Cation [M = H⁺, Li⁺, Na⁺, K⁺, Ca²⁺, Mg²⁺, NH₄⁺, and NMe₄⁺] Interactions with the\nAromatic Motifs of Naturally Occurring Amino Acids:  A Theoretical Study^†

Abstract

Ab initio (HF, MP2, and CCSD(T)) and DFT (B3LYP) calculations were done in modeling the cation (H⁺,\nLi⁺, Na⁺, K⁺, Ca²⁺, Mg²⁺, NH₄⁺, and NMe₄⁺) interaction with aromatic side chain motifs of four amino\nacids (viz., phenylalanine, tyrosine, tryptophan and histidine). As the metal ion approaches the π-framework\nof the model systems, they form strongly bound cation-π complexes, where the metal ion is symmetrically\ndisposed with respect to all ring atoms. In contrast, proton prefers to bind covalently to one of the ring\ncarbons. The NH₄⁺ and NMe₄⁺ ions have shown N−H···π interaction and C−H···π interaction with the\naromatic motifs. The interaction energies of N−H···π and C−H···π complexes are higher than hydrogen\nbonding interactions; thus, the orientation of aromatic side chains in protein is effected in the presence of\nammonium ions. However, the regioselectivity of metal ion complexation is controlled by the affinity of the\nsite of attack. In the imidazole unit of histidine the ring nitrogen has much higher metal ion (as well as\nproton) affinity as compared to the π-face, facilitating the in-plane complexation of the metal ions. The\ninteraction energies increase in the order of <b>1-M</b> < <b>2-M</b> < <b>3-M</b> < <b>4-M</b> < <b>5-M</b> for all the metal ion considered.\nSimilarly, the complexation energies with the model systems decrease in the following order: Mg²⁺ > Ca²⁺\n> Li⁺ > Na⁺ > K⁺ ≅ NH₄⁺ > NMe₄⁺. The variation of the bond lengths and the extent of charge transfer\nupon complexation correlate well with the computed interaction energies.