Exploring weak noncovalent interactions in a few halo-substituted quinolones.

Area of Science:

• Crystal Engineering
• Supramolecular Chemistry
• Medicinal Chemistry

Background:

• Active pharmaceutical ingredients (APIs) can be enhanced through crystal engineering using weak interactions.
• Quinolone derivatives are crucial in medicine, serving as antibacterials and antimalarials.

Purpose of the Study:

• To investigate weak interactions in chloro- and fluoroquinolones for supramolecular assembly.
• To explore how altering alkyl groups affects crystal structures and properties of quinolone-based APIs.

Main Methods:

• Systematic design and crystallographic characterization of chloro- and fluoroquinolones.
• Analysis of various weak interactions including N-H⋯X, C-H⋯X, π⋯π, halogen bonding, and lone pair interactions.
• Utilizing Hirshfeld surface analysis and Density Functional Theory (DFT) studies.

Main Results:

• Identified diverse weak interactions (N-H⋯X, C-H⋯X, π-interactions, halogen bonding) governing crystal packing.
• Observed co-crystallization of solvent molecules (water, chloroform) with N-ethyl derivatives, forming unique supramolecular structures.
• Hirshfeld surface analysis and DFT studies confirmed the significance of these weak interactions.

Conclusions:

• Subtle changes in alkyl groups can induce significant supramolecular transformations in quinolone crystals.
• Understanding and controlling weak interactions is vital for designing improved quinolone-based APIs.
• Crystal engineering offers a viable strategy to enhance the potential of pharmaceutical compounds.