The proton affinity and entropy of protonation of lysinamide. The effects of intramolecular proton solvation

The equilibrium constants for the gas-phase proton transfer from protonated tri-n-propylamine to lysinamide at several temperatures have been measured using Fourier transform ion cyclotron resonance mass spectrometric techniques. The thermodynamic values obtained from a van't Hoff plot are DeltaH = -4.36 +/- 0.85 kcal mol(-1) and DeltaS = -12.25 +/- 2.34 cal mol(-1) K-1. These values lead to derived values of the proton affinity. (PA) and entropy of protonation (DeltaS(p)) of lysinamide of 241.4 +/- 0.9 kcal mol(-1) and 10.9 +/- 2.2 cal mol(-1) K-1, respectively. A sophisticated calculation in the literature suggests that the former is identical with the PA of lysine as would be expected. The PA of lysinamide exceeds that of 1,5-diaminopentane by 2.5 kcal mol(-1), which is consistent with an expected favorable interaction between the carbonyl oxygen of the CONH2 group and the strong hydrogen bond in protonated lysinamide. The DeltaS(p) value is in good agreement with a kinetic-method determination of the entropy of protonation of lysine. It is suggested that the currently accepted PA of lysine, which was determined by the kinetic method, is 3-4 kcal mol(-1) too low. This discrepancy is suggested to be the result of the fact that the kinetic method measures activation entropies and enthalpies, rather than overall entropies and enthalpies, and thereby fails to measure the intramolecular proton-solvating interaction of the carbonyl group in lysine.