Phosphorus–nitrogen compounds: Part 26. Syntheses, spectroscopic and structural investigations, biological and cytotoxic activities, and DNA interactions of mono and bisferrocenylspirocyclotriphosphazenes

•The new DASD-substituted ferrocenylphosphazenes were synthesized.•The spectral and crystallographic data of the new compounds are presented.•The chirality of one phosphazene derivative was determined using chiral HPLC column.•Some of the phosphazenes were tested against HeLa cancer cell lines.•One of them had cytotoxic activity after 24 h treatment.

The condensation reactions of the tetrachloro mono (1 and 2) and bisferrocenylspirocyclotriphosphazenes (3–5) with 1,4-dioxa-8-azaspiro[4,5]decane (DASD) resulted in the formation of the partly and fully DASD-substituted phosphazenes. The reactions of equal amounts of 1–5 and DASD produced the mono-DASD-substituted ferrocenylphosphazenes (1a–5a), as the major product. When the reactions were carried out with 1 equiv of 1–5 and 2 equiv of DASD, corresponding geminal-phosphazenes (1b–5b) were isolated. Moreover, the reactions of 1 equiv of 1–5 and 3 equiv of DASD gave the tri- (1c–4c) and tetra-substituted (1d–5d) phosphazenes. When the excess DASD was used, the fully-substituted phosphazenes (1d–5d) were obtained. The chirality of 3a was evaluated using chiral HPLC column. The structures of all the phosphazenes were verified by FTIR, MS, 1H, 13C and 31P NMR, and HSQC spectral data. The crystal structures of 4a, 2b, 5b, and 1d were determined by X-ray diffraction techniques. The 10 phosphazene derivatives were screened for antimicrobial activity. Meanwhile, interactions between the compounds and pBR322 plasmid DNA were presented by agarose gel electrophoresis. The compounds 2b, 1d, 2d, and 4d were tested against HeLa cancer cell lines. Among these compounds, 4d had cytotoxic effect on HeLa cell after 24 h treatment.

Graphical abstractThe new partly and fully-DASD-substituted ferrocenylphosphazenes containing pendant ferrocenyl arms were obtained. The crystal structures of four compounds were determined using X-ray crystallography. As an example, the chirality of one phosphazene derivative was determined using chiral HPLC column. Some of the phosphazenes were tested against HeLa cancer cell lines, and one of them had cytotoxic effect on HeLa cell.Figure optionsDownload full-size imageDownload as PowerPoint slide