Photosensitized Singlet Oxygen Research Articles

Synthesis, optical and electrochemical properties of propeller-type 3,5,8-trithienyl-BODIPY dyes

Propeller-type 3,5,8-trithienyl-BODIPY dyes have been developed and their optical and electrochemical properties, and photosensitized singlet oxygen generation ability were investigated.

Acid–base controllable singlet oxygen generation in supramolecular porphyrin–gold nanoparticle composites tethered by rotaxane linkers

Mechanically-interlocked photosensitizer–quencher systems based on free-base tetraphenylporphyrin (H2TPP)–gold nanoparticle (AuNP) composites has been designed and synthesized by utilizing a rotaxane architecture comprised of secondary ammonium and crown ether subunit. The H2TPP-substituted 24-crown-8 was able to shuttle along the alkanethiolate axle, triggered by deprotonation/protonation at the ammonium station, altering the H2TPP–AuNP distance and the photoexcitation energy transfer efficiency. Upon switching, quantum yields for photosensitized singlet oxygen (1O[Formula: see text] generation and fluorescence after deprotonation were quenched by 46% and 42%, respectively. External environment-responsive1O2generation based on such a protonation/deprotonation-driven molecular switch is potentially advantageous for a variety of applications including photodynamic therapies.

Protective Fabrics: Metal-Organic Framework Textiles for Rapid Photocatalytic Sulfur Mustard Simulant Detoxification

Summary Metal-organic frameworks (MOFs) can catalyze toxic chemical decontamination, but new MOF materials and synthesis strategies are needed to improve performance, particularly in field-usable MOF-textile formats. This article reports for the first time the exceptional photocatalytic reactivity of Al-PMOF (Al-porphyrin-based MOF), composed of an earth-abundant metal-containing Al(OH)O4 cluster bridged by H2TCPP (5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin) chromophores, against the toxic sulfur mustard simulant 2-chloroethyl ethyl sulfide (CEES) under visible-light irradiation. Furthermore, Al-PMOF is strongly immobilized into polymeric fibers via well-controlled Al2O3 solid film conversion using dimethylformamide/water cosolvent. The approach enables a secure integration of conformal Al-PMOF films onto polymer fibers at a relatively low synthesis temperature (120°C). In addition, on a per-unit mass of MOF basis, the surface-bound Al-PMOF films enable extremely rapid CEES detoxification turnover frequency, up to 170 mol CEES mol chromophore − 1 min − 1 , more than 10-fold faster than the best MOF powders and 2-fold better than MOF films reported to date.

Phosphinate Apical Ligands: A Route to a Water-Stable Octahedral Molybdenum Cluster Complex.

Recent studies have unraveled the potential of octahedral molybdenum cluster complexes (Mo6) as relevant red phosphors and photosensitizers of singlet oxygen, O2(1Δg), for photobiological applications. However, these complexes tend to hydrolyze in an aqueous environment, which deteriorates their properties and limits their applications. To address this issue, we show that phenylphosphinates are extraordinary apical ligands for the construction of Mo6 complexes. These new complexes display unmatched luminescence quantum yields and singlet oxygen production in aqueous solutions. More importantly, the complex with diphenylphosphinate ligands is the only stable complex of these types in aqueous media. These complexes internalize in lysosomes of HeLa cells, have no dark toxicity, and yet are phototoxic in the submicromolar concentration range. The superior hydrolytic stability of the diphenylphosphinate complex allows for conservation of its photophysical properties and biological activity over a long period, making it a promising compound for photobiological applications.

Nanoscale View of Amyloid Photodynamic Damage.

