Tautomerism, Conformational Analysis, and Intramolecular Interactions in Triketone–Chalcogenazole Hybrids

Triketone compounds are a significant class of herbicides due to their HPPD enzyme inhibition capabilities. The active form and the required induced fit within the enzyme's active site may be influenced by additional interactions facilitated by conformational changes, particularly in chalcogenazole hybrids. To explore these effects, the DFT‐B3LYP method combined with NBO analysis was employed to investigate the role of noncovalent hydrogen and chalcogen bonds in stabilizing tautomeric forms, including triketones and keto‐enols. The aromatic moiety was incrementally rotated by 30° to identify minimum energy conformations, while electron delocalization within these structures was analyzed using the NBO approach. The resulting energy profiles revealed that enolic forms exhibited more perturbed energy outlines than ketonic tautomers, indicating the promotion of intramolecular interactions. Notably, the tautomeric forms stabilized by hydrogen bonds were identified as the most energetically favorable, with exoenolic and endoenolic forms alternating based on structural dependencies. Finally, electron delocalization analysis highlighted that chalcogen bond interactions occurred exclusively with heavier atoms, such as sulfur and selenium, underscoring their unique role in the stabilization of specific conformers.