DFT and docking analysis of stability, conformational dynamics, and interaction behavior in linear C6 triketo and diketo scaffolds

Abstract

Linear polycarbonyl motifs constitute flexible chemical frameworks with relevance to conformational analysis, molecular stability, and interaction modeling. Here, we report a combined density functional theory (DFT) and molecular docking study of the structural stability, conformational preferences, and interaction behavior of linear C₆ triketo and diketo scaffolds. Equilibrium geometries, intramolecular hydrogen-bonding patterns, and relative Gibbs free energies were evaluated at the B3LYP/6–311 +  + G(d,p) level. Symmetric diketone isomers were identified as the most stable conformers, whereas arrangements containing adjacent carbonyl groups exhibited pronounced conformational flexibility accompanied by energetic destabilization of up to ~ 18 kcal mol⁻¹. Across the scaffold series, a consistent instability window of ~ 12–16 kcal mol⁻¹ was observed, associated with characteristic geometric …