Photophysical properties of crowned porphyrins

In this study, we evaluated the photophysical properties of 5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxacyclopentadecane-2-aminomethyl)2,3,5,6-(tetrafluoro)-phenyl]-porphyrin (H2C4P) and Zn(II)5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxacyclopenta-decane-2-aminomethyl)2,3,5,6-(tetrafluoro)-phenyl]-porphyrinate (ZnC4P). We observed that these porphyrins have unique properties when compared with classical porphyrins. The porphyrins H2C4P and ZnC4P showed efficient transfer energy S1 to T1 by intersystem crossing with high and reasonable yields of triplet excited state and singlet oxygen production. These amphiphilic structures of these porphyrins could improve its localization in the tumor cells due to the presence of the crown ether in its framework. We also believed that the crown ether could modulate the change in ion homeostase (Ca(+2), K+, Na+) as already described by some new phthalocyanine dye. This fact makes us believe that it could be reasonably used as a photosensitizer for PDT purposes.     

Synthesis, photophysical and photochemical properties of substituted zinc phthalocyanines

The synthesis, photophysical and photochemical properties of the 4-({3,4,5-tris-[2-(2-ethoxyethoxy)ethyloxy]benzyl}oxy) and 4-({3,4,5-tris-[2-(2-ethoxyethoxy)ethyloxy]benzyl}thio) zinc(ii) phthalocyanines are reported for the first time. The new compounds have been characterized by elemental analysis, IR, (1)H and (13)C NMR spectroscopy, electronic spectroscopy and mass spectra. General trends are described for photodegradation, singlet oxygen, fluorescence and triplet excited state quantum yields, and triplet state and fluorescence lifetimes of these compounds in dimethylsulfoxide (DMSO). The fluorescence of the complexes was quenched by benzoquinone (BQ). The effects of the substitution on the photophysical and photochemical parameters of the zinc(II) phthalocyanines (6, 7 and 8) are also reported. Photophysical and photochemical properties of phthalocyanine complexes are very useful for PDT applications. The substituted Zn(II) phthalocyanines showed high triplet and singlet oxygen quantum yields. High singlet oxygen quantum yields are very important for Type II mechanism. Thus, these complexes show potential as Type II photosensitizers.     

PHOTOPHYSICAL PROPERTIES OF meso-TETRAPHENYLPORPHYRIN and SOME meso-TETRA(HYDROXYPHENYL)PORPHYRINS

Abstract— The o-, m-, and p-isomers of 5, 10, 15, 20- tetra(hydroxyphenyl)-porphyrin have been of recent interest as potential second-generation sensitisers in tumour phototherapy. Fluorescence spectroscopy, nanosecond laser flash photolysis and pulse radiolysis have been used to characterise the singlet and triplet excited states of tetraphenylporphyrin and the o, m-, and p-isomers of tetra(hydroxyphenyl)porphyrin. This has included evaluation of fluorescence yields and lifetimes, triplet spectra, lifetimes, oxygen quenching rate constants, extinction coefficients, and yields and singlet oxygen yields. Whilst the fluorescence quantum yields were low, the triplet yields were all 0.7 ± 10% and the singlet oxygen yields 0.6 ± 10%: all these parameters are in the ranges shown by other efficient porphyrin photosensitisers. The similar photophysical properties found for these compounds suggest that their differing tumour sensitising efficiencies are likely to be due to other factors.     

Synthesis, photophysical and photochemical properties of poly(oxyethylene)-substituted zinc phthalocyanines

The synthesis, photophysical and photochemical properties of the tetra- and octa-poly(oxyethylene)substituted zinc (II) phthalocyanines are reported for the first time. The new compounds have been characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy, electronic spectroscopy and mass spectra. General trends are described for photodegradation, singlet oxygen, triplet state and fluorescence quantum yields, and triplet and fluorescence lifetimes of these compounds in dimethylsulfoxide (DMSO). Photophysical and photochemical properties of phthalocyanine complexes are very useful for PDT applications. The effects of the substituents on the photophysical and photochemical parameters of the zinc(II) phthalocyanines (3a, 5a and 6a) are also reported. The singlet oxygen quantum yields (Phi(Delta)), which give an indication of the potential of the complexes as photosensitizers in applications where singlet oxygen is required (Type II mechanism) ranged from 0.60 to 0.72. Thus, these complexes show potential as Type II photosensitizers. The fluorescence of the complexes was quenched by benzoquinone (BQ).     

