Rationalizing the stability and interactions of 2,4-diamino-5-(4-chlorophenyl)-6-ethylpyrimidin-1-ium 2-hydroxy-3,5-dinitrobenzoate salt

The crystal structure of the salt produced by the reaction of pyrimethamine (an antimalarial drug) with 2-hydroxy-3,5-dinitrobenzoic acid [systematic name: 2,4-diamino 5 (4 chlorophenyl)-6- ethylpyrimidin-1-ium 2-hydroxy-3,5-dinitrobenzoate] has been investigated using X-rays diffraction data collected at room temperature. The results showed that there are strong intermolecular C-H center dot center dot center dot O, N-H center dot center dot center dot N, O-H center dot center dot center dot O types of hydrogen bonding interactions that play a key role in the crystal structure stabilization while C-H center dot center dot center dot O and C-H...pi interaction further stabilize the structure. In addition, theo- retical calculations were done to compute the binding free energies and the electron densities associated to heterodimeric, heterotrimeric and heterotetrameric salt assemblies of the pyrimethamine-2-hydroxy-3,5-dinitrobenzoate salt. The molecular electron densities, electrostatic potential and the regions of electron density accumulation as well as depletion were explored for these assemblies. These analyses not only suggest the high salt stability but also appropriate electrostatic properties of the pyrimethamine drug for the interaction with a carboxylic group that is attached to the side chains of glutamate and aspartate residues in proteins. (C) 2019 Published by Elsevier B.V.