Complexation of Na+ and K+ to Aromatic Amino Acids: A Density Functional Computational Study of Cation-π Interactions

Binding energies were calculated for the complexes of Na+ and K+ with phenylalanine (Phe), tyrosine (Tyr), and tryptophane (Trp), along with energies of low-energy conformers of the neutral amino acids. Structures were optimized and energies determined by density functional theory (DFT) with the B3LYP functional, using a basis set of 6-31+g(d) on all, or nearly all, heavy atoms. For all but one cation/ligand system, the most energetically favorable binding geometry was the tridentate N/O/Ring chelate. For K+/Trp, however, the advantage of placing the metal ion over the phenyl region of the indole side chain was dominant, leading to a most favored bidentate O/Ring binding geometry. All of the systems, and particularly the Trp systems, have multiple conformers with stabilities within a few kcal mol-1 of the most stable. Zwitterion forms of the complexes were not unreasonable, but were less stable than the normal forms by ∼5 kcal mol-1. To assess the importance of cation−π interactions, conformers were examined in which the side chain was rotated out of chelation. This indicated cation−π stabilization energies of ∼5 kcal mol-1.