Synthesis and spectroscopic properties of (N/O) mono- and dispirocyclotriphosphazene derivatives with benzyl pendant arms: study of biological activity

Abstract

: The Cl replacement reactions of hexachlorocyclotriphosphazene (trimer; N3P3 Cl 6) with sodium (N-benzyl)-aminopropanoxides (1 and 2) produced monospiro- (3 and 4), cis-, and trans-dispirocyclotriphosphazenes (13–16). Themonospiro tetrakis-aminocyclotriphosphazenes (5–12) were obtained by the Cl substitutions of 3 and 4 with differentsecondary amines. The cis- (13 and 14) and trans-dispirophosphazenes (15 and 16) possessed 2 chiral P centers, andthey were able to present meso and racemic forms, respectively. Moreover, the structures of compounds 5 and 14were designated using X-ray data. The absolute configuration of compound 14 was found as SR in the solid state.Analytical and spectroscopic data of the phosphazenes were consistent with their suggested structures. Antimicrobialactivities of the benzyl-pendant-armed cyclotriphosphazenes were scrutinized against G(+) and G(−) bacteria andyeast strains. The bacterium most affected by the synthesized compounds was Pseudomonas aeruginosa. Minimuminhibitory concentrations and minimal bacterial concentrations were in the range of 125–500 µM. Interactions betweenthe phosphazenes (3–12 and 15) and plasmid DNA were studied with agarose gel electrophoresis. The phosphazeneDNA interaction studies of the cyclotriphosphazenes revealed that phosphazenes 3, 4, and 15 had a substantial effecton supercoiled DNA by cleavage of the double helix.