Singlet Oxygen Generation by Cyclometalated Complexes and Applications

While cyclometalated complexes have been extensively studied for optoelectronic applications, these compounds also represent a relatively new class of photosensitizers for the production of singlet oxygen. Thus far, singlet oxygen generation from cyclometalated Ir and Pt complexes has been studied in detail. In this review, photophysical data for singlet oxygen generation from these complexes are presented, and the mechanism of ¹O₂ generation is discussed, including evidence for singlet oxygen generation via an electron‐transfer mechanism for some of cyclometalated Ir complexes. The period from the first report of singlet oxygen generation by a cyclometalated Ir complex in 2002 through August 2013 is covered in this review. This new class of singlet oxygen photosensitizers may prove to be rather versatile due to the ease of substitution of ancillary ligands without loss of activity. Several cyclometalated complexes have been tethered to zeolites, polystyrene, or quantum dots. Applications for photooxygenation of organic molecules, including “traditional” singlet oxygen reactions (ene reaction, [4 + 2] and [2 + 2] cycloadditions) as well as oxidative coupling of amines are presented. Potential biomedical applications are also reviewed.     

Supramolecular Control of Singlet Oxygen Generation

Singlet oxygen (¹O₂) is the excited state electronic isomer and a reactive form of molecular oxygen, which is most efficiently produced through the photosensitized excitation of ambient triplet oxygen. Photochemical singlet oxygen generation (SOG) has received tremendous attention historically, both for its practical application as well as for the fundamental aspects of its reactivity. Applications of singlet oxygen in medicine, wastewater treatment, microbial disinfection, and synthetic chemistry are the direct results of active past research into this reaction. Such advancements were achieved through design factors focused predominantly on the photosensitizer (PS), whose photoactivity is relegated to self-regulated structure and energetics in ground and excited states. However, the relatively new supramolecular approach of dictating molecular structure through non-bonding interactions has allowed photochemists to render otherwise inactive or less effective PSs as efficient ¹O₂ generators. This concise and first of its kind review aims to compile progress in SOG research achieved through supramolecular photochemistry in an effort to serve as a reference for future research in this direction. The aim of this review is to highlight the value in the supramolecular photochemistry approach to tapping the unexploited technological potential within this historic reaction.     

Generation of Singlet Oxygen from Ozone Catalysed by Phosphinoferrocenes

A novel chemical source of singlet oxygen based on the conversion of ozone by 1,1-bis(triphenylphosphino)ferrocene as catalyst was developed into a feasible method for a preperative scale. This is, to our best knowledge, the first application of substituted ferrocenes as oxidation catalysts.     

Generation of Singlet Oxygen from Ozone Catalysed by Phosphinoferrocenes

Summary. A novel chemical source of singlet oxygen based on the conversion of ozone by 1,1-bis(triphenylphosphino)ferrocene as catalyst was developed into a feasible method for a preperative scale. This is, to our best knowledge, the first application of substituted ferrocenes as oxidation catalysts.     

亚磷酸三苯酯臭氧化合物分解产生单重态氧的研究

This letter reports a study on producing gas-phase O2（a1Δ）by decomposition of triphenyl phosphite ozonide（（C6H5O）3 PO3,TPPO3）under a number of reaction conditions. For the first time,the cooperative emission at wavelengths 634 and 703 nm of O2（a1Δ）generated by TPPO3 decomposition are observed. Specifically,under the condition of catalyzed decomposition by pyridine of TPPO3 solution in CFCl3 at low temperature,the emission spectrum is the same as that from the basic hydrogen peroxide plus chlorine reaction. This shows the feasibility of developing a new source for singlet delta oxygen. However,in the experiments of spontaneous decomposition of solid TPPO3 and thermal decomposition of TPPO3 solution on a high temperature surface,the spectra have a wide emission background around the 634 and 703 nm peaks,which indicates the production of some excited species than O2（a1Δ）. Besides,there are about 2%-3% CO and 1. 5%-2% CO2 in the gaseous products together with a small amount of insoluble in acetone solid product,which imply that other than the formation of O2（a1Δ）and TPPO by unimolecular decomposition of TPPO3,more complicated reactions may take place. The study of the reaction mechanism,the optimization of the expertise of O2（a1Δ）generation by TPPO3 decomposition as well as measurement of absolute concentration of O2（a1Δ）are under way.     

