Dipeptide structure determination by vibrational circular dichroism combined with quantum chemistry calculations

The solution structure and the local salvation environments of alanine dipeptide (AD, I a) and its isotopomer (AD*, 1b, C-13 on the acetyl end C=O) are studied by using infrared (IR) spectroscopy and vibrational circular dichroism (VCD). From the amide I IR spectra of AD* in various protic solvents, it is found that each of the two carbonyl groups is fully H-bonded to two water molecules. However, the number of alcohol molecules H-bonded to each C=O varies from one to two, and the local salvation environments are asymmetric around the two peptides of AD* in alcohol solutions. The amide I VCD spectra of AD and AD* in D2O are also measured, and a series of density functional theory (DFT B3LYP/6-311 ++G**) calculations are performed to obtain the amide/normal-mode rotational strengths of AD and the intrinsic rotational strengths of its two peptide fragments. By combining the VCD-measurement and DFT-calculotion results and employing a coupled oscillator theory, we show that the aqueous-solution structure of the dipeptide con be determined. We believe that the present method will be of use in building up a library of dipeptide solution structures in water.