Exploring BODIPY Derivatives as Singlet Oxygen Photosensitizers for PDT

This minireview is devoted to honoring the memory of Dr. Thomas Dougherty, a pioneer of modern photodynamic therapy (PDT). It compiles the most important inputs made by our research group since 2012 in the development of new photosensitizers based on BODIPY chromophore which, thanks to the rich BODIPY chemistry, allows a finely tuned design of the photophysical properties of this family of dyes to serve as efficient photosensitizers for the generation of singlet oxygen. These two factors, photophysical tuning and workable chemistry, have turned BODIPY chromophore as one of the most promising dyes for the development of improved photosensitizers for PDT. In this line, this minireview is mainly related to the establishment of chemical methods and structural designs for enabling efficient singlet oxygen generation in BODIPYs. The approaches include the incorporation of heavy atoms, such as halogens (iodine or bromine) in different number and positions on the BODIPY scaffold, and also transition metal atoms, by their complexation with Ir(III) center, for instance. On the other hand, low-toxicity approaches, without involving heavy metals, have been developed by preparing several orthogonal BODIPY dimers with different substitution patterns. The advantages and drawbacks of all these diverse molecular designs based on BODIPY structural framework are described.     

Metallophthalocyanine‐Based Conjugated Microporous Polymers as Highly Efficient Photosensitizers for Singlet Oxygen Generation

Singlet oxygen (¹O₂) is of great interest because of its potential applications in photodynamic therapy, photooxidation of toxic molecules, and photochemical synthesis. Herein, we report novel metallophthalocyanine (MPc) based conjugated microporous polymers (MPc‐CMPs) as photosensitizers for the generation of ¹O₂. The rigid microporous structure efficiently improves the exposure of the majority of the MPc units to oxygen. The MPc‐CMPs also exhibit an enhanced light‐harvesting capability in the far‐red region through their extended π‐conjugation systems. Their microporous structure and excellent absorption capability for long‐wavelength photons result in the MPc‐CMPs showing high efficiency for ¹O₂ generation upon irradiation with 700 nm light, as evident by using 1,3‐diphenylisobenzofuran as an ¹O₂ trap. These results indicate that MPc‐CMPs can be considered as promising photosensitizers for the generation of ¹O₂.     

双光子诱导产生单重态氧的三重态光敏剂的研究

自2001年以来,双光子敏化产生单重态氧的三重态光敏剂的研究取得了一定的进展。双光子三重态光敏剂对肿瘤组织的近红外激光和红外激光的光动力治疗作用具有广阔的应用前景。本文重点分析了近些年已报道的双光子三重态光敏剂种类,如疏水性、水溶性等不同的敏化剂;介绍了可以根据分子的激发态性质、利用化学手段对双光子三重态敏化剂的性质以及光敏产生单重态氧的量子产率进行调控;概括了双光子三重态敏化剂的相对和绝对双光子横截面的测量方法;总结了双光子三重态敏化剂发展中面临的一些关键问题,并展望了双光子三重态敏化剂的发展方向。     

Assessing the Applicability of Singlet Oxygen Photosensitizers in Leaf Studies

Singlet oxygen (¹O₂) is of special interest in plant stress physiology. Studies focused on internal, chlorophyll‐mediated production are often complemented with the use of artificial ¹O₂ photosensitizers. Here, we report a comparative study on the effects of Rose Bengal (RB), Methylene Violet (MVI), Neutral Red (NR) and Indigo Carmine (IC). These were infiltrated into tobacco leaves at concentrations generating the same fluxes of ¹O₂ in solution. Following green light‐induced ¹O₂ production from these dyes, leaf photosynthesis was characterized by Photosystem (PS) II and PSI electron transport and oxidative damage was monitored as degradation of D1, a PSII core protein. Cellular localizations were identified on the basis of the dyes’ fluorescence using confocal laser scanning microscopy. We found that RB and NR were both localized in chloroplasts but the latter had very little effect, probably due to its pH‐dependent photosensitizing. Both RB and intracellular, nonplastid MVI decreased PSII electron transport, but the effect of RB was stronger than that of MVI and only RB was capable of damaging the D1 protein. Intercellularly localized IC had no significant effect. Our results also suggest caution when using RB as photosensitizer because it affects PSII electron transport.     

