Phosphorus−Nitrogen Compounds. 18. Syntheses, Stereogenic Properties, Structural and Electrochemical Investigations, Biological Activities, and DNA Interactions of New Spirocyclic Mono- and Bisferrocenylphosphazene Derivatives

Abstract

The reactions of hexachlorocyclotriphosphazatriene, N(3)P(3)Cl(6), with mono- (1 and 2) and bisferrocenyldiamines (3-5), FcCH(2)NH(CH(2))(n)NHR(1) (R(1) = H or FcCH(2)-), produce mono- (6 and 7) and spirocyclic bisferrocenylphosphazenes (8-10). The fully substituted phosphazenes (11-15 and 18-21) are obtained from the reactions of corresponding partly substituted phosphazenes (6-10) with excess pyrrolidine and NH(2)(CH(2))(3)ONa, respectively. The reactions of 6 with 1-aza-12-crown-4 afford geminal (16) and tris (17) crown ether-substituted phosphazenes. The structural investigations of the compounds have been verified by elemental analyses, mass spectrometry, Fourier transform IR, (1)H, (13)C, and (31)P NMR, and DEPT, COSY, HETCOR, and HMBC techniques. The crystal structures of 7, 10, 11, and 15 have been determined by X-ray crystallography. In 16 and 17, there are one and two stereogenic P atoms, respectively, and they are expected to be in enantiomeric mixtures. The structures of 18-21 look similar to a propeller. In 20 and 21, there are two stereogenic P atoms, and they exist as cis (meso; 20a and 21a) and trans (racemic; 20b and 21b) geometric isomers, according to the chiral solvating agent (S)-(+)-2,2,2-trifluoro-1-(9'-anthryl)ethanol experiments. Moreover, the compounds 18 and 19 have three stereogenic P atoms, and they exist as enantiomeric mixtures. Cyclic voltammetric investigations of compounds 6-21a reveal that ferrocene redox centers undergo oxidation concurrently at the same potential with basically reversible peaks, and these compounds appear to be quite robust electrochemically. The compounds 11-15 have been screened for antibacterial activity against gram positive and gram negative bacteria and for antifungal activity against yeast strains.The compounds 11, 12, 14, and 15 are evaluated for antituberculosis activity against reference strain Mycobacterium tuberculosis H37Rv (ATCC 27294). Interactions between compounds 11-15 and pBR322 plasmid DNA are studied by agarose gel electrophoresis. These compounds induce conformational changes in the DNA helix.

Phosphorus–nitrogen compounds: part 30. Syntheses and structural investigations, antimicrobial and cytotoxic activities and DNA interactions of vanillinato-substituted NN or NO spirocyclic monoferrocenyl cyclotriphosphazenes

“…In the earlier paper [14], the yields of geminal products, N 3 P 3 [FcCH 2 N(CH 2 ) n NR 1 ](C 8 H 7 O 3 ) 2 Cl 2 (R 1 = H, n = 3, 4), were found to be higher than non-geminal ones. The isolation of geminal and non-geminal (cis and/or trans) products are considerably noteworthy in the present work, since the Cl replacement reactions of bulkycrypta and pendant-ferrocenyl spiro cyclotriphosphazenes with the secondary amines (pyrrolidine, morpholine, DASD and 1-aza-12-crown-4-substituted) gave only the geminal compounds [21,27,32,34]. In addition, if 1 equiv of 1-5 and 3 equiv of potassium vanillinate were used in the reactions, the tri-(1c-5c, as major products) and tetra-substituted phosphazenes (1d-5d) were prepared.…”

“…Interactions between compounds 2a, 3a, 4a, gem-1b, cis5b, 3c, 4c and 1d-5d, and pBR322 plasmid DNA were studied by agarose gel electrophoresis [32]. The compounds were dissolved in DMSO.…”

Synthesis of Some Novel Thiocyanotopurine Derivatives and Investigation of Their Antimicrobial Activity and DNA Interactions

“…29,30) DNA and Compound Interaction The interaction of the compounds 1-10 with pBR322 plasmid DNA was studied by agarose gel electrophoresis. 33,34) pBR322 DNA were incubated with decreasing concentrations of compounds ranging from 5000 to 312 µM in a shaking water bath at 37°C for 24 h and electrophoresed in 1% agarose gel. Electrophoresis was carried under 1× TAE (Tris acetic acid EDTA) buffer for approximately 3 h at 60 V. At the end of the electrophoresis, the gel was stained with ethidium bromide.…”

“…Therefore, interaction of the synthesized compounds 1-10 with supercoiled pBR322 DNA was studied by agarose gel electrophoresis. 33,34) pBR322 DNA was incubated with decreasing concentrations of compounds ranging from 5000 to 312 µM at 37°C for 24 h. Figure 1 gives the electrophoretograms applying to the interaction of pBR322 DNA with decreasing concentrations of compounds 1-10 ranging from 5000 to 312 µM. In the electrophoretograms, the untreated pBR plasmid DNA was used as a control.…”

The reactions of N$_{3}$P$_{3}$Cl$_{6}$ with monodentate and bidentate ligands: the syntheses and structural characterizations, in vitro antimicrobial activities, and DNA interactions of 4-fluorobenzyl(N/O)spirocyclotriphosphazenes

“…The 3 J P C coupling constants of these compounds (2a-2d) arise to triplets of the NCH 2 C H 2 carbons because of the second-order effects that have been previously observed for some cyclotriphosphazene derivatives. 20 The 3 J P C values were calculated using the external transitions of the peaks. The coupling and 1141-1198 cm −1 , attributed to the ν P =N bonds of the trimeric phosphazene skeletons.…”