Exploring the electronic and pharmacological properties of 1,2,3-triazole derivatives: Synthesis, DFT modeling, and AKT1 binding affinity

This study presents a comprehensive multi-step synthesis followed by the characterization of two salicyldehyde-based 1,2,3-triazoles using a variety of analytical techniques. The structural integrity of the 1,2,3-triazole-O-tosyl derivatives 8a-b was confirmed through extensive NMR ( 1 H and 13 C) and high-resolution mass spectrometry (HRMS) analyses. To investigate the behavior of each of the synthesized compounds 8a-b in molecular nano-electronic systems, each one was connected to gold electrodes and their geometric structure was optimized using the theoretical level of density functional theory (DFT)/B3LYP/6-311+G (d,p) in different electric field intensities. According to the obtained results, although the energy gap and as a result the electron potential barrier decreased for both structures with the increase of the electric field intensity, the response of compound 8b to the application of the electric field was more impressive. Also, the I-V curve for each structure was calculated using Landauer’s theory and the results confirmed the higher conductivity of compound 8b . The analysis of the electron potential barrier under applied electric fields shows that the 8b structure can change to the ON state at EF>120×10 -4 (a.u.) and act as a molecular switch of the field effect. Finally, findings from Quantum Theory of Atoms in Molecule (QTAIM) studies predicted lower Joule/Pelletier-like coefficients in compound 8b . To assess the pharmacological potential, in silico studies including molecular docking and absorption–distribution–metabolism–excretion–toxicity (ADMET) predictions were conducted. These investigations revealed the strong binding affinity of compound 8b to AKT1, with a binding energy score of -7.61 kJ/mol, highlighting its promising interactions for therapeutic applications.