Conformational analysis and spectroscopic properties of antichagasic nifurtimox

Abstract

Considering the health relevance of Chagas’ disease, recent research efforts have focused on developing moreefficient drug delivery systems containing nifurtimox (NFX). This paper comprehensively investigates NFXthrough conformational analysis and spectroscopic characterization. Using a conformer-rotamer ensemblesampling tool (CREST-xtb), five distinct conformers of NFX were sampled within a 3.0 kcal mol 1 relative energywindow. Subsequently, such structures were used as inputs for geometry optimization by density functionaltheory (DFT) at B3LYP-def2-TZVP level of theory. Notably, harmonic vibrational frequencies were calculated toestablish an in-depth comparison with experimental results and existing literature for the NFX or similar moleculesand functional groups, thereby achieving a widely reasoned assignment of the mid-infrared band absorptionsfor the first time. Moreover, UV–VIS spectra of NFX were obtained in several solvents, enabling thedetermination of the molar absorptivity coefficient for the two electronic transitions observed for NFX. Amongthe aprotic solvents, a bathochromic effect was observed in the function of the dielectric constants. Furthermore,a hypochromic effect was observed when the drug was dissolved in protic solvents. These findings offer crucialsupport for new drug delivery systems containing NFX while demonstrating the potential of spectrophotometricstudies in establishing quality control assays for NFX drug products.