A combination of time-resolved optical spectroscopy and nanoscale imaging has been used to study the complex binding to amyloids of a photocatalyst that selectively photo-oxygenates pathogenic aggregates, as well as the consequences of its irradiation. Correlative atomic force microscopy (AFM) and fluorescence microscopy reveals topography-dependent binding of the dye to model β-lactoglobulin fibers, which may also explain the observed difference in their response to photodegradation. We provide direct evidence of the photosensitization of singlet oxygen by the photocatalyst bound to amyloid fibers by direct detection of its NIR phosphorescence. The effect of singlet oxygen at the molecular level brings about nanoscale morphological changes that can be observed with AFM at the single-fiber level. We also find differential response of two α-synuclein mutants to photodamage, which can be rationalized by the presence of amino acids susceptible to photo-oxygenation. Overall, our results help to unravel some of the complexity associated with highly heterogeneous amyloid populations and contribute to the development of improved phototherapeutic strategies for amyloid-related disorders.

Photooxidation Reactions of Cyclometalated Palladium(II) and Platinum(II) Complexes.

New C,N,S-cyclometalated palladium(II) and platinum(II) complexes have been synthesized and their structural, electrochemical, and photochemical properties examined. The blue color of these complexes in solution changed to yellow under visible-light irradiation. By measurement of the absorption spectra for quantifying changes in color, isosbestic points for each complex clearly indicated the presence of only two species responsible for the change of color. X-ray analysis revealed that the visible-light-induced yellow species were S-oxygenated sulfinato complexes. Photosensitized generation of singlet oxygen (1O2) was confirmed by the direct detection of singlet oxygen luminescence at 1275 nm. The present cyclometalated palladium(II) and platinum(II) complexes are efficient photosensitizers of singlet oxygen, which rapidly reacts with coordinating sulfur atoms.

Single mutation in a novel bacterial LOV protein yields a singlet oxygen generator.

Mr4511 from Methylobacterium radiotolerans is a 164 amino acid protein built of a flavin mononucleotide (FMN) binding, blue-light responsive LOV (Light, Oxygen, Voltage) core domain plus flanking regions. In contrast to the majority of LOV domains, Mr4511 lacks a tryptophan residue that was previously identified as a major quencher for the FMN triplet state in photosensitizers for singlet oxygen (SO) engineered from these photoreceptors. Here we show that for Mr4511 it is sufficient to only mutate the reactive cysteine responsible for the photocycle (Cys71) in the native protein to generate an efficient SO photosensitizer: both C71S and C71G variants exhibit SO quantum yields of formation, ΦΔ, around 0.2 in air-saturated solutions. Under oxygen saturated conditions, ΦΔ reaches ∼0.5 in deuterated buffer. The introduction of Trp112 in the canonical position for LOV domains dramatically lowers ΦΔ to values comparable to miniSOG, one of the early FMN binding proteins touted as a SO sensitizer. Besides its SO properties, Mr4511 is also exceedingly robust against denaturation with urea and is more photostable than free FMN.

Photocatalytic Properties of a Palladium Metallosquare with Encapsulated Fullerenes via Singlet Oxygen Generation.

Singlet oxygen has recently attracted a great deal of attention due to its strong oxidizing properties, which makes it useful in organic synthesis and biological studies. However, the photosensitizers that are required for singlet oxygen generation remain inadequate due to their often low thermal and photochemical stabilities. Here we describe the use of a palladium-conjoined metallosquare with encapsulated fullerenes (C60 or C70), which behaves as an efficient and photochemically stable singlet oxygen photosensitizer. The metallocage with the encapsulated fullerenes can oxidize a series of cyclic and acyclic alkenes at room temperature via visible light-induced singlet oxygen generation, using oxygen molecules in air at atmospheric pressure. These reactions take advantage of the excellent spin-converting properties of fullerenes, which make them excellent agents for singlet oxygen production.

A dormant BODIPY-acrolein singlet oxygen photosensitizer intracellularly activated upon adduct formation with cysteine residues.

