Electronic Properties of Small Psychotropic Substances in WaterPhenylamines.

Small molecules containing phenyl and aliphatic amine groups belonging to psychotropic drugs were studied by quantum chemical computational methods. Each of the 9 studied species (phenethylamine, amphetamine, ephedrine, pseudoephedrine, methamphetamine, MDMA, MDEA, MDA, MDAI) was considered in three oxidation states: neutral molecule, molecular cation, and molecular anion. Protonated residues from the hydrochloride forms were also considered. This allows, after full geometry optimization followed by vibrational analysis, the evaluation of global adiabatic electronic properties such as ionization energy, electron affinity, molecular electronegativity, chemical hardness, electrophilicity index, and absolute oxidation and reduction potentials. The ground-state molecular properties include electrical properties (atomic charges, dipole moment, quadrupole moment, and dipole polarizability), atomic spin densities, magnetic properties (NMR shielding constants), molar-mass-dependent molecular properties (solvated surface area and molecular volume), and thermodynamic properties (zero-point vibrational energy, entropic contribution, and Gibbs energy). Several correlations were found between molecular descriptors, e.g., molar-mass-dependent properties (dipole polarizability and zero-point vibration energy) vs molar mass, absolute oxidation potential vs adiabatic ionization energy, absolute reduction potential vs electrophilicity index, and