Restricted rotation in six-membered cyclic nitrosamine compounds: an ab initio and DFT study and NBO analysis

Besides the fact that in nitrosamines, considered as a family of potent carcinogenic compounds, the barrier to internal rotation about the N-N bond is a significant conformational factor, it is as well important for understanding the mechanism of their bioactivity and detoxification. In this work, a detailed study of the internal rotation of the NO group about the N-N bond in various six-membered cyclic nitrosamine compounds was performed using ab initio (HF and MP2) and DFT methods with 6-31G** basis set. Between the two resulting rotational transition states (TS1 and TS2), TS1 was found to be more stable than TS2 according to the all used methods. The activation energy barriers obtained by ab initio methods were also in good agreement with the experimental values. In the studied compound series, the ab initio (HF and MP2) calculated internal rotation activation Gibbs free energies through TS1, lies between 80.01 and 96.26 kJ/mol. The results showed as well that the planar structure of the N-atom in ground state becomes pyramidal in transition states. In addition, in order to explore the origin of the internal rotation energy barrier, the natural bond orbital analysis (NBO) revealed, specifically, that the lp(N4)→BD*(NO) donor-acceptor interaction is the most significant interaction in nitrosamine compounds. NBO analysis showed also that the s-character of the N4 lone pair orbital and its occupation number increases as approaching the top of the rotational barrier in these studied compounds.