at 1.0 V vs. SCE was observed for dimethoxy curcumin. Pulse radiolysis induced one-electron oxidation of curcumin and dimethoxy curcumin was studied at neutral pH using •N3 radicals. This reaction with curcumin produced phenoxyl radicals absorbing at 500 nm, while in the case of dimethoxy curcumin a very weak signal in the UV region was observed. These results suggest that, although the energetics to remove hydrogen from both phenolic OH and the CH 2 group of the β-diketo structure are very close, the phenolic OH is essential for both antioxidant activity and free radical kinetics. This is further confirmed by DFT calculations where it is shown that the -OH hydrogen is more labile for abstraction compared to the -CH2 hydrogen in curcumin. Based on various experimental and theoretical results it is definitely concluded that the phenolic OH plays a major role in the activity of curcumin. {\circledC} 2003 Elsevier Inc.",
author = "K.I. Priyadarsini and D.K. Maity and G.H. Naik and M.S. Kumar and M.K. Unnikrishnan and J.G. Satav and H. Mohan",
note = "Cited By :316 Export Date: 10 November 2017 CODEN: FRBME Correspondence Address: Priyadarsini, K.I.; Radiat. Chem./Chem. Dynam. Division, Bhabha Atomic Research Centre, Trombay, Mumbai- 400085, India; email: kindira@apsara.barc.ernet.in Chemicals/CAS: 1,1 diphenyl 2 picrylhydrazyl, 1898-66-4; curcumin, 458-37-7; hydrogen, 12385-13-6, 1333-74-0 References: Sharma, O.P., Antioxidant activity of curcumin and related substances (1976) Biochem. Pharmacol, 25, pp. 1811-1812; Masuda, T., Toi, Y., Bando, H., Maekawa, T., Takeda, Y., Yamaguchi, H., Structural identification of new curcumin dimers and their contribution to antioxidant mechanism of curcumin (2002) J. Agric. Food Chem, 50, pp. 2524-2530; Mehta, K., Pantazis, P., McQueen, T., Agarwal, B., Antiproliferative effect of curcumin against human breast tumor cell lines (1987) Anticancer Drugs, 8, pp. 471-480; Nurfina, A.N., Reksoha Diprodjo, M.S., Timmerman, H., Jenie, U., Sugianto, D., Van Der Goot, H., Synthesis of some symmetrical curcumin derivatives and their antiimflammatory activity (1997) Eur. J. Med. Chem, 32, pp. 321-328; Sreejayan, N., Priyadarsini, K.I., Devasagayam, T.P.A., Rao, M.N.A., Inhibition of radiation induced lipid peroxidation by curcumin (1997) Int. J. Pharmacol., 151, pp. 125-129; Venkatesan, P., Rao, M.N.A., Structure-activity relationship for the inhibition of lipid peroxidation and scavenging of free radicals by synthetic symmetrical curcumin analogues (2000) J. Pharm. Pharmacol, 52, pp. 1123-1128; Jankun, E.S., McCabe, N.P., Selman, S.H., Jankun, J., Curcumin inhibits lipoxygenase by binding to central cavity: Theoretical and X-ray evidence (2000) Int. J. Mol. Med, 6, pp. 521-526; Huang, M.T., Lysz, T., Ferraro, T., Abidi, T.F., Laskin, J.D., Conney, A.H., Inhibitory effects of curcumin in vivo lipoxygenase and cyclooxygenase activitiesin mouse epidemis (1991) Cancer Res, 