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.

Antioxidant activity of an inclusion complex between rutin and β-cyclodextrin: experimental and quantum chemical studies

“…Flavonoid-based compounds found in many plants have strong biological activity, making them some of the most promising classes of pharmaceuticals. 1 Because of the ability to regulate immunological responses, viruses, and carcinogens, avonoids have been labeled "nature's biochemical repairmen". Flavonoid compounds have considerable antioxidant activity due to unique features in their chemical structure: (i) hydroxyl groups that bind to aromatic rings can give hydro atoms, and (ii) aromatic rings (e.g., benzene rings, hetero-element rings) and double bonds (e.g., C]C and C]O bonds) create a conjugated system, stabilizing free radicals.…”

Docking and Electronic Structure of Rutin, Myricetin, and Baicalein Targeting 3CLpro

“…In the last few years, different flavonoid studies have been applied to address the ability to inhibit SARS-CoV-2 3CLpro protein, relating the importance of catalytic dyad His41 and Cys145 [2,3,[9][10][11][12]. Among these, rutin, myrecetin, and baicalein have been extensively studied for this target (Figure 1) [1][2][3][4][5][6][7][9][10][11][13][14][15][16][17][18].…”

“…Rutin (quercetin-3-rhamnoglucoside) is composed of quercetin (flavonol) with the disaccharide rutinose [8,13,14], and binding to 3CLpro can modify the spectroscopic properties and tertiary structure of protease [2]. Rutin sugar groups are structural and functionally relevant because of their hydrophilic nature [2].…”

“…It was suggested that rutin interacts indirectly with protease through quercetin rings A and C through residues His41 and Cys145, while ring B could perform hydrogen binding with Leu141 residue or with a chain of Glu166 residue [2]. Rutin (quercetin-3-rhamnoglucoside) is composed of quercetin (flavonol) with the disaccharide rutinose [8,13,14], and binding to 3CLpro can modify the spectroscopic properties and tertiary structure of protease [2]. Rutin sugar groups are structural and functionally relevant because of their hydrophilic nature [2].…”

“…Several molecular modeling and computational chemistry techniques have been used to study the activity and relationships of flavonols against important targets [9,13,14,19]. In the context of these molecules, 3CLpro has been the target of relevance in the last few years [1][2][3][4][5][6][7][8]15].…”