Deducing the molecular properties of zwitterionic, protonated, deprotonated, and double-deprotonated forms of L-cysteine from vibrational spectroscopy (IR, Raman, VCD) and quantum chemical calculations

The behavior of L-cysteine (C3H7NO2S, (2R)-2-amino-3-sulfanylpropanoic acid) in water at different pH values was analyzed both experimentally and theoretically. The behavior was studied at pH values of 5.21 (at this pH, L-cysteine is a zwitterionic species), 1.00 (protonated species), 8.84 (monodeprotonated species), and 13.00 (dideprotonated species). We carried out a vibrational study using nonchiroptical (IR–Raman) and chiroptical (VCD) techniques complemented by quantum chemical calculations. We adopted a dual strategy, as follows. (i) The hybrid density functionals B3LYP and M062X and the ab initio MP2 method were employed, with the same 6-311++G (d,p) basis set, in order to characterize the relative energies and structures of an extensive set of conformers of L-cysteine. The presence of water was included by utilizing the IEF-PCM implicit solvation model. (ii) The vibrational analysis was made using a chirality-sensitive using a chirality-sensitive technique (VCD) and chirality-insensitive techniques (IR, including MIR and FIR, and Raman), especially in aqueous solution. The results obtained theoretically and experimentally were compared in order to deduce the most stable structures at each pH. Moreover, for the first time, the monodeprotonated anion of L-cysteine was detected in aqueous solution by means of IR, Raman and vibrational circular dichroism (VCD). Finally, analysis of the low-frequency region using the IR and Raman techniques was shown to be a very important way to understanding the conformational preference of the zwitterionic species.