51, pp. 813-819; Cheng, A.L., Hsu, C.H., Lin, J.K., Hsu, M.M., Ho, Y.F., Shen, T.S., Ko, J.Y., Hsieh, C.Y., Phase 1 clinical trails of curcumin: A chemopreventive agent in patients with high risk or pre-malignant lesions (2001) Anticancer Res, 21, pp. 2895-2900; Lin, J.K., Lin-Shiau, S.Y., Mechanisms of cancer chemoprevention by curcumin (2001) Proc. Natl. Sci. Counc. Repub. China B, 25, pp. 59-66; Ruby, A.J., Kuttan, G., Dinesh, B.K., Rajasekharan, K.N., Kuttan, R., Anti-tumor and antioxidant activity of natural curcuminoids (1995) Cancer Lett, 94, pp. 79-83; Onoda, M., Inano, H., Effect of curcumin on the production of nitric oxide by cultured rat mammary gland (2000) Nitric Oxide, 4, pp. 505-515; Das, K.C., Das, C.K., Curcumin (diferuloylmethane), a singlet oxygen quencher (2002) Biochem. Biophys. Res. Commun, 295, pp. 62-68; Gorman, A.A., Hamblett, V.S., Srinivasan, V.S., Wood, P.D., Curcumin derived transients: Aa pulsed laser and pulse radiolysis study (1994) Photochem. Photobiol, 59, pp. 389-398; Priyadarsini, K.I., Free radical reactions of curcumin in membrane models (1997) Free Radic. Biol. Med, 23, pp. 838-843; Khopde, S.M., Priyadarsini, K.I., Venkatesan, P., Rao, M.N.A., Free radical scavenging ability and antioxidant efficiency of curcumin and its substituted analogue (1999) Biophys. Chem, 80, pp. 85-91; Kapoor, S., Priyadarsini, K.I., Protection of radiation-induced protein damage by curcumin (2001) Biophys. Chem, 92, pp. 119-126; Jovanovic, S.V., Steenken, S., Borne, C.W., Simic, M.G., H-atom transfer is a preferred antioxidant mechanism of curcumin (1999) J. Am. Chem. Soc, 121, pp. 9677-9681; Jovanovic, S.V., Boone, C.W., Steenken, S., Trinoga, M., Kaskey, R.B., How curcumin works preferentially with water soluble antioxidants (2001) J. Am. Chem. Soc, 123, pp. 3064-3068; Barclay, L.R.C., Vinqvist, M.R., Mukai, K., Goto, H., Hashimoto, Y., Tokunaga, A., Uno, H., On the antioxidant mechanism of curcumin: Classical methods are needed to determine antioxidant mechanism and activity (2000) Org. Lett., 2, pp. 2841-2843; Pabon, H.J.J., A synthesis of curcumin and related compounds (1964) Recl. Trav. Chim. Pays Bas, 83, pp. 379-385; Satav, J.G., Katyare, S., Fatterpekar, P., Srinivasan, A., Further characterization of rat liver mitochondrial proteins: Lipid composition and synthesis and protein profile (1976) Biochem. J, 156, pp. 215-223; Khopde, S.M., Priyadarsini, K.I., Guha, S.N., Satav, J.G., Venkateswaran, P., Rao, M.N.A., Inhibition of radiation-induced lipid peroxidation by tetrahydrocurcumin: Possible mechanism by pulse radiolysis (2000) Biosci. Biotechnol. Biochem, 64, pp. 503-509; Buege, J. A.; Aust, S. D. Microsomal lipid peroxidation. In: Fleisher, S.; Packer, L., eds. Methods in enzymology. New York: Academic Press Inc.; 1978:302-310; Lowry, O.H., Rosbourgh, M.J., Farr, A.L., Randall, R.J., Protein measurements with folin phenol reagent (1951) J. Biol. Chem, 193, pp. 