Gamze Elmas

Phosphorus–nitrogen compounds. Part 35. Syntheses, spectroscopic and electrochemical properties, and antituberculosis, antimicrobial and cytotoxic activities of mono-ferrocenyl-spirocyclotetraphosphazenes

The reactions of octachlorocyclotetraphosphazene, N4P4Cl8, with N-alkyl-N-mono-ferrocenyldiamines, FcCH2NH(CH2)nNHR1 [n = 2, Fc = ferrocene, R1 = Me (1); n = 2, R1 = Et (2) and n = 3, R1 = Me (3)], led to the formation of monoferrocenyl-spirocyclotetraphosphazenes (4–6). When the reactions were carried out with excess pyrrolidine, morpholine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD), the fully substituted products (4a–6c) were obtained in high yields. The structures of all the phosphazene derivatives were characterized by MS, FTIR, 1H, 13C and 31P NMR, HSQC and HMBC techniques. The crystal structures of 4a and 5a were determined by X-ray crystallography. The electrochemically reversible one-electron oxidation of Fc redox centers was observed for cyclotetraphosphazenes. The fully substituted phosphazenes (4a–6c) were evaluated for their antituberculosis activity against reference strain Mycobacterium tuberculosis H37Rv, and compounds 4a–6a and 5c were found to be active. The antibacterial activities of phosphazenes 4a–6c against G(+) and G(−) bacteria and their antifungal activities against yeast strains were carefully scrutinized. The results indicate that compounds 4a–6a, 6b, 4c and 5c are very effective against yeast strains. The anticandidal activities of 6a and 6b make them promising anticandidal agents. The interactions of these compounds with plasmid DNA and their cytotoxic activity against L929 fibroblast and DLD-1 colon cancer cell lines were also investigated.

Phosphorus–nitrogen compounds. Part 37. Syntheses and structural characterizations, biological activities of mono and bis(4-fluorobenzyl)spirocyclotetraphosphazenes

The Cl substitution reactions of octachlorocyclotetraphosphazene, N4P4Cl8, with one equimolar amount of (4-fluorobenzyl)diamines (1–3) affords mono(4-fluorobenzyl)spirocyclotetraphosphazenes (4–6) as minor products. However, the reactions of N4P4Cl8 with two equimolar amounts of (4-fluorobenzyl)diamines (1–3) leads to the formation of mono (4–6), 2-trans-6-bis (7–9, as major products) and 2-cis-6-bis (4-fluorobenzyl)spirocyclotetraphosphazenes (10–12). The 2-cis-6-bis compounds (10 and 12) were separated and purified using column chromatography as minor products, whereas compound 11 could not be isolated. The mono-spiro (4–6) and 2-trans-6-bis-spiro (7–9) cyclotetraphosphazenes were reacted with excess pyrrolidine in THF to afford the fully substituted hexapyrrolidino (4a-6a) and tetrapyrrolidino (7a-9a) products in high yield. Compound 9 was also reacted with piperidine, morpholine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD) to obtain the tetraamino products (9b, 9c and 9d), respectively, due to its very high yield. The elemental analyses, mass spectra (ESI-MS), Fourier transform infrared (FTIR) spectra, and 1H, 13C{1H}, and 31P{1H} NMR data of the cyclotetraphosphazenes were in agreement with the suggested structures. The molecular structures of 7, 9 and 12 were established by X-ray crystallography. The antibacterial activities of the compounds against G(+) and G(−) bacteria and their antifungal activities against yeast strains were scrutinized. The results indicated that 4a and 5a were the most active compounds, especially to yeast strains. In addition, it was found that the most active compound toward DNA was 8. The cytotoxic activities of the cyclotetraphosphazenes against L929 fibroblast and MCF-7 breast cancer cell lines were elucidated. Compound 8a exhibited the most toxic effects against both types of cells.

The reactions of 2-trans-6-bis(4-fluorobenzyl)spirocyclotetraphosphazene with primary amines: spectroscopic and crystallographic characterizations

GRAPHICAL ABSTRACT ABSTRACT The substitution reactions of 2-trans-6-bis(4-fluorobenzyl)spirocyclotetraphosphazene (3; with a yield of 59%) are carried out with excess alkylamines, benzylamine, n-hexylamine, n-butylamine, n-propylamine and iso-propylamine in THF. As a result of these reactions, the fully substituted tetrabenzylamino (3a), tetrahexylamino (3b), tetrabutylamino (3c), tetrapropylamino (3d), and tetraisopropylamino (3e) 2-trans-6-bis-(4-fluorobenzyl)spirocyclotetraphosphazenes are obtained in high yields. The structural characterizations of the isolated compounds (3a-3e) were confirmed by elemental analyses, mass spectrometry (ESI-MS), Fourier transform infrared (FTIR), heteronuclear single quantum coherence (HSQC), heteronuclear multiple-bond correlation (HMBC) and 1H, 13C{1H}, 31P{1H} NMR techniques. The solid state and molecular structures of 3a were determined using X-ray crystallography. Two independent molecules were present in its unit cell.

Syntheses and structural characterizations of 2-pyridyl(N/O)spirocyclotriphosphazene derivatives

Abstract The Cl exchange reaction of hexachlorocyclotriphosphazene, N3P3Cl6 (1), with one equimolar amount of sodium salt of N/O donor type bidentate ligand containing a 2-pyridyl pendant arm (2) afforded, regioselectively, the partly substituted 2-pyridyl(N/O)spirocyclotriphosphazene (3; with a yield of 65%) in THF. The reactions of 3 with excess pyrrolidine, morpholine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD) led to the formation of the tetraamino-2-pyridyl(N/O)spirocyclotriphosphazenes (3a-3c) in high yields. Compound 3 also gave both tetrapiperidino (3d) and gem-bispiperidino (3e) products with excess piperidine. The structures of all the compounds were determined by elemental analyses, ESI-MS, FTIR, HSQC, HMBC and 1H, 13C, and 31P NMR techniques. The crystal structure of 3c was identified by single crystal X-ray crystallography. Besides, the compound 3e had one stereogenic P atom, and its chirality was verified by 31P NMR spectroscopy in the presence of (S)-(+)-2,2,2-trifluoro-1-(9’-anthryl)-ethanol (CSA). GRAPHICAL ABSTRACT