Synthesis,characterization and properties of some metallophthalocyanine complexes substituted by N -piperidineethanol

The preparation of eight metallophthalocyanine complexes substituted by N-piperidineethanol was achieved by tetramerization of 3-[2-(piperidin-1-yl)ethoxyl] phthalonitrile and 4-[2-(piperidin-1-yl)ethoxyl]phthalonitrile in the presence of a metal salt with n-pentanol as solvent and DBU as catalyst, respectively. These complexes were characterized by IR, elemental analysis, ¹H NMR and mass spectra. Some properties such as UV/visible absorption spectra, rate of singlet oxygen yields, fluorescence spectra and quantum yields were examined and discussed.     

Monomeric azaheterofullerene derivatives RC59N: influence of the R moiety on spectroscopic and photophysical properties

We have synthesised nine monomeric azaheterofullerene (AZA) derivatives, RC(59)N, with a wide variety of different side chains R and investigated their spectroscopic and photophysical properties in toluene and o-dichlorobenzene (ODCB). Measurements include their ground-state absorption spectra, molar absorption coefficient (epsilon(G)), fluorescence spectra, fluorescence quantum yields (Phi(F)), singlet-state lifetimes (tau(F)), triplet-state absorption spectra, triplet molar absorption coefficients (epsilon(T)), singlet oxygen (Phi(Delta)), and triplet state (Phi(T)) quantum yields. The replacement of a carbon by a nitrogen atom in the C(60) sphere strongly affects most of the spectroscopic and photophysical properties. The chemical nature of the R moiety has definite effects on these properties in contrast with minor effects on the chemical nature of the addends in [6,6]-ring bridged monoadduct methano[60]fullerene derivatives. These effects concern properties of the ground state, singlet excited state, and triplet states of our nine RC(59)N derivatives and in particular the values of photophysical parameters epsilon(G), epsilon(T), Phi(Delta), and Phi(T), which are significantly lower than those of analogous monoadduct [6,6]-ring bridged methano[60]fullerene derivatives.     

Novel sulfonated hydrophilic indium(III) and gallium(III) phthalocyanine photosensitizers: preparation and investigation of photophysicochemical properties

The new tetra-non-peripherally benzenesulfonic acid-substituted hydrophilic gallium chloride and indium chloride phthalocyanine complexes have been synthesized by cyclotetramerization of 4-(2,3-dicyanophenyl)benzenesulfonic acid (1). The newly synthesized phthalocyanines have been characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, mass and UV–vis spectroscopy techniques. The water-soluble gallium(III) phthalocyanine derivative (2) was aggregated in aqueous media but was fully disaggregated in the presence of a surfactant Triton X-100. The incorporation of sulfonate moieties of the phthalocyanine macrocycle provides hydrophilic character to the new compounds, which is useful for drug administration and serves as crucial in PDT application. So, the photochemical properties (singlet oxygen quantum yields and photodegradation quantum yields) and photophysical properties (fluorescence behavior) of the complexes were reported in different solutions (DMSO and water). The results of spectral measurements showed that both np-GaPc (2) and np-InPc (3) can be used as sensitizers in PDT because of their singlet oxygen efficiencies.     

Synthesis, characterization and comparative studies on the photophysical and photochemical properties of metal-free and zinc(II) phthalocyanines with phenyloxyacetic acid functionalities

The synthesis and characterization of new peripherally and non-peripherally tetra-substituted metal-free and zinc(II) phthalocyanines with 2-, 3- and 4-phenyloxyacetic acid functionalities are described for the first time in this study. The new compounds have been characterized by elemental analysis, FT-IR, UV-Vis, MALDI-TOF and ¹H-NMR spectra. Photodegradation, singlet oxygen and fluorescence quantum yields, and fluorescence lifetimes of these compounds are studied in dimethylformamide (DMF). The influence of the substituent position on the phthalocyanine framework (non-peripherally or peripherally), central metal ion (metal-free or zinc) and the position of the COOH group (2-, 3- or 4-position on the phenyloxyacetic acid) on the spectroscopic, photophysical and photochemical properties have been investigated. Non-peripherally zinc(II) phthalocyanines (1b and 2b) and peripherally zinc(II) phthalocyanine (4b) gave good singlet oxygen quantum yields (Φ_Δ) (0.37, 0.39 and 0.38, respectively) which indicate the potential of the complexes as photosensitizers in applications of PDT.     

