Microenvironment-switchable singlet oxygen generation by axially-coordinated hydrophilic ruthenium phthalocyanine dendrimers

A series of new metallodendrimers built around a ruthenium phthalocyanine core has been prepared. Employing a convergent synthetic strategy, pyridine-containing ligands were prepared and then assembled onto the ruthenium phthalocyanine through axial ligand coordination. The growing shell of oligoethylene glycol chains surrounding the lipophilic core allows solubilisation in water. Photophysical studies show that all the metallodendrimers are strongly phosphorescent and the deactivation pathway of their triplet state depends on the medium in which the compounds are dissolved. On one hand, quenching of the triplet state by the dendritic shell is observed and found to be substantially enhanced in aqueous media. On the other, the dendrimer shields the phthalocyanine from oxygen. This notwithstanding, the phthalocyanines are able to generate singlet oxygen in less polar environments such as in CHCl(3) or THF solution, while in water the generation of singlet oxygen is almost completely switched off.     

Controlled generation of singlet oxygen by a water-soluble meso-pyrenylporphyrin photosensitizer through interaction with DNA

An electron donor-connecting water-soluble porphyrin, meso-(1-pyrenyl)-tris(N-methyl-p-pyridinio)porphyrin, did not demonstrate singlet oxygen generating activity under photo-irradiation. The interaction with DNA successfully recovered the photosensitized singlet oxygen generation by this porphyrin.     

Stereoselective photooxidation of enecarbamates: reactivity of ozone vs singlet oxygen

[reaction: see text]. Oxazolidinone-functionalized enecarbamates show contrasting behavior upon oxidation by singlet oxygen and by ozone. The observed stereoselectivity difference indicates that the oxidation with ozone is subject to classic steric effects, whereas the very high selectivity in the photooxidation with singlet oxygen is derived from vibrational deactivation.     

Sensitized photooxidation of furanoeremophilane with singlet oxygen and their biogenetic relationship

In an attempt to explore the biogenetic relationship of furanoeremophilane derivatives and eremophilan-8alpha,12-olides, produced in Ligularia and their structure-activity relationship, we studied the photosensitized oxidation of furanoeremophilane-type sesquiterpenes. Under the condition of several solvents solution Irradiation with a 200 W incandescent lamp of furanoeremophilan-14beta,6alpha-olide isolated from Ligularia vellerea, in various solutions with methylene blue, rose bengal, toluidine blue and safranine T gave several products. The products were isolated by chromatographic procedure and their structures were elucidated as eremophilan-14beta,6alpha,8alpha,12-diolide derivatives by NMR, IR and MS methods. A reaction mechanism has been proposed.     

Fluorine end-capped optical fibers for photosensitizer release and singlet oxygen production

The usefulness of a fiber optic technique for generating singlet oxygen and releasing the pheophorbide photosensitizer has been increased by the fluorination of the porous Vycor glass tip. Singlet oxygen emerges through the fiber tip with 669-nm light and oxygen, releasing the sensitizer molecules upon a [2 + 2] addition of singlet oxygen with the ethene spacer and scission of a dioxetane intermediate. Switching from a nonfluorinated to a fluorinated glass tip led to a clear reduction of the adsorbtive affinity of the departing sensitizer with improved release into homogeneous toluene solution and bovine tissue, but no difference was found in water since the sensitizer was insoluble. High surface coverage of the nonafluorohexylsilane enhanced the cleavage efficiency by 15% at the ethene site. The fluorosilane groups also caused crowding and seemed to reduce access of (1)O(2) to the ethene site, which attenuated the total quenching rate constant k(T), although there was less wasted (1)O(2) (from surface physical quenching) at the fluorosilane-coated than the native SiOH silica. The observations support a quenching mechanism that the replacement of the SiOH groups for the fluorosilane C-H and C-F groups enhanced the (1)O(2) lifetime at the fiber tip interface due to less efficient electronic-to-vibronic energy transfer.     

