International Journal of Mass Spectrometry 227 (2003) 509–524 The Na + affinities of -amino acids: side-chain substituent effects Michelle M. Kish a , Gilles Ohanessian b , Chrys Wesdemiotis a,∗ a Department of Chemistry, The University of Akron, Akron, OH 44325, USA b Laboratoire des Mécanismes Réactionnels, UMR 7651 du CNRS, Ecole Polytechnique, F-91128 Palaiseau Cedex, France Received 28 March 2002; accepted 15 August 2002 Abstract Na + -bound heterodimers of amino acids (AA) are produced in the gas phase by electrospray ionization (ESI). The disso- ciation 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 (kJmol -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). © 2003 Elsevier Science B.V. All rights reserved. Keywords: Amino acids; Sodium ion affinities; Kinetic method; Charge solvation; Salt bridge 1. Introduction Sodium ion is one of the most abundant metal ions in biological systems, where it is involved in a variety of processes, including osmotic balance, the stabiliza- tion of biomolecular conformations and information transfer via ion pumps and ion channels [1–4]. Na + interacts with peptides and proteins to perform such ∗ Corresponding author. Tel.: +1-330-972-7699; fax: +1-330-972-7370. E-mail address: wesdemiotis@uakron.edu (C. Wesdemiotis). regulatory and structural functions. For a better un- derstanding of these interactions, information about the intrinsic binding modes of Na + to appropriate, simple model systems is necessary. The present study addresses this subject by using the kinetic method de- veloped by Cooks and coworkers [5,6] to determine the thus far largely unknown relative Na + affinities of -amino acids, the building blocks of peptides and proteins. The thermochemistry and structures of the Na + complexes of the -amino acids (AA) glycine (Gly), 1387-3806/03/$ – see front matter © 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S1387-3806(03)00082-4