A Translational Study of a Silicon Phthalocyanine Substituted with a Histone Deacetylase Inhibitor for Photodynamic Therapy.

In this study, we synthesized and characterized a silicon phthalocyanine substituted with 3-hydroxypyridin-2-thione (SiPc-HDACi), designed to be a chemophotodynamic therapy agent acting as a histone deacetylase inhibitor, and we determined its photophysical, photochemical, and photobiological properties. Next, we evaluated its anticancer efficacy on MCF-7, double positive and MDA-MB-231, triple negative breast cancer cell lines, as well as on a healthy human endothelial cell line (HUVEC). Our results indicate that SiPc-HDACi can target nucleoli of cells, effectively inducing apoptosis while promoting cell cycle arrest thanks to its high singlet oxygen yield and its histone deacetylase downregulating properties, suggesting a powerful anticancer effect on breast cancer in vitro. Our further studies will be conducted with primary breast cancer cell culture to give a better insight into the anticancer mechanism of the compound.

Electrophoresis and Biosensor-Based DNA Interaction Analysis of the First Paraben Derivatives of Spermine-Bridged Cyclotriphosphazenes.

Cancer is the uncontrolled growth of abnormal cells via malignant cell division and rapid DNA replication. While DNA damaging molecules can cause cancer, their role as anticancer drugs are very significant. For this purpose, the novel series of paraben substituted spermine bridged(dispirobino) cyclotriphosphazene compounds 2-6 were synthesized for the first time, and their structures were characterized by various spectroscopic techniques. The solid-state structures and geometries of compounds 2-6 were determined using single-crystal X-ray structural analysis. In addition, it was confirmed by TGA that all compounds 1-6 showed high thermal stability. Two methods were used in order to investigate DNA interaction properties of the targeted molecules. While biosensor-based screening test that measures DNA hybridization efficiency on a biochip surface, the agarose gel electrophoresis method examines the effect of compounds on plasmid DNA structure. The results collected from the automated biosensor device and agarose gel electrophoresis have indicated that compounds 1, 5, and 6 showed higher DNA damage than the compounds 2-4. According to the biosensor results, compounds 1, 5, and 6 showed 85%, 69%, and 77% activity, respectively.

Chemosensor properties of 7-hydroxycoumarin substituted cyclotriphosphazenes.

The newly synthesized cyclotriphosphazene cored coumarin chemosensors 5, 6, and 7 were successfully characterized by 1 H NMR, 31 P NMR, and MALDI-TOF mass spectrometry. Additionally, the photophysical and metal sensing properties of the targeted compounds were determined by fluorescence spectroscopy in the presence of various metals (Li + , Na + , K + , Cs + , Mg 2+ , Ca 2+ , Ba 2+ , Cr 3+ , Mn 2+ , Fe 3+ , Co 2+ , Al 3+ , Hg + , Cu 2+ , Zn 2+ , Ag + , and Cd 2+ ) . The fluorescence titration results showed that compounds 5, 6, and 7 could be employed as fluorescent chemosensors for Fe 3+ ions with high sensitivity. The complex stoichiometry between final cyclotriphosphazene chemosensors and Fe 3+ ions was also determined by Job's plots.

New perylenebisimide decorated cyclotriphosphazene heavy atom free conjugate as singlet oxygen generator.

Perylenebisimide-cyclotriphosphazene based inorganic-organic system was synthesized by a multistep procedure. The substitution reaction of asymmetric perylenebisimide (PBI) derivative with the hexachloroyclotriphosphazene (trimer) resulted in the formation of fully PBI decorated cyclotriphosphazene (5). The identity of newly synthesized compound (5) was confirmed by using 31P, 1H and 13C NMR spectroscopies and mass spectrometry. The photophysical (UV- Vis absorption, fluorescence emission, fluorescence lifetime and fluorescence quantum yield) and photochemical (the singlet oxygen generation, and photostability) properties of this conjugate were investigated as novel heavy atom free triplet photosensitizer. The singlet oxygen quantum yield of the PBI-cyclotriphosphazene (5) was calculated to be 0.86 which is good for a heavy atom free triplet photosensitizer. These results will add to the development of cyclotriphosphazene based heavy atom free singlet oxygen triplet photosensitizer systems for applications in organic oxygenation reactions.

Azaindole-BODIPYs: Synthesis, fluorescent recognition of hydrogen sulfate anion and biological evaluation.

The synthesized and sensing capability of two novel azaindole substituted mono and distyryl BODIPY dyes against bisulfate anion were reported. Structural characterizations of the targeted compounds were conducted by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, 1H and 13C NMR spectroscopies. Photophysical properties of the azaindole substituted BODIPY compounds were investigated employing absorption and fluorescence spectroscopies in acetonitrile solution. It was found that the final compounds 3 and 4 exhibited exclusively selective and sensitive turn-off sensor behavior on HSO4- anion. Additionally, the stoichiometry ratio of the targeted compounds to bisulfate anion was measured 0.5 by Job's method. Also, density function theory was performed to the optical response of the sensor for targeted compounds. Furthermore, the cytotoxicity of Azaindole-BODIPYs was examined against living human leukemia K562 cell lines.

