Phosphorus-nitrogen compounds. Part 64. Comparative reactions of spiro and ansa (N/O) cyclotetraphosphazenes with bulky (4-fluorobenzyl) N/N and N/O donor type bidentate reagents: structure, stereogenic properties and cytotoxic activity studies

ELMAS G., Binici A., YAKUT M., OKUMUŞ A., Kilic Z., ÇOŞUT B., ...More

NEW JOURNAL OF CHEMISTRY, vol.46, no.33, pp.16096-16113, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 46 Issue: 33
  • Publication Date: 2022
  • Doi Number: 10.1039/d2nj02280j
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, DIALNET
  • Page Numbers: pp.16096-16113
  • Hacettepe University Affiliated: Yes


The reaction of octachlorocyclotetraphosphazene, N4P4Cl8 (1) (OCCP, tetramer), with an equimolar amount of sodium 3-(N-ferrocenylmethylamino)-1-propanoxide (L1) resulted in the formation of ferrocenyl-spiro-(2) and ferrocenyl-2-cis-4-dichloro-ansa-(3) cyclotetraphosphazenes. Both of the starting compounds were used to produce the new inorganic-organic hybrid multiheterocyclic-spiro and ansa cyclotetraphosphazenes. Spiro (2) was treated with excess N-(4-fluorobenzyl)-N'-ethyl-1,2-diaminoethane (L2) to give 2-trans-6-dispiro (trans-2a) and 2-trans-4-cis-6-trans-8-tetraspiro (tetraspiro-2a) cyclotetraphosphazenes. Spiro (2) was also reacted with excess sodium 3-(4-fluorobenzylamino)-1-propanoxide (L3) to produce 2-trans-6-dispiro (trans-2b), 2-cis-6-dispiro (cis-2b), 2-cis-4-trans-6-trispiro (trans-2c), 2-cis-4-dispiro-6-trispiro (cis-2c), 2-cis-4-dichloro-ansa-4-trans-6-spiro(N/O) (ansa-2b) and 2-cis-4-dichloro-ansa-6-trans-8-dispiro(N/O) (ansa-2c). The reactions of 2,4-ansa (3) with excess L2 led to the formation of 2-cis-4-dichloro-ansa-2-trans-6-spiro(N/N) (trans-3a) and 2-cis-4-dichloro-ansa-2-cis-6-spiro(N/N) (cis-3a) cyclotetraphosphazenes. However, the reactions of 2,4-ansa (3) with excess L3 afforded monospiro {2-cis-4-dichloro-ansa-4-trans-6-spiro(N/O) (trans-3b) and 2-cis-4-dichloro-ansa-4-cis-6-spiro(N/O) (cis-3b)} and dispiro {2-cis-4-dichloro-ansa-6-trans-8-dispiro(N/O) (trans-3c) and 2-cis-4-dichEoro-ansa-6-cis-8-dispiro(N/O) (cis-3c)}. The obtained products were characterized by spectroscopic techniques. The crystal structures of trans-2b and cis-3b were clarified by single crystal X-ray analysis. The products had stereogenic P-centres except for trans-2a, tetraspiro-2a, trans-2b and cis-2b. The stereogenic properties of tetrameric phosphazenes were evaluated by X-ray crystallography and chiral high performance liquid chromatography (HPLC) methods. The structure of cis-3b revealed the absolute configurations of the enantiomers (SS'R ''/RR'S ''). The broad HPLC peak of cis-3b indicates that it may exist as a resamate in solution. The cytotoxic activities of the cyclotetraphosphazenes were evaluated using an MTT assay against L929 mouse fibroblasts, A549 non-small lung cancer and Caco-2 colorectal adenocarcinoma cells. Compound cis-3b was found to be very effective in all cell lines up to 104.1 mu M.