Phosphorus-nitrogen compounds. Part 67. The reactions of Mono/bis (4-fluorobenzyl)spiro(N/N)cyclotriphosphazenes with sodium(3-amino-1-propanoxide): investigation of spectral properties, DNA-cleavage and antimicrobial activities

Abstract

The starting reagents tetrachloro-mono- [1; R¹=(CH₂)₃, R²=H] and tetrachloro-bis- [2; R¹=(CH₂)₃, R²=FPhCH₂- and 3; R¹=(CH₂)₂, R²=FPhCH₂-] (4-fluorobenzyl)monospiro(N/N)cyclotriphosphazenes, were obtained from the condensation reactions of hexachlorocyclotriphosphazatriene (N₃P₃Cl₆; trimer; HCCP) with N-(4-fluorobenzyl)propane-1,3-diamine (L1), N,N'-bis(4-fluorobenzyl)propane-1,3-diamine (L2) and N,N'-bis(4-fluorobenzyl)ethane-1,2-diamine (L3), respectively. Substitution reactions of 1 and 2 with excess sodium(3-amino-1-propanoxide) separately yielded the only monospiro(N/O)amino-propanoxy-(4-fluorobenzyl)spiro(N/N) (1a) and monospiro-(N/O)aminopropanoxy-bis-(4-fluorobenzyl)spiro(N/N) (2a) cyclophosphazenes. Both monospiroaminopropanoxy (3a) and trans-bisspiroaminopropanoxy (3b) cyclotriphosphazenes were synthesized by the reactions of 3 with the excess sodium(3-amino-1-propanoxide). The structural features of all new products were identified using elemental analysis, FTIR, ESI-MS, ¹H, ¹³C and ³¹P NMR data. DNA-cleavage activities of 1a-3a and 3b were tested with pBR322 plasmid DNA, and the four cyclotriphosphazenes caused changes in DNA intensity and mobility. It was found that compounds 2a and especially 3b were highly active against DNA. Furthermore, antimicrobial activities of the obtained cyclotriphosphazenes on some bacteria and yeast strains were evaluated and minimum inhibitory concentrations of the active compounds were calculated. According to these results, the most effective compound is 3b. It appears that this compound is even more active against yeasts than the standard antibiotic ketoconazole, even at very low concentrations (156 µM for C. albicans and 312.5 µM for C. tropicalis).

Graphical Abstract

Keywords:

• Mono/bis(4-fluorobenzyl)spiro(N/N)cyclotriphosphazenes
• spectroscopy
• DNA-cleavage
• antimicrobial activity

Acknowledgment

Z. K. thanks to Turkish Academy of Sciences (TÜBA) for the partial support of this research.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Author contributions

The manuscript was written through the contributions of all authors.