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)

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 center dot center dot center dot O and comparatively weak C-H center dot center dot center dot pi 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. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The research discusses the preparation of a novel organic salt based on pyrimethamine and confirms its structure. The salt exhibits high reactivity and good drug delivery properties, as shown by the analysis.