ΦΔ Value Research Articles

Improved Singlet Oxygen Production of Zinc Phthalocyanine Bearing Pyridine-4-Thiol Groups Using Sonochemistry and Comparison with Photochemistry

The interest in research to enhance the ability of sensitizers to generate singlet oxygen using light and/or ultrasound in cancer treatment has increased significantly in recent years, and studies have attracted considerable interest. In addition, phthalocyanines (Pcs) have become increasingly important as sensitizers in photodynamic therapy (PDT) (stimulation source: light) and/or sonodynamic therapy (SDT) (stimulation source: light and ultrasound). Sonophotodynamic therapy (SPDT), a new technique that gives more effective results than PDT, is now gaining in importance. Although there are published articles on SPDT studies, studies in this field are limited. In this context, we synthesized a zinc(II) phthalocyanine molecule bearing 4-(pyridine-4-ylthio) substituents to determine its potential as a sensitizer in SPDT applications as well as PDT applications, and the structure of the synthesized complex was illuminated using FTIR,1H-NMR, UV-Vis, and MS spectroscopic techniques. When light and ultrasound were combined, the calculated ΦΔ value for zinc (II) phthalocyanine (3) increased to greater than 1, even though it was 0.76 after light excitation. When evaluating the two methods, it was observed that singlet oxygen production was greatly enhanced by the SPDT method. In this way, the research will add to the enhancement of knowledge on the subject of the SPDT method's enhancement of singlet oxygen generation.

Synthesis of phenanthroline substituted five-nuclear phthalocyanine zinc complex and exploring of photochemical and sono-photochemical properties

Sono-photodynamic therapy (SPDT) which is the combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) is an alternative and efficient method among cancer treatments achieving high singlet oxygen quantum yield. This study aimed to synthesize Schiff base substituted Zn phthalocyanine containing phenanthroline group to obtain suitable sono-photosensitizer. The target phthalocyanine (4) was obtained by cyclotetramerization reaction of phenanthroline-Zn(II) complex substituted phthalonitrile (3) with zinc acetate. The synthesized compounds were characterized by various spectroscopic techniques including FT-IR, Mass, UV–Vis, and 1H NMR spectroscopy. The singlet oxygen quantum yield was calculated in both photochemical and sono-photochemical method for compound 4. While the ΦΔ value was calculated as 0.72 for photochemical method, the ΦΔ value reached to 0.98 for sono-photochemical method.

The ultrasound and light combination as a new approach for BODIPY dyes with the enhanced singlet oxygen formation

Sonophotodynamic Therapy (SPDT) is a new approach that uses the light of photodynamic therapy (PDT) and ultrasound of sonodynamic therapy (SDT) together. Although it is known that singlet oxygen production in phthalocyanine-derived photosensitizers increases significantly with the use of the SPDT method, there is no study in the literature investigating the singlet oxygen generating capacity of BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) compounds with the SPDT method. This study was motivated by the desire to evaluate the singlet oxygen production capacity of BODIPY compounds by using SPDT method. For this reason, in this study, we present the synthesis of novel BODIPY derivative withmeso-dibenzothienyl segment, diiodine moieties at 2-,6-positions and distyryl structure at 3-,5-positions. The resulting compound was illuminated by applying spectroscopic techniques including 1H-NMR, UV–Vis, MS and elemental analysis. This study aimed to demonstrate and compare the potentials of BODIPY compound in PDT and SPDT applications based on the photochemical and sonophotochemical measurements. While the calculated ΦΔ value was 0.34 for BDPY4 after light irradiation, this value increased to 0.76 after combination of light and ultrasound irradiation used together. Based on the fact that the synthesized BDPY4 may be a suitable agent in SPDT applications, this study will be a precursor in understanding the sonophotochemical measurements of BODIPY compounds for in vivo or in vitro studies in the future.

