Gönül Yenilmez Çiftçi

Novel Coumarin Substituted Water Soluble Cyclophosphazenes as “Turn-Off” Type Fluorescence Chemosensors for Detection of Fe 3+ ions in Aqueous Media

In the present work, 3-[2-(diethylamino)ethyl]-7-oxy-4-methylcoumarin substituted cyclotriphosphazene (4) and cyclotetraphosphazene (5) derivatives were synthesized by the reactions of hexachlorocyclotriphosphazene (1) or octachlorocyclotetraphosphazene (2) with 3-[2-(diethylamino)ethyl]-7-hydroxy-4-methylcoumarin (3) for the first time. The quaternized cationic (6 and 7) and zwitterionic (8 and 9) derivatives of these compounds (4 and 5) were obtained by the reactions of dimethyl sulfate and 1,3-propanesultone, respectively. All newly synthesized cyclophosphazene compounds (4–9) were fully characterized by elemental analysis and general spectroscopic techniques such as FT-IR, 31P-NMR, 1H-NMR and MALDI-TOF mass. All these coumarin substituted cyclophosphazene compounds (4–9) were soluble in most of organic solvents and quaternized ionic and zwitterionic compounds (6–9) also showed excellent solubility in water. The fluorescence behaviors of novel cyclophosphazene compounds were investigated in methanol and water solutions. The chemosensor properties of newly synthesized water soluble quaternized ionic and zwitterionic cyclotriphosphazene and cyclotetraphosphazene derivatives (6–9) were investigated in aqueous media. These cyclophosphazene derivatives showed fluorescence chemosensor behavior with high selectivity for Fe3+ ions in aqueous solution.

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.

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.

BODIPY decorated dendrimeric cyclotriphosphazene photosensitizers: synthesis and efficient singlet oxygen generators

In the present work, syntheses of BODIPY decorated dendrimeric cyclotriphosphazenes (8–10) are described. The newly synthesized dendrimeric cyclotriphosphazenes have been characterized by 1H, 13C, 31P NMR spectroscopies, and UV-Vis electronic absorption spectra. These derivatives show absorption in the NIR region with good molar extinction coefficients. Singlet oxygen generation capacities of novel compounds (8–10) are measured using the trap molecule 1,3-diphenylisobenzofuran. BODIPY decorated dendrimeric cyclotriphosphazenes (8–10) demonstrate high singlet oxygen quantum yields. Also, each of them shows chemical and photostability under the conditions of singlet oxygen measurement. The dendrimeric cyclotriphosphazenes are proposed as potential photosensitizers that can be used as efficient singlet oxygen generators.

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.

Structural investigations of phosphorus–nitrogen compounds. 6. Relationships between molecular parameters in per-X-substituted bridged spermine derivatives and basicity constants ΣαR of substituents

A systematic study is reported of the products of the nucleophilic substitution reactions of the spermine-bridged cyclotriphosphazene, [N3P3X4(NHCH2CH2CH2N)CH2CH2]2 [where X = Cl (2a)], to give a number of new structures [(2b)-(2g)] in which X = OPh, [spiro-O(CH2)3O]0.5, Ph, NHPh, NC4H8 and NHBut, respectively. A comparison has been made between the sum of the substituent basicity constants, Sigmaalpha(R), obtained in nitrobenzene solution, and ten molecular parameters of the N3P3 ring (the internal bond angles alpha, beta, gamma, delta and theta;, and the P-N bond lengths a, b, c, d and e) as well as the difference between the bond lengths a and b, Delta(P-N). It is found that the systematic change in molecular parameters of compounds (2a)-(2g) is in line with changes in alphaR values, indicating the similarity in relative electron-releasing capacity of substituents X in the solid state and in solution. It is also found that the effect on molecular parameters of (2a)-(2g) with two X substituents in PX2 groups is greater than that for one X substituent in P(OR)X groups in an analogous series of compounds observed previously [Besli et al. (2002). Acta Cryst. B58, 1067-1073].

Characterization of paraben substituted cyclotriphosphazenes, and a DNA interaction study with a real-time electrochemical profiling based biosensor

AbstractThis paper describes an amperometric method for studying DNA-drug candidate interactions. It uses an automatted electrochemical biosensor (MiSens®) based on real-time electrochemical profiling and gold nanoparticles. A biochip was prepared from a 10 x 20 mm silicon dioxide wafer. The biochip surface is modified with a self-assembled monolayer and integrated into the microfluidic system. All the steps of the DNA-drug interaction assay have been performed during fluid flow. Biotinylated surface DNA has been captured on a NeutrAvidin -modified biochip surface. Hybridization of the complementary target sequence and biotinylated detection probe to the surface DNA strand was studied with and without the addition of newly synthesised drug candidates. NeutrAvidin and enzyme modified gold nanoparticles were then injected to bind to the biochip surface. The real-time reading of the amperometric response during the substrate injection results in the biosensor signal. The DNA interaction analysis was exemplarily applied to test the activity of paraben-substituted cyclotriphosphazenes as potential anticancer agents. Two of the synthesised compounds were identified that are capable of inducing DNA damage by 27 and 34%, respectively. Graphical abstractDNA-drug interactions can be investigated by an automated biosensor device that relies on Real-time Electrochemical Profiling (REP™).

Study on the Synthesis, Photophysical Properties and Singlet Oxygen Generation Behavior of Bodipy-Functionalized Cyclotriphosphazenes.

A new series of bodipy-functionalized cyclotriphosphazene derivatives were designed and synthesized. The identities of all newly synthesized compounds were confirmed by using 1H, 13C, 31P NMR spectroscopies. The photophysical properties of bodipy-functionalized cyclotriphosphazenes were investigated via absorption and fluorescense spectroscopies in dichloromethane. Singlet oxygen generation capacities of new compounds were also examined using the trap molecule 1,3-diphenylisobenzofuran. The targeted compounds showed high molar extinction coefficients in the NIR region and respectable singlet oxygen quantum yields when compared to that of methylene blue. The new bodipy-functionalized cyclotriphosphazenes are efficient photosensitizers to be potentially used for the singlet oxygen generation.

THE REACTIONS OF N3P3Cl4[NH(CH2)3NMe] WITH DIFUNCTIONAL FLUORO ALCOHOLS

The reactions of N 3 P 3 Cl 4 [NH(CH 2 ) 3 NMe] (1) in one stoichiometry (1:1) with the sodium derivatives of the fluorinated diols 2,2,3,3-tetrafluorobutane-1,4-diol (2) and 2,2,3,3,4,4-hexafluoropentane-1,5-diol (3) in THF solution at room temperature yielded the following five products, whose structures (4-8) have been characterized by elemental analysis, mass spectrometry, FT-IR, 1 H and 31 P NMR spectroscopy: the mono-spiro compound, N 3 P 3 Cl 2 [NH(CH 2 ) 3 NMe](OCH 2 CF 2 CF 2 CH 2 O) (4), a di-spiro derivative N 3 P 3 [NH(CH 2 ) 3 NMe](OCH 2 CF 2 CF 2 CH 2 O) 2 (6) and the mono-spiro compound, N 3 P 3 C1 2 [NH(CH 2 ) 3 NMe](OCH 2 CF 2 CF 2 CF 2 CH 2 O) (5), its ansa isomer (8), a di-spiro derivative N 3 P 3 [NH(CH 2 ) 3 NMe](OCH 2 CF 2 CF 2 CF 2 CH 2 O) 2 (7). Besides, the thermal properties of the compounds (1, 4-8) were investigated by thermal analysis, namely by DSC and TGA.