Computational study of substituent effects on the physicochemical properties and chemical reactivity of selected antiparasitic 5-nitrofurans

• Published in: Journal of molecular structure 2018-12, Vol.1173, p.92-99
• Main Authors: Barrientos-Salcedo, Carolina, Espinoza, Bertha, Soriano-Correa, Catalina
• Format: Article
• Language: English
• Subjects: 5-Nitrofurans; Acidity; Chagas disease; Chemical reactivity; Proton affinities; Trypanosoma cruzi
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2018.06.089

American Trypanosomiasis is a disease caused by the protozoan parasite Trypanosoma cruzi agent. Nifurtimox and benznidazole are effective drugs in the acute phase; however, are toxic and have adverse effects. Nonetheless, the nitroheterocycles are good models to design other compounds with less side effects. Theoretical and experimental studies have been performed about the structure and mode action of these drugs and at present, no effective treatment of this disease has been established yet, and the parasitic infections increase each year. The aim of this work, was to analyze the substituent effects on the physicochemical properties and chemical reactivity of selected antiparasitic 5-nitrofurans, using quantum-chemical descriptors: acidity, proton affinities, SESE, potential ionization, hardness, electrophilicity, aromaticity, dipole moment and Fukui functions at the DFT-M06-2X level in aqueous solution. The acidity of the azomethine group increases with the presence of the electron-withdrawing groups. The electron-donating groups favor the basicity and the energy of stabilization in the active molecule (NFX). The atomic charges, the quantum chemical descriptors and Fukui function (fk+) showed that the main reactivity takes place on the Ar-NO2. These results reinforce the importance of the nitro group in the redox processes of the 5-nitrofurans that are involved in the trypanocidal effect. [Display omitted] •Electronic structure plays an important role on the molecular design.•The electron-attractor substituent groups favor the acidity and the chemical reactivity of 5-nitrofurans.•Chemical reactivity and the physicochemical features are crucial in the trypanocidal effect of 5-nitroheterocycles.