ABSTRACT
Anthocyanidins, leucoanthocyanidins, and flavonols are natural compounds mainly known due to their reported biological activities, such as antiviral, antifungal, anti-inflammatory activities, and antioxidant activity. In the present study, we performed a comparative structural, conformational, electronic, and nuclear magnetic resonance analysis of the reactivity of the chemical structure of primary anthocyanidins, leucoanthocyanidins, and flavonoids. We focused our analysis on the following molecular questions: (i) differences in cyanidin catechols ( +)-catechin, leucocyanidin, and quercetin; (ii) the loss of hydroxyl presents in the R1 radical of leucoanthocyanidin in the functional groups linked to C4 (ring C); and (iii) the electron affinity of the 3-hydroxyl group (R7) in the flavonoids delphinidin, pelargonidin, cyanidin, quercetin, and kaempferol. We show unprecedented results for bond critical point (BCP) of leucopelargonidin and leucodelphirinidin. The BCP formed between hydroxyl hydrogen (R2) and ketone oxygen (R1) of kaempferol has the same degrees of covalence of quercetin. Kaempferol and quercetin exhibited localized electron densities between hydroxyl hydrogen (R2) and ketone oxygen (R1). Global molecular descriptors showed quercetin and leucocyanidin are the most reactive flavonoids in electrophilic reactions. Complementary, anthocyanidins are the most reactive in nucleophilic reactions, while the smallest gap occurs in delphinidin. Local descriptors indicate that anthocyanidins and flavonols are more prone to electrophilic attacks, while in leucoanthocyanidins, the most susceptible to attack are localized in the ring A. The ring C of anthocyanidins is more aromatic than the same found in flavonols and leucoanthocyanidins. METHODS: For the analysis of the molecular properties, we used the DFT to evaluate the formation of the covalent bonds and intermolecular forces. CAM-B3LYP functional with the def2TZV basis set was used for the geometry optimization. A broad analysis of quantum properties was performed using the assessment of the molecular electrostatic potential surface, electron localization function, Fukui functions, descriptors constructed from frontier orbitals, and nucleus independent chemical shift.
Subject(s)
Anthocyanins , Flavonols , Flavonols/chemistry , Anthocyanins/chemistry , Quercetin/chemistry , Kaempferols/chemistry , Flavonoids/chemistry , Hydrogen/chemistry , OxygenABSTRACT
Understanding the antioxidant activity of flavonoids is important to investigate their biological activities as well as to design novel molecules with low toxicity and high activity. Aromaticity is a chemical property found in cyclic structures that plays an important role in their stability and reactivity, and its investigation can help us to understand the antioxidant activity of some heterocyclic compounds. In the present study, we applied the density functional theory (DFT) to investigate the properties of seven flavonoid structures with well-reported antioxidant activity: flavan, anthocyanidin, flavanone, flavonol, isoflavone, flavone, and flavan-3-ol. Conformational, structural, magnetic, and electronic analyses were performed using nuclear magnetic resonance, ionization potentials, electron affinity, bond dissociation energy, proton affinity, frontier molecular orbitals (highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO)), and aromaticity through nucleus-independent chemical shifts to analyze these seven flavonoid structures. We revised the influence of hydroxyl groups on the properties of flavonoids and also investigated the influence of the aromaticity of these seven flavonoids on the antioxidant activity.