Cobalt(III) dibromo-BODIPY-8-hydroxyquinolinate for mitochondria-targeted red light photodynamic therapy

The photophysical properties of boron-dipyrromethene (BODIPY) dyes have made them suitable for cellular imaging and photodynamic therapy (PDT). The efficacy of these dyes can be augmented by designing their dibromo/diiodo derivatives. Heteroleptic Co(III) complexes of a tetradentate N,N,N,O-donor polypyridyl phenolate (HL) and bidentate N,O-donor 8-hydroxyquinoline (HL1) and its BODIPY (HL2) or dibromo-BODIPY (HL3) pendants, [CoIII(L)(L1−3)]X (1–3) (where X = ClO4 for 1, 2 and Cl for 3) were synthesized and studied. The dibromo-BODIPY ligand HL3 was structurally characterized. The dibromo-BODIPY complex 3, showing singlet oxygen quantum yield (ϕΔ) value of ∼0.25, displayed remarkable apoptotic photo-cytotoxicity in HeLa cancer cells upon red light (600–720 nm) irradiation giving half-maximal inhibitory concentration (IC50) value of 0.36 μM (photocytotoxicity index: >277). It was less toxic in normal cells. Cellular imaging studies revealed mitochondrial colocalization. This work exemplifies Co(III)–dibromo-BODIPY complex as a new class of metal-based PDT agent with higher efficacy than the dyes alone.

A new approach for BODIPY derivatives: Increasing the singlet oxygen formation by sonophotochemical technique

Research to explore the therapeutic capacities of sensitizers in Photodynamic Therapy (PDT) has been among the topics that have been frequently explored in recent years. In this context, studies that improve the ability of sensitizers to produce singlet oxygen with the help of ultrasound draw so much attention. In addition, the importance of BODIPYs used as sensitizers in photodynamic and/or sonodynamic therapy (SDT) is increasing. Although the positive effect of sonophotodynamic therapy (SPDT) on phthalocyanine derivatives has been shown in both photophysicochemical and in vivo studies, according to the best of our knowledge, the effect of sonophotochemical measurements for BODIPY derivatives has not been reported in the literature yet. Evaluation of the sonophotochemical potentials of BODIPY derivatives and meeting this need in the literature are the biggest impetus of this study.In this context, we have synthesized a new BODIPY compound (BDPY2) with methoxystyryl substituents to evaluate the capability of singlet oxygen production by sonophotochemical method. Synthesized compound was illuminated using different spectroscopic techniques encompassing 1H-NMR, 13C-NMR,19F-NMR, UV-Vis, MS, and elemental analysis. ΦΔ value of BDPY2 was calculated by the photochemical method as 0.33, while ΦΔ value reached 0.68 by applying the sonophotochemical method. The obtained data proved that the singlet oxygen production increased considerably by changing the method from light irradiation to ultrasound/light. This result will be a pioneer study to comprehend the sonophotochemical measurements of BODIPY derivatives for in vivo or in vitro studies in the future.

Meticulously Designed Carbon Dots as Photo-Triggered RNA-Destroyer for Evoking Pyroptosis.

An ideal photosensitizer for photodynamic therapy should not only possess high reactive oxygen species (ROS) generation efficiency but also maximize utilization of the in situ produced ROS species, where the latter is closely related to its intracellular location. However, rational design of such photosensitizer without tedious conjugation procedures remains a grand challenge. Here, we report the one-pot preparation of carbon dots (CDs)-based photosensitizer from levofloxacin and neutral red featuring both high 1O2 quantum yield (φΔ = 38.85%) and superior RNA selectivity. Moreover, the φΔ value shows a further 40% improvement and reaches 54.33% in response to RNA binding. Owing to these combined attributes, the CDs could exert great damage to the cellular RNA system (termed the RNA-destroyer) under extremely low dosage of light irradiation (15 mW cm-2, 1 min). It induces pyroptotic cell death and causes rapid release of different cytokines that served as molecular markers in photodynamic immunotherapy. This work represents the meticulously designed CDs with high ROS generation and utilization efficiency via good organization of the photosensitive and targeting modularity. Moreover, it is the first CDs-based pyroptosis inducer to the best of our knowledge.