A New Nonconjugated Naphthalene Derivative of Meso-tetra-(3-hydroxy)-phenyl-porphyrin as a Potential Sensitizer for Photodynamic Therapy

A new 5,10,15,20-tetra-(phenoxy-3-carbonyl-1-amino-naphthyl)-porphyrin was prepared by an isocyanate condensation reaction and its photophysical properties fully evaluated, both in terms of photostability and singlet oxygen production. It shows considerably enhanced photostability when compared with the parent 5,10,15,20-tetra-(3-hydroxy-phenyl)-porphyrin, with the photodegradation quantum yields for T(NAF)PP and T(OH)PP being 4.65 × 10⁻⁴ and 5.19 × 10⁻³, respectively. Its photodynamic effect in human carcinoma HT-29 cells was evaluated. The new porphyrin showed good properties as a sensitizer in photodynamic therapy with an in vitro cytotoxicity IC₅₀ value of 6.80 μg mL⁻¹ for a 24 h incubation. In addition to the potential of this compound, the synthetic route used provides possibilities of extension to a wide range of new sensitizers.     

Design and photophysical properties of new RGD targeted tetraphenylchlorins and porphyrins

The synthesis, characterization, fluorescence, and singlet oxygen quantum yields of tetraphenylporphyrin and tetraphenylchlorin coupled to RGD type peptide are reported. C-terminus protected RGD derivatives were synthesized in liquid phase at the gram scale via an efficient convergent process. C-terminus unprotected RGD derivatives were synthesized on solid support. The UV-vis, fluorescence, and singlet emission spectra showed that the photophysical properties of the photosensitizers were retained in all compounds and some of them are very promising for potential PDT applications.     

Syntheses and properties of octa-, tetra-, and di-hydroxy-substituted phthalocyanines

The synthesis and photophysical properties of a new series of zinc(II) phthalocyanines (ZnPcs) bearing multiple hydroxy and tert-butyl groups are reported. The X-ray structures of two phthalonitriles and one ZnPc are presented. All hydroxy-substituted ZnPcs show low fluorescence quantum yields in DMSO and complete fluorescence quenching in aqueous solutions, but high singlet oxygen quantum yields in DMSO (0.2-0.7). Our results suggest that the tetra- and octa-hydroxy ZnPcs might find application as photosensitizers in the PDT treatment of cancer.     

Towards tuning PDT relevant photosensitizer properties: comparative study for the free and Zn2+ coordinated meso-tetrakis[2,6-difluoro-5-(N-methylsulfamylo)phenyl]porphyrin

The spectroscopic, photochemical, and biological studies of 5,10,15,20-tetrakis[2,6-difluoro-5(N-methylsulfamylo)phenyl]porphyrinate Zn(II) (ZnF₂PMet) were carried out including absorption and fluorescence spectra, fluorescence quantum yields, triplet absorption spectra, triplet lifetimes, singlet oxygen quantum yield, and reactive oxygen species (ROS) detection under biological conditions and compared with its free-base analog (F₂PMet). Zinc coordination into the porphyrin ring results in decrease of hydrophobicity and in higher cellular uptake. F₂PMet localized specifically in endoplasmic reticulum and mitochondria while the ZnF₂PMet is more diffused all over the cell, bonded to membrane proteins, as assessed by fluorescence microscopy. Zn-porphyrin exhibits greater singlet oxygen quantum yield than its free-base analog. Studies with fluorescent probes confirm that the ZnF₂PMet produces mostly singlet oxygen, whereas F₂PMet generates more hydroxyl radicals as the ROS. F₂PMet is a more effective photosensitizer in vitro than its zinc complex, thus, the final photodynamic effect depends more on the nature of ROS than on the higher cellular uptake.     

