Structural, supramolecular and computational insights into the ALS inhibitor pyroxsulam: crystal structure, reactivity and bioactivity

Triazolopyrimidine-2-sulfonanilides, recognized as bioisosteres of sulfonylurea herbicides, represent an important class of acetohydroxyacid synthase (AHAS/ALS) inhibitors widely employed for the selective control of broadleaf and grass weeds in cereal crops. Despite their extensive agricultural applications, detailed understanding of the structural, electronic, intermolecular, and biological characteristics governing their inhibitory behavior remains limited. In this context, the present work reports a comprehensive experimental and computational investigation of Pyroxsulam (PS; IUPAC name: N-(5,7-dimethoxy-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)-2-methoxy-4-(trifluoromethyl)pyridine-3-sulfonamide) to elucidate its structural stability, reactivity, sensitivity, and molecular interaction properties. Single-crystal X-ray diffraction analysis reveals that Pyroxsulam adopts an “L”-shaped conformation with two nearly planar fragments connected through the sulfur atom, exhibiting a dihedral angle of 78.42(5)° and a gauche C–S–N–C torsion angle of 55.9(2)°. The crystal packing is stabilized by C–H···O, N–H···N, C–H···π, and π···π interactions, forming one-dimensional supramolecular ribbons. Hirshfeld surface and energy framework analyses confirm the dominant role of dispersion and hydrogen-bonding interactions in crystal stabilization. Density functional theory (DFT) calculations performed at the B3LYP/6–311++ G(d,p) level provided optimized geometrical parameters and electronic descriptors consistent with the experimental observations. Molecular electrostatic potential (MEP), reduced density gradient (RDG), ELF, and QTAIM analyses identified electrophilic and nucleophilic regions and highlighted the significance of weak intermolecular interactions. Molecular docking and molecular dynamics simulations demonstrated favorable binding affinity of Pyroxsulam toward ALS with a binding energy of − 6.69 kcal mol −1 , stabilized through hydrogen bonding and π–π stacking interactions within the active site. The combined findings provide deeper insight into the structural and electronic behavior of Pyroxsulam and contribute to advancing the understanding of triazolopyrimidine-based ALS inhibitors as selective agrochemical agents.