Gadolinium(III) Porpholactones as Efficient and Robust Singlet Oxygen Photosensitizers

Construction of Gd^III photosensitizers is important for designing theranostic agents owing to the unique properties arising from seven unpaired f electrons of the Gd³⁺ ion. Combining these with the advantages of porpholactones with tunable NIR absorption, we herein report the synthesis of Gd^III complexes Gd‐1 – 4 ( 1 , porphyrin; 2 , porpholactone; 3 and 4 , cis‐ and trans‐porphodilactone, respectively) and investigated their function as singlet oxygen (¹O₂) photosensitizers. These Gd complexes displayed ¹O₂ quantum yields (Φ_Δs) from 0.64–0.99 with the order Gd‐1 < Gd‐2 < Gd‐3 < Gd‐4 . The gradually enhanced ¹O₂ sensitization after β‐oxazolone moiety replacement was ascribed to the narrowing of the energy gap (ΔE) between the lowest triplet states (T₁) of the ligand and the energy level of the ¹Δ_g→³Σ_g transition of ¹O₂. In particular, Gd‐4 is capable of excitation in the visible to NIR region (400–700 nm) with a quantum yield near unity. These Gd complexes were first demonstrated as efficient photosensitizers in photocatalysis such as oxidative C?H bond functionalization of secondary or tertiary amines, and the oxygenation of the natural product cholesterol. Finally, after glycosylation, these water‐soluble Gd complexes showed potential applications in photodynamic therapy (PDT) in HeLa cells. This work revealed that Gd^III complexes of “bioinspired” β‐modified porpholactones are efficient NIR photosensitizers and form a chemical basis to construct appealing photocatalysts and theranostic agents based on lanthanides.     

Water-Soluble Metalloporphyrins as Mimics of Heme-containing Enzymes

Hemin is a naturally occurring metalloporphyrin (M-P), which is the common prosthetic group of heme-containing enzymes. Many M-Ps with different ligand structures and central metal ions were synthesized to mimic heme-containing enzymes1-3. To improve the catalytic capability and specificity of mimic enzyme, the effect of axial ligand was studied as well4-8. Similar to the active center of all heme-containing enzymes, M-P should show more or less catalytic activities of heme-containing enz…     

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.     

New Reagents for Determination of the Quantum Efficiency of Singlet Oxygen Generation in Aqueous Media

Water-soluble anthracene derivatives containing carboxy, dihydroxyphosphinyl, or pyridinium fragments bound via methylene groups to 9- and 10-carbon atoms were prepared, and their spectra, solubility, and reactivity toward singlet oxygen were studied. Using sodium ,'-(anthracene-9,10-diyl)bis(methyl- malonate) as acceptor, it is possible to determine the quantum efficiency of singlet oxygen generation in aqueous solutions and in microheterogeneous media in the presence of biomacromolecules.     

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.     

水溶性金属卟啉肿瘤靶向磁共振成像造影剂的研究

利用显微荧光－阿达玛变换三维图像分析研究了Ｃｕ－ＴＳＰＰ，Ｍｎ－ＴＳＰＰ，Ｃｕ－ＴＭＡＰ，Ｍｎ－ＴＭＡＰ４种水溶性金属卟啉人细胞间质进入肿瘤细胞内的富集过程，对金属卟啉的自旋－晶格驰豫性能（Ｒ１）的天空结果表明，Ｍｎ（Ⅱ）卟啉配合物的Ｒ１、值结Ｇｄ－ＤＴＰＡ提高１．５－２倍。     

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.     

