Phosphorus-nitrogen compounds: Part 69. Unsymmetrical Dispiro(N/N)cyclotriphosphazenes Containing Different Pendant Arms: Syntheses, Characterization, Stereogenism, Photophysical and Bioactivity Studies

Abstract

In this research, the starting compounds tetrachloromonospirocyclotriphosphazenes, (BzSpiro-5)R1(N3P3)Cl4 [Bz: Benzyl; R1: Me (1) and R1: Et (2)], were synthesized from the reactions of hexachlorocyclotriphosphazene, N3P3Cl6 (HCCP, trimer) with N/N-donor type benzyldiamines. Both phosphazenes were reacted with 9-ethyl-N-methyl-3-carbazolyldiamines (3 and 4) to form dichloro trans/cis N/N-dispirocyclotriphosphazenes, [(BzSpiro-5)R1(N3P3)(CzSpiro-n)R2]Cl2 (Cz: Carbazolyl; R1, R2: Me or Et; n= 5 or 6; (5a-8a and 5b-8b), containing unsymmetrical diamino precursors. The structure of the cis-5b was clarified by single crystal X-ray crystallography. The space group of the chiral cis-5b isomer is P -1, which is centrosymmetric, and both enantiomers must be present in the unit cell. Since the absolute configuration of an enantiomer is found as SR' according to the X-ray crystallography, the other must be RS'. The chiralities of the compounds were also confirmed by 31P NMR spectroscopy recorded upon addition of chiral solvating agent [(S)-(+)-2,2,2-trifluoro-1-(9’-anthryl)ethanol; CSA] (for 5a, 5b and 8b) and the circular dichroism (CD) (for 5a, 5b, 6a and 6b) spectra. All N/N-dispirocyclotriphosphazenes (5a-8b) bearing carbazole units exhibited a fluorescence profile with a lifetime of about 4.9-6.5 ns and a quantum yield in the range of 0.11-0.20. On the other hand, P. aeruginosa was sensitive to compounds 5b, 7a, 8a and 8b, while E. coli was sensitive to most of the phosphazenes. The cytotoxic activities of phosphazenes against Vero cells (healthy) and MDA-MB-231 breast cancer cells were determined. In addition, compounds 5a and 5b appear to have very high antioxidant activity with respect to radical scavenging activities of 55.1% and 68.3%, respectively.