Table 2. Summary of Inputs to and Outputs from the TCPD Approach Used for Estimating Values of Free Energies of Hydration for Arg⁺, Lys⁺, Asp^–, and Glu^–

side chain mimicked by the model compound	measured67 pKa	gas-phase basicity (kcal/mol)19,68	measured values of ΔμhB,Δμh (kcal/mol)64	ΔμhBH+,Δμh derived from TCPD analysis using the mean valuea for ΔμhH+ (kcal/mol)c
Arg+	13.665	234.6 ± 2.0b	–10.9 ± 1.9	–55.76 ± 6.44
Lys+	10.769	211.3 ± 0.5	–4.3 ± 1.9	–68.51 ± 6.15
Asp–	4.7670	341.4 ± 1.2	–6.7 ± 1.9	–80.71 ± 6.24
Glu–	4.8870	340.4 ± 1.4	–6.5 ± 1.9	–79.35 ± 6.28

^aThe mean and standard deviation of Δμ_h^H+ calculated from the literature values (Table 1) are −260.89 ± 5.82 kcal/mol. Irrespective of the value used for the free energy of hydration of the proton, the free energy of hydration of the model compound mimic of Arg⁺ is 12.75 kcal/mol less favorable than that of Lys⁺. Conversely, the free energies of hydration of model compound mimics of Asp^– and Glu^– are ∼25 and ∼24 kcal/mol more favorable than that of Arg⁺ and ∼12 and ∼11 kcal/mol more favorable than that of Lys⁺ when we set Δμ_h = −260. 89 kcal/mol.

^bThis is the calculated gas-phase basicity for 1-methylguanidinium. Note that the value of the gas-phase basicity for guanidinium is 226.9 kcal/mol. The value we use is more appropriate for 1-propylguanidinium.

^cThe large error bars in this column are entirely due to the large standard deviation of 5.82 kcal/mol that we compute across the 72 distinct values we collated for the hydration free energy of the proton.