Cation-π effects in the complexation of Na⁺ and K⁺ with Phe, Tyr, and Trp in the gas phase

Abstract

Na+ and K+ gas-phase affinities of the three aromatic amino acids Phe, Tyr, and Trp were measured by the kinetic method. Na+ binds these amino acids much more strongly than K+, and for both metal ions the binding strength was found to follow the order Phe < or = Tyr < Trp. Quantum chemical calculations by density functional theory (DFT) gave the same qualitative ordering, but suggested a somewhat larger Phe/Trp increment. These results are in acceptable agreement with predictions based on the binding of Na+ and K+ to the side chain model molecules benzene, phenol, and indole, and are also in reasonable agreement with the predictions from purely electrostatic calculations of the side-chain binding effects. The binding energies were compared with those to the aliphatic amino acids glycine and alanine. Binding to the aromatic amino acids was found to be stronger both experimentally and computationally, but the DFT calculations indicate substantially larger increments relative to alanine than shown by the experiments. Possible reasons for this difference are discussed. The metal ion binding energies show the same trends as the proton affinities.

Hydration of potassiated amino acids in the gas phase

“…The charge density on the metal ion in AAK ϩ (H 2 O) should decrease as the metal ion affinity of AA increases. The effect of the side chain illustrated here by a decrease in the water binding energies in AAK ϩ (H 2 O) n ϭ 1,2 and previously [39] for AANa ϩ (H 2 O) n ϭ 1,2 with increasing K ϩ and Na ϩ affinities to AA, respectively, is in line with observations [4,14,18] that the binding of K ϩ and Na ϩ to amino acids is dominated by the interaction with the amino acid backbone and enhanced by interaction with the sidechain substituent. The binding enhancement effect of the phenyl substituent is manifested by the difference in the K ϩ binding energies to Ala (29.6 kcal/mol [13] and Phe (34.8 kcal/mol [13], while the electron withdrawing effect is demonstrated by the observed difference between the hydration energies for AlaK ϩ and PheK ϩ , Table 1.…”

“…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 .…”

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

“…The capability of cation-π complexation is provided by phenylalanine, which is the simplest amino acid having the possibility of a cation-π interaction in addition to the usual interactions of the ion with the Lewis-basic oxygens and nitrogens. The present results for the two Phe-containing dipeptide substrates explored here, PheAla and AlaPhe, have many features in common with previous work on M + Ala [12] and M + Phe [7,8,[13][14][15][16] complexes; the outstanding new feature introduced in progressing to the dipeptides is that the amide oxygen binding site appears for the first time, and turns out to be a dominant feature for complexation.…”

Recognition and quantification of binary and ternary mixtures of isomeric peptides by the kinetic method: metal ion and ligand effects on the dissociation of metal-bound complexes

“…In view of observations made in the present study we also note that the kinetic method has been of value as a source of information on auxiliary bonding, including cationinteractions [27], salt-bridging [28], and especially agostic bonding [29] (two-electron, three-center bonds where a hydrogen atom bridges two heavier elements, often carbon and a metal) [30].…”