Exploring anticancer properties of novel Nano-Formulation of BODIPY Compound, Photophysicochemical, in vitro and in silico evaluations

A new BODIPY complex (C4) composed of meso- thienyl-pyridine substituted core unit diiodinated from 2- and 6- positions and distyryl moieties at 3- and 5- positions is synthesized. Nano-sized formulation of C4 is prepared by single emulsion method using poly(ε-caprolactone)(PCL) polymer. Encapsulation efficiency and loading capacity values of C4 loaded PCL nanoparticles (C4@PCL-NPs) are calculated and in vitro release profile of C4 is determined. The cytotoxicity and anti-cancer activity are conducted on the L929 and MCF-7 cell lines. Cellular uptake study is performed and interaction between C4@PCL-NPs and MCF-7 cell line is investigated. Anti-cancer activity of C4 is predicted with molecular docking studies and the inhibition property on EGFR, ERα, PR and mTOR are investigated for its anticancer properties. Molecular interactions, binding positions and docking score energies between C4 and EGFR, ERα, PR and mTOR targets are revealed using in silico methods. The druglikeness and pharmacokinetic properties of C4 are evaluated using the SwissADME and its bioavailability and toxicity profiles are assessed using the SwissADME, preADMET and pkCSM servers. In conclusion, the potential use of C4 as an anti-cancer agent is evaluated in vitro and in silico methods. Also, photophysicochemical properties are studied to investigate the potential of using Photodynamic Therapy (PDT). In photochemical studies, the calculated singlet oxygen quantum yield (ΦΔ) value was 0.73 for C4 and in photopysical studies, the calculated fluorescence quantum yield ΦF value was 0.19 for C4.

Heterometallic Au(I)–Cu(I) Clusters: Luminescence Studies and1O2Production

Two different organometallic gold(I) compounds containing naphthalene and phenanthrene as fluorophores and 2-pyridyldiphenylphosphane as the ancillary ligand were synthesized (compounds 1 with naphthalene and 2 with phenanthrene). They were reacted with three different copper(I) salts with different counterions (PF6-, OTf-, and BF4-; OTf = triflate) to obtain six Au(I)/Cu(I) heterometallic clusters (compounds 1a-c for naphthalene derivatives and 2a-c for phenanthrene derivatives). The heterometallic compounds present red pure room-temperature phosphorescence in both solution, the solid state, and air-equilibrated samples, as a difference with the dual emission recorded for the gold(I) precursors 1 and 2. The presence of Au(I)-Cu(I) metallophilic contacts has been identified using single-crystal X-ray diffraction structure resolution of two of the compounds, which play a direct role in the resulting red-shifted emission with respect to the gold(I) homometallic precursors. Polystyrene (PS) and poly(methyl methacrylate) (PMMA) polymeric matrices were doped with our luminescent compounds, and the resulting changes in their emissive properties were analyzed and compared with those previously recorded in the solution and the solid state. All complexes were tested to analyze their ability to produce 1O2 and present very good values of ΦΔ up to 50%.

Development of water-soluble phenazine-2,3-diol-based photosensitizers for singlet oxygen generation.

Phenazine-2,3-diol-based dyes, KY-1Na and KY-2Na bearing one and two carboxylic acid sodium salts, respectively, have been newly developed as water-soluble photosensitizers (PSs) possessing the ability to generate singlet oxygen (1O2). In order to evaluate the solubility of KY-1Na and KY-2Na in water, the hydrophobicity/hydrophilicity of the two PSs was investigated by experimental measurement of the logarithms (log Po/w) of the 1-octanol/water partition coefficient (Po/w) for the PS. The log Po/w values of both KY-1Na and KY-2Na were determined to be -0.9, indicating that both the PSs are more hydrophilic than Rose Bengal (-0.6) and have hydrophilicity equivalent to methylene blue (-0.9). Both the PSs in water show a broad photoabsorption band in the range of 500 to 600 nm. Thus, we estimated the 1O2 quantum yields (ΦΔ) of KY-1Na and KY-2Na in water by using 9,10-anthracenediyl-bis(methylene)dimalonic acid (ABDA) as a water-soluble 1O2 scavenger. It was found that in water the ΦΔ value (0.19) of KY-2Na is higher than that of KY-1Na (0.06). Density functional theory (DFT) calculations suggested that the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) distributions for the molecular structure of KY-2Na are adequately separated, leading to a decrease in the energy gap (ΔEST) between the singlet state (S1) and the triplet state (T1) that causes efficient intersystem crossing (ISC), compared to that for the molecular structure of KY-1Na. Indeed, time-dependent DFT (TD-DFT) calculations demonstrated that the ΔEST(S1-T1) value (0.82 eV) of KY-2Na is smaller than that (0.98 eV) of KY-1Na, resulting in a relatively high ΦΔ value of KY-2Na. Consequently, we demonstrate that phenazine-2,3-diol-based PSs bearing carboxylic acid salts possess high solubility and moderate 1O2 generation ability in water.