265-275; Guha, S.N., Moorthy, P.N., Kishore, K., Naik, D.B., Rao, K.N., One-electron reduction of thionine studied by pulse radiolysis (1987) Proc. Indian Acad. Sci. (Chem. Sci.), 99, pp. 261-271; Priyadarsini, K. I.; Naik, D. B.; Moorthy, P. N.; Mittal, J. P. Energy transfer studies of coumarin dyes using electron pulse radiolysis. In: Dobo, J. ; Nykis, L.; Shiller, R., eds. Proc. 7th Tihany Conference on Radiation Chemistry. Budapest, Hungary: Hungarian Chemical Society; 1991:105-107; Fielden, E. M. Chemical dosimetry of pulsed electron and x-ray source in the MeV region. In: Baxendale, J. H.; Busi, R. D., eds. The study of fast processes and transient species by elelctron pulse radiolysis. London: Reidel Publishing Co; 1982:59; Buxton, G.V., Greenstock, C.L., Helmon, W.P., Ross, A.B., Critical review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals in aqueous solutions (1988) J. Phys. Chem. Ref. Data, 17, pp. 513-886; http://allen.rad.nd.edu/NDRL Radiation Chemistry Data Center; Wolfende B. S, Wilson R. L. Radical cations as reference chromogens in kinetic studies of one-electron transfer reactions: pulse radiolysis studies of 2,2′-azinobis (3-ethylbenthiazoline-6-sulphonate). J. Chem. Soc. [Perkin II] 805-812; 1982; Schmidt, M.W., Badridge, K.K., Boatz, J.A., Elbert, S.T., Gordon, M.S., Jensen, J.H., Koseki, S., Montgomery, J.A., General atomic and molecular electronic structure system (1993) J. Comput. Chem, 14, pp. 1347-1363; Borsari, M., Ferrari, E., Grandi, R., Saladini, M., Curcumin as potential new iron- agents: Spectroscopic, polarographic and potentiometric study on their Fe(II) complexing ability (2002) Inorg. Chem. Acta, 328, pp. 61-68; Wang, M., Jin, Y., Ho CT. Evaluation of resveratrol derivatives as potential antioxidants and identification of a reaction product of resveratrol and 2,2-diphenyl- picrylhydrazyl (1999) J. Agric. Food. Chem, 47, pp. 3974-3977; Heim, K.L., Tagliaferro, A.R., Bobilya, D.J., Flavonoid antioxidants: Chemistry, metabolism and structure activity relationships (2002) J. Nutr. Biochem, 13, pp. 572-584; Alfassi, Z.B., Harriman, A., Huie, R.E., Mosseri, S., Neta, P., The redox potential of the azide/azidyl couple (1987) J. Phys. Chem, 91, pp. 2120-2122; Chandra, A.K., Uchimaru, T., The O-H bond energies of substituted phenols and proton affinities of substituted phenoxide ions: A DFT study (2002) Int. J. Mol. Soc, 3, pp. 407-422. , (and the references therein); Priyadarsini, K.I., Guha, S.N., Rao, M.N.A., Physico-chemical properties and antioxidant activities of methoxy phenols (1998) Free Radic. Biol. Med, 24, pp. 933-941; Bors, W., Michel, C., Stettmaier, K., Structure activity relationship governing antioxidant capacities of plant polyphenols (2001) Methods Enzymol, 335, pp. 166-180",
year = "2003",
doi = "10.1016/S0891-5849(03)00325-3",
language = "English",
volume = "35",
pages = "475--484",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "5",

