Sevinc Zehra Topal

Methylsulfonyl Zn phthalocyanine: A polyvalent and powerful hydrophobic photosensitizer with a wide spectrum of photodynamic applications

BACKGROUND The biomedical photodynamic principle is based on the light-induced and photosensitizer-mediated killing of unwanted or harmful cells by overproduction of reactive oxygen species. Motivated by the success of photodynamic therapy (PDT) against several types of tumors, further applications of this approach are constantly identified which require the design and synthesis of novel photosensitizers with specifically tailored properties for a particular clinical application. METHODS Hydrophobic photosensitizers are currently gaining attention and hence a tetramethylsulfonyl Zn(II) phthalocyanine (2) was designed with respect to the desired photoproperties. The photodynamic potential of 2 was assessed by the determination of its photophysical and photochemical properties, and by a large range of biological tests including its phototoxicity against cancer cells and Gram(+) bacteria. Unsubstituted ZnPc was used as a reference compound for comparison purposes. RESULTS Phthalocyanine 2 has a better oxygen generation and is more photostable than ZnPc. 2 is a polyvalent and powerful hydrophobic photosensitizer with a wide spectrum of photodynamic applications against cancer (tested on A431 cells) and for Gram(+) PDI. Against Staphylococcus aureus, a maximum photokilling efficiency of more than 6 log10 steps was induced by a 5μM concentration of 2, outperforming the 3 log10 criterion for an antimicrobial effect (according to the recommendation of the American Society for Microbiology) by more than three orders of magnitude. CONCLUSIONS Phthalocyanine 2 has attractive photophysical and -chemical characteristics. Initial evaluation of its application in anti-tumor PDT and PDI suggest potential for further pre-clinical and clinical development of this compound.

Design of oxygen sensing nanomaterial: synthesis, encapsulation of phenylacetylide substituted Pd(II) and Pt(II) meso-tetraphenylporphyrins into poly(1-trimethylsilyl-1-propyne) nanofibers and influence of silver nanoparticles

Room temperature phosphorescent oxygen sensors have been designed by embedding symmetric palladium(II) or platinum(II) meso-tetraphenylporphyrins in poly(1-trimethylsilyl-1-propyne) in the form of nanofibers along with/without silver nanoparticles. These materials combine the advantages of the high oxygen sensitivity of porphyrins and the enhanced surface area of porous nanofibers. Phenylacetylide bearing palladium(II) or platinum(II) meso-tetraphenylporphyrins (Pd-TPA, Pt-TPA, Pd-TPP and Pt-TPP) were designed to enhance phosphorescence quantum yields as well as sensitivity towards oxygen. Their syntheses were achieved by 2 alternative methods including successive metallation reactions and Sonogashira coupling via optimization of the synthetic strategies and conditions. The respective effect of the metal (Pd or Pt) and substituent on phosphorescence quantum yield as well as other photophysical properties was considered. The sensing performances of the corresponding silver-free and silver doped nanofibers were tested in the oxygen concentration range of 0.0–100.0%. The offered composites provided the advantages of fast response, enhanced sensitivity, reversible and long lasting response, higher Stern–Volmer constants (KSV) and low limit of detection values extending to 7.5 ppm for oxygen.

Significant sensitivity and stability enhancement of tetraphenylporphyrin-based optical oxygen sensing material in presence of perfluorochemicals

Emission-based oxygen sensing properties of highly luminescent tetraphenylporphyrin molecules were investigated in polystyrene, ethyl cellulose, poly(1-trimethylsilyl-1-propyne) and poly(isobutylmethacrylate) matrices. The effect of perfluorochemicals (PFCs) on oxygen sensitivity and stability of the sensor materials was also examined. Fluorescence intensity and lifetime measurements of meso-tetraphenylporphyrinato Zn(II) (ZnTPP) and meso-tetraphenylporphyrin (H2TPP) materials were performed in the concentration range of 0–100% pO2. The fluorescence intensity variation of H2TPPvs. oxygen was 86%. H2TPP-based composite also yielded higher Stern–Volmer constant, faster response and regeneration time, excellent long term photostability and larger linear response range with respect to ZnTPP. The detection limit of oxygen for H2TPP was less than 0.5%. When stored in sealed bags protected from sunlight, no decrease in oxygen sensitivity was observed during approximately five months. As far as we know, the gathe...

Synthesis, Photophysical and Photochemical Properties of a Set of Silicon Phthalocyanines Bearing Anti-Inflammatory Groups

In this study, a series of novel silicon (IV) phthalocyanines conjugated axially with anti-inflammatory (sulindac) and triethylene glycol groups has been synthesized. Different synthetic strategies were attempted to obtain the targeted molecules in high yield. The compounds were fully characterized by using different analyses techniques. Our objectives were to generate a system with sulindac group which enhances the singlet oxygen generation and exhibits anti-cancer effect. Therefore, photophysical and photochemical properties of these compounds were investigated in different solvents. The substituent effect on fluorescence quantum yield and singlet oxygen generation was evaluated for efficiency in photodynamic therapy (PDT) as photosensitizer. The molecules exhibited no aggregation tendency, solubility in common organic solvents, high singlet oxygen quantum yield and high photostability in DMSO so these favourable properties make them good candidates as photosensitizer for PDT. In addition, their stabilities were investigated in DMSO, THF, acetonitrile and DMF.