Comparison of singlet oxygen production of ethyl vanillin substituted silicon phthalocyanine using sonophotodynamic and photodynamic methods

Although Sonophotodynamic Therapy (SPDT) studies, which are a new approach that give better results than Photodynamic Therapy (PDT) in which light and sound are used together, are encountered in the literature, studies in this area are limited. Therefore, this study aimed to demonstrate the potentials of the synthesized compound in PDT and SPDT applications. While the calculated ΦΔ value was 0.50 for compound 1 after light irradiation, this value increased to 0.81 after light and ultrasound irradiation were used together. When the PDT and SPDT methods were compared, it proved that the singlet oxygen production increased significantly when the excitation method was changed to light and ultrasound. This study will enrich the literature on increasing singlet oxygen production by SPDT method.

A Sn(iv) porphyrin with mitochondria targeting properties for enhanced photodynamic activity against MCF-7 cells

A Sn(iv) porphyrin with a mitochondria targeting triphenylphosphonium moiety has a high ΦΔ value (ca. 0.72) and does not aggregate in aqueous solution. The dye exhibits favorable photodynamic activity against MCF-7 cells with an IC50 value of 2.9 μM.

Excited States of Thio-2′-deoxyuridine Bearing an Extended π-Conjugated System: 3′,5′-Di-O-acetyl-5-phenylethynyl-4-thio-2′-deoxyuridine

A new thio-2'-deoxyuridine with an extended π-conjugated group was successfully synthesized: 3',5'-di-O-acetyl-5-phenylethynyl-4-thio-2'-deoxyuridine. The thio-2'-deoxyuridine derivative has a large red-shifted absorption band in the UVA region and also shows fluorescence, a rare photo-property among thionucleobases/thionucleosides. The triplet-triplet absorption spectrum and the rate constants (the intrinsic decay rate constant of the triplet state, the self-quenching rate constant, and the quenching rate constant of the triplet state by an oxygen molecule) of the thio-2'-deoxyuridine were obtained by transient absorption spectroscopy. The quantum yield of intersystem crossing and the quantum yield of singlet molecular oxygen formation (ϕΔ) under an oxygen atmosphere were also determined. The ϕΔ value of the new thio-2'-deoxyuridine was found to be substantially higher than all reported values of other thio-2'-deoxyribonucleosides in low oxygen concentrations similar to cancer cell environments. The fluorescence quantum yield depended on the excitation wavelength, revealing certain photochemical reactions in the higher excited singlet states. However, when excited into the higher excited state with non-resonant two-photon absorption, the ϕΔ of the thio-2'-deoxyuridine derivative was found to remain sufficiently large. These findings should be very useful for the development of thio-2'-deoxyribonucleoside-based pharmaceuticals as DNA-specific photosensitizers for photochemotherapy.

Short-lived and Nonphosphorescent Triplet state of Mexoryl SX, a UV-A Sunscreen

Mexoryl SX (terephthalylidene-3,3′-dicamphor-10,10′-disulfonic acid, Ecamsule) is a water-soluble UV-A absorber. The near-IR phosphorescence spectrum of singlet oxygen generated by photosensitization with Mexoryl SX was not observed in air-saturated water. On the other hand, the time-resolved near-IR phosphorescence spectrum was observed in oxygen-saturated phosphate buffer (pH 7.4). The quantum yield of the singlet oxygen generation (ΦΔ) was determined to be 0.0021 ± 0.0005. The ability of Mexoryl SX as a photosensitizer is quite low. The question arises as to the quite low ΦΔ value. No phosphorescence was detectable from Mexoryl SX in ethanol at 77 K. We elucidated the nature of the lowest excited triplet (T1) state of Mexoryl SX using a time-resolved EPR technique, because this technique is powerful for the study of short-lived and nonphosphorescent T1 molecules. The strong time-resolved EPR signals were observed. This fact shows that a considerable proportion of the lowest excited singlet (S1) state molecules undergoes intersystem crossing (ISC) to the T1 state and the deactivation process of the T1 state is mainly radiationless. The observed zero-filed splitting parameters, T1 lifetime, and S1 → T1 ISC anisotropy suggest that the T1 state can be regarded as a 3nπ*–3ππ* mixing state in character and the two unpaired electrons in the T1 state do not localize on (4-methylbenzylidene)camphor, a closely related component. Although the shorter T1 lifetime (47 ns) prevents T1 state quenching by ground-state oxygen, the 3nπ* character may contribute something to the low ΦΔ value.

