Theoretical Determination of the pK a Values of Betalamic Acid Related to the Free Radical Scavenger Capacity: Comparison Between Empirical and Quantum Chemical Methods

Abstract

Health benefits of dietary phytochemicals have been suggested in recent years. Among 1000s of different compounds, Betalains, which occur in vegetables of the Cariophyllalae order (cactus pear fruits and red beet), have been considered because of reducing power and potential to affect redox-modulated cellular processes. The antioxidant power of Betalains is strictly due to the dissociation rate of the acid moieties present in all the molecules of this family of phytochemicals. Experimentally, only the pK avalues of betanin were determined. Recently, it was evidenced it was evidenced as the acid dissociation, at different environmental pHs, affects on its electron-donating capacity, and further on its free radical scavenging power. The identical correlation was studied on another Betalains family compound, Betalamic Acid. Experimental evidences showed that the free radical scavenging capacity of this compound drastically decreases at pH [ 5, but pK a values were experimentally not measured. With the aim to justify the Betalamic Acid behavior as free radical scavenger, in this paper we tried to predict in silico the pK a values by means different approaches. Starting from the known experimental pK a s of acid compounds, both phytochemicals and small organic, two empirical approaches and quantum-mechanical calculation were compared to give reliable prediction of the pK a s of Betalamic Acid.Results by means these computational approaches are consistent with the experimental evidences. As shown herein, in silico, the totally dissociated species, at the experimental pH [ 5 in solution, is predominant, exploiting the higher electron-donating capability (HOMO energy). Therefore, the computational estimated pK a values of Betalamic Acid resulted very reliable.

Solvent Effects on Protonation Constants of Betanin in Different Aqueous Solutions of Methanol at T = 25 ºC

“…In fourth step (L 3-+ H + ⇄ HL 2-) which occurs around pcH =7-9.5, proton is added to the the phenolic group that is attached to C6 atom. These processes for deprotonation of betanin have been extensively studied by several researchers and some of them have demonstrated that two deprotonation reactions (second and third steps) are so close together and therefore, both of them can be assigned only to one reaction equilibrium [24]. In this research work, the obtained protonation constants are in fine agreement with those previously reported [20].…”

Phytochemical Antioxidants: Past, Present and Future

“…In contrast with flavonoids, however, the chemistry of the antioxidant mechanism of betalains is less understood. It has been suggested that the common skeleton betalamic acid may contribute to their antioxidant activities [57][58][59]. Phenolic hydroxy group in cyclo-dopa moiety of betacyanin and the amino acid/amine portion of betaxanthin may increase the radical scavenging activities of betalamic acids [58].…”

Revisiting the Mechanism of Hydrolysis of Betanin

“…Also, in both cases, the S 0 ⟶S 1 transitions are well behaved, showing p-p* character and involving exclusively HOMO-LUMO transitions. We also calculated the pK a of the acidic groups in Bn using the empirical method implemented in MarvinSketch, which has been used to estimate the pK a of betalamic acid (76). This method predicts the CO 2 H group at C2 to be the most acidic (pK a 1.5), followed by the carboxylic groups at C17 (pK a 3.0) and C15 (pK a 3.7) and the 5-OH group (pK a 8.5), agreeing with the experimental values.…”