New Bioprecursor Prodrugs of Sulfadiazine: Synthesis, X-ray Structure and Hirshfeld Analysis

Abstract

Sulphonamide motif is found extensively in numerous chemotherapeutic drug candidates, it acts by stopping the production of folate inside the bacterial cell. Current research has established the synthesis and characterization of new bioprecursor prodrugs of sulfadiazine. The first prodrug, 3, was synthesized via the coupling of diazonium salt of sulfadiazine with ethyl acetoacetate in AcONa at 0 °C. The second prodrug, sulfadiazine-pyrazole, 5, was furnished via cyclocondensation of the hydrazono derivative, 3, and 2-pyridyl hydrazine, 4. The generated data from the X-ray analysis is interpreted and refined to obtain the crystal structure of the target compound, 5. Density functional theory (DFT) method was used to calculate the optimized geometrical parameters, electronic state (HOMO–LUMO), and the electronic properties. Moreover, Hirshfeld analysis revealed that the most important contributions to the crystal packing of the prodrug 5 are H···H, O···H and H···C contacts.