Excellent capacity of singlet oxygen generation by gadolinium labelled sinoporphyrin sodium

The singlet oxygen quantum yield (ΦΔ) represents the ability of a photosensitizer to produce the photodynamic therapy effect. However, the pursuiting of strong phosphorescence properties of metalloporphyrins hindered the fact that they may have high ΦΔ. In this paper, we studied the effect of imidazole, a small organic molecule used as a solvent in the synthesis of multifunctional photosensitizers (PSs), on the ΦΔ of the PS, gadolinium-containing sinoporphyrin sodium (Gd-DVDMS), using a relative method with Rose Bengal as the reference and 1,3-diphenylisobenzofuran as the singlet oxygen trapping reagent. After completely removal of imidazole by dialysis, the ΦΔ value of Gd-DVDMS was obtained to be as high as 0.97. In addition, with an increase in the imidazole concentration, the ΦΔ of Gd-DVDMS gradually decreased, and stabilized at a value of 0.37. To understand the above phenomenon, the ultraviolet–visible absorption and photoluminescence spectra of Gd-DVDMS for different imidazole concentrations were analyzed. The triplet state quantum yield of Gd-DVDMS was constant, while the O2 quenching rate of the triplet state decreased; this indicated that the energy exchange between the PS and O2 was reduced by imidazole. We deduced that decrease in ΦΔ was attributable to the increase in the distance between Gd-DVDMS and O2, owing to imidazole wrapping around Gd-DVDMS. It is speculated that as the wrapping progressed, the effects of the dissolution and attachment of imidazole reached a balance, and hence, the ΦΔ remained constant.

DNA interaction and anticancer properties of new peripheral phthalocyanines carrying tosylated 4-morpholinoaniline units

In this paper, tosylated 4-morpholinoaniline units fused peripherally tetra-substituted free-base (5), copper(II) (6), zinc(II) (7), cobalt(II) (8) and magnesium(II) (9) phthalocyanines (Scheme 1) were reported and these new phthalocyanine conjugates were characterized through Fourier Transform–Infrared (FT–IR) with ATR sampling accessory, Mass Spectra Analysis [Matrix Assisted Laser Desorption/Ionization–Time of Flight–Mass Spectral (MALDI–TOF–MS)] and Ultraviolet–visible (UV–vis) (for all new phthalocyanines), elemental analysis, as well as 1H and 13C NMR spectroscopic techniques [for the compounds (2), (4), (5), (7) and (9)]. The potential utilization of the new peripheral phthalocyanine compounds (7–9) as the new pharmaceutical agents in PDT applications (in oncology and molecular biology) were determined in aspects of pBR322 plasmid DNA cleavage on agarose gel electrophoresis. The results showed that compound (7) cleaved pBR322 plasmid DNA with irradiation. Compound (7) displayed hypochromism without any shift on the addition of increasing concentrations of ct-DNA and Kb of compound (7) was calculated as 2.45 ± (0.20) × 104 M−1. In photochemical studies, the ΦΔ value of compound (7) was determined as 0.11. The cytotoxic/phototoxic properties of compound (7) which had the best photocleavage effects among tested compounds were investigated using MTT assay toward human colorectal (HCT-116) and cervical (HeLa) cancer cells. The cell viabilities of compound (7) were found to be 73 ± 1.6% (HCT-116) and 65 ± 5.5% (HeLa) at 100 µM with irradiation.

Crystal structure, DNA crosslinking and photo-induced cytotoxicity of oxovanadium(IV) conjugates of boron-dipyrromethene

