Experimental and computational insights into polymorphism in an antimicrobial sulfadrug: discovery of a novel monoclinic form of sulfamerazine

Sulfamerazine (4-Amino-N-(4-methylpyrimidin-2-yl) benzenesulfonamide) is a polymorphic molecule crystallizing in three forms: Form I: Pn2₁a polymorph (with three entries in the Cambridge Structural Database CSD), Form II: Pbca polymorph (with two entries in the CSD) and Form III: P2₁/c polymorph with only one entry in the CSD). We have experimentally prepared a novel monoclinic P2₁/c polymorph (Form IV) of the sulfadrug and also obtained crystals of Form II (Pbca polymorph) by following a different synthesis procedure. Both crystals were structurally characterized by single-crystal X-ray diffraction XRD and geometrically optimized by density functional theory DFT. The five crystal structures (1), (3)–(6) of the four mentioned polymorphs were analyzed and discussed in terms of crystal packing, Hirshfeld surface analysis HSA of the intermolecular interactions, voids’ distribution in the crystal packing, their related energies and the resulting underlying topologies. The energy and activity relations of the compounds were also investigated by DFT.