Quantum chemical study on phenethylamines reveals new cation structures

Abstract Phenethylamines are compounds known by their psychoactive and stimulant effects. Their physiological activity is strongly conformer dependent. In this work, the quantum chemical investigation of neutral and cationic phenylethylamine, amphetamine and methamphetamine was performed in order to determine the most stable physiologically relevant conformers. Calculations were performed employing density functional theory and ωB97XD functional. A previously unknown double-ring cation structure formed by cyclization of aliphatic tail was found for all three molecular species. Calculations performed on several levels of theory reveal significant stability of these double-ring cations relative to other conformers. The transition state structures and energies for the cyclization reactions have been determined. Their stability and structural properties are discussed, as well as the possibility for their experimental observation. The significance of dispersion and NH⋯π interactions between side chain and phenyl ring on stability of phenethylamines and their charged forms were pointed out.