Protoporphyrin IX nanoparticle carrier: preparation, optical properties, and singlet oxygen generation

The present study is focused on developing a nanoparticle carrier for the photosensitizer protoporphyrin IX for use in photodynamic therapy. The entrapment of protoporphyrin IX (Pp IX) in silica spheres was achieved by modification of Pp IX molecules with an organosilane reagent. The immobilized drug preserved its optical properties and the capacity to generate singlet oxygen, which was detected by a direct method from its characteristic phosphorescence decay curve at near-infrared and by a chemical method using 1,3-diphenylisobenzofuran to trap singlet oxygen. The lifetime of singlet oxygen when a suspension of Pp IX-loaded particles in acetonitrile was excited at 532 nm was determined as 52 micros, which is in good agreement with the value determined for methylene blue in acetonitrile solution under the same conditions. The Pp IX-loaded silica particles have an efficiency of singlet oxygen generation (eta Delta) higher than the quantum yield of free porphyrins. This high efficiency of singlet oxygen generation was attributed to changes on the monomer-dimer equilibrium after photosentisizer immobilization.     

A hand-held fiber-optic implement for the site-specific delivery of photosensitizer and singlet oxygen

We have constructed a fiber optic device that internally flows triplet oxygen and externally produces singlet oxygen, causing a reaction at the (Z)-1,2-dialkoxyethene spacer group, freeing a pheophorbide sensitizer upon the fragmentation of a reactive dioxetane intermediate. The device can be operated and sensitizer photorelease observed using absorption and fluorescence spectroscopy. We demonstrate the preference of sensitizer photorelease when the probe tip is in contact with octanol or lipophilic media. A first-order photocleavage rate constant of 1.13 h(-1) was measured in octanol where dye desorption was not accompanied by readsorption. When the probe tip contacts aqueous solution, the photorelease was inefficient because most of the dye adsorbed on the probe tip, even after the covalent ethene spacer bonds have been broken. The observed stability of the free sensitizer in lipophilic media is reasonable even though it is a pyropheophorbide-a derivative that carries a p-formylbenzylic alcohol substituent at the carboxylic acid group. In octanol or lipid systems, we found that the dye was not susceptible to hydrolysis to pyropheophorbide-a, otherwise a pH effect was observed in a binary methanol-water system (9:1) at pH below 2 or above 8.     

Synthesis and photophysics of benzotexaphyrin: a near-infrared emitter and photosensitizer

Texaphyrins are pentaazadentate macrocycles with interesting photophysical properties and potential applications as nonlinear optical (NLO) materials, photosensitizers, magnetic resonance imaging (MRI) contrasting reagents, and radiation sensitizers, etc. To further red-shift the Q-like band of the texaphyrins, a benzotexaphyrin with an extensively delocalized pi-electron system was synthesized for the first time. Its photophysical characteristics were systematically investigated. Due to the extended pi-conjugation, the Q(0,0) band of benzotexaphyrin bathochromically shifts to 810 nm, and it emits at 825 nm with a singlet excited-state lifetime of 895 ps. Its triplet excited-state energy is estimated to be 119 kJ/mol. The triplet excited-state lifetime is approximately 2.2 micros, and the quantum yield of the triplet excited-state formation is 0.78. It also exhibits a triplet-triplet transient absorption in the region 505-590 nm. In addition, benzotexaphyrin exhibits high efficiency in generating singlet oxygen in methanol (Phi(Delta) = 0.65). Therefore, benzotexaphyrin could potentially be a NIR photosensitizer and emitter for photodynamic therapy and bioimaging applications.     

Effect of intramolecular charge transfer on fluorescence and singlet oxygen production of phthalocyanine analogues

Intramolecular charge transfer (ICT) was studied on a series of magnesium, metal-free and zinc complexes of unsymmetrical tetrapyrazinoporphyrazines and tribenzopyrazinoporphyrazines bearing two dialkylamino substituents (donors) and six alkylsulfanyl or aryloxy substituents (non-donors). The dialkylamino substituents were responsible for ICT that deactivated excited states and led to considerable decrease of fluorescence and singlet oxygen quantum yields. Photophysical and photochemical properties were compared to corresponding macrocycles that do not bear any donor centers. The data showed high feasibility of ICT in the tetrapyrazinoporphyrazine macrocycle and significantly lower efficiency of this deactivation process in the tribenzopyrazinoporphyrazine type molecules. Considerable effect of non-donor peripheral substituents on ICT was also described. The results imply that tetrapyrazinoporphyrazines may be more suitable for development of new molecules investigated in applications based on ICT.     

