Phosphorus–nitrogen compounds: Part 28. Syntheses, structural characterizations, antimicrobial and cytotoxic activities, and DNA interactions of new phosphazenes bearing vanillinato and pendant ferrocenyl groups

• Published in: Journal of molecular structure 2013-10, Vol.1049, p.112-124
• Main Authors: Tümer, Yasemin, Asmafiliz, Nuran, Kılıç, Zeynel, Hökelek, Tuncer, Yasemin Koç, L., Açık, Leyla, Yola, Mehmet Lütfi, Solak, Ali Osman, Öner, Yağmur, Dündar, Devrim, Yavuz, Makbule
• Format: Article
• Language: English
• Subjects: Antiinfectives and antibacterials; Antituberculosis activity; Bacteria; Chirality; Columns (structural); Crystal structure; Derivatives; Diffraction; Electrochemistry; Ferrocenylphosphazenes; HeLa cell line; Jewelry; Molecular structure; Mycobacterium tuberculosis; Spectroscopy
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2013.06.036

The vanillinato-substituted phosphazenes containing pendant ferrocenyl arms were obtained. The spectral characterizations of all the phosphazenes and crystal structures of two compounds were determined. Some of the phosphazenes were tested against HeLa cancer cell lines and H37Rv Mycobacterium tuberculosis. •The partly and fully vanillinato-substituted ferrocenylphosphazenes were synthesized.•The spectral and crystallographic data of the new compounds are presented.•The electrochemical behaviors of the phosphazenes were investigated.•The chirality of one phosphazene derivative was determined using chiral HPLC column.•Some of the phosphazenes were tested against HeLa cells and H37Rv M. tuberculosis. The gradually Cl replacement reactions of spirocyclic mono (1 and 2) and bisferrocenyl cyclotriphosphazenes (3–5) with the potassium salt of 4-hydroxy-3-methoxybenzaldehyde (potassium vanillinate) gave mono (1a–5a), geminal (gem-1b–5b), non-geminal (cis-1b, cis-5b and trans-2b–5b), tri (1c–5c) and tetra-substituted phosphazenes (1d–5d). Some phosphazenes have stereogenic P-center(s). The chirality of 4c was verified using chiral HPLC column. Electrochemical behaviors were influenced only by the number of ferrocene groups, but not the length of the amine chains and the substituent(s). The structures of the new phosphazenes were determined by FTIR, MS, 1H, 13C and 31P NMR, HSQC and HMBC spectral data. The solid-state structures of cis-1b and 4d were examined by single crystal X-ray diffraction techniques. The twelve phosphazene derivatives were screened for antimicrobial activity and the compounds 5a, cis-1b and 2c exhibited the highest antibacterial activity against G(+) and G(−) bacteria. In addition, it was found that overall gem-1b inhibited the growth of Mycobacterium tuberculosis. The compounds 1d, 2d and 4d were tested in HeLa cancer cell lines. Among these compounds, 2d had cytotoxic effect on HeLa cell in the first 48h. Moreover, interactions between compounds 2a, gem-1b, gem-2b, cis-1b, 2c, 3c, 4c, 5c, 1d, 2d and 4d, and pBR322 plasmid DNA were investigated.