Synthesis of new N-alkylated 6-bromoindoline-2.3-dione derivatives: Crystal structures, spectroscopic characterizations, Hirschfeld surface analyses, molecular docking studies, DFT calculations, and antibacterial activity

Ten new isatin derivatives (2-11) were synthesized by alkylation reactions under phase transfer catalysis (PTC) conditions. Structural characterization of all compounds was performed using 1H and 13C NMR spectroscopy. The molecular and crystal structures of three compounds (4, 7, and 8) were confirmed through single -crystal X-ray diffraction analysis. Spectral data were also calculated using density function theory (DFT) at the B3LYP/ 6-311++G(d, p) level and compared to the experimental results, to understand the non -binding intermolecular interactions in the solid phase crystal packing. The closest contacts between atoms of the three molecules studied were identified by 2D and 3D Hirshfeld surface analyses. The structures of 4, 7 and 8 are optimized and their HOMO and LUMO energies, as well as their orbital pictures were evaluated. The experimental results correlated well with the calculated results. Finally, molecular docking studies of 4, 7 and 8 were performed to investigate their binding patterns with inhibitory targets from the Protein Data Bank (PDB: 3G7B and PDB: 3T0T using the AutoDock Vina program. The antibacterial activities of 2-11 against Gram-positive and Gram-negative microbial strains, such as Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were evaluated, and the findings indicated that 4 and 8 exhibited the highest efficacy, as reflected in their minimal inhibitory concentration (MIC) values.