Revista Brasileira de Farmacognosia Brazilian Journal of Pharmacognosy 23(3): 542-558, May/Jun. 2013 Flavonoid electrochemistry: a review on the electroanalytical applications Eric S. Gil,1 Renê O. Couto*,2 1Faculdade de Farmácia, Universidade Federal de Goiás, Brazil, 2Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Review Paulo, Brazil. Abstract: Flavonoids are polyphenolic compounds widespread in vegetal kingdom. Received 17 Dec 2012 They present a C-15 skeleton, which is divided into three units A, B and C. Unit C is an Accepted 28 Feb 2013 oxygen containing heterocyclic, whose oxidation state and saturation level defi ne major Available online 10 May 2013 subclasses. Units A and B are aromatic rings, in which four major types of substituents, i.e. hydroxyl, methoxyl, prenyl and glycosides, lead to over 8000 different fl avonoids. Keywords: The great healthy-protecting value of these phytochemical biomarkers has attracted antioxidant activity the attention of scientifi c community. Their main biological actions include anticancer phytopharmaceuticals and anti-infl ammatory properties, which are strictly linked to antioxidant activities. So quality control that, electroanalysis have been extensively applied on mechanistic studies and also for structure-activity relationship analytical determinations. This review presents the state of the art regarding the main redox behavior applications of electroanalysis on the fl avonoid research. The approaches on redox voltammetry behavior characterization leading to a better understanding of structure antioxidant activity relationships are highlighted. ISSN 0102-695X DOI: 10.1590/S0102-695X2013005000031 Introduction 2010). Hence, despite the lack of diversity of recognized substituents, it is already known the existence of almost Flavonoid is a generic name for a large group of thousand fl avonoids (Tsao, 2010; Mülazımoğlu et al., plant metabolites, which as other polyphenols are mostly 2011). derived from the biosynthetic route of shikimic acid. They Among such subgroups, fl avones, fl avonols, have a C6-C3-C6 general core, which is represented by fl avanones and fl avanonols are almost ubiquitous in the three units, A, B and C (1). Units A and B are essentially plant kingdom. They can be isolated from fruits, seeds, aromatic rings of phenolic nature, whilst unit C is an fl owers and other vegetal tissues of uncountable number oxygen containing hetereocycle, benzo-γ-pirone, whose of plants (Cook & Samman, 1996; Rice-Evans et al., level of oxidation, namely the presence or absence of: 1996; Harborne & Williams, 2000; Erlund, 2004; Taylor C2=C3 double bond; C3-OH hydroxyl group; and C4-keto & Grotewold, 2005; Tsao, 2010; Hidalgo et al., 2010; group defi nes their subclasses and also the controversial Mülazımoğlu et al., 2011). In turn, anthocyanins and nomenclature (Cook & Samman, 1996; Tsao, 2010). their precursors catechins, also named as fl avan-3-ols or Accordingly to these narrow structural differences they fl avanols, are mostly found in the peel of red fruits, tea have been divided in six major classes, fl avones (1), leaves, coffee and cacao bean. Yet, isofl avones are typical fl avonols (1), fl avanones (2), fl avanonol (3), catechins, biomarkers in soybeans and other leguminous plants fl avonols and fl avan-3-ols (4) and anthocyanins (5), which (Tsao, 2010). On the other hand, the open ring chalcones can be extended to ten by the inclusion of isofl avonoids have been detected in apples, hops and beers, whereas the (6), neofl avonoids (7) and also the open ring chalcones scarcer occurrence neofl avonoids is mainly represented by (8) and aurones (9) (Cook & Samman, 1996; Rice-Evans dalgerbin, a 6-hydroxy-7-methoxy-neofl avonoid (Tsao, et al., 1996; Harborne & Williams, 2000; Narayana et al., 2010). 2001; Erlund, 2004; Taylor & Grotewold, 2005; Tsao, The relevance of such widespread class of 2010; Hidalgo et al., 2010; Mülazımoğlu et al., 2011). phytochemicals refers to the chemical properties of phenol Furthermore, the hydrogen atoms in each unit A, and benzenediol isomers (Cook & Samman, 1996; Rice- B or C, can be replaced by three main types of substituent, Evans et al., 1996; Harborne & Williams, 2000; Tsao, hydroxyl (-OH), acetyl (-OR), or sugar (CxHyOz). Whereas, 2010). In fact, they have been explored as precursors in the low molecular weight aglycones can coexist with organic synthesis of drugs, antioxidants and other complex numerous glycosides, dimeric, oligomeric and polymeric molecules (Cook & Samman, 1996; Rice-Evans, et al., derivatives (Cook & Samman, 1996; Erlund, 2004; Tsao, 1996; Harborne & Williams, 2000). 