Thermal Generation of Singlet Oxygen on Zeolite ZSM-5

The thermal generation of equilibrium singlet oxygen in air at T > 140°C and the effect of the nonequilibrium thermal desorption of singlet oxygen from zeolites ZSM-5 substituted by cations of alkaline (Cs) and alkaline-earth (Ca) metals are found. Possible mechanisms of singlet oxygen generation during desorption are discussed.     

Generation of Singlet Oxygen with Anionic Aluminum Phthalocyanines in Water

The dependence of the quantum yield of photogeneration of singlet oxygen with aluminum sulfophthalocyanines on the degree of their sulfonation was studied. Experiments showed that Fotosens preparation containing, on the average, about three sulfo groups in the macroring in aqueous buffer solution (pH 7.4) exists in the monomeric form and sensitizes singlet oxygen with a quantum yield 0.42±0.06. Aluminum tetra-4-sulfophthalocyanine forms dimers, and correspondingly is lower: 0.22±0.03. Sulfonated aluminum phthalocyanine containing, on the average, about two sulfo groups in the macroring is aggregated to a significant extent. Addition of Triton X-100 detergent results in partial deaggregation of the dye, and increases from 0.01 to 0.15±0.02. In the series including previously unknown aluminum phthalocyanines containing residues of phosphonic acids or their esters, and also aluminum and zinc octacarboxyphthalocyanines, the influence of the dye structure on the quantum yield of generation of singlet oxygen suggests participation of axial hydroxy groups in associate formation. These associates are not manifested spectroscopically and generate singlet oxygen inefficiently. The quantum yields for the monomers and associates are 0.3 and 0.1, respectively.     

Activatable Singlet Oxygen Generation from Lipid Hydroperoxide Nanoparticles for Cancer Therapy

Reactive oxygen species (ROS)-induced apoptosis is a widely practiced strategy for cancer therapy. Although photodynamic therapy (PDT) takes advantage of the spatial–temporal control of ROS generation, the meticulous participation of light, photosensitizer, and oxygen greatly hinders the broad application of PDT as a first-line cancer treatment option. An activatable system has been developed that enables tumor-specific singlet oxygen (¹O₂) generation for cancer therapy, based on a Fenton-like reaction between linoleic acid hydroperoxide (LAHP) tethered on iron oxide nanoparticles (IO NPs) and the released iron(II) ions from IO NPs under acidic-pH condition. The IO-LAHP NPs are able to induce efficient apoptotic cancer cell death both in vitro and in vivo through tumor-specific ¹O₂ generation and subsequent ROS mediated mechanism. This study demonstrates the effectiveness of modulating biochemical reactions as a ROS source to exert cancer death.     

Comparing Singlet Oxygen Generation of Schiff Base Substituted Novel Silicon Phthalocyanines by Sonophotochemical and Photochemical Applications

Although the sonophotodynamic method has an effective therapeutic outcome for anticancer treatment compared with the photodynamic method, there are not enough related studies in the literature and this study aims to contribute to the development of sonophotodynamic studies. For this purpose, the Schiff base substituted silicon phthalocyanines were designed and synthesized as effective sensitizer candidates and the photophysicochemical and sonophotochemical features of the phthalocyanines were examined to increase singlet oxygen efficiency. The calculated Φ_Δ values indicate that the contribution of substituent groups improved the production of singlet oxygen compared with silicon (IV) phthalocyanine dichloride (SiPcCI₂) and also the sonophotochemical applications increased the singlet oxygen yields. The Φ_Δ values (Φ_Δ = 0.76 for axially bis-{4-[(E)-(pyridin-3-ylimino)methyl]phenol} substituted silicon (IV) phthalocyanine ( 2a ), 0.68 for axially bis-4-[(E)-{[(pyridin-3-yl)methyl]imino}methyl]phenol substituted silicon (IV) phthalocyanine ( 2b ) in photochemical study) reached to Φ_Δ = 0.98 for 2a , 0.94 for 2b in sonophotochemical study. This article will enrich the literature on increasing singlet oxygen yield.     

