A theoretical and matrix-isolation FT-IR investigation of the conformational landscape of N-acetylcysteine

The conformational landscape of N-acetylcysteine (NAC) has been investigated by a combined experimental matrix-isolation FT-IR and theoretical methodology. This combination is a powerful tool to study the conformational behavior of relatively small molecules. Geometry optimizations at the HF/3-21 level resulted in 438 different geometries with an energy difference smaller than 22 kJ mol−1. Among these, six conformations were detected with a relative energy difference smaller than 10 kJ mol−1 at the DFT(B3LYP)/6-31++G∗∗ level of theory. These were finally subjected to MP2/6-31++G∗∗ optimizations which resulted in five minima. The vibrational and thermodynamical properties of these conformations were calculated at both the DFT and MP2 methodologies. Experimentally NAC was isolated in an argon matrix at 16 K after being sublimated at 323 K. The most stable MP2 form appeared to be dominant in the experimental spectra but the presence of three other conformations with ΔEMP2 < 10 kJ mol−1 was also demonstrated. The experimentally observed abundance of the H-bond containing conformations appeared to be in good accordance with the predicted MP2 value.