New bis-piperazine derivatives: synthesis, characterization (IR, NMR), gamma-ray absorption, antimicrobial activity, molecular docking and dynamics study

A series of novel bis-piperazine derivatives (2a-2f) were synthesized and structurally characterized via Fourier transform-infrared and nuclear magnetic resonance spectroscopic techniques. Their gamma-ray shielding efficiencies were investigated through simulations on the Monte Carlo-based Geant4-GATE platform, and the results were benchmarked against data obtained from the XCOM and Phy-X software. A simulation model incorporating an NaI scintillation detector and a point gamma source was developed. Key shielding parameters, including mass attenuation coefficient, linear attenuation coefficient, half-value layer, and mean free path (MFP), were evaluated at gamma energies of 80, 120, 662, 1173, and 1332 keV. Additionally, the energy absorption buildup factor was calculated using EpiXS software, and penetration depths were assessed in the 0.015-15 MeV energy range for 10, 20, and 40 MFP values. Among the synthesized compounds, compound 2f (C₃₅H₅₄N₆O₂) had the highest gamma attenuation performance. The antimicrobial potential of compounds 2a-2f was evaluated in vitro against various microbial strains, including Gram-positive and Gram-negative bacteria as well as a fungal species. Furthermore, in silico molecular docking studies targeting DNA gyrase and GlcN-6-P synthase were performed for compounds 2d and 2f. Docking results indicated significant interactions, supporting their potential as antimicrobial agents. To assess the dynamic stability and binding persistence of the top-scoring complex (2VF5-2d), a 100 ns molecular dynamics simulation was conducted. The complex remained structurally stable throughout the trajectory, and binding free energy calculated via MM/PBSA (ΔG_bind = -27.31 kcal/mol) further supported the strong and favorable interaction. These results highlight compound 2d as a promising candidate for further antibacterial development.