Phosphorus-nitrogen compounds: part 30. Syntheses and structural investigations, antimicrobial and cytotoxic activities and DNA interactions of vanillinato-substituted NN or NO spirocyclic monoferrocenyl cyclotriphosphazenes.

The gradual Cl replacement reactions of NN (1-3) or NO spirocyclic monoferrocenyl cyclotriphosphazenes (4 and 5) with the potassium salt of 4-hydroxy-3-methoxybenzaldehyde (potassium vanillinate) resulted in the mono (1a-5a), geminal (gem-1b-5b), non-geminal (cis-5b and trans -1b-4b), tri (1c, 3c-5c) and tetra-vanillinato-substituted phosphazenes (1d-5d). All the phosphazene derivatives have stereogenic P-center(s), except tetra-substituted ones. The vanillinatophosphazenes have reversible voltammograms with one-electron anodic and cathodic peaks which are attributed to ferrocenyl redox probe. The structures of the new phosphazene compounds were determined by FTIR, MS, (1)H, (13)C{(1)H} and (31)P{(1)H} NMR spectral data. The solid-state structure of cis -5b was examined by single-crystal X-ray diffraction techniques. In addition, the compounds were tested in HeLa cancer cell lines using MTT assay. The 12 phosphazene derivatives were screened for antimicrobial activity, and 3c was very effective against S. aureus even at 4.88 µM concentration, taking into account the MIC values. Besides, interactions between the phosphazenes and pBR322 plasmid DNA were also investigated.

Phosphorus-nitrogen compounds. Part 29. Syntheses, crystal structures, spectroscopic and stereogenic properties, electrochemical investigations, antituberculosis, antimicrobial and cytotoxic activities and DNA interactions of ansa-spiro-ansa cyclotetraphosphazenes.

A number of novel ansa-spiro-ansa (asa) cyclotetraphosphazenes (1a-5b) was prepared in the range of 63-90 % yields. The structures of the compounds were verified by MS, FTIR, (1)H, (13)C{(1)H} and (31)P{(1)H} NMR, heteronuclear single quantum coherence (HSQC), and heteronuclear multiple-bond correlation (HMBC) techniques. The crystal structures of 1b, 2c and 5a were determined by X-ray crystallography. The compound 2c was analyzed by the changes in the (31)P{(1)H}NMR spectrum in addition of the chiral solvating agent; (R)-(+)-2,2,2-trifluoro-1-(9'-anthryl)-ethanol (CSA), to investigate its stereogenic properties. The result supports that compound 2c was found to be in the racemic mixture. Cyclic voltammetric and chronoamperometric data of the mono-ferrocenyl-spiro-asa-cyclotetraphosphazenes exhibited electrochemically reversible one-electron oxidation of Fe redox centres. The mono-ferrocenyl-spiro-asa compounds (3a-5b) were evaluated for antituberculosis activity against reference strain Mycobacterium tuberculosis H37Rv and M. tuberculosis clinical strain, which is resistant to rifampicin and isoniazid. These compounds appear not to be good candidates for being antituberculosis agents to clinical strains. All of the compounds were screened for antibacterial activities against G(+) and G(-) bacteria, and for antifungal activities against yeast strains. They seem to be more active against Gram positive bacteria than Gram negative. The interactions of the phosphazenes with plasmid DNA and the evaluations for cytotoxic activity against MCF-7 breast cancer cell lines were investigated. The compounds 1b, 2b, 3a and 4a were found to be more effective than Cisplatin against MCF-7 breast cancer cell lines at lower concentrations.