Interplay of Halogen and Hydrogen Bonding through Co-Crystallization in Pharmacologically Active Dihydropyrimidines: Insights from Crystal Structure and Energy Framework.
A solvent-assisted grinding method has been used to prepare co-crystals in substituted dihydropyrimidines (DHPM) that constitutes pharmacologically active compounds. These were characterized using FT-IR, PXRD, and single-crystal X-ray diffraction. In order to explore the possibility of formation of halogen (XB) and hydrogen bonding (HB) synthons in the solid state, co-crystallization attempts of differently substituted DHPM molecules, containing nitro, hydoxy, and chloro substituents, with different co-formers, such as 1,4-diiodo tetrafluorobenzene (1,4 DITFB) and 3-nitrobenzoic acid (3 NBA) were performed. The XB co-crystals (C2aXB, C2bXB, and C2cXB) prefer the formation of C-I⋅⋅⋅O/C-I⋅⋅⋅S XB synthon, whereas the HB co-crystal (C2dHB) is stabilized by N-H⋅⋅⋅O H-bond formation. Hirshfeld surface analysis revealed that the percentage contribution of intermolecular interactions for XB co-crystals prefer equal contribution of XB synthon along with HB synthon. Furthermore, the interaction energy was analyzed using energy frameworks, which suggests that their stability, a combination of electrostatics and dispersion, is enhanced through XB/HB in comparison to the parent DHPMs.
['Bairagi|Keshab M|KM|', 'Ingle|Kapil S|KS|', 'Bhowal|Rohit|R|', 'Mohurle|Smital A|SA|', 'Hasija|Avantika|A|', 'Alwassil|Osama I|OI|', 'Venugopala|Katharigatta N|KN|', 'Chopra|Deepak|D|http://orcid.org/0000-0002-0018-6007', 'Nayak|Susanta K|SK|']
hydrogen bonding solvent-assisted grinding co-crystals pharmacologically active compounds halogen bonding