Microwave-assisted, facile and green synthesis of aryl and heteroaryl sulfonyl fluorides in [BMIM][F] ionic liquid: Molecular docking and biological studies

Abstract

Encouraged by one of principles of green chemistry, A microwave assisted synthesis of variety of aryl/heteroaryl sulfonyl fluorides were demonstrated by utilizing catalytic amount of KF in [BMIM][F] ionic liquid medium at 100 °C. All the synthesized compounds were characterized by spectroscopic methods such as ¹H NMR, ¹³C NMR, ¹⁹F NMR, GC–MS and X-Ray data of compounds was also reported. The efficiency of the green solvent employed for synthesizing these molecules is determined by its recycle and reuse for a maximum of 5 cycles. From the Density Functional Test, 3D plots of molecular Electrostatic Potential were used to identify nucleophilic and electrophilic sites. Additionally, Global Chemical Reactivity Descriptor parameters like chemical hardness, softness, chemical potential, electronegativity, and electrophilicity index were also estimated. The antibacterial study of the newly synthesized compounds revealed that compounds 13 and 12 were found to exhibit higher antimicrobial activities as compare to reference therapeutics having both bactericidal and fungicidal properties. The antioxidant activity of compounds was done by using the DPPH radical scavenging assay with ascorbic acid as a control. Amoung the tested compounds, Compound 12 was most active, while compounds 09, 11, and 13 had comparatively weaker activities. Structure–activity relationship indicates that chromenesulfonamide fragment of compound 12 was responsible in improved radical stabilization. Molecular docking simulations with bacterial mevalonate diphosphate decarboxylase and fungal sterol 14-alpha demethylase showed that Compounds 12 and 13 exhibited the highest binding affinities towards the former, while compound 13 demonstrated superior binding to the latter, exceeding fluconazole. These interactions suggest strong enzyme inhibition potential. Overall, compound 13 emerges as a promising dual-target antimicrobial candidate. The molecular interaction profile highlighted key interactions with critical active site residues in both the targets, emphasizing their promising potential as broad-spectrum antimicrobial inhibitors.