Pyrimethamine-Based Novel Co-Crystal Salt: Synthesis, Single-Crystal Investigation, Hirshfeld surface analysis and DFT inspection of the 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 2,4-dichlorobenzoate (1:1) (DECB)

Abstract

The antimalarial drug, pyrimethamine is not used any more for the treatment of malaria due to the resistance phenomenon, though, it can be modified for the potential reuse in medicinal chemistry. The current research article is about the possibility of obtaining novel form of the drug with better drug delivery properties by the preparation of new pyrimethamine-based organic salt: 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 2,4-dichlorobenzoate (1:1) (DECB). The salt was prepared via neutralization reaction utilizing pyrimethamine and 2,4-dichlorobenzoic acid as the base and acid components respectively. The structure of the salt was confirmed by the single crystal analysis. The single crystal X-ray diffraction (SC-XRD) investigation shows that strong N-H…O and comparatively weak C-H…π bonding are responsible for crystal packing forming the infinite 3D network. Hirshfeld surface analysis proposes high reactivity due to unequal distribution of the intermolecular interactions. The high chemical reactivity was confirmed by performing the density functional theory (DFT) calculations that showed high electrophilic properties of the DECB.