Calculation of singlet oxygen dose using explicit and implicit dose metrics during benzoporphyrin derivative monoacid ring A (BPD-MA)-PDT in vitro and correlation with MLL cell survival

Photodynamic therapy (PDT) oxygen consumption, clonogenic cell survival, fluorescence photobleaching and photoproduct formation were investigated during benzoporphyrin derivative monoacid (BPD-MA)-PDT of MAT-LyLu cells in vitro. Cells were incubated with BPD-MA concentrations of 0.1, 0.5 or 2.5 μg mL(-1) for 2 h and then treated with 405 nm light under oxygenated and hypoxic conditions. Fluorescence spectra were acquired during treatment, and photobleaching and photoproduct generation were quantified using singular value decomposition of the spectra. Cell survival was measured at set times during the treatment using a colony-forming assay. The amount of oxygen consumed by PDT per photon absorbed decreased with BPD-MA intracellular concentration. Survival was correlated with the total amount of oxygen consumed by PDT per unit volume, which is assumed to be equivalent to the amount of singlet oxygen that reacted. A photobleaching-based singlet oxygen dose metric was also found to predict survival independent of intracellular BPD-MA concentration. The BPD-MA photoproduct was bleached during the treatment. Two singlet oxygen dose metrics based on photoproduct kinetics could not be correlated with cell survival over the full range of intracellular BPD-MA concentrations used.     

Synthesis and photophysical properties of silicon phthalocyanines with axial siloxy ligands bearing alkylamine termini

Eleven silicon phthalocyanines which can be grouped into two homologous series [SiPc[OSi(CH3)2(CH2)(n)N(CH3)2]2, n = 1-6 (series 1), and SiPc[OSi(CH3)2(CH2)3N((CH2)(n)H)2]2, n = 1-6 (series 2)] as well as an analogous phthalocyanine, SiPc[OSi(CH3)2(CH2)3NH2]2, were synthesized. The ground state absorption spectra, the triplet state dynamics, and singlet oxygen quantum yields of 10 of these phthalocyanines were measured. All compounds displayed similar ground state absorption spectral properties in dimethylformamide solution with single Q band maxima at 668 +/- 2 nm and B band maxima at 352 +/- 1 nm. Photoexcitation of all compounds in the B bands generated the optical absorptions of the triplet states which decayed with lifetimes in the hundreds of microseconds region. Oxygen quenching bimolecular rate constants near 2 x 10(9) M(-1) s(-1) were measured, indicating that energy transfer to oxygen was exergonic. Singlet oxygen quantum yields, phi(delta), were measured, and those phthalocyanines in which the axial ligands are terminated by dimethylamine residues at the end of alkyl chains having four or more methylene links exhibited yields near > or = 0.35. Others gave singlet oxygen quantum yields near 0.2, and still others showed singlet oxygen yields of <0.1. The reduced singlet oxygen yields are probably caused by a charge transfer quenching of the 1pi,pi* state of the phthalocyanine by interaction with the lone pair electrons on the nitrogen atoms of the amine termini. In some cases, these can approach and interact with the electronically excited pi-framework, owing to diffusive motions of the flexible oligo-methylene tether.     

Chromenone 12-crown-4 substituted zinc phthalocyanine complexes: investigation of spectral, photophysical and photochemical properties

The synthesis of novel 6,7-[(12-crown-4)-3-[p-(3,4-dicyanophenoxy)phenyl]coumarin (1), 6,7-[(12-crown-4)-3-[p-(2,3-dicyanophenoxy)phenyl]coumarin (2), and their corresponding tetra-(chromenone 12-crown-4)-substituted zinc (II) phthalocyanine complexes (3 and 4) have been prepared. These new compounds have been characterized by elementel analysis, (1)H NMR (1 and 2), MALDI-TOF, IR and UV-Vis spectral data. The fluorescence intensity changes for 1 and 2 by addition of Na(+) or K(+) ions have been determined at 25°C in THF. Intensity of the binding Na(+)- and K(+)-complexes (1 and 2) have decreased. The effects of the chromenone crown ether on the phthalocyanine molecule concerning photophysical and photochemical properties are also investigated. Photodegredation, singlet oxygen, fluorescence quantum yields, and fluorescence lifetimes of zinc phthalocyanine complexes (3 and 4) are also examined in DMSO.     