Cis-dichloro-oxovanadium(IV) complexes [VO(L1/L2)Cl2], where L1 is N-(4-(5,5-difluoro-1,3,7,9-tetramethyl-5H-4ʎ4,5ʎ4-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-10-yl)benzyl)-1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine in 1 and L2 is N-(4-(5,5-difluoro-2,8-diiodo-1,3,7,9-tetramethyl-5H-4ʎ4,5ʎ4-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-10-yl)benzyl)-1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine in 2) having 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene as boron-dipyrromethene (BODIPY) appended dipicolylamine bases were prepared, characterized and their photocytotoxicity studied. X-ray crystal structure of 1 showed distorted octahedral geometry with a VIVON3Cl2 core having Cl-V-Cl angle of 91.93(4)°. The complexes showed variable solution conductivity properties. They were non-electrolytes in dry DMF at 25 °C but showed 1:1 electrolytic behavior in an aqueous medium due to dissociation of one chloride ligand as evidenced from the mass spectral study. Complexes 1 and 2 showed absorption bands at 500 and 535 nm, respectively. The calf thymus DNA melting study revealed their interaction through DNA crosslinking on exposure to light which was further confirmed from the alkaline agarose gel electrophoresis using plasmid supercoiled pUC19 DNA. Complex 2 showed disruption of the mitochondrial membrane potential in the JC-1 (1,1′,3,3′-tetraethyl-5,5′,6,6′-tetrachloroimidacarbocyanine iodide) assay. The complexes were photocytotoxic in visible light (400–700 nm, power: 10 J cm−2) in cervical cancer HeLa and breast cancer MCF-7 cells. Complex 2 having a photoactive diiodo‑boron-dipyrromethene moiety gave a singlet oxygen quantum yield (ΦΔ) value of ~0.6. It showed singlet oxygen mediated apoptotic photodynamic therapy activity with remarkably low IC50 (half maximal inhibitory concentration) value of ~0.15 μM. The cis-disposition of chlorides gave a cis-divacant 4-coordinate intermediate structure from the density functional theory (DFT) study thus mimicking the DNA crosslinking property of cisplatin.

Selective Photokilling of Human Pancreatic Cancer Cells Using Cetuximab-Targeted Mesoporous Silica Nanoparticles for Delivery of Zinc Phthalocyanine.

Background: Photodynamic therapy (PDT) is a non-invasive and innovative cancer therapy based on the photodynamic effect. In this study, we sought to determine the singlet oxygen production, intracellular uptake, and in vitro photodynamic therapy potential of Cetixumab-targeted, zinc(II) 2,3,9,10,16,17,23,24-octa(tert-butylphenoxy))phthalocyaninato(2-)-N29,N30,N31,N32 (ZnPcOBP)-loaded mesoporous silica nanoparticles against pancreatic cancer cells. Results: The quantum yield (ΦΔ) value of ZnPcOBP was found to be 0.60 in toluene. In vitro cellular studies were performed to determine the dark- and phototoxicity of samples with various concentrations of ZnPcOBP by using pancreatic cells (AsPC-1, PANC-1 and MIA PaCa-2) and 20, 30, and 40 J/cm2 light fluences. No dark toxicity was observed for any sample in any cell line. ZnPcOBP alone showed a modest photodynamic activity. However, when incorporated in silica nanoparticles, it showed a relatively high phototoxic effect, which was further enhanced by Cetuximab, a monoclonal antibody that targets the Epidermal Growth Factor Receptor (EGFR). The cell-line dependent photokilling observed correlates well with EGFR expression levels in these cells. Conclusions: Imidazole-capped Cetuximab-targeted mesoporous silica nanoparticles are excellent vehicles for the selective delivery of ZnPcOBP to pancreatic cancer cells expressing the EGFR receptor. The novel nanosystem appears to be a suitable agent for photodynamic therapy of pancreatic tumors.

Phospholipid multilamellar vesicles entrapping phenothiazine photosensitizers. Preparation, characterization and evaluation of their photodynamic properties

The aim of the present paper was to optimize the properties of phenothiazine photosensitizers (PSs), Azure B and its monobrominated derivative. They were entrapped in multilamellar liposomes of egg phosphatidylcholine (EPC) and dipalmitoylphosphatidylcholine (dpPC). The higher partition coefficient of both PSs in the EPC/water system compared with that of both PSs in the dpPC/water system allowed the selection of EPC to be used for the development of third generation photosensitizers. The optimal phospholipid/phenothiazine ratio and the location of these dyes in the lipid bilayer systems were established. These dyes were found to be located within the polar head group region of the lipid bilayer, which would enhance the effectiveness of the irradiation procedure. In addition, the encapsulation of both photosensitizers in liposomes led to a decrease in the aggregation of these compounds, and consequently to an increase in their singlet oxygen quantum yield (ϕΔ). The encapsulation of the PSs in lipid vesicles significantly increased their photochemical reactivity, doubling the ϕΔ value of AzBBr and increasing that of AzB by 60%. The results obtained demonstrate that the vehiculization of these PSs in liposomes allowed the development of third generation photosensitizers with better photochemical properties to be used in potential therapeutic applications.

