Trolox, structure

This effect was seen only in hypoxia, not normoxia, was dose-dependent within the range 0.2-200 /rM, and provided a simple in vitro model for investigating the mode of action of the vitamin. By examining the structure-activity relationship of the response, compounds with a phytyl side-chain, phytol and vitamin K-l (phytomenadione), of similar length to vitamin E (9) were found to be also active, but compounds that had structures which resembled the chroman ring of the vitamin, vitamin K-3 (menaphthone) and Trolox, were antagonists of the responses to the phytol side-chain effects. 

Fig. 7. Structure of Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a common standard for the determination of TAC.

Since alpha-tocopherol was an essential component of the Swoboda and Peers system (52) which yielded metallic/fIshy flavors, its structural role in the directing of the flavor was of Interest. Either alpha-tocopherol (670 ppm) or Trolox C (1000 ppm) were added to steam deodorized menhaden oils (2 h at 130°C, 4 mm Hg 32) and allowed to oxidize while exposed to air and protected from the light at 65 C. As observed In previous studies (54-56), the high level of alpha-tocopherol exhibited a prooxldant effect whereas Trolox C possessed a distinct antioxidant effect in oxidizing menhaden oils (57). 

The antioxidant activity of a compound depends upon which free radical or oxidant is used in the assay (Halliwell and Gutteridge, 1995), and a different order of antioxidant activity is therefore to be expected when analyses are performed using different methods. This has been demonstrated by Tsuda et al. (1994) in their study of antioxidative activity of an anthocyanin (cyanidin-3-O-p-D-glucosidc) and an anthocyanidin (cyanidin) in four different lipophilic assay systems. Both compounds had antioxidative activity in all four systems, but the relative activity between them and their activity, compared with Trolox, varied with the method used. Fukumoto and Mazza (2000) reported that antioxidant activity of compounds with similar structures gave the same trends, although not always the same results, when measured by P-carotene bleaching, DPPH and HPLC detection of malonaldehyde formation in linoleic acid emulsion. 

Flavonoids as antioxidants have been reviewed several times 45s including an outline of many claims to their beneficial health effects . Due to their complex structures and different classes (eight thousand different compounds are known ), researchers often resorted to qualitative screening methods to evaluate their antioxidant potentials in mixed aqueous/lipid phases. For example, the so-called Trolox equivalent antioxidant capacity (TEAC), the concentration of Trolox with equivalent antioxidant activity of a 1 mM concentration of the substrate, is frequently used in heterogeneous systems. Unfortunately, this can be an unreliable measure of the activity of the substance, especially if initiation is also carried out in the aqueous phase. Nevertheless, there have been some efforts made to evaluate antioxidant activities of specific flavonoids using more quantitative methods in heterogeneous systems in order to mimic natural environments. A few examples are cited below to illustrate some approaches to determine flavonoid activities in micelles or lipid membranes. 

Organic radicals in the reactions of Cr(VI) with substrates can be detected directly, such as in the case of ascorbate and derivatives (21, 50), vitamin E (ot-tocopherol) or its water-soluble analogue, Trolox (51, 52), and catechols (25, 53, 54). For species such as thiyl radicals and carbon-based radicals that are much less stable, spin traps are used to trap the radicals and identify their structures. 

FIGURE 15.2 Chemical structures of cinnamic acids derivatives (la) and Trolox (2a). 

---