542 Flavonoid electrochemistry: a review on the electroanalytical applications Eric S. Gil and Renê O. Couto 6' 4' O O O 7 2' 3 5 R OH O O O R=H Flavones 2 3 R=OH Flavonols or flavon-3-ols OH O O O O OH OH 4 5 6 O O O O O 7 8 9 Indeed, flavonoids are crucial for the plant survival, Narayana et al., 2001; Tsao, 2010; Chaves et al, 2011; playing important physiological roles, which include Mülazımoğlu et al., 2011). UV protection, antifungal and phytoalexin properties, as It was demonstrated that the plant phenolic well as some contributions as plant regulators (Harborne compounds have protective effects against liver, colon & Williams, 2000; Taylor & Grotewold, 2005). On the and tongue carcinogenesis. According to some data, other hand, the sensorial characteristics of flavonoids, i.e. onion, lettuce, apples and red wine are important sources color and tasting properties have also key functions on of dietary flavonoids, which are probably responsible the plant life cycle. For instance, the attractive colors of for the anti-mutagenic activity associated with food and flowers and fruit peel are useful for pollination and seeds beverages. It was further suggested that smokers ingesting dissemination, yet in leaves such coloring properties are dietary flavonoids are partly protected against harmful hidden by the intense green of chlorophylls; meanwhile effects of tobacco carcinogens within their bladder the bitter taste preserves the photosynthesis level by mucosal cells (Cook & Samman, 1996; Rice-Evans et al., repulsing herbivorous (Harborne & Williams, 2000; Taylor 1996; Harborne & Williams, 2000; Narayana et al., 2001; & Grotewold, 2005). Nijveldt et al., 2001; Erlund, 2004; Taylor & Grotewold, In turn, flavonoids have proved to be essential for 2005; Hidalgo et al., 2010; Tsao, 2010; Mülazımoğlu et al., animal kingdom, though they must be supplied by vegetal 2011). intake. Furthermore, the biological relevance of flavonoids Perhaps, the mechanism of action for all these has driven the nutritional human habits, leading to upsurge biological actions, as a rule, lay on their antioxidant and/ of consume of natural foodstuffs (Cook & Samman, 1996; or radical scavenging properties, which is centered on their Rice-Evans et al., 1996; Harborne & Williams, 2000; phenolic groups (Rice-Evans et al., 1996; Narayana et al., Erlund, 2004; Tsao, 2010; Hidalgo et al., 2010). Hence, 2001; Nijveldt et al., 2001; Montoro et al., 2005). In fact, many plant derivatives containing high levels of such the electron/hydrogen donor and metal chelator ability healthy-protecting biomarkers have been extensively of flavonoids depend on the number and position of their commercialized as phytopharmaceuticals, whereas some oxygenated substituent (Rice-Evans et al., 1996; Nijveldt isolated compounds, i.e. rutin and diosmin have been et al., 2001; Montoro et al., 2005). classified as vitamins and drugs (Hidalgo et al., 2010). These compounds donate hydrogen and the Some pharmacological actions that highlight the mechanism of their action as antioxidants involves the health benefits of flavonoids include antibacterial, antiviral, ability of flavonoids to scavenge radicals by an H-atom antineoplasic, antiinflammatory, antiallergic, vasodilactory or electron transfer process. The resulting antioxidant free and cardioprotective activity (Cook & Samman, 1996; radical does not lead to formation of another free radical Rice-Evans et al., 1996; Harborne & Williams, 2000; due to the stabilization by delocalization of radical electron, Rev. Bras. Farmacogn. Braz. J. Pharmacogn. 23(3): May/Jun. 2013 543 Flavonoid electrochemistry: a review on the electroanalytical applications Eric S. Gil and Renê O. Couto thus terminating the chain reaction (Cook & Samman, Accordingly, for a representative number of 1996; Rice-Evans et al., 1996; Harborne & Williams, compounds and also for the great biological importance 2000; Erlund, 2004; Taylor & Grotewold, 2005; Hidalgo of flavonoids, many reviews of treasured value have been et al., 2010; Tsao, 2010; Mülazımoğlu et al., 2011). published. However, their biological properties have Furthermore, it has been found that they been often discussed by means of electron donor ability can inhibit some redox active enzymes, such as and no review has focused their redox behavior and cyclooxygenase, lipoxygenase and NADPH oxidase electrochemical profile (Cook & Samman, 1996; Rice- (Nijveldt et al., 2001; Tsao, 2010). Indeed, it is well Evans et al., 1996; Cao et al., 1997; Harborne & Williams, known that the extension of enzymatic inhibition lay on 2000; Narayana et al., 2001; Nijveldt et al., 2001; Erlund, chemical interaction strengthens, which in this case is 2004; Montoro et al., 2005; Tsao, 2010). Nevertheless, again enhanced by electrostatic interactions, i.e. hydrogen the aim of this review is to present the state of the art bonds, ionic interactions, and once more favored by