Green synthesis of pyrazole derivatives via one-pot three component Knoevenagel–Michael addition utilizing TiO2/RuO2/CuO as a ternary nanocatalytic system: characterization, DFT and molecular docking studies

Abstract

TiO₂/RuO₂/CuO was used as a ternary nanocatalytic system to develop novel pyrazole derivatives in one-pot, three-component reaction via Knoevenagel–Michael addition. These pyrazoles were synthesized under optimized green and conventional methods using key reactants including 2-hydroxy-1-naphthaldehyde, phenyl hydrazine, and various active methylene compounds such as 1,3-dimethyl barbituric acid, barbituric acid, thiobarbituric acid, Meldrum's acid and dimedone. Chemical structures were established using various spectroscopic methods (IR, ¹H NMR and ¹³C NMR). The density functional theory (DFT) computations were performed using Gaussian 09 and Gaussview 5 software, and used the B3LYP technique and the higher-order basis set 6-311G++ (d,p). The DFT analysis of compounds 4a-e provided valuable insights into their electronic properties and chemical reactivity with compound 4e exhibiting highly reactive characteristics. The analysis also provided insights into stability and chemical reactivity, electrophilicity index and electronegativity values. The molecular electrostatic potential helped to identify reactive sites and predicting chemical interactions. The molecular docking revealed promising interactions and binding affinities for inhibiting c-Src. The binding energies and hydrogen bond interactions that have been calculated show that these compounds might be able to become useful inhibitors. This comprehensive analysis not only sheds light on specific binding interactions contributing to inhibitory activity but also sets the stage for future research. The Molecular dynamic analysis reveals a protein with distinct regions of high flexibility and stability. This pattern suggests a complex structure with potential for dynamic functional processes.