Cation effects on proteins have been a challenge to understand. Herein, we present two-dimensional infrared (2DIR) spectroscopic measurements, coupled with molecular dynamics and spectroscopic calculations, of N-methylacetamide (NMA), a common model of the peptide backbone, in aqueous CaCl2. The 2DIR spectra reveal that the dynamics of the amide carbonyl of NMA is dominated by exchange between two states of varying hydration, one possessing a structure similar to aqueous NMA and one that is dehydrated by one hydrogen bond. In addition, we demonstrate that at high (>5 M) CaCl2 concentrations, direct binding of Ca2+ to the carbonyl of NMA occurs, stabilizing an iminium-type resonance structure of NMA, with a characteristic C=N+ stretch frequency at 1680 cm(-1). This species is only marginally populated and is only detectable in 2DIR spectra due to its larger transition strength.