Here we report the activatable photosensitizer BromoAcroB, a brominated BODIPY dye incorporating a reactive acrolein warhead. The acrolein moiety serves as an intramolecular switch, deactivating the BODIPY dye in its singlet and triplet excited states via internal conversion. Thiolate addition to this moiety disables the intramolecular quenching mechanism restoring the photosensitizing properties of the parent dye, characterized by a quantum yield of singlet oxygen photosensitization of 0.69 ± 0.02. In cell cultures, and upon thiol adduct formation, BromoAcroB induced light-dependent cell death in MRC-5 and HeLa cell lines. Using fluorescence microscopy and upon measuring the low yet non-negligible emission of the activated compound, we show that the phototoxicity of the dormant photosensitizer correlated with the quantity of BromoAcroB adducts generated. BromoAcroB thus serves as a dormant photosensitizer sensitive to intracellular electrophile response. Our results highlight the effective control of a triplet state process by modulation of an unsaturated moiety on the BODIPY scaffold and underscore the mechanistic opportunities arising for controlled singlet oxygen production in cells specifically sensitive to electrophile stress.

Porpholactone Chemistry: An Emerging Approach to Bioinspired Photosensitizers with Tunable Near-Infrared Photophysical Properties.

Chlorophylls, known as the key building blocks of natural light-harvesting antennae, are essential to utilize solar energy from visible to near-infrared (NIR) region during the photosynthesis process. The fundamental studies for the relationship between structure and photophysical properties of chlorophylls disclosed the importance of β-peripheral modification and thus boosted the fast growth of NIR absorbing/emissive porphyrinoids via altering the extent of π-conjugation and the degree of distortion from the planarity of macrocycle. Despite the tremendous progress made in various porphyrin-based synthetic models, it still remains a challenge to precisely modulate photophysical properties through fine-tuning of β-peripheral structures in the way natural chlorophylls do. With this in mind, we initiated a program and focused on meso-C6F5-substituted porpholactone (F20TPPL), in which one β-pyrrolic double bond was replaced by a lactone moiety, as an attractive platform to construct the bioinspired library of NIR porphyrinoids. In this Account, we summarize our recent contributions to the bioinspired design, synthesis, photophysical characterization, and applications of porpholactones and their derivatives. We have developed a general, convenient method to directly prepare porpholactones in large scale up to gram, which forms the chemical basis of porpholactone chemistry. By modulation of the saturation level and in particular regioisomerization of β-dilactone moieties, a synthetic library constituted by a series of porpholactones and their derivatives has been established. Thanks to the electron-withdrawing nature of lactone moiety, derivation of the saturation levels gives help to build stable models for chlorin, bacteriochlorin, and tunichlorin. It is worth noting that regioisomerization of dilactone moieties mimics the relative orientation of β-substituents in natural chlorophylls and hemes, which was considered as the key factor to tune NIR absorption and reactivity. Porpholactones can illustrate the capability of fine-tuning photophysical properties including the excited triplet states by subtle alteration of β-peripheral structures in the presence of transition metals and lanthanides (Ln). Furthermore, they can serve as efficient photosensitizers for singlet oxygen and NIR Ln, showing potential applications in cell imaging and photocytotoxicity studies. The high luminescence, tunable structures, high cellular uptake, and intense NIR absorption render them as promising and competitive candidates for theranostics in vitro and in vivo. Therefore, extending the studies of "porpholactone chemistry" not only tests the fundamental understanding of the structure-function relationship that governs NIR photophysical properties of natural tetrapyrrole cofactors such as chlorophylls but also provides the guiding principles for the bioinspired design of NIR luminescent molecular probes with various applications. Taken together, as a new synthetic porphyrin derivative, porpholactone chemistry shines light on synthetic porphyrin, bioinorganic, and lanthanide chemistry.

