An NMR and ab Initio Quantum Chemical Study of Acid−Base Equilibria for Conformationally Constrained Acidic α-Amino Acids in Aqueous Solution

The protonation states of a series of piperidinedicarboxylic acids (PDAs), which are conformationally constrained acidic α-amino acids, have been studied by ¹³C NMR titration in water. The resulting data have been correlated with theoretical results obtained by HF/6-31+G* calculations using the polarizable continuum model (PCM) for the description of water. The PDAs are highly ionizable and contain one or two possible internal hydrogen bonds. In the present study, we show that the PCM model is able to reproduce the relative stabilities of the different protonation states of the PDAs. Furthermore, our results show that prediction of relative pK_a values for two different types of ionizable functional groups covering a pK_a range from 1.6 to 12.1 is possible with a high degree of accuracy.