Theoretical Studies on the Structure and Properties of Bisubstituted Derivatives of Curcumin

Abstract Curcumin is a diketone compound extracted from the rhizomes of a number of plants in the Zingiberaceae family and has a wide range of pharmacological activities. In order to improve its shortcomings such as poor stability and low bioavailability, it is often modified into monocarbonyl derivatives. In the present study, fluoro‐ and hydroxy‐substituted monocarbonyl curcumin derivatives (compounds 1a–1e and 2a–2e) are systematically investigated through chemical calculations. Based on the most stable geometry of each substituent, vibrational frequencies, Conceptual Density Function Theory index (CDFT), Atoms in Molecule (AIM), and molecular docking are analyzed and structure‐activity relationships (SAR) are derived. The results show that both fluorine substitution and hydroxyl substitution contribute to the reactivity of the molecules, with the hydroxyl substituents showing a stronger willingness to react. The presence of aqueous solution in the system improves the reactivity of the compounds. The results provide new and important information to further grasp the structure and properties of curcumin derivatives and also provide reference and guidance for the design and development of such drugs.