Comparative analysis of the reactivity of anthocyanidins, leucoanthocyanidins, and flavonols using a quantum chemistry approach

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.

Keywords: Antioxidant activity; Flavonoids; Fukui functions; Reactivity.

Fig. 1

Molecular structure of nine primary flavonoids investigated in the present study

Fig. 2

Conformational analysis using CAM-B3LYP/def2TZV of the τ torsion angle (in degrees) of anthocyanidins, leucoanthocyanidins, and flavonols

Fig. 3

Bond critical points (3, − 1) of the nine investigated molecules

Fig. 4

ELF contour map of anthocyanidins and flavonols

Fig. 5

ELF contour map of leucoanthocyanidins

Fig. 6

MEP surfaces of anthocyanidins, leucoanthocyanidins, and flavonols. Dipole moment vectors are displayed in blue

Fig. 7

Fukui functions $f^{-}$ of the nine investigated molecules for sites favorable to electrophilic attacks

Fig. 8

Fukui functions $f^{+}$ of the nine investigated molecules for sites favorable to nucleophilic attacks

Fig. 9

NICS (ppm per distance r in Å) in the isotropic field of the nine molecules. Values in red refers to the ring C NICS