Exploring weak noncovalent interactions in a few halo-substituted quinolones

Abstract

Crystal engineering utilizing weak interactions provides a real solution to increase the potential of active pharmaceutical ingredients (APIs). Quinolone derivatives represent one of the most widely used molecules, having potential applications in medical fields as antibacterials and antimalarials. This study addresses a few systematically designed and crystallographically characterized chloro- and fluoroquinolones in order to investigate the weak interactions leading to the formation of supramolecular assemblies. The interactions in crystal packing are discussed in terms of N–H⋯X, C–H⋯X (X = F, Cl), π⋯π, C–H⋯π, and lone pair (lp)⋯π interactions, along with unique homo- and hetero-halogen bonding, viz. F⋯F, F⋯Cl, Cl⋯O, and C–F⋯π, as well as C–H⋯H–C interactions. N-Ethyl derivatives exhibited the co-crystallization of solvent molecules, viz., water and chloroform, creating unique supramolecular structures. Fingerprint plots generated directly from the Hirshfeld surface further supported the noncovalent interactions. The DFT studies also supported the importance of weak interactions in crystal packing. This report shows how merely switching different alkyl groups may lead to various supramolecular transformations that are valuable for designing crystals, particularly quinolone-based active pharmaceutical ingredients.