BOPHYs versus BODIPYs: A comparison of their performance as effective multi-function organic dyes

The computationally-aided photophysical and lasing properties of a selected battery of BOPHYs are described and compared to those of related BODIPY counterparts. The present joined theoretical-experimental study helps to put into context the weaknesses and strengths of both dye families under different irradiation conditions. The chemical versatility of the BOPHY scaffold has been also comparatively explored to modulate key photonic properties towards the development of red-emitting dyes, chiroptical dyes and singlet oxygen photosensitizers. Thus, BOPHY BINOLation by fluorine substitution with enantiopure BINOLs endows the BOPHY chromophore with chiroptical activity, as supporting by the simulated circular dichroism, decreasing deeply its fluorescent response due to the promotion of fluorescence-quenching intramolecular charge transfer (ICT). Interestingly, the sole alkylation of the BOPHY core strongly modulates the promotion of ICT, allowing the generation of highly bright BINOL-based BOPHY dyes. Moreover, 3,3′-dibromoBINOLating BOPHYs can easily achieve singlet-oxygen photogeneration, owing to spin-orbit coupling mediated by heavy-atom effect feasible in view of the theoretically predicted disposition of the bromines surrounding the chromophore. From this background, we have established the master guidelines to design bright fluorophores and laser dyes, photosensitizers for singlet oxygen production and chiroptical dyes based on BOPHYs. The possibility to finely mix and balance such properties in a given molecular scaffold outstands BOPHYs as promising dyes competing with the well-settled BODIPY dyes.

Can Rose Bengal resilience be used as a marker for photosynthetic resilience of Nannochloropsis oceanica strains in excess light environments?

Singlet oxygen (1O2) is an interesting candidate for study due to the widely held opinion that it plays a key role in photoinhibition of photo system II (PSII). Many studies have been conducted to elucidate the exact role of singlet oxygen (1O2) in photo-damage/repair, photoprotection, oxidative protection, and signaling. However, few studies have addressed the potential role of singlet oxygen as a marker for resilience to excess light environments. In the present study, we focus on the question of whether singlet oxygen resilience correlates with a strain's robustness in excess light environments. In order to address this question, two Nannochloropsis oceanica mutant strains, RB2 and RB113, both selected for heightened resilience to Rose Bengal (RB), a singlet oxygen (1O2) photosensitizer, were characterized. This included the characterization of the photosynthetic apparatuses and specific growth rate in relation to photosynthetic photon flux density (PPFD) in the growth media.Both of the RB resistant mutants showed higher photosynthetic capabilities when grown in high PPFD environments relative to the wild type (WT) strain. This was evident by higher photosynthetic capacity (namely 27% higher in the RB113 mutant and 94% higher in the RB2 mutant) relative to the WT strain when grown in an optimal temperature and an excess light environment (25 °C and 500 photons μmol s−1 m−2). In addition to the increase in photosynthetic capacity in the excess light environment of 25 °C and 500 photons μmol s−1 m−2, mutant strains also showed higher specific growth rates reflected by a 38% and 48% increase in the RB113 and RB2 mutant strains respectively. These results lead us to propose that Rose Bengal resilience in Nannochloropsis may serve as a marker for selecting species or strains better suited for growth in high light environments.

Can BODIPY-Electron Acceptor Conjugates Act As Heavy Atom-Free Excited Triplet State and Singlet Oxygen Photosensitizers via Photoinduced Charge Separation-Charge Recombination Mechanism?

To examine if BODIPY-electron acceptor conjugates can generate excited triplet state and singlet oxygen efficiently via a photoinduced charge separation–charge recombination (CS-CR) mechanism, seve...

A novel characteristic of salicylate UV absorbers: suppression of diethylhexyl 2,6-naphthalate (Corapan TQ)-photosensitized singlet oxygen generation.

