Synthesis, crystal structure, DFT studies and biological activity of (Z)-3-(3-bromophenyl)-1-(1,5-dimethyl-1H-pyrazol-3-yl)-3-hydroxyprop-2-en-1-one

Abstract

Background: Nowadays, is emerging a new generation of highly promising inhibitors bearing the β-ketoenol functionality. The present work relates to the first synthesis, the structure determination, the DFT studies and the use of a new biomolecule designed with a β-ketoenol group bounded to a pyrazolic moiety.

Result: A novel β-ketoenol-pyrazole has been synthesized, well characterized and its structure was confirmed by single crystal X-ray diffraction. The electron densities and the HOMO-LUMO gap have been calculated using the DFT method with BLYP, PW91, PWC functionals and 6-31G* basis set. An evaluation of the molecule stability is provided by a NBO analysis and the calculated Fukui and Parr functions have been used to locate the reactive electrophile and nucleophile centers in the molecule. The synthesized compound, screened for its in vitro antifungal behavior against the Fusarium oxysporum f.sp. albedinis FAO fungal strains, shows a moderate activity with an inhibition percentage of 46%. The product was also tested against three bacterial strains (Escherichia coli, Bacillus subtilis and Micrococcus luteus), but no significant effect was observed against these organisms.

Conclusions: Density functional calculations are used to evaluate the HOMO-LUMO energy gap, the molecular electrostatic potential and to provide a natural bond orbital analysis. The measured antimicrobial activities encourage us to continue searching for other structures, likely to be good antifungal candidates.

Keywords: Biological activity; Fukui and Parr functions; NBO analysis; Reactivity indices; Single-crystal structure; β-Keto-enol-pyrazole.

Scheme 1

Synthesis of the target compound 1

Fig. 1

Ortep molecular representation of C₁₄ H₁₃ Br N₂ O₂ (30% probability ellipsoids)

Fig. 2

Molecular packing in the triclinic lattice enhancing the peculiar layered arrangement of molecules in planes parallel to ($1\overline{1}\overline{1}$)

Fig. 3

Experimental molecule and hypothetical models built by changing the rings orientation

Fig. 4

Representation of the 3D isosurface electron density (volumic contour) mapped with the deformation density. Positive value (yellow domains) indicate electron localization

Fig. 5

Atomic spin density spatial distribution mapped onto the electrostatic potential showing the electrophilic (left image) and nucleophilic (right image) centers as red zones

Fig. 6

Molecular structures of compounds 1–6