Lifetime-Based Oxygen Sensing Properties of palladium(II) and platinum(II) meso-tetrakis(4-phenylethynyl)phenylporphyrin

High oxygen permeable [poly(TMSP)] nanofibers incorporating porphyrin macrocycle as luminescence indicators were prepared by electrospinning technique. The porphyrins involves were modified by i) introducing phenylacetylide substituents on the para position of the phenyl moieties and ii) varying the metal centers [Pt(II) or Pd(II)] of the meso-tetrakisphenylporphyrins. A set of nanofibers; (Pt-TPP)NF, (Pd-TPP)NF, (Pt-TPA)NF and (Pd-TPA)NF were obtained to study their structure-activity relationship toward oxygen. The lifetime-based technique was privileged to take advantage of their long-lived phosphorescent properties. A two-fold enhancement was observed for (Pt-TPA)NF and (Pd-TPA)NF compared to (Pt-TPP)NF and (Pd-TPP)NF demonstrating the positive effect of the phenylacetylide moieties on the lifetime. Also, Silver nanoparticles were included in nanofibers to investigate their influence on lifetime-based oxygen sensitivity, showing that the presence of AgNPs only affects (Pd-TPA)NF.

Structure-Photoproperties Relationship Investigation of the Singlet Oxygen Formation in Porphyrin-Fullerene Dyads

A systematic structure-photoproperties relationship study of the interactions of porphyrin-fullerene dyads with molecular oxygen was conducted on a set of three porphyrin-fullerene dyads, as this approach of related applications - oxygen sensitivity and photo-induced singlet oxygen generation - of such dyads remained to be endeavoured. To promote energy transfers between the porphyrin and fullerene units and limit undesired charge separation, a particular attention was devoted to the choice of the solvents for the photoproperties determination. Toluene, in which in addition the compounds investigated are not aggregated, was selected accordingly. The molecular orbital levels and energy gaps of the dyads were determined by electrochemistry and theoretical calculations. Their ground state absorption, steady-state fluorescence-based oxygen sensitivity and photo-induced singlet oxygen generation were determined. The dyads were designed to benefit from a facilitated synthetic porphyrin-fullerene coupling thanks to an easy access to formyl-functionalized porphyrins. The effect of two structural parameters was investigated: the presence of electron-donating hexyloxy chains at the para position of the meso-phenyl, and the presence of a phenylacetylene spacer. This latest factor appeared to have the most predominant effect on all these properties.

Subtle variations of the behavior of a silylated tetraethylene glycol-substituted Zn phthalocyanine towards acids

An organosoluble phthalocyanine substituted by four silylated tetraethyleneglycol chains was designed. This phthalocyanine become water-soluble after acid-promoted removal of the TBDMS moieties (which does not occur in acetonitrile), and is therefore a naked-eye observation system of acid aqueous media. Fluoride anion sensitivity based on the same principle proved unfortunately unsuccessful.

Assessment of the relevance of GaPc substituted with azido-polyethylene glycol chains for photodynamic therapy. Design, synthetic strategy, fluorescence, singlet oxygen generation, and pH-dependent spectroscopic behaviour

A new efficient synthetic route was used to obtain symmetrically and asymmetrically substituted gallium(III) phthalocyanines (5-GaCl and 6-GaCl) containing azido groups with chlorine atoms at axial positions, using corresponding ZnPc derivatives (5-Zn and 6-Zn) as precursors. The photophysical and photochemical properties—fluorescence, singlet oxygen generation, and photodegradation—of 5-GaCl and 6-GaCl were compared with that of 5-Zn and 6-Zn. Their pH-sensitive spectral changes were also investigated in detail, as tumours are more acidic than healthy tissues. Their amphiphilicity, quantified by their partition coefficient, appeared suitable for biological applications. 5-GaCl and 6-GaCl exhibited higher photodynamic potential than unsubstituted gallium(III) phthalocyanine, suggesting potential to be used as a photodynamic therapy agent.

Investigation of optical and electrochemical properties as well as metal ion sensitivities of different number of crown ether appended phthalocyanines

We report herein, the synthesis, and spectral and electrochemical characterization of a series of phthalocyaninato zinc complexes where two biomedically potential structures; crown ether and phthalocyanine moities were gathered on the same molecule. The effect of number of crown ether moieties on metal ion binding properties, as well as proton sensitivity were investigated by using electronic absorption and fluorescence emission spectra. Spectral behaviors of the zinc phthalocyanine complexes fused with one crown ether; Zn[Pc(15C5)(C6H13)6] and four crown ether; Zn[Pc(15C5)4] in presence of Na+ and K+ ions were investigated into detail because of host-guest interactions of subjective ions with crown ether moieties, and compared with the crown ether free phthalocyanine; Zn[Pc(C6H13)8].