Synthesis, crystal structure, Hirshfeld surface analysis, computational investigations and molecular docking studies of (Z)-3-N-(methyl)-2-N'-(4-methoxyphenylimino) thiazolidin-4-one dihydrate.

• The synthesis of a new thiazole derivative has been achieved. • The structural characterization was performed using experimental and theoretical methods. • Intermolecular interactions in molecular stacking are discussed using hydrogen bonds and a reduced density gradient (RDG) has been generated. • To examine charge transfer, delocalization and conjugative interactions in molecules, the natural bonding orbital (NBO) was determined. • Biological activity prediction was performed using scsicivment: Pass Online predictions, Docking molecular simulation. Thiazolidinones, widely utilized as a framework for synthesizing diverse molecules, demonstrate pharmacological activity and contribute to the creation of compounds with various biological effects, including antimicrobial, analgesic, antitumor, anti-inflammatory, anti-HIV, and antitubercular properties. The primary objective of this study was to develop a novel organic heterocyclic compound. Researchers successfully achieved this goal by synthesizing (Z)-2-((4-methoxycyclohexa-2,5‑dien-1-yl) imino)-3-methyl thiazolidin-4-one dihydrate (ZMThD), and the structural features of this newly synthesized compound were determined using single crystal X-ray diffraction (XRD). The compound crystallized in the orthorhombic system's P2 1 2 1 2 1 space group. A notable feature of the structure is the precisely measured dihedral angle of 45.0° between the benzene and thiazolidinone rings, indicating a lack of π-π stacking and confirming the non-planar nature of the structure.To further support and elucidate the experimental findings, density functional theory (DFT) calculations were conducted using the B3LYP functional in conjunction with a 6–311 G (d, p) basis set. The optimized geometry results obtained from these calculations closely mirrored the experimental results. Additionally, the stability of the crystal structure was examined through Hirshfeld surface analysis and 2D fingerprint plots, revealing that H...H interactions (50.7%) and H...C/C...H interactions (24.3%) were the primary contributors to the intermolecular forces stabilizing the crystalline structure. The potent inhibitory activity of the screened compounds was rationalized through in-silico molecular modeling studies against the Insulin-degrading enzyme (IDE) enzyme. The compound exhibited a remarkable docking score of −6.8 Kcal/mole, characterized by hydrogen-bond and hydrophobic interactions. [Display omitted] [ABSTRACT FROM AUTHOR]