Phosphorus-nitrogen compounds. Part 56. Comparative syntheses and spectral properties of multiheterocyclic 2-cis-4-ansa and spiro-ferrocenyl (N/O)cyclotetraphosphazenes: Antituberculosis and antimicrobial activity and DNA interaction studies

Abstract

In the present study, two types of starting compounds; hexachloro(N/O)-cyclotetraphosphazenes containing mono-ferrocenyl-pendant arm, namely, mono-ferrocenyl-2-cis-4-dichloro-ansa-(2,4-ansa; 2) and mono-ferrocenyl-spiro-(spiro; 3) were prepared by the reaction of N₄P₄Cl₈ (1) with sodium 3-(N-ferrocenylmethylamino)-1-propanoxide (L). Reactions of 2,4-ansa (2) with excess benzylamine and n-hexylamine resulted in the formation of partly substituted 2-cis-4-dichloro-ansa-cyclotetraphosphazenes (2a and 2b). In contrast, spiro (3) gave fully substituted mono-ferrocenyl-spiro-cyclotetraphosphazenes (3a and 3b) with excess benzylamine and n-hexylamine. As expected, the 2,4-ansa cyclotetraphosphazenes (2, 2a, and 2b) have two distinct stereogenic P-centers. The structures of cyclotetraphosphazenes were evaluated by elemental analysis, ESI-MS, FTIR, ¹H, ¹³C, and ³¹P-NMR techniques. The antibacterial and antifungal activities against some selected bacteria and yeast strains, antituberculosis activities against Mycobacterium tuberculosis H37Rv, and DNA cleavage activities of mono-ferrocenyl-cyclotetraphosphazenes were also discussed. Compounds 2b, 3a, and 3b exhibited antifungal activity against C. albicans (MIC= 156.3 µM) higher than reference antibiotic Ketoconazole. Moreover, four compounds displayed antituberculosis activity against the M. tuberculosis H37RV. Compound 2a (20 μg/mL) is the most potent of the four compounds.

Graphical abstract

KEYWORDS:

• Mono-ferrocenyl-ansa/spirocyclotetraphosphazenes
• spectroscopy
• antimicrobial activity
• DNA interactions
• antituberculosis activity

Additional information

Funding

The authors thank the “Scientific and Technical Research Council of Turkey” (Grant No. 215Z496), and Z. K. thanks to Turkish Academy of Sciences (TÜBA) for partial support of this work.