Pyrene-BODIPY-substituted novel water-soluble cyclotriphosphazenes: synthesis, characterization, and photophysical properties.

In the present work, pyrene-boron-dipyrromethene (BODIPY)-substituted novel water-soluble cyclotriphosphazene derivatives (6 and 7) were synthesized by click reactions between a cyclotriphosphazene derivative with a hydrophilic glycol side group (2) and BODIPYs (4 and 5). All of the new compounds (2, 6, and 7) were characterized by Fourier-transform infrared and nuclear magnetic resonance spectroscopy, as well as mass spectrometry and elemental analysis. The photophysical properties of the BODIPY-substituted cyclotriphosphazenes (6 and 7) were investigated by UV-Vis and fluorescence emission spectroscopy in water and water/solvent mixtures. It was found that the target compounds were soluble in water and could be potential candidates as water-soluble fluorescent dyes for the desired applications.

Novel Water-Soluble Cyclotriphosphazene-Bodipy Conjugates: Synthesis, Characterization and Photophysical Properties.

In the present work, novel water-soluble cyclotriphosphazene derivatives (3b and 4b) were synthesized by 'click' reactions between cyclotriphosphazene derivative with hydrophilic glycol side groups (2) and Bodipy's (3a and 4a). All newly synthesized compounds (2, 3b and 4b) were characterized by fourier-transform infrared (FTIR), mass and NMR spectroscopy techniques and elemental analysis (EA). The photophysical properties of Bodipy substituted novel cyclotriphosphazenes (3a and 4a) were examined via UV-Vis absorption and fluorescence emission spectroscopy inside water and many organic solvents such as acetone, tetrahydrofuran, dichloromethane, dimethyl sulfoxide, etc., and the results were compared with the each other. Graphical Abstract.

Hexa-BODIPY Linked-Triazole Based on a Cyclotriphosphazene Core as a Highly Selective and Sensitive Fluorescent Sensor for Fe(2+) Ions.

A new type of fluorescent chemosensor based on tethered hexa-borondipyrromethene cyclotriphosphazene platform (HBTC) linked via triazole groups was designed and synthesized. Its sensing behavior toward metal ions was investigated by ultraviolet-visible and fluorescence spectroscopies. Addition of a Fe(2+) ion to a tetrahydrofuran solution of HBTC gave a visual color change as well as a significantly quenched fluorescence emission, while other tested 19 metal ions induced no color or spectral changes. This compound was found to be highly selective and sensitive for Fe(2+) with a low limit of detection (2.03 µM) which is, to the best of our knowledge, the superior than the previously studied chemosensors for Fe(2+). Graphical Abstract ᅟ.

First paraben substituted cyclotetraphosphazene compounds and DNA interaction analysis with a new automated biosensor.

Cancer, as one of the leading causes of death in the world, is caused by malignant cell division and growth that depends on rapid DNA replication. To develop anti-cancer drugs this feature of cancer could be exploited by utilizing DNA-damaging molecules. To achieve this, the paraben substituted cyclotetraphosphazene compounds have been synthesized for the first time and their effect on DNA (genotoxicity) has been investigated. The conventional genotoxicity testing methods are laborious, take time and are expensive. Biosensor based assays provide an alternative to investigate this drug/compound DNA interactions. Here for the first time, a new, easy and rapid screening method has been used to investigate the DNA damage, which is based on an automated biosensor device that relies on the real-time electrochemical profiling (REP™) technology. Using both the biosensor based screening method and the in vitro biological assay, the compounds 9 and 11 (propyl and benzyl substituted cyclotetraphosphazene compounds, respectively), have resulted in higher DNA damage than the others with 65% and 80% activity reduction, respectively.

Pilot and full scale applications of sulfur-based autotrophic denitrification process for nitrate removal from activated sludge process effluent.

Sulfur-based autotrophic denitrification of nitrified activated sludge process effluent was studied in pilot and full scale column bioreactors. Three identical pilot scale column bioreactors packed with varying sulfur/lime-stone ratios (1/1-3/1) were setup in a local wastewater treatment plant and the performances were compared under varying loading conditions for long-term operation. Complete denitrification was obtained in all pilot bioreactors even at nitrate loading of 10 mg NO3(-)-N/(L.h). When the temperature decreased to 10 °C during the winter time at loading of 18 mg NO3(-)-N/(L.h), denitrification efficiency decreased to 60-70% and the bioreactor with S/L ratio of 1/1 gave slightly better performance. A full scale sulfur-based autotrophic denitrification process with a S/L ratio of 1/1 was set up for the denitrification of an activated sludge process effluent with a flow rate of 40 m(3)/d. Almost complete denitrification was attained with a nitrate loading rate of 6.25 mg NO3(-)-N/(L.h).

