Metronidazole-Picric acid salt formation: Synthesis, characterization, Hirshfeld surface analysis, single crystal X-ray diffraction, computational studies, and molecular docking studies against Clostridioides difficile

Abstract

The salt formation of metronidazole (MET) and picric acid (PA) is obtained via slow evaporation of their mixture in methanol which afforded a novel organic salt, C6H10N3O3+⋅C6H2N3O7- (METPA). The structure of METPA salt was analyzed using single crystal X-ray diffraction. METPA crystallizes in the triclinic space group P-1 with cell dimensions: a = 8.2446(1), b = 9.1843(1), c = 11.5832(2) Å, α = 106.190(1)°, β = 99.483(1)°, γ = 106.635(1)°, Volume (Å3) = 778.02(2) and Z = 2. The formation of METPA salt was analyzed by comparing the IR spectrum of MET, PA and METPA salt. In order to visualize the intermolecular interactions in the crystal of METPA salt, Hirshfeld surface analysis was employed. QTAIM calculations were performed using the AIMALL program package to estimate the strength of hydrogen bonding interactions in terms of bond critical points (BCP) and ring critical points (RCP). Molecular docking of the MET and METPA was conducted against three toxins of Clostridioides difficile such as C. difficile toxin A (TcdA), C. difficile toxin B (TcdB), C. difficile transferase (CDT). The results showed that the docking score calculated based on the knowledge-based iterative scoring function ITScore-PP indicates that METPA with higher negative value of docking score in case of all three toxins when compared to MET. This shows that the binding model of METPA salt is more favorable than MET.