Solvent free synthesis of three cyclotriphosphazene derivatives containing piperazine substituents using microwave irradiation. Spectral, theoretical, solution and docking studies

Three new cyclotriphosphazene-based compounds, 2,2,4,4,6,6-hexakis(4-methylpiperazin-1-yl)-1,3,5,2λ⁵,4λ⁵,6λ⁵-cyclotriazatriphosphinine (1), 2,2,4,4,6,6-hexakis(4-ethylpiperazin-1-yl)-1,3,5,2λ⁵,4λ⁵,6λ⁵-cyclotriazatriphosphinine (2) and 2,2,4,4,6,6-hexakis(4-phenylpiperazin-1-yl)-1,3,5,2λ⁵,4λ⁵,6λ⁵-cyclotriazatriphosphinine (3) were prepared and identified by elemental analysis, FT-IR, Raman as well as ¹H and 31P NMR spectroscopy. The redox properties of the compounds were investigated by cyclic voltammetry. The predicted structures and charge distribution patterns of the compounds were obtained by DFT calculations and NBO analysis. The geometrical parameters in these optimized structures are in good agreement with the average values obtained for analogs from the CSD database. The theoretical studies confirm presence of a strong resonance in the cyclotriphosphazene ring. Finally, the ability of the three new derivatives to interact with ten selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II, B-DNA) was investigated by docking calculations and compared with that of doxorubicin.