Heterotrophic and elemental-sulfur-based autotrophic denitrification processes for simultaneous nitrate and Cr(VI) reduction.

Nitrate and chromate can be present together in water resources as nitrate is a common co-contaminant in surface and ground waters. This study aims at comparatively evaluating simultaneous chromate and nitrate reduction in heterotrophic and sulfur-based autotrophic denitrifying column bioreactors. In sulfur-based autotrophic denitrification process, elemental sulfur and nitrate act as an electron donor and an acceptor, respectively, without requirement of organic supplementation. Autotrophic denitrification was complete and not adversely affected by chromate up to 0.5 mg/L. Effluent chromate concentration was <50 µg/L provided that influent chromate concentration was ≤0.5 mg/L. Heterotrophic denitrification performance was not adversely affected even at 20 mg/L chromate and complete chromate reduction was attained up to 10 mg/L. Although autotrophic denitrification rate was much lower compared with heterotrophic one, it may be preferred in drinking water treatment due to the elimination of organic supplementation and the risk of treated effluent contamination.

Intramolecular excimer formation in hexakis(pyrenyloxy)cyclotriphosphazene: photophysical properties, crystal structure, and theoretical investigation.

A hexakis(pyrenyloxy)cyclotriphosphazene is synthesized by the reaction of N3P3Cl6 with 2-hydroxypyrene, and its excimer emission through intramolecular interactions in solution and in the solid state has been investigated by fluorescence spectroscopy and X-ray crystallography. Thermal and electrochemical properties were investigated. A DFT benchmark study has been performed to evaluate the intramolecular interactions and molecular orbital levels by comparing with the experimental results.

Simultaneous bioreduction of nitrate and chromate using sulfur-based mixotrophic denitrification process.

This study aims at evaluating simultaneous chromate and nitrate reduction using sulfur-based mixotrophic denitrification process in a column reactor packed with elemental sulfur and activated carbon. The reactor was supplemented with methanol at C/N ratio of 1.33 or 2. Almost complete denitrification was achieved at influent NO3(-)-N and Cr(VI) concentrations of 75 mg/L and 10mg/L, respectively, and 3.7h HRT. Maximum denitrification rate was 0.5 g NO3(-)-N/(L.d) when the bioreactor was fed with 75 mg/L NO3(-)-N, 150 mg/L methanol and 10mg/L Cr(VI). The share of autotrophic denitrification was between 12% and 50% depending on HRT, C/N ratio and Cr(VI) concentration. Effluent total chromium was below 50 µg/L provided that influent Cr(VI) concentration was equal or below 5mg/L. DGGE results showed stable microbial community throughout the operation and the presence of sulfur oxidizing denitrifying bacteria (Thiobacillus denitrificans) and Cr(VI) reducing bacteria (Exiguobacterium spp.) in the column bed.

Fluorenylidene bridged cyclotriphosphazenes: 'turn-off' fluorescence probe for Cu(2+) and Fe(3+) ions.

A first series of the 4,4'-(9-fluorenylidene)diphenol (), () and 4,4'-(9-fluorenylidene)dianiline (), () bridged cyclotriphosphazene derivatives (, ) were synthesized by nucleophilic SN2(P) and SN1(P) reactions, respectively. The structural investigations of the compounds were verified by elemental analyses, mass spectrometry, UV-vis, FT-IR, (1)H and (31)P NMR techniques, X-ray crystallography (for , , ) and fluorescence spectroscopy. The metal sensing properties of novel bridged cyclotriphosphazene derivatives were also examined by fluorescence spectroscopy. These complexes showed high selectivity for Cu(2+) and Fe(3+) ions in solution.

Conversion of a cyclotriphosphazene to a cyclohexaphosphazene by ring expansion.

Deprotonation of a cyclotriphosphazene with a tert-butylamino group in the side chain results in ring expansion to a very stable, planar cyclohexaphosphazene derivative that still contains eight P-Cl bonds suitable for forming macromolecular structures.

Synthesis, cytotoxicity and apoptosis of cyclotriphosphazene compounds as anti-cancer agents.