DNA Damage and Apoptosis Induced by Photosensitization of 5,10,15,20-Tetrakis (N-methyl-4-pyridyl)-21H,23H-porphyrin via Singlet Oxygen Generation

Cancer photodynamic therapy (PDT) requires photosensitizers that efficiently and selectively destroy tumor cells. We investigated 5,10,15,20-tetrakis ( N -methyl-4-pyridyl)-21 H ,23 H -porphyrin (TMPyP) as a potential cancer treatment. Confocal fluorescence microscopy showed that TMPyP was localized in the nuclei, whereas 5-aminolevulinic acid (ALA)-derived protoporphyrin IX (PPIX) was localized diffusely in the cytoplasm of human leukemia (HL-60) cells. In HL-60 cells under UVA irradiation, TMPyP effectively induced apoptosis. Moreover, 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidative product of 2'-deoxyguanosine, was accumulated in the DNA of cells treated with photoirradiated TMPyP, whereas only small amounts were observed in ALA-treated cells in the presence of UVA light. TMPyP and UVA caused extensive damage at every guanine residue in DNA fragments obtained from the human p 53 tumor suppressor gene and the c-Ha- ras -1 proto-oncogene, whereas PPIX induced little DNA damage under these conditions. Electron spin resonance spectroscopy using a singlet oxygen (¹O₂) probe and D₂O showed that photoexcited TMPyP generated ¹O₂. These results suggest that photoexcited TMPyP reacts with oxygen to generate ¹O₂, which in turn, oxidizes guanine residues. Taken together, the results demonstrated that TMPyP was localized in the nucleus where it was photosensitized to induce DNA damage, suggesting that TMPyP may have clinical utility as a nucleus-targeted PDT.     

Derivative UV-VIS Spectrophotometry for Porphyrins Interactions in Photodynamic Therapy

Derivative spectrophotometry is an analytical technique of great utility for extracting both qualitative and quantitative information from spectra composed of unresolved bands by calculating and plotting one of the mathematical derivatives of a spectral curve. In photodynamic therapy (PDT) by irradiation with light, the porphyrin used as drugs induced DNA cleavage mainly via a Type II (singlet oxygen mediated) mechanism, and more rarely a Type I (radicals mediated) mechanism. In the present paper, it is estimated the distinct interactions between DNA and 5,10,15,20-tetra-sulphonated-phenyl-porphyrin (TSPP) by means of: UV-Vis derivative spectrophotometry coupled with melting point, fluorescence, and polarization fluorescence techniques. An exemplification of TSPP effect on DNA from K562 cells is also discussed.     

In vitro and in vivo investigations on the photodynamic activity of core-modified expanded porphyrin--ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29-trithia sapphyrin

The core modification of expanded porphyrins has been proved to have better photochemical properties, which are favorable for photodynamic therapy (PDT) applications. In this context, this study was aimed to investigate the in vitro and in vivo photodynamic activity of one such core-modified expanded porphyrin, namely, ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29-trithia sapphyrin. For the in vitro studies, human erythrocytes were used as a membrane semimodel system to investigate the partitioning ability and drug-uptake characteristics. The partition studies on the membrane semimodel system revealed that maximum partitioning occurs at 12 microgm/mL concentration, and from the drug-uptake studies it is observed that maximum amount of the sensitizer is bound to the erythrocyte membranes during a 45 min incubation period. Photohemolysis studies at different concentrations of the sensitizer and exposure time showed maximum damage at 5 microgm/mL and 30 min exposure time. In vivo studies were performed on 7,12-dimethylbenz(a)nthracene-induced superficial squamous cell carcinoma on mouse skin. The sensitizer at a concentration of 2.5% in 2.0% dimethyl sulfoxide was applied topically on the tumor spot. After 1 h incubation the tumor spot was exposed to laser irradiation from Nd-YAG laser at its second harmonic wavelength of 532 nm. The photodynamic efficacy was estimated by tumor volume measurements at regular intervals after the treatment. One month after PDT exposure a 3.9-fold decrease in the tumor volume was observed with respect to the tumor volume before treatment. The treatment efficacy was further confirmed by histological and fluorescence spectroscopic evaluations of the tissue biopsy sample from the treated area. The results of our study suggest that the ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29-trithia sapphyrin may find possible applications in the new modality of cancer treatment.     

