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.
Highlights
Introduction and Soumaya KouidhiQuantitative structure–activity relationship (QSAR) techniques provide a valuable approach to establishing a direct relationship between the quantum chemical properties and the biological activities of chemical compounds
Except from QSAR analysis, the biological properties can be theoretically assessed by calculation of the thermochemical parameters describing the physicochemical characteristic of different chemical groups in the structure of compounds
TFMP derivatives with the two hydroxyl groups located in the side chain
Summary
Introduction and Soumaya KouidhiQuantitative structure–activity relationship (QSAR) techniques provide a valuable approach to establishing a direct relationship between the quantum chemical properties and the biological activities of chemical compounds. The quantum theory of atoms in molecules (QTAIM) describes atomic and bond properties based on molecular electron-density distributions [3] Both DFT and QTAIM have been used in theoretical investigations on different compounds with anticancer activity [4,5,6]. Mary et al [5] used DFT theory to investigate the molecular geometries, vibrational spectra, electronic properties, and molecular electrostatic potential of pharmaceutically active chromone derivatives. The results of these calculations, together with the QTAIM studies, allowed for the conclusion
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