The first solid state porphyrin-weak acid molecular complex: A novel metal free, nanosized and porous photocatalyst for large scale aerobic oxidations in water

The first solid state porphyrin dication of a weak carboxylic acid was synthesized through the reaction of meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (H2TMPyP) supported on the sodium salt of Amberlyst 15 nanoparticles (nanoAmbSO3Na) with formic acid. The polymer-porphyrin hybrid compound, nanoAmbSO3@H2TMPyP(HCOOH)2, was characterized by FT-IR and diffuse reflectance (DR) UV–vis spectroscopy, EDX, BET, DLS, FESEM and TGA methods. Interestingly, the diacid was quite stable towards decomposition to the corresponding porphyrin and carboxylic acid in neat water as well as in acetonitrile. The protonation reaction was accompanied with the shift of the Soret band from 435 to 454 nm in DR UV–vis spectrum and a rapid color change from red brown to green. A particle size of 190 and <50 nm was estimated for the nanoparticles by DLS and FESEM, respectively. Also, the macroporous structure of the catalyst was revealed by BET experiments. nanoAmbSO3@H2TMPyP(HCOOH)2 was used as photosensitizer for the highly chemoselective and large scale aerobic oxidation of sulfides to the corresponding sulfoxide in water within 3 h at room temperature. A conversion of ca. 95% was observed for the oxidation of sulfides to their corresponding sulfoxide in water with a selectivity of ca. 100%. The use of acetonitrile as solvent led to a significant decrease in the conversion values while retaining selectivity. The higher efficiency of the catalyst in water was in accord with greater singlet oxygen quantum yield (ΦΔ) value of the photosensitizer in this solvent (ΦΔ = 0.41) relative to that in acetonitrile (ΦΔ = 0.08). Apparently, cooperative acid catalysis caused by the protic solvent and porphyrin diacid is involved in the preference of water over acetonitrile as the solvent for efficient oxidation of sulfides to sulfoxides. Furthermore, the photosensitizer was used for the efficient oxidation of 1,5-dihydroxynaphthalene (DHN) in water within 15 min. The photocatalyst was remarkably stable towards oxidative degradation so that it could be recovered and reused for at least 5 times without loss of activity. It is noteworthy that large scale photooxidation of sulfides (TON ≈ 5 × 3000) and DHN (TON ≈ 6 × 1000) were achieved in water, using nanoAmbSO3@H2TMPyP(HCOOH)2 as the photosensitizer.

In vitro photodynamic activity of lipid vesicles with zinc phthalocyanine derivative against Enterococcus faecalis

Zinc(II) phthalocyanine bearing eight non-peripheral 2-propoxy substituents was subjected to physicochemical study and, after incorporation in lipid vesicles, assessed as a potential photosensitizer for antibacterial photodynamic therapy. The phthalocyanine derivative obtained in the macrocyclization reaction was characterized by MS and NMR techniques. Moreover, its chemical purity was confirmed by HPLC analysis. X-ray structural analysis revealed that overcrowding of the phthalocyanine derivative leads to a strong out-of-plane distortion of the π-system of the macrocycle core. In the UV–Vis absorption spectra of zinc(II) phthalocyanine two characteristic bands were found: the Soret (300–450 nm) and the Q band (600–800 nm). Photophysical properties of mono- and diprotonated forms of phthalocyanine derivative were studied with time-resolved fluorescence spectroscopy. Its tri- and tetraprotonated forms could not be obtained, because compound decomposes in higher acid concentrations. The presented zinc(II) phthalocyanine showed values of singlet oxygen generation ΦΔ = 0.18 and 0.16, the quantum yield of the photodecomposition ΦP = 3.06∙10−4 and 1.23∙10−5 and the quantum yield of fluorescence ΦFL = 0.005 and 0.004, designated in DMF and DMSO, respectively. For biological studies, phthalocyanine has been incorporated into modified liposome vesicles containing ethanol. In vitro bacteria photoinactivation study revealed no activity against Escherichia coli and 5.7 log reduction of the Enterococcus faecalis growth.