title: Competition between pi and non-pi cation-binding sites in aromatic amino acids: a theoretical study of alkali metal cation (Li+, Na+, K+)-phenylalanine complexes.
abstract: To understand the cation-pi interaction in aromatic amino acids and peptides, the binding of M(+) (where M(+) = Li(+), Na(+), and K(+)) to phenylalanine (Phe) is studied at the best level of density functional theory reported so far. The different modes of M(+) binding show the same order of binding affinity (Li(+)>Na(+)>K(+)), in the approximate ratio of 2.2:1.5:1.0. The most stable binding mode is one in which the M(+) is stabilized by a tridentate interaction between the cation and the carbonyl oxygen (O[double bond]C), amino nitrogen (--NH(2)), and aromatic pi ring; the absolute Li(+), Na(+), and K(+) affinities are estimated theoretically to be 275, 201, and 141 kJ mol(-1), respectively. Factors affecting the relative stabilities of various M(+)-Phe binding modes and conformers have been identified, with ion-dipole interaction playing an important role. We found that the trend of pi and non-pi cation bonding distances (Na(+)-pi>Na(+)-N>Na(+)-O and K(+)-pi>K(+)-N>K(+)-O) in our theoretical Na(+)/K(+)-Phe structures are in agreement with the reported X-ray crystal structures of model synthetic receptors (sodium and potassium bound lariat ether complexes), even though the average alkali metal cation-pi distance found in the crystal structures is longer. This difference between the solid and the gas-phase structures can be reconciled by taking the higher coordination number of the cations in the lariat ether complexes into account.
authors.affiliation: Department of Applied Biology and Chemical Technology and Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.
authors.forename: Fung Ming
authors.initials: FM
authors.lastname: Siu
authors.forename: Ngai Ling
authors.initials: NL
authors.lastname: Ma
authors.forename: Chun Wai
authors.initials: CW
authors.lastname: Tsang