Damage to Isolated DNA Mediated by Singlet Oxygen

In the present work, we study the reaction of singlet oxygen (¹O₂) with isolated DNA. Emphasis is placed on the identification and quantitative measurement of the DNA modifications that are produced by the reaction of ¹O₂ with DNA. For this purpose, calf‐thymus DNA was incubated with the endoperoxide of N,N′‐di(2,3‐dihydroxypropyl)‐1,4‐naphthalenedipropanamide, a chemical generator of ¹O₂. Thereafter, DNA was digested, and the resulting oxidized nucleosides were measured by means of a recently optimized high‐performance‐liquid‐chromatography tandem‐mass‐spectrometry assay. It was found that, among the different DNA lesions observed, 7,8‐dihydro‐8‐oxo‐2′‐deoxyguanosine is the major ¹O₂‐mediated DNA‐damage product. Interestingly, cyclobutane pyrimidine dimers, oxidized pyrimidine bases, 7,8‐dihydro‐8‐oxo‐2′‐deoxyadenosine, and 2,6‐diamino‐5‐formamido‐4‐hydroxypyrimidine are not formed, at least not in detectable amounts, following treatment of DNA with the ¹O₂ generator. The reported results strongly suggest that the decomposition of the endoperoxide provides a pure source of ¹O₂, and that reaction of ¹O₂ with isolated DNA induces the specific formation of 7,8‐dihydro‐8‐oxo‐2′‐deoxyguanosine.     

Conditional Singlet Oxygen Generation through a Bioorthogonal DNA‐targeted Tetrazine Reaction

We report the use of bioorthogonal reactions as an original strategy in photodynamic therapy to achieve conditional phototoxicity and specific subcellular localization simultaneously. Our novel halogenated BODIPY‐tetrazine probes only become efficient photosensitizers (Φ_Δ≈0.50) through an intracellular inverse‐electron‐demand Diels–Alder reaction with a suitable dienophile. Ab initio computations reveal an activation‐dependent change in decay channels that controls ¹O₂ generation. Our bioorthogonal approach also enables spatial control. As a proof‐of‐concept, we demonstrate the feasibility of the selective activation of our dormant photosensitizer in cellular nuclei, causing cancer cell death upon irradiation. Thus, our dual biorthogonal, activatable photosensitizers open new venues to combat current limitations of photodynamic therapy.     

Photochromic Metal–Organic Frameworks: Reversible Control of Singlet Oxygen Generation

The controlled generation of singlet oxygen is of great interest owing to its potential applications including industrial wastewater treatment, photochemistry, and photodynamic therapy. Two photochromic metal–organic frameworks, PC‐PCN and SO‐PCN, have been developed. A photochromic reaction has been successfully realized in PC‐PCN while maintaining its single crystallinity. In particular, as a solid‐state material which inherently integrates the photochromic switch and photosensitizer, SO‐PCN has demonstrated reversible control of ¹O₂ generation. Additionally, SO‐PCN shows catalytic activity towards photooxidation of 1,5‐dihydroxynaphthalene.     

A Novel Singlet Oxygen Reaction

Abstract— 1-Aryl-2-methyl-4,5-dihydropyrrol-3-carboxylic acid ethyl ester (a cyclic enamine) was observed to dehydrogenate to give 1-aryl-2-methyl-pyrrol-3-carboxylic acid ethyl ester upon irradiation in the presence of oxygen and in the presence or absence of meso -tetraphenylporphine (TPP). N -Aryl cyclic amines were shown to be singlet oxygen sensitizers.     

pH Controlled Intersystem Crossing and Singlet Oxygen Generation of 8-Azaadenine in Aqueous Solution

