spiro-Cyclotriphosphazenes containing 4-hydroxyphenylethyl pendant arm: Syntheses, structural characterization and DNA interaction study

The reaction of hexachlorocyclotriphosphazene, N3P3Cl6, with tyramine podand (2) afforded partly substituted spiro-cyclotriphosphazene (3). Amine-substituted spiro-cyclotriphosphazenes 4a-g were prepared by substitution of the Cl-atoms in 3 with pyrrolidine, piperidine, morpholine, 1,4-dioxa-8-azaspiro[4,5]decane, 1-(2-aminoethyl)pyrrolidine, 1-(2-aminoethyl) piperidine, and 4-(2-aminoethyl)-morpholine, respectively. All of the cyclotriphosphazene derivatives were characterized by elemental analysis, FTIR, MS, 1D H-1, C-13 and P-31 NMR and 2D HSQC techniques, and the crystal structures of 3 and 4b were verified by X-ray diffraction analysis. The relationships delta P-OPN shifts with exocyclic OPN (alpha') and endocyclic NPN (alpha) bond angles, and electron density transfer parameters Delta(P-N) for spiro-cyclotriphosphazenes were presented. The DNA cleavage activity of cyclotriphosphazene derivatives (3, and 4a-g) was studied on double-stranded pBR322 DNA using gel electrophoresis experiments. It was found that 4e and 4f caused the highest level of DNA damage. The interactions of 3 and 4e with calf thymus DNA were also investigated using absorption spectrometry. The molecular docking was performed to identify the interaction of the compounds (3 and 4b) with the DNA (PDB ID:3V9D for A-DNA and PDB ID:1BNA for B-DNA). (C) 2018 Elsevier B.V. All rights reserved.