2-Ethylhexyl salicylate (EHS, octyl salicylate) and homomenthyl salicylate (HMS, homosalate) are UV-B absorbers used in cosmetic sunscreens. Diethylhexyl 2,6-naphthalate (DEHN, tradename Corapan TQ) used as a mildly effective photostabilizer for labile butylmethoxydibenzoylmethane, the most widely used UV-A absorber, is an efficient singlet oxygen photosensitizer with a high quantum yield of singlet oxygen generation ΦΔ = 0.44 in ethanol. The effects of EHS, HMS, l-ascorbic acid (AA, vitamin C), 3-O-ethyl-l-ascorbic acid (3-EtAA) and Trolox (TX, a water-soluble analogue of vitamin E) on DEHN-photosensitized singlet oxygen generation have been studied through measurements of time-resolved near-infrared phosphorescence in ethanol. These compounds suppress DEHN-photosensitized singlet oxygen generation. 40% of ΦΔ is decreased by adding 32 mmol dm-3 EHS or HMS. ΦΔ is decreased to a half by adding 3.0 mmol dm-3 TX. Fluorescence and transient absorption measurements suggest that the observed suppression is due to the quenching of the excited singlet state of DEHN by EHS, HMS, AA and 3-EtAA. These compounds do not quench the excited triplet state of DEHN. On the other hand, TX quenches both the excited singlet and triplet states of DEHN. It was shown that these UV-B absorbers have a novel characteristic as a suppressor of photosensitized singlet oxygen generation. Suppressing singlet oxygen generation is an important method for the prevention of skin damage. To the best of our knowledge, this is the first report on the suppression of photosensitized singlet oxygen generation by UV absorbing molecules.

"Three-Bullets" Loaded Mesoporous Silica Nanoparticles for Combined Photo/Chemotherapy.

This contribution reports the design, preparation, photophysical and photochemical characterization, as well as a preliminary biological evaluation of mesoporous silica nanoparticles (MSNs) covalently integrating a nitric oxide (NO) photodonor (NOPD) and a singlet oxygen (1O2) photosensitizer (PS) and encapsulating the anticancer doxorubicin (DOX) in a noncovalent fashion. These MSNs bind the NOPD mainly in their inner part and the PS in their outer part in order to judiciously exploit the different diffusion radius of the cytotoxic NO and 1O2. Furthermore this silica nanoconstruct has been devised in such a way to permit the selective excitation of the NOPD and the PS with light sources of different energy in the visible window. We demonstrate that the individual photochemical performances of the photoactive components of the MSNs are not mutually affected, and remain unaltered even in the presence of DOX. As a result, the complete nanoconstruct is able to deliver NO and 1O2 under blue and green light, respectively, and to release DOX under physiological conditions. Preliminary biological results performed using A375 cancer cells show a good tolerability of the functionalized MSNs in the dark and a potentiated activity of DOX upon irradiation, due to the effect of the NO photoreleased.

A Three‐Color Fluorescent Supramolecular Nanoassembly of Phototherapeutics Activable by Two‐Photon Excitation with Near‐Infrared Light

A supramolecular nanoassembly, of about 30 nm in diameter, that consists of a green-fluorescent, β-cyclodextrin-based, branched polymer co-encapsulating a red-emitting singlet oxygen (1 O2 ) photosensitizer and a nitric oxide (NO) photoreleaser, which comprises a blue fluorescent reporter, is here reported. The system exhibits "five-in-one" photofunctionalities. All components can be simultaneously excited in the phototherapeutic window with two-photons by using near-infrared light at 740 nm and despite their close proximity, behave as independent units. This allows for their in vitro visualization in carcinoma cancer cells, due to their distinct green, red, and blue fluorescence, and for the production of both cytotoxic 1 O2 and biofunctional NO.

Фотосенсибилизированный синглетный кислород и кислородные комплексы в возникновении и изменении пространственно-неоднородной люминесценции в растворах антрахинона