Tetrakis(thiadiazole)porphyrazines. 8. Singlet oxygen production, fluorescence response and liposomal incorporation of tetrakis(thiadiazole)porphyrazine macrocycles [TTDPzM] (M = Mg(II)(H2O), Zn(II), Al(III)Cl, Ga(III)Cl, Cd(II), Cu(II), 2H(I))

The photoactivity for the generation of singlet oxygen, (1)O(2), the key cytotoxic agent in the anticancer treatment known as photodynamic therapy (PDT), and the fluorescence response of the highly electron-deficient tetrakis(thiadiazole)porphyrazines of formula [TTDPzM] (M = Mg(II)(H(2)O), Zn(II), Al(III)Cl, Ga(III)Cl, Cd(II), Cu(II), 2H(I)) were examined (c ? 10(-5) M) in dimethylformamide (DMF) and/or in DMF preacidified with HCl (DMF/HCl; [HCl] = 1-4 × 10(-4) M). The singlet oxygen quantum yield (Φ(Δ)) of all the compounds was determined by using a widely employed procedure based on the selective oxidation of the 1,3-diphenylisobenzofuran (DPBF), modified in part as reported. The list of the Φ(Δ) values indicates excellent photosensitizing properties for the series of compounds carrying "closed shell" metal ions, with values measured in DMF/HCl respectful of the "heavy atom effect" for the first four lighter centers, increasing in the order Mg(II) < Al(III) < Zn(II) < Ga(III). Data of Φ(Δ) concerning the unmetalated species [TTDPzH(2)], present in solution in the form of the corresponding anion [TTDPz](2-), and the Cd(II) and Cu(II) complexes are also presented and discussed. Extensive discussion is also developed on the fluorescence quantum yield values Φ(F), with data on the Mg(II) and Al(III) compounds in DMF/HCl (0.44 and 0.53, respectively) indicative of promising perspectives for applications in fluorescence imaging techniques. The Φ(F) data of the studied porphyrazine series, Φ(F)(Pz), correlate linearly with those of the homologous phthalocyaninato complexes, Φ(F)(Pc), suggesting a closely similar behaviour between the two classes of compounds. The incorporation of [TTDPzZn] into liposomes was successfully achieved following the detergent depletion method (DDM) from a mixed micellar solution by means of gel-filtration. Retention of [TTDPzZn] (~40%) in its photoactive monomeric form into liposomes is proved by absorption and fluorescence spectra, this proposing the Zn(II) complex as a promising candidate for use in PDT.     

1H-INDENYLFURAN AND THIOPHENE DERIVATIVES– A NEW CLASS OF SINGLET OXYGEN SENSITIZERS

Abstract— Photophysical and photochemical properties of 1H-indenylfuran and thiophene derivatives were studied. UV spectra showed that all the compounds tested absorbed UV light in the region 350–380 nm. The fluorescence spectra of 4a-e showed bands in the region 410–470 nm and quantum yields (φ_F) in the range 0.25–0.88. Attempts to calculate the triplet energy of 4a-e failed except for 4c and 4d , which showed E_T= 43–44 kcal mol^-1. These compounds are a new class of singlet oxygen sensitizers. The sensitized reaction of 2,5-dimethylfuran with singlet oxygen was followed showing that 4a and 4e are more reactive than α-terthiophene (4.0 and 2.5 times respectively), while the other compounds show the same reactivity as 1 . This behavior can be explained considering the different intersystem crossing quantum yields of compounds 4a-e . Diazabicyclo[2. 2. 2]octane is a quencher of singlet oxygen in this reaction, while we can exclude superoxide ion formation using the photooxidation of α, α-dimethylstilbene.