Cation-pi Interactions and oxidative effects on Cu+ and Cu2+ binding to Phe, Tyr, Trp, and His amino acids in the gas phase. Insights from first-principles calculations

J Phys Chem B. 2006 Nov 30;110(47):24189-99. doi: 10.1021/jp064957l.

Abstract

The coordination properties of the four natural aromatic amino acids (AA(arom) = Phe, Tyr, Trp, and His) to Cu+ and Cu2+ have been exhaustively studied by means of ab initio calculations. For Cu+-Phe, Cu+-Tyr and Cu+-Trp, the two charge solvated tridentate N/O/ring and bidentate N/ring structures, with the metal cation interacting with the pi system of the ring, were found to be the lowest ones, relative DeltaG(298K) energies being less than 0.5 kcal/mol. The Cu+-His ground-state structure has the metal cation interacting with the NH2 group and the imidazole N. For these low-lying structures vibrational features are also discussed. Unlike Cu+ complexes, the ground-state structure of Cu2+-Phe, Cu2+-Tyr, and Cu2+-Trp does not present cation-pi interactions due to the oxidation of the aromatic ring induced by the metal cation. The ground-state structure of Cu2+-His does not present oxidation of the amino acid, the coordination to Cu2+ being tridentate with the oxygen of the carbonyl group, the nitrogen of the amine, and the N of the imidazole. Other less stable isomers, however, show oxidation of His, particularly of the imidazole ring, which can induce spontaneous proton-transfer reactions from the NH of the imidazole to the NH2 of the backbone. Finally, the computed binding energies for Cu+-AA(arom) and Cu2+-AA(arom) systems have been computed, the order found for the single charged systems being Cu+-His > Cu+-Trp > Cu+-Tyr > Cu+-Phe, in very good agreement with the experimental data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Amino Acids, Aromatic / chemistry*
  • Binding Sites
  • Cations, Divalent
  • Copper / chemistry*
  • Gases*
  • Histidine / chemistry
  • Hydrogen Bonding
  • Models, Molecular
  • Nitrogen / chemistry
  • Oxidation-Reduction
  • Oxygen / chemistry
  • Phenylalanine / chemistry
  • Solvents / chemistry
  • Spectrophotometry, Infrared
  • Tryptophan / chemistry
  • Tyrosine / chemistry

Substances

  • Amino Acids, Aromatic
  • Cations, Divalent
  • Gases
  • Solvents
  • Tyrosine
  • Phenylalanine
  • Histidine
  • Copper
  • Tryptophan
  • Nitrogen
  • Oxygen