Theoretical Study on the Antioxidant Activity of Alizarin, Purpurin, and Pseudopurpurin

Introduction

Hydroxyanthraquinone derivatives are a large group of natural polyphenolic compounds found widely in plants, and some of these are used as herbal medicines or food pigments. Investigations have demonstrated the preventive effect of hydroxyanthraquinone against genotoxicity or cytotoxicity (Wu & Yen, 2004; Chen et al., 2004) and the modulation of metabolic enzyme activities in response to xenobiotics (Marczylo et al., 2000; Marczylo et al., 2003; Sun et al., 2000; Wang et al., 2001). It has been demonstrated that purpurin and alizarin inhibit the activity of human recombinant cytochrome P450 (CYP), isozymes CYP 1A1, CYP 1A2, and CYP 1B1, resulting in the antimutagenic effect observed in recombinant salmonella that possess these CYPs (Takahashi et al., 2002). Some papers have been published on the cytotoxic activities of hydroxyanthraquinone derivatives using cancer cell lines such as L1210 (Koyama et al., 1989), HL-60 (Koyama et al., 1989), LNCap (Cha et al., 2005), PC3, and A431 (Zhou et al., 2006). The intake of antimutagens and anticarcinogens present in food ingredients may lead to a decreased risk of cancer onset. Modern authorised physicians are increasing their use of hydroxyanthraquinone derivatives to treat many important common diseases, due to their proven ability to inhibit specific enzymes, and to scavenge free radicals (Havsteen, 2002). In fact, the structures, the procedures of isolation, and approaches to the organic synthesis of hydroxyanthraquinone derivatives have been studied extensively in experiment. Experimental and theoretical studies of flavonols by Van Acker et al. (1996) revealed that the excellent antioxidant activity of the flavonols could be explained by the formation of an intramolecular hydrogen bond. The antioxidant activity of apigenin, luteolin, and taxifolin were studied using the B3LYP functional coupled with the 6-311++G(d,p) basis set (Leopoldini et al., 2004). The phenolic antioxidants action mechanisms were investigated using DFT/B3LYP method (Klein & Lukes, 2006). Several interesting classes of phenolic antioxidants are studied using the density functional theory (DFT) method, including commercial antioxidants used as food additives, compounds related to Vitamin E, flavonoids in tea, aminophenols, stilbenes related to resveratrol, and sterically hindered phenols (Wright et al 2001). Quercetin is one of the most representative flavonoid compounds. The structural, electronic, and energetic characteristics of quercetin, as well as the influence of a copper ion on all of these parameters, are studied by means of quantum chemical electronic structure calculations (Fiorucci et al. 2007). However, to the best of our knowledge, no calculation about the antioxidant activity of hydroxyanthraquinone derivatives has been reported so far.

In this work, we have investigated the conformational and electronic features of three hydroxyanthraquinone derivatives: alizarin (1,2-dihydroxyanthraquinone), purpurin (1,2,4-trihydroxyanthraquinone), and pseudopurpurin (1,2,4-trihydroxy-3-carboxyanthraquinone) at the DFT level. They were chosen for their peculiar chemical structure, to evaluate the effect of the functional groups on the antioxidant ability. Bond dissociation energy (BDE) and ionization potential (IP) values computed for these systems were used as indicators of the ease by which hydroxyanthraquinone derivatives can deactivate free radicals. The spin densities were reported to give better insight into delocalization of the unpaired electron and conjugation effects. The geometrical structures studied in this work are shown in Figure 1, along with the atom numbering.

Figure 1.

Main geometrical parameters of (A) alizarin, (B) purpurin, and (C) pseudopurpurin, along with the atom numbering