Photochemistry of phytoalexins containing phenalenone-like chromophores: photophysics and singlet oxygen photosensitizing properties of the plant oxoaporphine alkaloid oxoglaucine

Oxoglaucine (OG) is an oxoaporphine alkaloid, which has been linked to plant defense mechanisms. It contains a phenalenone (PN)-like chromophore, which suggests a role as singlet oxygen ((1)O(2)) photosensitizer. Indeed, OG is able to photosensitize (1)O(2) with 100% efficiency in nonpolar environments, similar to PN. However, this efficiency decreases in polar and protic media, although (1)O(2) is formed in all environments ranging from benzene to water. OG is a rather inefficient (1)O(2) quencher (k(q) = 8 x 10(5) M(-1) s(-1)) unlike the related alkaloids boldine and glaucine, for which an antioxidant role has been suggested. The results of this study contribute to the view that plant defense mediated by PN-like secondary metabolites may have a photochemical component.     

Base-assisted regio- and diastereoselective conversion of functionalized furans to butenolides using singlet oxygen

A facile synthesis of beta-functionalized gamma-hydroxybutenolides was achieved using a Baylis-Hillman reaction followed by singlet oxygen oxidation. The conversion from 3-furfural was regio- and diastereoselective. [reaction: see text].     

Aqueous micellar solution of C60: Preparation, properties, and capability for generation of singlet oxygen

Conditions for preparing stable aqueous micellar solution of nonmodified fullerene C₆₀ were optimized. The size distribution of the micellar particles was determined by transmission electron microscopy, and the negative charge of the micelles was proved. The mean particle diameter appeared to be ～2.5 times smaller than that determined by dynamic light scattering. The possibility of generation of singlet oxygen in the modified system C₆₀/H₂O was demonstrated. The ¹O₂ luminescence signal at λ = 1268 nm lasts for ～3 μs.     

One- and two-photon singlet oxygen generation with new fluorene-based photosensitizers.

The spectral properties of new fluorene-based photosensitizers for efficient singlet oxygen production are investigated at room temperature and 77 K. Two-photon absorption (2PA) cross-sections of the fluorene derivatives are measured by the open aperture Z-scan method. The quantum yields of singlet oxygen generation under one- and two-photon excitation (phi(delta) and 2PAphi(delta), respectively), are determined by the direct measurement of singlet oxygen luminescence at approximately 1270 nm. The values of phi(delta) are independent of excitation wavelength, ranging from 0.6-0.9. The singlet oxygen quantum yields under two-photon excitation are 2PAphi(delta) approximately 1/2 phi(delta), indicating that the two processes exhibit the same mechanism of singlet oxygen production, independent of the mechanism of photon absorption.     

Studies on the photooxidation mechanism of polymers. V. Oxidation of polybutadienes by singlet oxygen from microwave discharge and in dye-photosensitized reactions

The singlet oxygen oxidation of cis- and trans- 1,4-polybutadienes was studied by using singlet oxygen generated in a microwave generator and in dye-photosensitized reactions of these polymers in the solid state and in solution. It was shown that the reactions of singlet oxygen result in formation of hydroperoxide groups, whereas ultraviolet oxidation by molecular oxygen in addition leads to formation of carbonyl groups. During dye-photosensitized oxidation of polydienes in benzene solution, a very rapid decrease in the molecular weight was observed.     

Synthesis,photophysics, and photochemistry of peripherally Schiff base-zinc complex substituted zinc phthalocyanine

The content of this work is based on the introduction of the salicylhydrazone-zinc complexes into the phthalocyanine core. The reaction of the salicylhydrazone substituted ZnPc (1) with the related zinc(II) salt in basic conditions in DMF yielded bis[bis(salicyhydrazone)phenoxy)zinc(II)] phthalocyaninato zinc(II) (5) in which two salicylhydrazone-Zn complexes are linked through oxygen bridges to the macrocyclic core as three-nuclear complex. The novel compound synthesized in this study was fully characterized by general spectroscopic techniques such as FT-IR, UV-vis, ¹H NMR, ¹³C NMR, elemental analysis and mass spectroscopy. In addition, spectral, photophysical (fluorescence quantum yields), and photochemical (generation of singlet oxygen and photo stability under light irradiation) properties of newly synthesized phthalocyanine (5) and the starting Pcs molecules used to obtain this molecule were investigated in DMSO solutions, comparatively.     

