Interaction between metal cation and unnatural peptide backbone mediated by polarized water molecules: study of...

In this work, the interaction between metal cation and a model β-peptide N-ethylpropionamide (NEPA) in aqueous solution is investigated using infrared absorption spectroscopy. Monovalent (Na(+)), divalent (Ca(2+), Mg(2+)), and trivalent (Al(3+)) metal cations added to NEPA/water solution at moderate concentrations split the amide-I frequency into a red- and blue-shifted component. Molecular dynamics simulations of NEPA in moderate cationic strength are conducted to gain insight into the structural details of the peptide-salt-water system, particularly in the vicinity of the amide group. Our results do not suggest a direct contact between cation and amide oxygen in the solution phase; otherwise, only a significant red shift in the amide-I frequency would occur due to the vibrational Stark effect, as evidenced by quantum chemistry computations. Instead, our results suggest it is the dynamical interaction between the formed cation/water/anion complexes and the amide group that causes the observed split in the amide-I peak, which indicates the presence of both salting-in (red-shifted) and salting-out (blue-shifted) NEPA species. The presence of dynamic and polarized water molecules between the amide oxygen and the cation complex is believed to be the key to the split amide-I peaks in the cation-rich environment. Our results can be useful to better understand the cationic Hofmeister series.