The Na + affinities of α-amino acids: side-chain substituent effects

Abstract

Na +-bound heterodimers of amino acids (AA) are produced in the gas phase by electrospray ionization (ESI). The dissociation kinetics of these AA 1Na +AA 2 ions are determined by collisionally activated dissociation (CAD) and converted to a ladder of relative Na + affinities via the Cooks kinetic method. The affinities derived follow the order (kJ mol −1, relative to Gly): Gly (0), Ala (6), Val (12), Leu (13), Cys (14), Ile (15), Ser (31), Pro (35), Thr (36), Phe (37), Tyr (40), Asp (42), Glu (43), Asn (45), Trp (49), Gln (51), His (57). Absolute Na + binding energies are estimated by anchoring the relative values to the Na + affinity of Ala (167 kJ mol −1), measured by the same approach using Na +-bound dimers of Ala and a series of acetamide derivatives. The Na + binding energies of the acetamide reference bases and of representative aliphatic and side-chain functionalized amino acids (Gly, Ala, Pro, Cys and Ser) are determined by ab initio theory. Experimental and ab initio affinities agree very well. The combined data show that functional side chains increase the AANa + bond strength by providing an extra ligand to the metal ion. Aromatic and carbonyl substituents in the side chain bring about substantial increases in the Na + binding energy, with particularly large increments observed for amide and electron-rich (N-containing) aromatic groups. A poor correlation is found between sodium ion and proton affinities, strongly suggesting that the Na + complexes do not have salt-bridge structures involving zwitterionic amino acids (in which the most basic site is protonated).