}

Priyadarsini, KI, Maity, DK, Naik, GH, Kumar, MS, Unnikrishnan, MK, Satav, JG & Mohan, H 2003, 'Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin', Free Radical Biology and Medicine, vol. 35, no. 5, pp. 475-484. https://doi.org/10.1016/S0891-5849(03)00325-3

Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin. / Priyadarsini, K.I.; Maity, D.K.; Naik, G.H.; Kumar, M.S.; Unnikrishnan, M.K.; Satav, J.G.; Mohan, H.

In: Free Radical Biology and Medicine, Vol. 35, No. 5, 2003, p. 475-484.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin

AU - Priyadarsini, K.I.

AU - Maity, D.K.

AU - Naik, G.H.

AU - Kumar, M.S.

AU - Unnikrishnan, M.K.

AU - Satav, J.G.

AU - Mohan, H.

N1 - Cited By :316 Export Date: 10 November 2017 CODEN: FRBME Correspondence Address: Priyadarsini, K.I.; Radiat. Chem./Chem. Dynam. Division, Bhabha Atomic Research Centre, Trombay, Mumbai- 400085, India; email: kindira@apsara.barc.ernet.in Chemicals/CAS: 1,1 diphenyl 2 picrylhydrazyl, 1898-66-4; curcumin, 458-37-7; hydrogen, 12385-13-6, 1333-74-0 References: Sharma, O.P., Antioxidant activity of curcumin and related substances (1976) Biochem. Pharmacol, 25, pp. 1811-1812; Masuda, T., Toi, Y., Bando, H., Maekawa, T., Takeda, Y., Yamaguchi, H., Structural identification of new curcumin dimers and their contribution to antioxidant mechanism of curcumin (2002) J. Agric. Food Chem, 50, pp. 2524-2530; Mehta, K., Pantazis, P., McQueen, T., Agarwal, B., Antiproliferative effect of curcumin against human breast tumor cell lines (1987) Anticancer Drugs, 8, pp. 471-480; Nurfina, A.N., Reksoha Diprodjo, M.S., Timmerman, H., Jenie, U., Sugianto, D., Van Der Goot, H., Synthesis of some symmetrical curcumin derivatives and their antiimflammatory activity (1997) Eur. J. Med. Chem, 32, pp. 321-328; Sreejayan, N., Priyadarsini, K.I., Devasagayam, T.P.A., Rao, M.N.A., Inhibition of radiation induced lipid peroxidation by curcumin (1997) Int. J. Pharmacol., 151, pp. 125-129; Venkatesan, P., Rao, M.N.A., Structure-activity relationship for the inhibition of lipid peroxidation and scavenging of free radicals by synthetic symmetrical curcumin analogues (2000) J. Pharm. Pharmacol, 52, pp. 1123-1128; Jankun, E.S., McCabe, N.P., Selman, S.H., Jankun, J., Curcumin inhibits lipoxygenase by binding to central cavity: Theoretical and X-ray evidence (2000) Int. J. Mol. Med, 6, pp. 521-526; Huang, M.T., Lysz, T., Ferraro, T., Abidi, T.F., Laskin, J.D., Conney, A.H., Inhibitory effects of curcumin in vivo lipoxygenase and cyclooxygenase activitiesin mouse epidemis (1991) Cancer Res, 51, pp. 813-819; Cheng, A.L., Hsu, C.H., Lin, J.K., Hsu, M.M., Ho, Y.F., Shen, T.S., Ko, J.Y., Hsieh, C.Y., Phase 1 clinical trails of curcumin: A chemopreventive agent in patients with high risk or pre-malignant lesions (2001) Anticancer Res, 21, pp. 2895-2900; Lin, J.K., Lin-Shiau, S.Y., Mechanisms of cancer chemoprevention by curcumin (2001) Proc. Natl. Sci. Counc. Repub. China B, 25, pp. 59-66; Ruby, A.J., Kuttan, G., Dinesh, B.K., Rajasekharan, K.N., Kuttan, R., Anti-tumor and antioxidant activity of natural curcuminoids (1995) Cancer Lett, 94, pp. 79-83; Onoda, M., Inano, H., Effect of curcumin on the production of nitric oxide by cultured rat mammary gland (2000) Nitric Oxide, 4, pp. 505-515; Das, K.C., Das, C.K., Curcumin (diferuloylmethane), a singlet oxygen quencher (2002) Biochem. Biophys. Res. Commun, 295, pp. 62-68; Gorman, A.A., Hamblett, V.S., Srinivasan, V.S., Wood, P.D., Curcumin derived transients: Aa pulsed laser and pulse radiolysis study (1994) Photochem. Photobiol, 59, pp. 389-398; Priyadarsini, K.I., Free radical reactions of curcumin in membrane models (1997) Free Radic. Biol. Med, 23, pp. 838-843; Khopde, S.M., Priyadarsini, K.I., Venkatesan, P., Rao, M.N.A., Free radical scavenging ability and antioxidant efficiency of curcumin and its substituted analogue (1999) Biophys. Chem, 80, pp. 85-91; Kapoor, S., Priyadarsini, K.I., Protection of radiation-induced protein damage by curcumin (2001) Biophys. Chem, 92, pp. 119-126; Jovanovic, S.V., Steenken, S., Borne, C.W., Simic, M.G., H-atom transfer is a preferred antioxidant mechanism of curcumin (1999) J. Am. Chem. Soc, 121, pp. 9677-9681; Jovanovic, S.V., Boone, C.W., Steenken, S., Trinoga, M., Kaskey, R.B., How curcumin works preferentially with water soluble antioxidants (2001) J. Am. Chem. Soc, 123, pp. 3064-3068; Barclay, L.R.C., Vinqvist, M.R., Mukai, K., Goto, H., Hashimoto, Y., Tokunaga, A., Uno, H., On the antioxidant mechanism of curcumin: Classical methods are needed to determine antioxidant mechanism and activity (2000) Org. Lett., 2, pp. 2841-2843; Pabon, H.J.J., A synthesis of curcumin and related compounds (1964) Recl. Trav. Chim. Pays Bas, 83, pp. 379-385; Satav, J.G., Katyare, S., Fatterpekar, P., Srinivasan, A., Further characterization of rat liver mitochondrial proteins: Lipid composition and synthesis and protein profile (1976) Biochem. J, 156, pp. 215-223; Khopde, S.M., Priyadarsini, K.I., Guha, S.N., Satav, J.G., Venkateswaran, P., Rao, M.N.A., Inhibition of radiation-induced lipid peroxidation by tetrahydrocurcumin: Possible mechanism by pulse radiolysis (2000) Biosci. Biotechnol. Biochem, 64, pp. 503-509; Buege, J. A.; Aust, S. D. Microsomal lipid peroxidation. In: Fleisher, S.; Packer, L., eds. Methods in enzymology. New York: Academic Press Inc.; 1978:302-310; Lowry, O.H., Rosbourgh, M.J., Farr, A.L., Randall, R.J., Protein measurements with folin phenol reagent (1951) J. Biol. Chem, 193, pp. 265-275; Guha, S.N., Moorthy, P.N., Kishore, K., Naik, D.B., Rao, K.N., One-electron reduction of thionine studied by pulse radiolysis (1987) Proc. Indian Acad. Sci. (Chem. Sci.), 99, pp. 261-271; Priyadarsini, K. I.; Naik, D. B.; Moorthy, P. N.; Mittal, J. P. Energy transfer studies of coumarin dyes using electron pulse radiolysis. In: Dobo, J. ; Nykis, L.; Shiller, R., eds. Proc. 7th Tihany Conference on Radiation Chemistry. Budapest, Hungary: Hungarian Chemical Society; 1991:105-107; Fielden, E. M. Chemical dosimetry of pulsed electron and x-ray source in the MeV region. In: Baxendale, J. H.; Busi, R. D., eds. The study of fast processes and transient species by elelctron pulse radiolysis. London: Reidel Publishing Co; 1982:59; Buxton, G.V., Greenstock, C.L., Helmon, W.P., Ross, A.B., Critical review of rate constants for reactions of hydrated electrons, hydrogen atoms and hydroxyl radicals in aqueous solutions (1988) J. Phys. Chem. Ref. Data, 17, pp. 513-886; http://allen.rad.nd.edu/NDRL Radiation Chemistry Data Center; Wolfende B. S, Wilson R. L. Radical cations as reference chromogens in kinetic studies of one-electron transfer reactions: pulse radiolysis studies of 2,2′-azinobis (3-ethylbenthiazoline-6-sulphonate). J. Chem. Soc. [Perkin II] 805-812; 1982; Schmidt, M.W., Badridge, K.K., Boatz, J.A., Elbert, S.T., Gordon, M.S., Jensen, J.H., Koseki, S., Montgomery, J.A., General atomic and molecular electronic structure system (1993) J. Comput. Chem, 14, pp. 1347-1363; Borsari, M., Ferrari, E., Grandi, R., Saladini, M., Curcumin as potential new iron- agents: Spectroscopic, polarographic and potentiometric study on their Fe(II) complexing ability (2002) Inorg. Chem. Acta, 328, pp. 61-68; Wang, M., Jin, Y., Ho CT. Evaluation of resveratrol derivatives as potential antioxidants and identification of a reaction product of resveratrol and 2,2-diphenyl- picrylhydrazyl (1999) J. Agric. Food. Chem, 47, pp. 3974-3977; Heim, K.L., Tagliaferro, A.R., Bobilya, D.J., Flavonoid antioxidants: Chemistry, metabolism and structure activity relationships (2002) J. Nutr. Biochem, 13, pp. 572-584; Alfassi, Z.B., Harriman, A., Huie, R.E., Mosseri, S., Neta, P., The redox potential of the azide/azidyl couple (1987) J. Phys. Chem, 91, pp. 2120-2122; Chandra, A.K., Uchimaru, T., The O-H bond energies of substituted phenols and proton affinities of substituted phenoxide ions: A DFT study (2002) Int. J. Mol. Soc, 3, pp. 407-422. , (and the references therein); Priyadarsini, K.I., Guha, S.N., Rao, M.N.A., Physico-chemical properties and antioxidant activities of methoxy phenols (1998) Free Radic. Biol. Med, 24, pp. 933-941; Bors, W., Michel, C., Stettmaier, K., Structure activity relationship governing antioxidant capacities of plant polyphenols (2001) Methods Enzymol, 335, pp. 166-180