New hexa-bodipy functionalized dendrimeric cyclotriphosphazene conjugates as highly selective and sensitive fluorescent chemosensor for Co2+ ions.

In the study, the new hexa-bodipy functionalized dendrimeric cyclotriphosphazene conjugates (HBCP 1 and 2) have been successfully synthesized and characterized by using general spectroscopic techniques such as 1H, 13C and 31P NMR spectroscopies. The photophysical and metal sensing properties in THF solutions of dendrimeric cyclotriphosphazene conjugates (HBCP 1 and 2) were investigated by UV-Vis and fluorescence spectroscopies in dilute tetrahydrofuran solutions. These dendrimers showed strong absorption bands 501 and 641nm at low concentration with high molar extinction coefficients. In addition, the stoichiometry of the complex between the conjugate (HBCP 2) and Co2+ ions were determined by a Job's plot obtained from fluorescence titrations. The metal sensing data showed that the hexa-bodipy functionalized dendrimeric cyclotriphosphazene conjugate (HBCP 2) is a candidate for fluorescent chemosensor for Co2+ ions due to showing high selectivity with a low limit of detection.

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.

Octa-BODIPY derivative dendrimeric cyclotetraphosphazenes; photophysical properties and fluorescent chemosensor for Co2+ ions.

We have designed and synthesized the first examples of fluorescent chemosensors based on octa-BODIPY decorated dendrimeric cyclotetraphosphazenes. The structures these synthesized compounds were verified by 1H, 13C, 31P NMR spectroscopies and UV-vis electronic absorption spectra. The photophysical and metal sensing properties in THF solutions of dendrimeric cyclotetraphosphazenes (OBCP 1-3) were investigated by fluorescence spectroscopy. OBCP 1-3 showed strong absorption in the 500-640nm region with high molar extinction coefficients. Additionally, octa-BODIPY decorated dendrimeric cyclotetraphosphazenes are candidate for fluorescent chemosensor for Co2+ showing high selectivity with a low limit of detection.

Silver(I) coordination polymers assembled from flexible cyclotriphosphazene ligand: structures, topologies and investigation of the counteranion effects.

The reactions of a flexible ligand hexakis(3-pyridyloxy)cyclotriphosphazene (HPCP) with a variety of silver(I) salts (AgX; X = NO3(-), PF6(-), ClO4(-), CH3PhSO3(-), BF4(-) and CF3SO3(-)) afforded six silver(I) coordination polymers, namely {[Ag2(HPCP)]·(NO3)2·H2O}n (1), {[Ag2(HPCP)(CH3CN)]·(PF6)2}n (2), {[Ag2(HPCP)(CH3CN)]·(ClO4)2}n (3), [Ag3(HPCP)(CH3PhSO3)3]n (4), [Ag2(HPCP)(CH3CN)(BF4)2]n (5) and {[Ag(HPCP)]·(CF3SO3)}n (6). All of the isolated crystalline compounds were structurally determined by X-ray crystallography. Changing the counteranions in the reactions, which were conducted under similar conditions of M/L ratio (1:1), temperature and solvent, resulted in structures with different types of topologies. In complexes (1)-(6), the ligand HPCP shows different coordination modes with Ag(I) ions giving two-dimensional layered structures and three-dimensional frameworks with different topologies. Complex (1) displays a new three-dimensional framework adopting a (3,3,6)-connected 3-nodal net with point symbol {4.6(2)}2{4(2).6(10).8(3)}. Complexes (2) and (3) are isomorphous and have a two-dimensional layered structure showing the same 3,6L60 topology with point symbol {4.2(6)}2{4(8).6(6).8}. Complex (4) is a two-dimensional structure incorporating short Ag...Ag argentophilic interactions and has a uninodal 4-connected sql/Shubnikov tetragonal plane net with {4(4).6(2)} topology. Complex (5) exhibits a novel three-dimensional framework and more suprisingly contains twofold interpenetrated honeycomb-like networks, in which the single net has a trinodal (2,3,5)-connected 3-nodal net with point symbol {6(3).8(6).12}{6(3)}{8}. Complex (6) crystallizes in a trigonal crystal system with the space group R\bar 3 and possesses a three-dimensional polymeric structure showing a binodal (4,6)-connected fsh net with the point symbol (4(3).6(3))2.(4(6).6(6).8(3)). The effect of the counteranions on the formation of coordination polymers is discussed in this study.

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.

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, (31)P-NMR, (1)H-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 Fe(3+) ions in aqueous solution.

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.

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.

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.