Oxygenation of benzyldimethylamine by singlet oxygen. Products and mechanism

[reaction: see text] A product study of the reaction of benzyldimethylamine (1) with thermally and photochemically generated 1O2 in MeCN was carried out. Benzaldehyde and N-benzyl-N-methylformamide are the reaction products, oxygenation representing ca. 9% of the overall quenching of 1O2 by 1. The temperature effect and the intermolecular and intramolecular kinetic deuterium isotope effects were also determined. It is suggested that the products derive from an intracomplex hydrogen atom transfer in a reversibly formed charge-transfer complex.     

Calculation of singlet oxygen dose from photosensitizer fluorescence and photobleaching during mTHPC photodynamic therapy of MLL cells

Predicting the therapeutic outcome of photodynamic therapy (PDT) requires knowledge of the amount of cytoxic species generated. An implicit approach to assessing PDT efficacy has been proposed where changes in photosensitizer (PS) fluorescence during treatment are used to predict treatment outcome. To investigate this, in vitro experiments were performed in which Mat-LyLu cells were incubated in meta-tetra(hydroxyphenyl)chlorin (mTHPC) and then irradiated with 652 nm light. PS concentration, fluence rate and oxygenation were independently controlled and monitored during the treatment. Fluorescence of mTHPC was monitored during treatment and, at selected fluence levels, cell viability was determined using a colony-formation assay. Singlet oxygen dose was calculated using four different models and was compared with cell survival. For the dose metric based on singlet oxygen-mediated PS photobleaching, a universal relationship between cell survival and singlet oxygen dose was found for all treatment parameters. Analysis of the concentration dependence of bleaching suggests that the lifetime of singlet oxygen within the cell is 0.05-0.25 micros. Generation of about 9 x 10(8) molecules of singlet oxygen per cell reduces the surviving fraction by 1/e.     

New cyclometalated transition-metal based photosensitizers for singlet oxygen generation and photodynamic therapy

The aim of this review article is to introduce recent studies on an emergent class of singlet oxygen photosensitizers of potential applications to the photodynamic therapy,with a primary focus on the cyclometalated transition-metal complexes.Singlet oxygen photosensitization performances of various cyclometalated Ir and Pt scaffolds are reviewed,and the general photophysical properties of relevant systems and the mechanisms of singlet oxygen production via photo-sensitization are also briefly discussed.Thus far,investigations of singlet oxygen sensitization by such Ir and Pt complexes are mainly carried out in organic solvents and under non-physiological conditions,while some research efforts have been made at examining the feasibility of applying pertinent cyclometalated complexes to photodynamic therapy.     

Kinetics and mechanism of the highly efficient generation of singlet oxygen in dimethyldioxirane decomposition induced by the chloride ion

The decomposition of dimethyldioxirane induced by the chloride anion has been investigated by methods of infrared chemiluminescence and quantum chemistry. The reaction leads to efficient generation of singlet excited molecular oxygen ¹O₂ (the excitation yield in acetone is 61%). A mechanism of peroxide decomposition is proposed in which the key reactions are the addition of the chloride ion to an oxygen atom of dioxirane, resulting in dioxirane ring opening and the formation of the 2-chlorooxy-2-hydroxy propane alcoholate (k ₁), and the interaction of the latter with another dimethyldioxirane molecule. This interaction results either in the formation of an adduct, which further decomposes to evolve ¹O₂, and catalyst regeneration (k ₂) or in the formation of the 2-chloroxyisopropyl radical, which leads to the irreversible consumption of the chloride ion catalyst (k ₃). The decay kinetics of the infrared chemiluminescence of ¹O₂ has been studied in a wide range of reactant concentrations. The temperature dependence of the rate constant of the reaction of dimethyldioxirane with the chloride ion has been determined by a kinetic analysis of the mechanism proposed: log(² k ₁) = (11.1 ± 0.7) − (46 ± 4)/Θ, where Θ = 2.3RT kJ/mol. Estimation of the ratio of the rates of the reaction of the 2-chlorooxy-2-hydroxy propane alcoholate with dimethyldioxirane via two pathways (k ₃/k ₂) has demonstrated that the fraction of the process involving electron transfer does not exceed 1.5% under the experimental conditions examined. Nevertheless, the latter reaction, which withdraws the chloride ion from the catalytic cycle of dimethyldioxirane decomposition yielding singlet oxygen, has a marked effect on the overall kinetics of the process.