Alkali Metal Ion Binding to Amino Acids Versus Their Methyl Esters: Affinity Trends and Structural Changes in the Gas Phase

Abstract

The relative alkali metal ion (M+) affinities (binding energies) between seventeen different amino acids (AA) and the corresponding methyl esters (AAOMe) were determined in the gas phase by the kinetic method based on the dissociation of AA–M+–AAOMe heterodimers (M=Li, Na, K, Cs). With the exception of proline, the Li+, Na+, and K+ affinities of the other aliphatic amino acids increase in the order AA<AAOMe, while their Cs+ affinities generally decrease in this direction. For aliphatic β‐amino acids, which are particularly basic molecules, the order AA>AAOMe is already observed for K+. Proline binds more strongly than its methyl ester to all M+ except Li+. Ab initio calculations on the M+ complexes of alanine, β‐aminoisobutyric acid, proline, glycine methyl ester, alanine methyl ester, and proline methyl ester show that their energetically most favorable complexes result from charge solvation, except for proline which forms salt bridges. The most stable mode of charge solvation depends on the ligand (AA or AAOMe) and, for AA, it gradually changes with metal ion size. Esters chelate all M+ ions through the amine and carbonyl groups. Amino acids coordinate Li+ and Na+ ions through the amine and carbonyl groups as well, but K+ and Cs+ ions are coordinated by the O atoms of the carboxyl group. Upon consideration of these differences in favored binding geometries, the theoretically derived relative M+ affinities between aliphatic AA and AAOMe are in good overall agreement with the above given experimental trends. The majority of side chain functionalized amino acids studied show experimentally the affinity order AA<AAOMe for all M+ ions, which is consistent with charge solvation. Deviations are only observed with the most basic amino acids lysine and arginine, whose K+ (for arginine) and Cs+ complexes (for both) follow the affinity order AA>AAOMe. The latter ranking is attributed to salt bridge formation.

Alkali Metal Complexes of the Dipeptides PheAla and AlaPhe: IRMPD Spectroscopy

“…[8,13,22,23] . Experimentally, sodium and/or potassium ion complexes of both Ala [12] and Phe [16] have been characterized by IRMPD spectroscopy, and we can also note examples of structural studies using this technique with other amino acid complexes.…”

Binding energies of water to lithiated valine: Formation of solution-phase structure in vacuo

“…For arginine, evidence suggests a nonzwitterion or charge-solvated form when Li ϩ or Na ϩ is attached, but a zwitterion or salt-bridge form with K ϩ , Rb ϩ , and Cs ϩ [30,34]. Attachment of an electron is sufficient to make the zwitterion form slightly more stable [23,35].…”

“…Calculations indicate that an attached alkali metal cation [23][24][25][26][27], silver (I) ion [28], or zinc (I) ion [29] can lower the relative energy of the zwitterion or salt-bridge form of glycine to only 1-4 kcal/mol higher in energy than the nonzwitterion or charge-solvated form of these ions. Experimental evidence indicates that only the chargesolvated form exists in the gas phase [26,30]. For Gly⅐Ni ϩ and Gly⅐Cu ϩ , the nonzwitterion forms are ϳ14 and 10 kcal/mol more stable, respectively [31,32].…”

“…Protonated octamers of serine are unusually stable in the gas phase [39 -41] and a structure in which all the serine molecules are zwitterionic has been proposed [39,40]. For proline, attachment of an alkali metal or Ag ϩ cation can make the zwitterion or salt-bridge form more stable than the nonzwitterion or charge-solvated form by 2-7 kcal/mol [30,42,43], but for Cu ϩ , the chargesolvated form is 3.4 kcal/mol more stable [32,44]. The higher propensity for arginine and proline to form zwitterion or salt-bridge structures is due in part to the higher gas-phase proton affinity of the proton acceptor and the poor charge-solvating ability in the case of proline.…”

Hydration of potassiated amino acids in the gas phase

“…They play an important role in several biochemical functions such as enzyme regulation, transfer of metal ions from intracellular to extracellular environments, electrical excitability of nerves, stabilization of DNA structures and so on [1]. Therefore, the interaction between alkali metal cations and various amino acids (AAs) has attracted considerable attention, and many experimental and theoretical studies have been conducted [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. These studies show that K ϩ binds to AAs quite differently than Na ϩ .…”