Gas phase proton affinities of proline-containing peptides. 1: ProGly, ProAla, ProVal, ProLeu, ProIle, and ProPro

The gas-phase proton affinities (PA) for a series of proline-containing dipeptides have been measured in an ESI triple quadrupole instrument using the extended kinetic method. Proton affinities for ProGly (1), ProAla (2), ProVal (3), ProLeu (4), ProIle (5), and ProPro (6) were determined to be 969.6 ± 7.8, 990.4 ± 7.7, 987.6 ± 7.9, 982.8 ± 8.0, 988.8 ± 10.1, and 996.5 ± 12.2 kJ/mol, respectively. Predictions for the proton affinities for 1–6 were also obtained through isodesmic calculations at the B3LYP/6-311++G(d,p)//B3LYP/6-31+G(d) level of theory. The predicted proton affinities for 1 and 6 of 966.9 and 991.0 kJ/mol are in agreement with the experimental values. However, the predicted proton affinities for 2–5 of 973.5, 975.9, 975.7, and 975.9 are between 8 and 15 kJ/mol lower than the experimental values. Additional calculations with a larger basis set (B3LYP/6-311++G(2df,2p), inclusion of dispersion (B3LYP-D3/6-311++G(d,p)), switching to second order perturbation theory (MP2/6-31++G(d,p) and MP2/6-311++G(2df,2p), or switching density functional (M06-2x/6-311++G(d,p) and M06-2x/6-311++G(2df,2p) show only modest changes in derived thermochemistry lending support to the original calculations. We recommend using the experimental proton affinities for ProGly and ProPro and using the calculated values for ProAla, ProVal, ProLeu, and ProIle with the experimental proton affinities as upper limits.