具有较高密度、形成热和氧平衡的高能杂环化合物，如吡啶、三氮唑和四氮唑，相比于其碳环对应物有更大优势，从而成为合成新型双四氮唑乙酰胺的有希望的途径。合成化合物A-F以及其中一些具有苯环上连接氯原子的化合物，可用作芳基偶联反应中的有价位的合成单体。通过1H-NMR和13C-NMR光谱分析，以及B3LYP泛函与6-311 + + G(d)和6-31G(d)基组的密度泛函考虑，揭示了所观察到的分子的LUMO / HOMO能量和电荷转移情况。此外，通过密度泛函理论研究计算了分子的偶极矩、化学硬度、软度、电离势、局部反应性势通过Fukui指数以及热力学性质（熵、焓和吉布斯自由能）。此外，还进行了分子对接研究，以研究合成杂环化合物对caspase 3、NF-KAPPA-B和P53蛋白的抗癌潜力。分子对接分析显示2,2'-(5,5'-(1,4-苯基)双(1H-四氮唑-5,1-二基))双-N-(2,4-二硝基苯基)乙酰胺(6d)与TP53和NF-KAPPA-B之间具有强烈交互作用，其结合能分别为-11.8 kJ/mol和-10.9 kJ/mol。类似地，2,2'-(5,5'-(1,4-苯基)双(1H-四氮唑-5,1-二基))双-N-(2-氯苯基)乙酰胺(6f)与caspase-3之间的相互作用很强，其结合能为-10.0 kJ/mol，表明它们作为这些蛋白质的治疗药物的潜力。此外，当前研究的发现得到了100 ns分子动力学（MD）模拟的进一步支持。最后，氧平衡和氮含量的理论研究表明，这些分子可以用作高能材料。© 2023. Springer Nature Switzerland AG.

Energetic heterocycles, including pyridines, triazoles, and tetrazoles, exhibit greater density, heats of formation, and oxygen balance compared to their carbocyclic counterparts, making them a promising approach for synthesizing novel bis-tetrazole acetamides. Synthesized compounds A-F, some of which feature a chlorine atom attached to the phenyl ring, serve as valuable synthons for aryl coupling reactions. Analysis via 1H-NMR and 13C-NMR spectroscopy, as well as density functional considerations through B3LYP functional correlation with 6-311 +  + G(d) and 6-31G(d) basis set, revealed the observed LUMO/HOMO energies and charge transfer within the molecule. Additionally, the dipole moment, chemical hardness, softness, ionization potential, local reactivity potential via Fukui indices and thermodynamic properties (entropy, enthalpy, and Gibbs free energy) of the molecule were calculated through density functional theory studies. In addition, Molecular Docking studies were conducted to investigate the anti-cancer potential of synthesized heterocyclic compounds against caspase 3, NF-KAPPA-B and P53 protein. Molecular docking analysis demonstrated a potent interaction between 2,2'-(5,5'-(1,4-phenylene)bis(1H-tetrazole-5,1-diyl))bis-N-(2,4-dinitrophenyl) acetamides (6d) and TP53 and NF-KAPPA-B with binding energies of - 11.8 kJ/mol and - 10.9 kJ/mol for TP53 and NF-KAPPA-B, respectively. Similarly, 2,2'-(5,5'-(1,4-phenylene)bis(1H-tetrazole-5,1-diyl))bis-N-(2-chlorophenyl) acetamides (6f) exhibited a strong interaction with caspase-3 with binding energy of -10.0 kJ/mol, indicating their potential as therapeutic agents against these proteins. Furthermore, the findings of current study was further strengthen by 100 ns molecular dynamics (MD) simulations. Finally, theoretical studies of oxygen balance and nitrogen percentage suggest that these molecules can be utilized as energetic materials.© 2023. Springer Nature Switzerland AG.