Azabases are intriguing DNA and RNA analogues and have been used as effective antiviral and anticancer medicines. However, photosensitivity of these drugs has also been reported. Here, pH-controlled intersystem crossing (ISC) process of 9H 8-azaadenine (8-AA) in aqueous solution is reported. Broadband transient absorption measurements reveal that the hydrogen atom at N9 position can greatly affect ISC of 8-AA and ISC is more favorable when 8-AA is in its neutral form in aqueous solution. The initial excited ππ* (S₂) state evolves through ultrafast internal conversion (IC) (4.2 ps) to the lower-lying nπ* state (S₁), which further stands as a door way state for ISC with a time constant of 160 ps. The triplet state has a lifetime of 6.1 μs. On the other hand, deprotonation at N9 position promotes the IC from the ππ* (S₂) state to the ground state (S₀) and the lifetime of the S₂ state is determined to be 10 ps. The experimental results are further supported by time-dependent density functional theory (TDDFT) calculations. Singlet oxygen generation yield is measured to be 13.8 % for the neutral 8-AA while the deprotonated one exhibit much lower yield (<2 %), implying that this compound could be a potential pH-sensitized photodynamic therapy agent.     

meso—四—（取代苯基）卟吩衍生物产生单线态氧的ESR研究

随着肿瘤光动力疗法(Photodynamic Therapy,PDT)的不断发展,出现了一系列新光敏剂,其中,meso-四-(取代苯基)卟吩衍生物是一类肿瘤选择性摄入率高、理化性质稳定的光动力敏化剂,近年来,作者设计并合成了一组meso-四-(取代苯基)卟吩衍生物,并初步观察了它们对细胞及小鼠移植瘤的光动力学效应,为了进一步比较不同卟吩衍生物的光敏化     

Photophysical Properties and Singlet Oxygen Generation Efficiencies of Water‐Soluble Fullerene Nanoparticles

As various fullerene derivatives have been developed, it is necessary to explore their photophysical properties for potential use in photoelectronics and medicine. Here, we address the photophysical properties of newly synthesized water‐soluble fullerene‐based nanoparticles and polyhydroxylated fullerene as a representative water‐soluble fullerene derivative. They show broad emission band arising from a wide‐range of excitation energies. It is attributed to the optical transitions from disorder‐induced states, which decay in the nanosecond time range. We determine the kinetic properties of the singlet oxygen (¹O₂) luminescence generated by the fullerene nanoparticles and polyhydroxylated fullerene to consider the potential as photodynamic agents. Triplet state decay of the nanoparticles was longer than ¹O₂ lifetime in water. Singlet oxygen quantum yield of a series of the fullerene nanoparticles is comparably higher ranging from 0.15 to 0.2 than that of polyhydroxylated fullerene, which is about 0.06.     

DNA-Triggered Enhancement of Singlet Oxygen Production by Pyridinium Alkynylanthracenes

There is an ongoing interest in ¹O₂ sensitizers, whose activity is selectively controlled by their interaction with DNA. To this end, we synthesized three isomeric pyridinium alkynylanthracenes 2 o – p and a water-soluble trapping reagent for ¹O₂. In water and in the absence of DNA, these dyes show a poor efficiency to sensitize the photooxygenation of the trapping reagent as they decompose due to electron transfer processes. In contrast, in the presence of DNA ¹O₂ is generated from the excited DNA-bound ligand. The interactions of 2 o – p with DNA were investigated by thermal DNA melting studies, UV/vis and fluorescence spectroscopy, and linear and circular dichroism spectroscopy. Our studies revealed an intercalative binding with an orientation of the long pyridyl-alkynyl axis parallel to the main axis of the DNA base pairs. In the presence of poly(dA : dT), all three isomers show an enhanced formation of singlet oxygen, as indicated by the reaction of the latter with the trapping reagent. With green light irradiation of isomer 2 o in poly(dA : dT), the conversion rate of the trapping reagent is enhanced by a factor >10. The formation of ¹O₂ was confirmed by control experiments under anaerobic conditions, in deuterated solvents, or by addition of ¹O₂ quenchers. When bound to poly(dG : dC), the opposite effect was observed only for isomers 2 o and 2 m , namely the trapping reagent reacted significantly slower. Overall, we showed that pyridinium alkynylanthracenes are very useful intercalators, that exhibit an enhanced photochemical ¹O₂ generation in the DNA-bound state.