Crystal structure of 3-methyl-2,6-diphenyl-1-(2-thiocyanatoacetyl)piperidin-4-one: A combined experimental and theoretical study

The structure of 3-methyl-2,6-diphenyl-1-(2-thiocyanatoacetyl)piperidin-4-one (3) was elucidated through single-crystal X-ray diffraction, revealing a distorted boat conformation of the piperidine ring. Phenyl and methyl groups occupy equatorial positions, with another phenyl group positioned axially. Molecular packing is stabilized by C–H⋯N, C–H⋯O and C–H⋯π interactions. DFT optimization at the B3LYP/6–311++G(d, p) level showed excellent agreement with experimental geometry, validating the model. HOMO-LUMO analysis revealed the electronic properties, while Mulliken charge and MEP identified reactivity and binding sites. Hirshfeld surface analysis quantified intermolecular interactions, highlighting H⋯H contacts (41.8 %), with energy framework analysis emphasizing dispersion forces. Docking studies with 3ERT protein demonstrated favorable interactions, supporting its anticancer potential. ADME predictions confirmed a suitable pharmacokinetic profile, underscoring its drug development potential. This study integrates crystallographic, computational, and biological evaluations showcasing the structural and therapeutic significance of the compound.