Effect of pyridyl nitrogen on the conformational landscape of 7-azaserotonin: A computational study

The conformational topology of gaseous neutral 7-azaserotonin has been investigated by employing systematic ab initio calculations. The whole conformational landscape has been explored by varying four dihedral angles which define the position of ethyl amine side chain and phenolic OH group with respect to the 7-azaindole plane. A total of 22 local minima have been located by geometry optimization of 216 possible trial structures at the B3LYP/6-31+G* level of theory. With the exception of a few conformers, in most cases the OH-syn conformers were more stable than their OH-anti counterparts. Vibrational frequency analysis for all 22 conformers computed at B3LYP/6-31+G* shows some interesting features in the pyrrole and pyridine CH stretches. In some of the conformers the presence of intramolecular blue shifted H-bonding is confirmed using the atoms in molecules (AIM) analysis. The AIM analysis explains the differences in the relative energy order of various conformers compared to that observed in the case of serotonin. It also explains the behavior of the pyrrole and pyridine CH stretches observed for some of the conformers. The conformational distribution of 7-azaserotonin at various temperatures is computed based on simple thermodynamic principle. At lower temperature of about 100 K only six conformers were significantly populated according to their electronic energies while at higher temperature of about 400 K the populations were determined by their vibrational partition functions.