Supramolecular architecture in Sulfonylurea, Sulfonyldiurea and Sulfonyltriurea drugs: Synthesis, X-ray structure and Hirshfeld surface analysis

Abstract Sulfonylureas provide a useful motif for carrying donor and acceptor sites capable of hydrogen bonding. These are a prominent class of therapeutic agents in the pharmaceutical industry. However, the use of aryl sulfonyl oligomers in drug discovery, supramolecular chemistry and crystal engineering are unexplored. This motivated us to design, synthesize and understand the structural features of aryl sulfonylurea oligomers (n =1-3). Here, we report the synthesis and spectroscopic characterization details such as 1H NMR, 13C NMR, mass spectrometry and single-crystal X-ray diffraction analysis for three sulfonylurea oligomer derivatives. Further, the molecular packing analysis of three derivatives reveals the significance of N-H…O and C-H…O intra and intermolecular hydrogen bonding. These hydrogen bonding contacts enable the sulfonylurea derivatives to form 2D framework/architecture. We quantify various intermolecular interactions in these derivatives by Hirshfeld analysis and 2D fingerprint plots. We have performed in-silico docking studies against Plasmodium falciparum (Pf) prolyl-tRNA synthetase (ProRS) to rationalize the binding affinity of title compounds.