PY - 2003

Y1 - 2003

N2 - To understand the relative importance of phenolic O-H and the CH-H hydrogen on the antioxidant activity and the free radical reactions of Curcumin, (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione), biochemical, physicochemical, and density functional theory (DFT) studies were carried out with curcumin and dimethoxy curcumin (1,7-bis[3, 4-dimethoxy phenyl]-1,6-heptadiene-3,5-dione). The antioxidant activity of these compounds was tested by following radiation-induced lipid peroxidation in rat liver microsomes, and the results suggested that at equal concentration, the efficiency to inhibit lipid peroxidation is changed from 82% with curcumin to 24% with dimethoxy curcumin. Kinetics of reaction of (2,2′-diphenyl-1- picrylhydrazyl) DPPH, a stable hydrogen abstracting free radical was tested with these two compounds using stopped-flow spectrometer and steady state spectrophotometer. The bimolecular rate constant for curcumin was found to be ∼1800 times greater than that for the dimethoxy derivative. Cyclic voltammetry studies of these two systems indicated two closely lying oxidation peaks at 0.84 and 1.0 V vs. SCE for curcumin, while only one peak at 1.0 V vs. SCE was observed for dimethoxy curcumin. Pulse radiolysis induced one-electron oxidation of curcumin and dimethoxy curcumin was studied at neutral pH using •N3 radicals. This reaction with curcumin produced phenoxyl radicals absorbing at 500 nm, while in the case of dimethoxy curcumin a very weak signal in the UV region was observed. These results suggest that, although the energetics to remove hydrogen from both phenolic OH and the CH 2 group of the β-diketo structure are very close, the phenolic OH is essential for both antioxidant activity and free radical kinetics. This is further confirmed by DFT calculations where it is shown that the -OH hydrogen is more labile for abstraction compared to the -CH2 hydrogen in curcumin. Based on various experimental and theoretical results it is definitely concluded that the phenolic OH plays a major role in the activity of curcumin. © 2003 Elsevier Inc.

AB - To understand the relative importance of phenolic O-H and the CH-H hydrogen on the antioxidant activity and the free radical reactions of Curcumin, (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione), biochemical, physicochemical, and density functional theory (DFT) studies were carried out with curcumin and dimethoxy curcumin (1,7-bis[3, 4-dimethoxy phenyl]-1,6-heptadiene-3,5-dione). The antioxidant activity of these compounds was tested by following radiation-induced lipid peroxidation in rat liver microsomes, and the results suggested that at equal concentration, the efficiency to inhibit lipid peroxidation is changed from 82% with curcumin to 24% with dimethoxy curcumin. Kinetics of reaction of (2,2′-diphenyl-1- picrylhydrazyl) DPPH, a stable hydrogen abstracting free radical was tested with these two compounds using stopped-flow spectrometer and steady state spectrophotometer. The bimolecular rate constant for curcumin was found to be ∼1800 times greater than that for the dimethoxy derivative. Cyclic voltammetry studies of these two systems indicated two closely lying oxidation peaks at 0.84 and 1.0 V vs. SCE for curcumin, while only one peak at 1.0 V vs. SCE was observed for dimethoxy curcumin. Pulse radiolysis induced one-electron oxidation of curcumin and dimethoxy curcumin was studied at neutral pH using •N3 radicals. This reaction with curcumin produced phenoxyl radicals absorbing at 500 nm, while in the case of dimethoxy curcumin a very weak signal in the UV region was observed. These results suggest that, although the energetics to remove hydrogen from both phenolic OH and the CH 2 group of the β-diketo structure are very close, the phenolic OH is essential for both antioxidant activity and free radical kinetics. This is further confirmed by DFT calculations where it is shown that the -OH hydrogen is more labile for abstraction compared to the -CH2 hydrogen in curcumin. Based on various experimental and theoretical results it is definitely concluded that the phenolic OH plays a major role in the activity of curcumin. © 2003 Elsevier Inc.

U2 - 10.1016/S0891-5849(03)00325-3

DO - 10.1016/S0891-5849(03)00325-3

M3 - Article

VL - 35

SP - 475

EP - 484

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 5

ER -