Asymmetrical curcumin derivative: synthesis, structural exploration, Hirshfeld surface analysis, and computational study

Abstract Curcumin derivatives are bioactive compounds with a linear structure and an α,β-unsaturated β-diketone moiety. The chemical reaction of 3-hydroxy-4-methoxybenzaldehyde and cinnamaldehyde in DMF in the presence of acetylacetone and boric oxide mixture resulted in the synthesis of a curcumin derivative named as (1E,4Z,6E,8E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-9-phenylnona-1,4,6,8-tetraen-3-one ( HPTO ). The compound was characterized by FT-IR, MS, 1H-, and 13C-NMR. Moreover, crystal structure was determined by single crystal XRD analysis, which displayed the presence of a solvent molecule along with the main molecule ( HPTO ). The geometry of the main molecule was stabilized by intramolecular O–H···O bonding. The molecule adopted a non-planar conformation with a dihedral angle between phenyl rings of 35.1 (1)°. The supramolecular assembly was stabilized by numerous intermolecular interactions that were explored by Hirshfeld surface analysis. Interaction energy calculations were carried out at B3LYP/6-31 g(d,p) electron density level to support the experimental findings. Void analysis was performed in order to predict the response of the crystal to the applied stress. The compound was studied using the DFT method, employing the 6-311 g(d,p) basis set, to evaluate its electronic and quantum chemical properties. Frontier molecular orbitals and density of states analyses revealed an energy gap of 3.08 eV. This finding indicates the compound’s significant chemical reactivity and potential for notable biological activity. Molecular docking studies were performed to evaluate the compound’s potential as a cancer treatment medication candidate. By employing a multidisciplinary methodology, this research provides a thorough understanding of the compound’s structural features, chemical properties, and prospective pharmaceutical applications, paving the way for its development in cancer treatment.