Single crystal, Hirshfeld surface, DFT analyses of (E)‐2‐(2‐chloro‐6‐fluorobenzylidene)hydrazinecarbothioamide: Elastase inhibition and DNA binding studies.

Here, a new (E)‐2‐(2‐chloro‐6‐fluorobenzylidene)hydrazinecarbothioamide hybrid 3 is reported for synthesis by using simple protocol. Compound was characterized, and its crystal structure was resolved by single crystal X‐ray analysis. The molecular structure showed perfect planarity with the 2,6‐halogen atoms disordered over the two positions. Hirshfeld surface (HS) analysis indicated H‐bonding and van der Waals interactions as leading intermolecular interactions in the crystal structure with most important contributions as H ... H (24.10%), H ... S/S ... H (20.80%) and H ... Cl/Cl ... H (13.50%). Density functional theory (DFT) analysis further highlighted on molecular orbital's energy transitions and comparison of absorption maxima with experimentally calculated λmax. Crystal was evaluated against elastase enzyme by using molecular docking and in vitro enzyme inhibition methods. An intuitive look at elastase inhibition demonstrated higher binding efficacy and lower IC50. Results from both studies have shown potent inhibitory activity of 3 against elastase. Kb and ΔG for 3‐DNA complex evaluated from molecular docking and UV/visible spectroscopy efficiently complemented each other, and the binding mode observed through docked structure was verified by viscometry. Theoretical and experimental investigations have provided evidence of substantial binding of the title compound with the DNA via intercalation. [ABSTRACT FROM AUTHOR]