Synthesis, crystallography, DFT, MTT assay, and molecular docking studies of an exocyclic double-bonded crystalline chalcone

Abstract

• Exocyclic double-bonded chalcone was synthesized by base-catalyzed Claisen-Schmidt reaction and crystallized using slow evaporation solution method. • C—C, C—O, C—H, H—H, and H—O interactions were identified from Hirshfeld surface analysis. • DFT/TD-DFT studies indicate π→π* transitions and intramolecular charge transfer. • The molecule shows promising anticancer activity against MCF-7 cancer cells. • Molecular docking studies indicate the inhibition of EGFR kinase protein via hydrogen bonding with methionine 769 amino acid residue. A bicyclic chalcone 2-(4-methoxybenzylidene)-3,4-dihydro- 2H -naphthalen-1-one (MDN) with an exocyclic double bond was synthesized using Claisen-Schmidt condensation reaction and subsequently crystallized through slow evaporation solution method. The newly synthesized chalcone was characterized using single-crystal X-ray diffraction, and FT-IR spectroscopy. The compound exhibits intermolecular interactions evident from Hirshfeld surface analysis. The bicyclic moiety has an IC 50 value of 0.59 mM against MCF-7 human breast cancer cell lines. The electronic structure of the compound, as obtained from DFT and TD-DFT calculations, reveals the presence of intramolecular charge transfer and π-π* electronic transitions. The in silico molecular docking study divulges the stabilizing interactions between the chalcone and EGFR receptor tyrosine kinase protein, namely hydrogen bonding and hydrophobic interactions. Overall, the synthesized chalcone could serve as a precursor for the functionalization of exocyclic double-bonded chalcone compounds.