Основное содержание исследования составляет анализ процессов, приводящих к неоднородной по пространству и времени люминесценции (к так называемым люминесцирующим пространственновременным структурам), наблюдаемой в видимой области (lmax= 490 нм) при ультрафиолетовом (УФ) облучении антрахинона в насыщенных кислородом растворах и в полимерных матрицах. Экспериментально регистрируемая люминесценция приписывается фотопродукту: кетильному радикалу антрахинона, чья концентрация в ходе инициируемых УФ излучением фотохимических реакций периодически возрастает и убывает в различных и разрозненных точках реакционного пространства. В работе обоснована значимость реакции тушения триплетных состояний молекул антрахинона кислородом О2(3Σ-g ), обсуждена возможность генерации синглетного кислорода O2(1Δg) на больших расстояниях от реакционного центра вследствие переноса электронно-колебательного возбуждения на молекулу растворителя и подчеркнута существенная роль сенсибилизированного синглетного кислорода в перераспределении концентраций реагентов и фотопродуктов. Предложена модель возникновения и развития пространственно-неоднородной люминесценции растворов антрахинона, включающая фотосенсибилизированное образование синглетного кислорода и диффузию кислородных комплексов с молекулами растворителя. Главное достоинство предлагаемой модели, учитывающей возникновение и присутствие именно синглетного кислорода O2(1Δg), — возможность не только объяснить экспериментально наблюдаемые эффекты возникновения и развития пространственновременных структур, но и предсказать условия изменения, характер поведения начальной стадии их развития и конечный результат. Обсуждаемая в работе зависимость феномена от концентрации растворенного кислорода может найти применение в сенсорных приложениях.

Cover Feature: Improvement of the ON/OFF Switching Performance of a pH‐Activatable Porphyrin Derivative by the Introduction of Phosphorus(V) (ChemPhotoChem 3/2019)

The Cover Feature illustrates the ON/OFF switching of the photosensitization of singlet oxygen and the fluorescence of a pH-activatable photosensitizer. The developed system facilitates photosensitization under acidic conditions. Therefore, this system satisfies both the requirements of high photoactivity and low photoinduced side effects for application in the photodynamic therapy of cancer. More information can be found in the Article by H. Horiuchi et al. on page 138 in Issue 3, 2019 (DOI: 10.1002/cptc.201800248).

Crosswise Phthalocyanines with Collinear Functionalization: New Paradigmatic Derivatives for Efficient Singlet Oxygen Photosensitization.

We describe here the preparation of a series of trans-ABAB Zn(II) phthalocyanines (ZnPcs, which combine several interesting features. First, these compounds present high solubility and hindered aggregation, due to the functionalization of two facing isoindole constituents (B) of the ZnPc with bis(trifluoromethylphenyl) units. Second, the other two isoindoles (A) bear extra-annulated phthalimide units containing different substituents in the nitrogen positions, this feature results in a collinear arrangement of a variety of functional groups. Some of these collinearly functionalized ZnPcs are interesting building blocks for constructing either homo- or heteroarrays containing ZnPc units. Furthermore, the amphiphilic nature of some members of the series renders them interesting candidates for photosensitization of singlet oxygen. Photophysical studies on a model compound of the series have shown that these molecules are efficient singlet oxygen photosensitizers in both polar and apolar media, with 1 O2 quantum yields (φΔ ) as high as 0.74.

Tungsten Iodide Clusters as Singlet Oxygen Photosensitizers: Exploring the Domain of Resonant Energy Transfer at 1 eV.

The photophysics of selected tungsten iodide clusters was examined with respect to their role as a photosensitizer for the production of singlet oxygen, O2(a1Δg). We examined all-iodo octahedral clusters, [W6I8(I6)]2-, and ligand-substituted octahedral clusters, [W6I8(L6)]2-, in which the ligand, L, occupies the outer apical positions surrounding the cluster core. We also examined a square-pyramidal cluster, [W5I8(I5)]-, in which the tungsten core was presumably more accessible to diffusional encounter with ground state oxygen, O2(X3Σg-). For the compounds examined, we find pronounced cluster-dependent changes in the yield of photosensitized O2(a1Δg) production. In particular, although the iodine-encased octahedral cluster, [W6I8(I6)]2-, is an efficient O2(a1Δg) sensitizer, the pyramidal cluster, [W5I8(I5)]-, does not make O2(a1Δg) at all. The latter provides fundamental insight into the important case where the sensitizer triplet state is nearly degenerate with the O2(X3Σg-)-O2(a1Δg) transition energy at 1 eV. Our data indicate that even with near resonance, energy transfer to form O2(a1Δg) will not occur within the 3sensitizer-O2(X3Σg-) encounter pair if other more efficient channels for energy dissipation are available.