The 1,4-naphthoquinones are an important group of compounds intensively studied because of their wide range of biological activities. Four 2-chloro-3-(substituted-phenylamino)-1,4 naphthoquinone derivatives were synthesized, and the vibrational modes of these molecules were assigned using Raman and Fourier transform infrared spectroscopy (FTIR) techniques. In addition, X-ray studies were performed for one of these derivatives. Density functional theory (DFT) calculations were also developed for these compounds and presented. In summary, the results obtained from these studies can assess chemical changes in the structures of functionalized quinones and the discovery of candidate biologically active compounds.

A series of drugs was investigated to determine structural, electronic and pharmacological properties, as well as the molecular affinity for the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The drugs were submitted to density functional theory calculations to optimize structures and predict binding preferences. The optimized geometries were used in molecular docking simulations. In the docking study, the receiver was considered rigid and the drugs flexible. The Lamarckian genetic algorithm with global search and Pseudo-Solis and Wets with local search were adopted for docking. Absorption, distribution, metabolism, excretion and toxicological properties were obtained from the Pre-ADMET online server. In this series, the antiviral atazanavir showed the potential to inhibit the main protease of SARS-CoV-2, based on the free binding energy, inhibition constant, binding interactions and its favorable pharmacological properties. Therefore, we recommend carrying out further studies with in vitro tests and subsequent clinical tests to analyze its effectiveness in the treatment of SARS-CoV-2.

Abstract Herbicides are agrochemicals applied in the control of weeds. With the frequent and repetitive use of these substances, serious problems have been reported. Compounds of natural origin and their derivatives are attractive options to obtain new compounds with herbicidal properties. By aiming to develop compounds with potentiated herbicidal activity, phenoxyacetic acids were synthesized from eugenol and guaiacol. The synthesized compounds were characterized and the herbicidal potential of phenoxyacetic acids and precursors was evaluated through bioassays regarding the germination and initial development of Lactuca sativa and Sorghum bicolor seedlings, with the induction of DNA damage. The induction of changes in the mitotic cycle of meristematic cells of roots of L. sativa was also analyzed. At the concentration of 3 mmol L-1, phenols and their respective phenoxyacetic acids presented phytotoxic and cytotoxic activities in L. sativa and S. bicolor. Eugenol and guaiacol also presented genotoxic action in L. sativa. The toxic effect of eugenoxyacetic acid was more pronounced in L. sativa than in S. bicolor, similar to the commercial 2,4-D herbicide. Molecular properties of the phenols and their derivatives phenoxyacetic acids were compared with the ones obtained for the herbicide 2,4-D, where it was found a correlation between their molecular properties and bioactivity.

We reported experimental and theoretical investigation of conformers of 1,2,3-triazole derivatives, substances of exclusively synthetic origin, subject of extensive studies, because of several biological properties, such as antiviral, antimicrobial and antileishmaniasis. We reported molecular/supramolecular X-ray structures of antiophidian compounds I and II. For I and II there are two crystallographic different molecules in the unit cell (A and B). To explore the causes of the similarities in the compound’s crystal structures, intermolecular interactions were explored using the Hirshfeld surface as the fingerprint plots. In addition, density functional theory (DFT) calculations were carried out at the ωB97x-D/6-31G(d,p)-PCM-CHCl3 level aiming to contribute to the interpretation of the experimental data and complement the experimental findings. Two structures named 2A and 5B were found in good agreement with the respective X-ray solid state ones (A and B). Theoretical 1H nuclear magnetic resonance (NMR) spectra calculated for 5B rotated structure (torsion angles deviation around 40° to 90°) was in fine agreement with experimental results (in CDCl3) indicating that the solution molecular structure is considerably different from optimized equilibrium geometries and solid-state structure. Therefore, care is needed when using X-ray structures or DFT geometries to model interaction of drugs with biological targets since significant conformational changes may take place in solution.

The Z-E isomerization of γ-alkylidenebutenolide analogues to natural nostoclides and other natural butenolides was investigated using 1H nuclear magnetic resonance (NMR) and high performance liquid chromatography (HPLC) data as well as density functional theory (DFT) calculations at the wB97x-D/6-31G(d,p) level, including solvent effects with the polarizable continuum solvation approach. The experimental data supported the Z to E isomerization of γ-alkylidenebutenolides under acid catalysis. Newly prepared samples have predominantly Z configuration, which partially isomerizes to the E isomer under acidic conditions. Density functional theory studies corroborate the experimental findings. While neutral γ-alkylidenebutenolides are more stable in the Z form, protonation of the γ-lactone carbonyl group results in preferential stabilization of the E isomer.

A reação de tert-butil 2-(3-cloro-1,4-dioxo-1,4-di-hidronaftalen-2-ilamino)etilcarbamato com CF3COOH/CH2Cl2 fornece 5-cloro-3,4-di-hidrobenzo[f]quinoxalin-6(2H)-ona. Este composto sofre desidrogenação promovida por ácido na presença de água para dar a 5-clorobenzo[f]quinoxalin-6-ol, inédita. A estrutura molecular no estado sólido, determinada por um estudo de difração de raios X (XRD), e os dados em solução confirmam que a benzoquinoxalina existe na forma do tautômero enol-imina, tanto no estado sólido, quanto em solução, diferentemente de 5-cloro-3,4-di-hidrobenzo[f]quinoxalin-6(2H)-ona que exibe o arranjo ceto-amino. Cálculos de teoria do funcional da densidade (DFT) confirmam a preferência da benzoquinoxalina e dos compostos análogos contendo grupos H ou CH3 no lugar do Cl pela forma enol-imina. Sugere-se que a preferência da benzoquinoxalina pela estrutura enol-imina se deva ao maior caráter aromático desta estrutura em comparação com a forma ceto-amina. Os cálculos DFT dos dois tautômeros das benzo[a]fenazin-5(7H)-onas análogas às benzo[f]quinoxalin-6(4H)-onas indicaram que as estabilidades relativas são dominadas por efeitos de solvatação, no primeiro caso, e pelo grau de aromaticidade no segundo.

The reaction of tert-butyl 2-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-ylamino) ethylcarbamate with CF3COOH/CH2Cl2 yields 5-chloro-3,4-dihydrobenzo[f]quinoxalin6(2H)-one which undergoes acid-promoted dehydrogenation in the presence of water to give novel 5-chlorobenzo[f]quinoxalin-6-ol. The molecular structure of 5-chlorobenzo[f]quinoxalin6-ol in the solid state, determined by an X-ray diffraction (XRD) study, and the solution data confirm that it exists as the enol-imine tautomer, both in the solid state and in solution, differently from 5-chloro-3,4-dihydrobenzo[f]quinoxalin-6(2H)-one, which exhibits the keto-amine arrangement. Density functional theory (DFT) calculations confirmed the preference of 5-chlorobenzo[f]quinoxalin-6-ol and of the derivatives containing H and CH3 groups in place of the Cl atom for the enol-imine tautomer. It is suggested that the enol-imine structure is preferred for 5-chlorobenzo[f]quinoxalin-6-ol as a consequence of the higher aromatic character of this structure in comparison with the keto-amine form. DFT calculations carried out on the two tautomers of the benzo[a]phenazin-5(7H)-ones analogous to the benzo[f]quinoxalin-6(4H)-ones showed that the relative stabilities are dominated by solvation effects in the first case and the degree of aromaticity, in the latter.