Tetrahydroisoquinoline derivative

This work involves synthesis, characterization, crystal data investigation, Hirshfeld surface analysis, and DFT calculations of a new tatrahydroisoquinoline derivative, namely, 7-Acetyl-4-cyano-1,6-dimethyl-3-ethoxycarbonylmethylthio-6-hydroxy-8-(3-pyridyl)-5,6,7,8-tetrahydroisoquinoline (ACTQ). The crystal structure is determined by single crystal XRD, which showed that O-H⋯O, C-H⋯O, C-H⋯N hydrogen bonding interactions, along with C-N⋯π and C-H⋯π, participate in the stabilization of the supramolecular assembly. A density functional theory (DFT) study was performed to investigate the electronic and geometric properties of ACTQ in its gaseous state. Geometry optimization revealed that the S–C bonds exhibited the longest bond lengths, whereas the O–H bond was the shortest. The subsequent NBO, QTAIM and NCI analyses showed that a weak intramolecular O-H⋯O hydrogen bond exists in ACTQ. Although NCI also derived from the Bader's AIM theory, the NCI result showed a difference with respect to the QTAIM result in this study. The ACTQ was subjected to structural activity relationship analysis, based on which GSK-3β was taken, and molecular docking analysis was performed. In addition to this, ADMET was also carried out to understand the future drug candidacy.