Exploring the structural intricacies of 1D HOF in a novel hydrazone derivative exhibiting anticancer potential: A crystallographic and computational approach

•A novel hydrozone derivative was synthesized.•The structural and the electronic properties were studied.•ADMET study was performed to evaluate the pharmacokinetic properties.•In silico studies such as molecular docking and molecular dynamics were performed. This study provides a detailed structural investigation of 5-(diethylamino)-2-hydroxyphenylmethylidenebenzohydrazide (H1B), using both experimental techniques and computational methods to explore its non-covalent interactions and potential anticancer properties. Through single crystal X-ray diffraction, we determined that H1B crystallizes in the monoclinic system, revealing significant intermolecular interactions which contribute to the stability of a 1D hydrogen-bonded organic framework (HOF). Hirshfeld surface analysis quantified the role of these interactions, showing the dominance of van der Waals forces, while void analysis gave insights into the crystal's structural integrity and mechanical stability. DFT calculations gave us a deeper look into the electronic structure of the molecule, especially the HOMO-LUMO gap, which points to its high chemical reactivity and potential to interact biologically. The NBO analysis further highlighted how charge transfer within the molecule helps stabilize it, particularly through hyper conjugative interactions. In addition, molecular docking studies predicted a strong binding affinity between H1B and the JAK2 Kinase protein, supporting its potential anticancer activity, which was further validated by molecular dynamics simulations over a 100 ns period. These findings collectively underscore the structural and biological relevance of H1B, positioning it as a promising candidate for anticancer applications. [Display omitted]