Proton and potassium affinities of aliphatic and N-methylated aliphatic α-amino acids: Effect of alkyl chain length on relative stabilities of K+ bound zwitterionic complexes

Abstract

The relative and absolute K+ affinities of a full series of aliphatic amino acids (Gly, Ala, Val, Leu, Ile and α-amino-isobutyric acid (α-AiB)) and N-methylated aliphatic amino acids (N-Me-(Gly/Ala/α-AiB/Val/Leu)) were investigated theoretically by density functional theory calculations at the B3–LYP/6-311+G(3df,2p)//B3-LYP/6-31G(d) level, and experimentally measured by the standard mass spectrometric kinetic method. Very good quantitative agreement was found between the theoretical and experimental results. The experimental K+ affinities were found to be consistent with the most stable charge-solvated CS1 binding mode (bidentate form with K+ bonded between two carboxylic oxygens, OC, OH) for aliphatic amino acids, and the zwitterionic ZW1 binding mode (bidentate form with K+ bonded between two carboxylate oxygens, COO−) for the N-methylated aliphatic amino acids. A steeper rising trend in ZW1 stabilities (affinities) relative to that of CS1 was found in the smaller aliphatic amino acids (Gly/Ala/α-AiB), but leveling off among the larger aliphatic amino acids (Val/Leu/Ile). This observed trend was rationalized in terms of greater deformation energy, Edef, found for the smaller Gly/Ala, and the leveling off of stabilizing ion-induced dipole (molecular polarizability) contributions from the non-interacting alkyl side chain in the larger aliphatic amino acids. The leveling off effect is aided by the relatively large size and soft, not so polarizing nature of the potassium cation. A good linear correlation (r2≥0.95) was found between the proton affinities (PA) and the ZW1/CS1K+ affinities, but because of the leveling off effect, the cross over or transition from CS1 to ZW1K+ binding mode was not found for isoleucine.