Phosphorus–Nitrogen Compounds. Part 24. Syntheses, Crystal Structures, Spectroscopic and Stereogenic Properties, Biological Activities, and DNA Interactions of Novel Spiro-ansa-spiro- and Ansa-spiro-ansa-cyclotetraphosphazenes

Abstract

The reactions of octachlorocyclotetraphosphazene, N(4)P(4)Cl(8), with N(2)O(2) donor-type aminopodands (1a, 1b, 1g, and 1h) afforded two kinds of derivatives, namely, spiro-ansa-spiro (sas) (2a, 2b, 2g, and 2h) and ansa-spiro-ansa (asa) (3a and 3b) phosphazenes. The partly substituted sas phosphazenes (2a and 2b) reacted with excess pyrrolidine and morpholine in tetrahydrofuran to produce the tetrapyrrolidino (2c and 2d) and morpholino (2e and 2f) derivatives. The reactions of the asa phosphazenes (3a and 3b) with excess pyrrolidine and morpholine produced gem-2-trans-6-dichloropyrrolidinophosphazenes (3c and 3d) and -morpholinophosphazenes (3e and 3f). However, the fully substituted products were not obtained in these solvents. In addition, the expected fully substituted compound was not obtained from the reaction of 3a with excess pyrrolidine by standard or microwave-assisted methods. The reaction of the long-chain starting compound (1g) with N(4)P(4)Cl(8) gave sas (2g) and the interesting 2,6-ansa-spiro-bicyclo product (bicyclo-2,6-as; 4g), while the reaction of 1h with N(4)P(4)Cl(8) yielded only sas (2h). The structural investigations of the compounds were verified by elemental analyses, mass spectrometry, Fourier transform infrared, and DEPT, HSQC, HMBC, (1)H, (13)C, and (31)P NMR techniques. The crystal structures of 2b, 3a, 3b, 3e, and 4g were determined by X-ray crystallography. Compounds 2a-2h, 3a-3f, and 4g had two stereogenic P atoms. Compound 3b had one enantiomer according to the Flack parameter, and 3f was a racemic mixture, as shown by chiral high-performance liquid chromatography and chiral-solvating-agent, (R)-(+)-2,2,2-trifluoro-1-(9'-anthryl)ethanol, experiments. Furthermore, compounds 2a, 2c, and 2d exhibited weak antibacterial activity against (G+) bacterium, and 3c and 3d displayed moderate antifungal activity against Candida tropicalis. Gel electrophoresis data demonstrated that 2e, 3c, and 3e promoted the formation of DNA cleavage. The prevention of BamHI digestion by 2a-2f and 3a-3f, except 2b and 2e, disclosed binding with GG nucleotides in DNA.

Phosphorus–nitrogen compounds. Part 65. Novel diansa-spiro-cyclotetraphosphazenes: synthesis, characterization, bioactivity and electrochemical properties, and dye-sensitized solar cell fabrication studies

“…Wide peaks of Ar-OH protons of 3 and 4 are observed at 7.53 and 7.94 ppm, respectively, indicating that they form intramolecular hydrogen bonds. Finally, it was observed that these results for cyclotetraphosphazene derivatives containing N 2 O 2 donor-type aminopodand 38 and ferrocenyl pendant arm(s) 4 a , b are in good agreement with the literature data.…”

“…In ferrocene rings, the ipso-C 1 carbons of both compounds were determined to be 83.55 ppm (for 3 ) and 82.95 ppm (for 4 ), and the average 3 J P̲NCC̲ value between ipso-C 1 atoms of the ferrocene rings and P atoms was estimated to be 7.7 Hz. These findings are appropriate with literature data of cyclotetraphosphazene derivatives containing N 2 O 2 donor-type aminopodand 38 and ferrocenyl pendant arm(s). 4 a , b…”

“…Compounds 3 and 4 showed various degrees of inhibition against eleven bacterial and three fungal strains using the microdilution method. 38 The lowest MIC values obtained with 3 in E. hirae bacterial strains and some yeast strains were recorded as 312.5 μM. Moreover, the lowest MIC values (312.5 μM) of 4 were obtained against C. krusei and C. tropicalis yeast strains.…”

“…37 A bicyclo-2,6-as product was also obtained from the reaction of OCCP and a similar N 2 O 2 donor-type aminopodand with a longer alkyl chain [R = (CH 2 ) 4 ] by our group. 38 As a result, these three cis Cl atoms in dias structures were found to be quite robust for substitution reactions. The expected fully substituted products were not able to be synthesized by microwave-assisted experiments in THF, toluene, or o -xylene.…”

The Syntheses and Structural Characterizations, Antimicrobial Activity and in Vitro Dna Binding of 4-Fluorobenzylspiro(n/O)cyclotriphosphazenes and Their Phosphazenium Salts

“…The compound/DNA mixtures were loaded onto the 1% agarose gel with a loading buffer (0.1% bromophenol blue, 0.1% xylene cyanol). Electrophoresis was made in 0.05 M Tris base, 0.05 M glacial acetic acid, and 1 mM EDTA (TAE buffer, pH = 8.0) for 3 h at 60V [30]. Subsequently, the gel was stained with ethidium bromide (0.5 μg/mL), visualized under UV light using a transilluminator (BioDoc Analyzer, Biometra), photographed with a video camera, and saved as a TIFF file.…”