BODIPY precursors and their cyclotriphosphazene Derivatives: Synthesis, photochemical properties and their application in PDT.

Photodynamic therapy (PDT) is a treatment method consisting of common combination of oxygen, light energy and a light absorbing molecule called a photosensitizer. In this work, four new compounds consisting of BODIPY precursors and BODIPY-cyclotriphosphazene derivatives were synthesized to investigate the PDT effects. The chemical structures of the compounds were characterized and then their photophysical properties were determined by spectroscopic techniques. The precursor BODIPYs and their cyclotriphosphazene derivatives exhibited similar properties such as strong absorption intensity, high photostability and low fluorescence profile in the NIR region. Additionally, the singlet oxygen production capacities of these compounds were determined using the photobleaching technique of 1,3-diphenylisobenzofuran (DPBF) under light illumination. By introducing iodine atoms into the molecule, which are responsible for the intersystem transition (ISC) enhancement, a more efficient singlet oxygen production was achieved in both the iodinated-BODIPY and its cyclotriphosphazene derivative. Anticancer activities of the precursor BODIPYs and their cyclotriphosphazene derivatives in the absence and presence of light illumination were evaluated on cancerous cell lines (PC3 and DU145) and non-tumorigenic prostate epithelial PNT1a cell. The compounds triggered the death of cancer cell PC3 the more significantly in the presence of red light compared to the healthy cells (PNT1a).

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.

Nucleophilic substitution reactions of monofunctional nucleophilic reagents with cyclotriphosphazenes containing 2,2-dioxybiphenyl units.

The nucleophilic substitution reactions of mono- and bis-spiro-2,2' -dioxybiphenyl cyclotriphosphazenes (3 and 4) with cyclopropanemethylamine (5) and aniline (6) were performed in the presence of trimethylamine in THF. Five novel cyclopropanemethylamino- and anilino-substituted spiro-2,2' -dioxybiphenyl cyclotriphosphazene derivatives (7-11) were obtained from these reactions. The molecular structures of the new cyclotriphosphazene derivatives (7-11) were characterized by elemental analysis, MALDI-TOF MS, FT-IR, and NMR ( 31 P and 1 H) spectroscopies. The structure of the spiro-(2,2' -dioxybiphenyl)-bis-(anilino)-cyclotriphosphazene (11) was also determined by single-crystal X-ray crystallography.

Novel ruthenium(ii) and iridium(iii) BODIPY dyes: insights into their application in photodynamic therapy in vitro.

Organic-metal complexes are promising molecules for use in photodynamic therapy (PDT). The aim of this study was to investigate in vitro effects of novel Ru(ii) and Ir(iii) BODIPY complexes for PDT. These hybrid organic-metal molecules (Ru-BD and Ir-BD) have been synthesized via reactions of a BODIPY precursor (BD) with a phenanthroline unit bearing Ru(ii) (3) and novel Ir(iii) (4) compounds. The crystal structures of the new distyryl BODIPY (BD) and Ru(ii) complex (3) are also reported. The photophysical and singlet oxygen generation properties of Ru-BD and Ir-BD were investigated in comparison with unsubstituted BODIPY (BD). Moreover, Ru-BD and Ir-BD have been biologically evaluated in vitro in chronic myeloid leukemia and cervical cancer cell lines in terms of photodynamic therapy efficacy in the presence of BD control. These complexes were not toxic in the dark but red light was needed to induce cell death. These data support the fact that Ru-BD could be accepted as a valuable photosensitizer-drug for further PDT treatment.

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.

Anomalous NMR behavior of meso compounds with remote stereogenic centers on addition of chiral shift reagent or chiral solvating agent.

A problem has arisen in using chiral shift reagents (CSR) and chiral solvating agents (CSA) to determine meso and racemic forms of diastereoisomers in which the stereogenic centers of the molecules are separated by achiral spacers. It is found that NMR signals of both meso and racemic forms of diastereoisomers may exhibit doubling on addition of CSR/CSA, which means that unequivocal assignments cannot be made without characterizing the effects for separate meso and racemic forms; this is particularly important for additions of CSR/CSA at relatively low concentrations, which always result in the splitting of some NMR signals of diastereoisomers. The phenomenon is demonstrated in the (31)P NMR spectra of meso and racemic forms of three spermine-bridged gem-disubstituted cyclotriphosphazatrienes, 1a-c, and compared with analogous achiral molecules, the per-substituted spermine-bridged cyclotriphosphazatrienes 2a-d. As expected, only one set of (31)P NMR signals was observed for the achiral compounds 2a-d, even on addition of CSA. Two sets of (31)P NMR ABX multiplets corresponding to meso and racemic diastereoisomers were observed for compounds 1a-c; on addition of CSA, the signals of at least one of the multiplets for each compound separated into more than the expected groups of three lines with an intensity distribution of 2:1:1. To understand this phenomenon, the meso and racemic forms of 1a and 1b and the meso form of 1c have been separated and characterized by X-ray crystallography. On addition of CSA to the racemic forms of 1a and 1b, the (31)P NMR spectrum shows the expected doubling of signals, but, unexpectedly, the same is observed for each of the meso forms of 1a-c. Analogous results using both CSA and CSR have been obtained for the meso and racemic forms of the diastereoisomeric piperazine-bridged macrocyclic-phosphazene compound, 3, whereas no effect was observed for the two meso forms of the doubly bridged macrocyclic-phosphazene compound 4. The phenomenon of doubling of the (31)P NMR signals of the meso form of singly bridged cyclotriphosphazatrienes, 1a-c and 3, is explained by consideration of the equilibrium in solution of independent complexation of a chiral ligand with molecules that have two chiral cyclophosphazene moieties separated by an achiral spacer group. The results show that the stereogenicity of such diastereoisomeric molecules in solution cannot be characterized unequivocally by NMR measurements on addition of either CSR or CSA.