Directed self-assembly with salicylic acid provides new crystalline complexes for fluoroquinolone antimicrobials to improve drug properties and synergies: Theoretical and experimental integration research

• A novel molecular salt of gatifloxacin conjugated to salicylic acid was synthesized. • The physicochemical properties and antibacterial efficacy of it were improved. • These findings are supported by theoretical calculations. To improve the physicochemical characteristics of gatifloxacin (GAT) and refine its antibacterial efficacy, a novel crystalline molecular complex combining GAT with salicylic acid (SAL), namely GAT-SAL has been successfully synthesized. Precise salt structure revealed by single crystal X-ray diffraction displayed that the entry of SAL into the GAT lattice destroyed the zwitterionic structure of GAT itself, resulting in the formation of a tetramer structure between GAT and SLA molecules, thus laying a foundation for improving the physicochemical properties of GAT. The pharmaceutical research indicated that the molecular salt exhibited concurrent enhancements in both solubility and permeability surpassing the parent drug gatifloxacin. Notably, the refined physicochemical attributes bestow GAT-SAL with heightened in vitro antibacterial potency, showing larger inhibition rings and smaller MIC values. These observations can be supported by theoretical studies involving theoretical research based on density functional theory (DFT) , Hirshfeld surfaces and molecular docking. The present contribution emphasizes the effectiveness of combining theory and experiment to solve the GAT problem by means of the cocrystallization approach, thus providing the new idea for the rapid screening of novel antimicrobial agents.