Protonation thermochemistry of β-alanine: An evaluation of proton affinities and entropies determined by the extended kinetic method

Abstract

The extended kinetic method is employed to determine the proton affinity (PA) of β-alanine and four other difunctional molecules that can develop intramolecular hydrogen bonds after protonation, including α-alanine and three α,ω-diaminoalkanes. Proton-bound dimers of each of these molecules (AA) and reference bases of similar protonation entropy (B i) are formed by fast atom bombardment ionization and the dissociation kinetics of the AA–H +–B i ions into the individual protonated monomers are assessed as a function of internal energy using tandem mass spectrometry and low energy collisionally activated dissociation (CAD). This procedure accounts for any difference in the activation entropies of the competitive dissociations, Δ(Δ S ‡), which is assumed to be negligible in the conventional kinetic method (one internal energy), thereby leading to more accurate PA data. The proton affinities derived for α-Ala (902±4 kJ mol −1) and 1,2-diaminoethane (951±4 kJ mol −1), i.e., difunctional molecules that form relatively weak hydrogen bonds after protonation, are in excellent agreement with literature values. A PA of 927±4 kJ mol −1 is found for β-Ala, the substantial rise vs. PA(α-Ala) reflecting an increased intrinsic basicity upon moving the electron-withdrawing COOH group further away from the amine group and an improved hydrogen bonding arrangement with the β-substitution pattern. The PAs measured for 1,3-diaminopropane (978±4 kJ mol −1) and 1,4-diaminobutane (993±4 kJ mol −1), which develop markedly stronger hydrogen bonds after protonation, are 9 and 13 kJ mol −1, respectively, lower than reported data. The underestimation is attributed to small reverse barriers and/or an underestimation of Δ(Δ S ‡). Our measurements confirm that the Δ(Δ S ‡) parameter obtained by the extended kinetic method is not a thermodynamic quantity equal to the relative protonation entropy between AA and B i, but a relative entropy between the dissociating transition states at the actual, generally non-Boltzmann energy distribution of the AA–H +–B i heterodimers. Recommendations are given, when to apply the extended kinetic method (involving activation entropy corrections) vis-à-vis its conventional variant.