In the present study, a number of new dispirobino and dispiroansa spermine derivatives of cyclotriphosphazene (8-10, 13) were synthesized and characterized by elemental analysis, mass spectrometry, (1)H and (31)P NMR spectroscopy. At first, in vitro cytotoxic activity of cyclotriphosphazene compounds (1-14) against HT-29 (human colon adenocarcinoma), Hep2 (Human epidermoid larynx carcinoma), and Vero (African green monkey kidney) cell lines was investigated. Our study showed that most of these compounds stimulate apoptosis and they have cytotoxic effects for HT-29 and Hep2 cells. Additionally, these compounds (1-14) were investigated for their antibacterial activity against gram-positive (Staphylococcus aureus), gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and for their antifungal activity against Candida albicans, and were shown to be inactive.

Hexavalent chromium reduction in a sulfur reducing packed-bed bioreactor.

The most commonly used approach for the detoxification of hazardous industrial effluents and wastewaters containing Cr(VI) is its reduction to the much less toxic and immobile form of Cr(III). This study investigates the cleanup of Cr(VI) containing wastewaters using elemental sulfur as electron acceptor, for the production of hydrogen sulfide that induces Cr(VI) reduction. An elemental sulfur reducing packed-bed bioreactor was operated at 28-30°C for more than 250 days under varying influent Cr(VI) concentrations (5.0-50.0 mg/L) and hydraulic retention times (HRTs, 0.36-1.0 day). Ethanol or acetate (1000 mg/L COD) was used as carbon source and electron donor. The degree of COD oxidation varied between 30% and 85%, depending on the operating conditions and the type of organic carbon source. The oxidation of organic matter was coupled with the production of hydrogen sulfide, which reached a maximum concentration of 750 mg/L. The biologically produced hydrogen sulfide reduced Cr(VI) chemically to Cr(III) that precipitated in the reactor. Reduction of Cr(VI) and removal efficiency of total chromium always exceeded 97% and 85%, respectively, implying that the reduced chromium was retained in the bioreactor. This study showed that sulfur can be used as an electron acceptor to produce hydrogen sulfide that induces efficient reduction and immobilization of Cr(VI), thus enabling decontamination of Cr(VI) polluted wastewaters.

Stereo-selectivity in a cyclotriphosphazene derivative bearing an exocyclic P-O moiety.

Nucleophilic substitution reactions of N(3)P(3)Cl(4)[O(CH(2))(2)NCH(3)], (1) with the sodium salts of mono- and di-functional alcohols [methanol (2), phenol (3), tetraethyleneglycol (4) and 1,3-propanediol (5)] were carried out in order to investigate a possible directing effect of the spiro O-moiety on the formation of mono-substituted (2a, 3a), non-geminal di-substituted (2c, 3c) and ansa (4a, 5a) derivatives. Compounds isolated from the reactions were characterized by elemental analysis, mass spectrometry, (1)H and (31)P NMR spectroscopy and X-ray crystallographic analysis showed that the substituent OR in compounds (2a, 3a and 2c, 3c) and the ansa-ring in compounds (4a, 5a) formed cis to the P-O moiety of the exocyclic [O(CH(2))(2)NCH(3)] spiro ring. The formation of products (2a-d, 3a-d, 4a, 5a and 5b) was quantified from the (31)P NMR spectra of the reaction mixtures, which showed an overwhelming preference for derivatives (2a, 3a, 2c, 3c, 4a, 5a) with the substituent cis to the P-O moiety of the exocyclic spiro ring (2a, 3a, 2c, 3c, 4a, 5a), except for reaction with 1,3-propanediol where the six-membered ring spiro derivative (5b) was about three times more abundant than the eight-membered ring ansa-derivative (5a). Overwhelming formation of products with the substituent cis to the exocyclic P-O moiety is proof that the cation-assisted mechanism is responsible for the stereo-selectivity in the reactions with alkoxides.

Simultaneous heterotrophic and sulfur-oxidizing autotrophic denitrification process for drinking water treatment: control of sulfate production.

A long-term performance of a packed-bed bioreactor containing sulfur and limestone was evaluated for the denitrification of drinking water. Autotrophic denitrification rate was limited by the slow dissolution rate of sulfur and limestone. Dissolution of limestone for alkalinity supplementation increased hardness due to release of Ca(2+). Sulfate production is the main disadvantage of the sulfur autotrophic denitrification process. The effluent sulfate concentration was reduced to values below drinking water guidelines by stimulating the simultaneous heterotrophic and autotrophic denitrification with methanol supplementation. Complete removal of 75 mg/L NO(3)-N with effluent sulfate concentration of around 225 mg/L was achieved when methanol was supplemented at methanol/NO(3)-N ratio of 1.67 (mg/mg), which was much lower than the theoretical value of 2.47 for heterotrophic denitrification. Batch studies showed that sulfur-based autotrophic NO(2)-N reduction rate was around three times lower than the reduction rate of NO(3)-N, which led to NO(2)-N accumulation at high loadings.

