Halide anion binding to Gly3, Ala3 and Leu3

Abstract

The structures of Gly3·X−, Ala3·X− and Leu3·X− (X=Cl, Br and I) are investigated with computational chemistry and infrared multiple-photon dissociation (IRMPD) spectroscopy. Low-energy structures calculated at the B3LYP/6-31+G** level of theory (or with the CRENBL basis set and effective core potential implemented for Br and I) for these complexes have similar structural motifs in which the halide anion binds to the peptide via hydrogen bonds at amide, amine, and/or carboxylic acid H atoms. The IRMPD spectra do not depend significantly on anion identity. Comparisons between measured spectra and those calculated for low-energy structures of each of the chloridated complexes indicate that all three complexes have similar binding motifs. These results suggest that the size of the alkyl side chain does not significantly influence how halide anions bind to these peptides. The coordination geometries of Gly3·X− and Ala3·X− are “inverted” compared to those for the Na+ cationized peptides, where the peptides coordinate to Na+ via lone pair electrons of O and N atoms. The “inversion” in structures between Ala3·Na+ and Ala3·X− results in greater steric hindrance for some geometries of the latter. There is a subtle blue shift in the C-terminal CO stretch frequency with increasing halide anion size for each peptide, consistent with contributions from Stark and charge transfer effects. In contrast, the NH bends red shift with increasing halide anion size, which can only be attributed to the charge transfer effect. This is the first report of IR spectra of peptides complexed with anions, and these results provide insights into anion-peptide binding interactions.