Theoretical Study of 2-(Trifluoromethyl)phenothiazine Derivatives with Two Hydroxyl Groups in the Side Chain-DFT and QTAIM Computations

Abstract

Phenothiazines are known as synthetic antipsychotic drugs that exhibit a wide range of biological effects. Their properties result from the structure and variability of substituents in the heterocyclic system. It is known that different quantum chemical properties have a significant impact on drug behavior in the biological systems. Thus, due to the diversity in the chemical structure of phenothiazines as well as other drugs containing heterocyclic systems, quantum chemical calculations provide valuable methods in predicting their activity. In our study, DFT computations were applied to show some thermochemical parameters (bond dissociation enthalpy—BDE, ionization potential—IP, proton dissociation enthalpy—PDE, proton affinity—PA, and electrontransfer enthalpy—ETE) describing the process of releasing the hydrogen/proton from the hydroxyl group in the side chain of four 2-(trifluoromethyl)phenothiazine (TFMP) derivatives and fluphenazine (FLU). Additional theoretical analysis was carried out based on QTAIM theory. The results allowed theoretical determination of the ability of compounds to scavenge free radicals. In addition, the intramolecular hydrogen bond (H-bond) between the H-atom of the hydroxyl group and the N-atom located in the side chain of the investigated compounds has been identified and characterized.

Synthesis, optical properties and DFT-TDDFT computational study of phenothiazine dye: donor-acceptor molecules

“…In the D-A molecules, the positive charges of S atoms rise together with a significant increase in the negative charges of N atoms. The conjugated D-A compounds' bigger N and S atomic charge differences may result in higher ground-state dipole moments (8.11 D for PTZIDM) than the parent PTZ molecule (2.46 D)(Poła et al , 2021). Therefore, it may be concluded that both the acceptor as well as the donor of the D-A molecule interact intramolecularly.…”