Bridged cyclophosphazenes resulting from deprotonation reactions of cyclotriphophazenes bearing a P-NH group.

Cyclotriphosphazene derivatives containing a P-NHR group in the side-chain react in the presence of a strong base to form stable intermolecular bridged products. Reaction of sodium hydride with mono-spiro cyclophosphazene derivatives having a P-NH group, N(3)P(3)Cl(4)[O(CH(2))(3)NH], (1a) or N(3)P(3)Cl(4)[CH(3)N(CH(2))(3)NH], (1b) leads to formation of bis-cyclophosphazenes bridged with an eight-membered cyclophosphazene ring in an ansa arrangement (2a, 2b) whereas reaction of sodium hydride with mono-amino cyclophosphazene derivatives [N(3)P(3)Cl(5)(NHR), R = n-hexyl, 3a; i-Pr, 3b; Ph, 3c] give bis-cyclophosphazenes bridged with a four-membered cyclophosphazane ring in a spiro arrangement (4a-c). In the latter reaction P-O-P bridged compounds (5a-c) were also obtained as a result of hydrolysis reactions associated with the amount of moisture in the solvent tetrahydrofuran. In addition, it was found that reaction of a mixture of cyclotriphosphazene with either mono spiro compound, (1a) or (1b), in the presence of sodium hydride lead to formation of the first examples of asymmetrically-bridged cyclophosphazenes (6a-b).

Competitive formation of cis and trans derivatives in the nucleophilic substitution reactions of cyclophosphazenes having a mono-spiro P-NHR group.

Nucleophilic substitution reactions of N(3)P(3)Cl(4)[NH(CH(2))(3)NMe] (1) and N(3)P(3)Cl(4)[NH(CH(2))(3)O] (2) with mono-functional alcohols (methanol, 2,2,2-trifluoroethanol, phenol) and a secondary amine (pyrrolidine) were used to investigate the relationship between the incoming nucleophile and the proportions of products with substituents that are cis or trans to the spiro NH moiety. The reaction products were characterized by elemental analysis, mass spectrometry, (1)H and (31)P NMR spectroscopy and the configurational isomers by X-ray crystallography. Six products have been characterised with the substituent cis to the spiro NH group for the alcohol (methanol, phenol) and pyrrolidine derivatives of both compounds 1 and 2, compared to just one derivative with the substituent trans to the spiro NH group, that for the pyrrolidine derivative of compound 2. For each reaction the relative proportions of cis and trans isomers were determined by (31)P NMR measurements of the reaction mixtures. It was found that the reactions of compound 1 with all three alcohols and of compound 2 with methanol lead to exclusive formation of isomers with the substituent cis to the NH moiety, whereas all other reactions lead to mixtures of cis and trans isomers in different ratios under standard reaction conditions. However, when crown ether is included in the reaction medium for the reactions of compound 2 with both 2,2,2-trifluoroethanol and phenol, it is found that only cis isomers are formed. All these results are rationalised in terms of the competition between at least two effects; the cis-directing effect by hydrogen bonding of the incoming nucleophile to the spiro N-H group already present on the cyclophophazene ring and the cis-directing effect of the sodium cation coordinating to the oxygen lone pairs of the P-O moiety of the spiro ring.

Phosphorus-nitrogen compounds. 21. Syntheses, structural investigations, biological activities, and DNA interactions of new N/O spirocyclic phosphazene derivatives. The NMR behaviors of chiral phosphazenes with stereogenic centers upon the addition of chiral solvating agents.

