Synthesis of dimeric 1,2-benzothiazine 1,1-dioxide scaffolds: molecular structures, Hirshfeld surface analysis, DFT and enzyme inhibition studies

1,2-Benzothiazines are bioactive compounds with diverse pharmacological properties. We report here the synthesis of a series of dimers containing 1,2-benzothiazine scaffolds as potential pharmacophores. The characterization of compounds was done using analytical techniques such as FT-IR, 1 H NMR, and elemental analyses. The molecular structures of the compounds ( 5-8 ) were confirmed by X-ray crystallography. The molecular interactions in compounds ( 5-8 ) were determined by Hirshfeld Surface Analysis (HSA). Density functional theory (DFT) investigations were carried out to calculate vibrational properties, NMR behaviour, dipole moments, molecular electrostatic potential (MEP), frontier molecular orbital (FMO), natural bonding orbital (NBO) analysis and global reactivity descriptors. The global reactivity descriptors indicated the charge transfer reactions and stabilized as follows: 8 > 7 > 6 > 5 . In FMO analysis a substantial HOMO-LUMO gap, ranging from 4.43 to 5.12 eV, with high LUMO values was observed for all compounds, while the highest value for linear polarizability was found in compound 8 . The in vitro and in silico studies confirm that compound 8 is more active toward AChE and BChE enzymes. DFT optimized geometry, Hirshfeld surface plot, and AChE and BChE docking studies for compound 8 .