氯氰菊酯光敏降解中单线态氧机理研究

光敏剂亚甲兰,核黄素及玫瑰红Ｂ可加速氯氰菊酯（ＣＰＭ）的光解作用。这些物质的敏化作用主要通过激发基态氧为单线态氧来实现。光敏剂和氧均是敏化光降解不可缺陷少的条件。１／Ｋｅｘｐｔｌ与「Ａ」的关系证实了单线态氧氧化机理。在亚甲兰、核黄素存在下氯氰菊酯ＫＡ分别为６．４９＊１０＾６ｌ．ｍｏｌ＾－１．ｓ＾－１和２．２７＊１０＾６Ｌ．＾－１。氯氰菊酯的光解速率在一定范围内,随光敏剂浓度的增加而增加,过量的光敏剂将减少体系的透光率而导致氯氰菊酯光解速率降低,单线态氧探针性物质即竞争反应的引入将明显降低氯氰菊酯的光解速率,同时,不同极性溶剂因其对单线态氧猝灭能力的不同也会明显改变氯氰菊酯的光解速率。     

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.     

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.     

Determination of Fluorescence Yields, Singlet Lifetimes and Singlet Oxygen Yields of Water-Insoluble Porphyrins and Metalloporphyrins in Organic Solvents and in Aqueous Media

Abstract— Fluorescence quantum yields and singlet lifetimes for a wide range of hydrophilic to hydrophobic porphyrins and metalloporphyrins have been determined in toluene, methanol or acetone. Photosensitized singlet oxygen yields have been determined in the same solvents. For some porphyrins, the same quantities were determined in an aqueous medium, through use of an amphiphilic polymer to solubilize the porphyrin sensitizer and target molecule, 1, 3-diphenylisobenzofuran. Because rate constants for the deactivation of singlet oxygen ( k _d) and for its reaction with a target molecule (k _a ) are unknown in such aqueous polymer systems, a new method was developed for evaluating yields of singlet oxygen formation that also provides a value for the ratio k_d/k_a. A variation observed in quantum yield of singlet oxygen production for the aqueous polymer system with variation in initial concentration of the target molecule is discussed.     

水溶性卟啉及金属卟啉在DNA中的研究进展

近年来, 卟啉及金属卟啉与DNA的相互作用已成为研究的热点. 通过对卟啉及金属卟啉与DNA相互作用的研究将有助于更深地认识DNA本身的结构和功能, 有助于卟啉及金属卟啉在医学上的应用, 对认识很多疾病的治病机制和药物的设计也起到非常重要的作用. 本文阐述了卟啉及金属卟啉与DNA相互作用的方式和影响因素, 并将水溶性卟啉及金属卟啉分为三类: 具有吡啶基或铵基的阳离子型卟啉及金属卟啉, 具有磺酸基或羧基的阴离子型卟啉及金属卟啉, 以及非离子型的卟啉及金属卟啉. 重点论述了这三类水溶性卟啉及金属卟啉与DNA之间的相互作用, 以及这三类水溶性卟啉及金属卟啉在DNA中的应用研究进展.     

Fluorescent Imidazo[1,2-a]pyrimidine Compounds as Biocompatible Organic Photosensitizers that Generate Singlet Oxygen: A Potential Tool for Phototheranostics

Photodynamic therapy has been used to treat a variety of diseases, however, there is continuing search for new biocompatible photosensitizers. Herein, we demonstrate for the first time that imidazo[1,2-a]pyrimidine compounds are able to generate singlet oxygen species and can act as photosensitizers in the intracellular environment. Our results show that this class of compounds absorb and emit in the 400–500 nm region, present low cytotoxicity in the dark, are efficiently uptaken by cells, are fluorescent in intracellular medium, and generate singlet oxygen upon irradiation, killing cancer cells within 2 h at low concentration (2.0 μm ). The imidazo[1,2-a]pyrimidine compounds are a potential new tool for phototheranostics, because they can be simultaneously used for fluorescence imaging and photodynamic therapy.