Effects of ring size and polar functional groups on the glutathione peroxidase-like antioxidant activity of water-soluble cyclic selenides.
To elucidate the effects of ring structure and a substituent on the glutathione peroxidase- (GPx-) like antioxidant activities of aliphatic selenides, series of water-soluble cyclic selenides with variable ring size and polar functional groups were synthesized, and their antioxidant activities were evaluated by NADPH-coupled assay using H2O2 and glutathione (GSH) in water and also by NMR spectroscopy using H2O2 and dithiothreitol (DTT(red)) in methanol. Strong correlations were found among the GPx-like activity in water, the second-order rate constants for the oxidation of the selenides, and the HOMO energy levels calculated in water. The results support the conclusion that the oxidation process is the rate-determining step of the catalytic cycle. On the other hand, such correlations were not obtained for the activity observed in methanol. The optimal ring size was determined to be five. The type of substituent (NH2 < OH < CO2H) and the number can also control the activity, whereas the stereoconfiguration has only marginal effects on the activity in water. In methanol, however, the activity rank could not be explained by the simple scenarios applicable in water.
Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan.
Kenta
K
Arai
Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan.
Fumio
F
Kumakura
Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan.
Motoi
M
Takahira
Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan.
Natsumi
N
Sekiyama
Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan.
Nozomi
N
Kuroda
Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan.
Toshiki
T
Suzuki
Department of Chemistry, School of Science, Tokai University, Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan.
Michio
M
Iwaoka
D000975:Antioxidants / Q000737:chemistry; D002384:Catalysis; D005978:Glutathione / Q000737:chemistry*; D005979:Glutathione Peroxidase / Q000737:chemistry* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000378:metabolism
D000975:Antioxidants; D016566:Organoselenium Compounds; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005978:Glutathione