title: 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 a values 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 as of acid compounds, both phytochemicals and small organic, two empirical approaches and quantum-mechanical calculation were compared to give reliable prediction of the pK as 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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Via Archirafi 32, 90123, Palermo, Italy. marco.tutone@unipa.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Tutone
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Via Archirafi 32, 90123, Palermo, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Lauria
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Via Archirafi 32, 90123, Palermo, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Almerico
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D050858:Betalains / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry*; D008956:Models, Chemical; D011725:Pyridines / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D011725:Pyridines; C000252:betalamic acid; D050858:Betalains
keywords: Antioxidants; Betalamic Acid; DFT calculation; Empirical methods; pK a prediction