CHIN-HUNG LAI2026-10-162026-10-162025-06-05Pure ID: 15049695Pure UUID: 25460b18-91ac-4fe1-95a9-be58e5c3e10910.1016/j.molstruc.2025.141527https://www.scopus.com/pages/publications/85216641288https://scholars.csmu.edu.tw/handle/123456789/27523In this work, we report on a highly substituted isoquinolinethione, namely 7-acetyl-8-(4-chlorophenyl)-4-cyano-1,6-dimethyl-2,3,7,8-tetrahydro-3(2H)-isoquinolinethione acetic acid solvate (3∙AcOH), which was obtained by dehydrating of 7-acetyl-8-(4-chlorophenyl)-4-cyano-1,6-dimethyl-6-hydroxy-5,6,7,8-tetrahydro-3(2H)-isoquinolinethione (2). The obtained compound 3∙AcOH was characterized by the means of the FTIR and 1H NMR spectroscopy. The crystal structure of 3∙AcOH comprises two isomers of 3, namely (7R,8S)-7-acetyl-8-(4-chlorophenyl)-4-cyano-1,6-dimethyl-2,3,7,8-tetrahydro-3(2H)-isoquinolinethione (3-R,S) and (7S,8R)-7-acetyl-8-(4-chlorophenyl)-4-cyano-1,6-dimethyl-2,3,7,8-tetrahydro-3(2H)-isoquinolinethione (3-S,R). The crystal packing of 3∙AcOH was additionally analyzed using the Hirshfeld surface analysis to quantify intermolecular interactions. The molecule 3-R,S was studied by the DFT-based computations, electron localization function (ELF), localized orbital locator (LOL), non-covalent interactions (NCI) and reduced density gradient (RDG) plots to reveal its electronic and structural properties. Potential biological and medical activities of both isomers of 3 were predicted using the SwissADME, BOILED-Egg and ProTox 3.0 tools. Both isomers of 3 were predicted to belong to the 4th class of toxicity, with the calculated LD50 value of 657 mg/kg, and can potentially inhibit a series of the studied SARS-CoV-2 proteins, of which the best activity was revealed toward Papain-like protease (PLpro) with the ligand efficiency scores characteristic for a Hit.enjournal article