The reactions of hexachlorocyclotriphosphazatriene, N(3)P(3)Cl(6), with N/O-donor-type N-alkyl (or aryl)-o-hydroxybenzylamines (1a-1e) produce mono- (2a-2e), di- (3a-3d), and tri- (4a and 4b) spirocyclic phosphazenes. The tetrapyrrolidino monospirocyclic phosphazenes (2f-2i) are prepared from the reactions of partly substituted compounds (2a-2d) with excess pyrrolidine. The dispirodipyrrolidinophosphazenes (3e-3h) and trispirophosphazenes (3i-3k) are obtained from the reactions of trans-dispirophosphazenes with excess pyrrolidine and sodium (3-amino-1-propanoxide), respectively. Compounds 3a-3d have cis and trans geometric isomers. Only the trans isomers of these compounds are isolated. Compounds 3a-3h have two stereogenic P atoms. They are expected to be in cis (meso) and trans (racemic) geometric isomers. In the trans trispiro compounds (3i-3k), there are three stereogenic P atoms. They are expected to be in racemic mixtures. The stereogenic properties of 3a-3k are confirmed by (31)P NMR spectroscopy upon the addition of the chiral solvating agent; (S)-(+)-2,2,2-trifluoro-1-(9'-anthryl)ethanol. The molecular structures of 3i-3k, 4a, and 4b look similar to a propeller, where the chemical environment of one P atom is different from that of others. Additionally, 4a and 4b are also expected to exist as cis-trans-trans and cis-cis-cis geometric isomers, but both of them are found to be in cis-trans-trans geometries. The solid-state structures of 2a, 2e, 2f, 3e, and 3f are determined by X-ray crystallography. The compounds 2f-2i, 3e-3i, and 3k are screened for antibacterial activity against gram-positive and gram-negative bacteria and for antifungal activity against yeast strains. These compounds (except 3f) have shown a strong affinity against most of the bacteria. Minimum inhibitory concentrations (MIC) are determined for 2f-2i, 3e-3i, and 3k. DNA binding and the nature of interaction with pUC18 plasmid DNA are studied. The compounds 2f-2i, 3e-3i, and 3k induce changes on the DNA mobility. The prevention of BamHI and HindIII digestion (except 2g) with compounds indicates that the compounds bind with nucleotides in DNA.

Structural and fluorescence properties of phenolphthalein bridged cyclotriphosphazatrienes.

This study dealt with the reactions of hexachlorocyclotriphosphazatriene, N(3)P(3)Cl(6) (trimer) (1) with phenolphthalein (2) to give the phenolphthalein bridged compounds 3, 4 and 5. The phenolphthalein bridged cyclotriphosphazatriene derivatives are reported for the first time. The new compounds (3-5) are characterized by elemental analysis, mass spectrometry, UV-vis, FT-IR, (1)H, (31)P NMR and fluorescence spectroscopy. The more bridged phenolphthalein groups show the higher intensity of the absorption bands in the UV-vis spectra. Fluorescence spectrum of compound 3 shows a small band in the lower spectral range, while the spectra of compounds 4 and 5 show more intense and a band in higher spectral range.

Absolute structure determination as a reference for the enantiomeric resolution of racemic mixtures of cyclophosphazenes via chiral high-performance liquid chromatography.

Reversed-phase chiral high-performance liquid chromatography (HPLC) is a potentially powerful technique for the enantiomeric resolution of racemic mixtures, although the elution order of enantiomers is only relative and it is necessary to fully characterize reference systems for this method to provide absolute configurational information. The enantiomeric resolution of a series of racemic di-spiro cyclotriphosphazene derivatives, N3P3X2[O(CH2)(3)NH]2 (X = Cl, Ph, SPh, NHPh, OPh) [(1)-(5), respectively] was carried out by reversed-phase chiral HPLC on a commercially available Pirkle-type chiral stationary phase (R,R)-Whelk-01 using 85:15 (v/v) hexane-thf as the mobile phase. The absolute configurations of the resulting enantiomers of compounds (3) (X = SPh) and (5) (X = OPh) were determined unambiguously by X-ray crystallography. For both (3) and (5) it was found that the SS enantiomer eluted before the RR enantiomer, indicating a convenient method to determine the absolute configurations of enantiomers of this series of cyclophosphazene derivatives and providing the first set of enantiomeric reference compounds for cyclophosphazene derivatives. These structures demonstrate an interesting anomaly in that the pair of enantiomers of (3) crystallize in enantiomorphically paired space groups whilst, under the same conditions, the solid-state forms of the enantiomers of (5) form structures in Sohncke space groups that are not enantiomorphous.

Stable P-N bridged cyclophosphazenes with a spiro or ansa arrangement.

Deprotonation reactions of cyclophosphazenes containing secondary amino groups in the side chain lead to a doubly bridged tricyclophosphazene structure or to a cyclophosphazene-cyclophosphazane-cyclophosphazene compound, which are very stable and could be used as building blocks for larger structures.