title: Prediction of pKaUsing DFT: the Nicotianamine Polyacid Example.
abstract: The determination of pKavalues for molecules containing multiple acidic groups in solution is challenging both experimentally and theoretically. We propose a general method to obtain these values by combining a graphical analysis based on a predominance diagram, for amino acids and nicotianamine polyacid, with first principle DFT calculations. Implicit and semiexplicit water solvent models were included to account for solvation. This strategy enables the investigation of the protonation states of compounds containing acidic moieties in solution depending on the pH domain. The method was first validated on a set of amino acids with pKavalues calculated with an accuracy within 0.5-1.0 pKaunit and then on the chalenging nicotianamine polyacid with six pKavalues. This approach is particularly well suited for such a complex system including both zwitterionic structures and unknown experimental pKavalues.
authors.affiliation: Institut Charles Gerhardt, MACS, UMR 5253 CNRS-ENSCM-UM, 8, rue de l'Ecole Normale, 34296 Montpellier cedex 5, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Giard
authors.affiliation: Institut Charles Gerhardt, CTMM, UMR 5253 CNRS-ENSCM-UM, Place Eugène Bataillon, 34296 Montpellier cedex 5, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Filhol
authors.affiliation: LPCNO, UMR 5215 CNRS-INSA-UPS, 135 avenue de Rangueil 31077 Toulouse Cedex 4, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Jolibois
authors.affiliation: Institut des Biomolécules Max Mousseron UMR 5247, CNRS -ENSCM-UM Place Eugène Bataillon, 34095 Montpellier cedex 5, France.
authors.forename: Florine
authors.initials: F
authors.lastname: Cavelier
authors.affiliation: Institut Charles Gerhardt, MACS, UMR 5253 CNRS-ENSCM-UM, 8, rue de l'Ecole Normale, 34296 Montpellier cedex 5, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Berthomieu
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008968:Molecular Conformation; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; C082893:nicotianamine; D001383:Azetidinecarboxylic Acid