Skip to main content

Tetrahydroisoquinoline derivative: Design, synthesis, characterization, crystal structure investigation, and computational studies approach

Research Abstract

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-HO, C-HO, C-HN hydrogen bonding interactions, along with C-Nπ and C-Hπ, 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-HO 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.

Research Authors
Shaaban K Mohamed, Muhammad Ashfaq, Subramani Karthikeyan, Esraa Khamies, Etify A Bakhite, Maher MA Hamed, Islam S Marae, Aziz Bakhtiyarovich Ibragimov, Chin-Hung Lai, Youness El Bakri, Rashad Al-Salahi
Research Date
Research Department
Research Journal
Journal of Molecular Structure
Research Pages
143484
Research Publisher
Elsevier
Research Rank
Q2
Research Website
https://www.sciencedirect.com/science/article/pii/S0022286025021519
Research Year
2025