Identifying dominant conformations of N-acetyl-l-cysteine methyl ester and N-acetyl-l-cysteine in water: VCD signatures of the amide I and the C[dbnd]O stretching bands

Abstract

Infrared (IR) and vibrational circular dichroism (VCD) spectra of N-Acetyl-l-Cysteine Methyl Ester (NALCME) and N-Acetyl-l-Cysteine (NALC) in D2O under different pHs were measured. We focus on the VCD signatures of the amide I and the CO stretching spectral signatures of the neutral NALCME and NALC species and the related ones of the deprotonated NALC species in the region of 1800–1500cm−1. A sign inversion is observed for the amide I VCD band going from the neutral NALCME and NALC to the deprotonated NALC species. Density functional theory (DFT) calculations were carried out to search for the possible conformations of these three species and to simulate their IR and VCD spectra at the B3LYP/aug-cc-pVTZ level in the gas phase and with the polarization continuum model of water solvent. The most stable conformations found for neutral NALCME and NALC exhibit drastically difference VCD patterns, whereas those of deprotonated NALC show similar patterns. We establish an empirical structural–spectral relationship where the aforementioned VCD signatures can be used as spectral markers to identify dominant conformations of these two amino acid derivatives under different pHs. It is recognized that the dominant conformers identified using the VCD spectral markers differ from those based on the relative DFT energies for neutral NALCME and NALC. The influence of solvent on both the conformational geometries and their relative stabilities is discussed. The aforementioned discrepancy can be attributed to the explicit solute–solvent hydrogen-bonding interactions which are not accounted for in the calculations. The empirical structural–spectral relationship identified can potentially be applied to large, related amino acids and polypeptides in water.