Synthesis of aza-BODIPY dyes bearing the naphthyl groups at 1,7-positions and application for singlet oxygen generation

Near-infrared absorbing aza-BODIPYs with the naphthyl groups at 1,7-positions were prepared for the first time. The singlet oxygen generation of aza-BODIPY with the naphthyl groups at 1,7-positions was more effective than that of the corresponding aza-BODIPY with the phenyl groups at 1,7-positions.     

Control of singlet oxygen generation photosensitized by meso-anthrylporphyrin through interaction with DNA

To control the activity of photosensitized singlet oxygen ((1)O(2)) generation, the electron donor-connecting porphyrin, 5-(9'-anthryl)-10,15,20-tris(p-pyridyl)porphyrin (AnTPyP), was designed and synthesized. AnTPyP became water-soluble by the protonation of the pyridyl moieties in the presence of 5 mM trifluoroacetic acid (pH 2.3). The photoexcited state of the porphyrin ring in an AnTPyP molecule was effectively deactivated by intramolecular electron transfer from the anthracene moiety within 0.04 ns in an aqueous solution. The deactivation was suppressed by the interaction with a DNA strand, resulting in the elongation of the lifetime of the porphyrin excited state and the enhancement of the fluorescence intensity. Furthermore, it was confirmed that the interaction enabled the photoexcited AnTPyP to generate (1)O(2). Selective (1)O(2) generation by forming a complex with DNA should be the initial step to realize the target selective photodynamic therapy.     

Two-photon photosensitized production of singlet oxygen.

Singlet molecular oxygen (a(1)Delta(g)) has been produced and optically detected upon two-photon nonlinear excitation of a sensitizer with a focused laser beam. The experiments were performed using toluene solutions with either a substituted difuranonaphthalene or a substituted distyryl benzene as the sensitizer. The data indicate that the two-photon absorption cross sections of the difuranonaphthalenes are comparatively large and depend significantly on the functional groups attached to the chromophore. The time-resolved 1270 nm phosphorescence signals used to characterize the production of singlet oxygen are limited in much the same way as signals from other two-photon spectroscopic studies (e.g., weak signals that can be masked by scattered radiation). Nevertheless, the two-photon singlet oxygen signals also reflect the unique advantages of this nonlinear optical technique (e.g., depth penetration in the sample afforded by irradiation in a spectral region void of the more dominant one-photon linear transitions and spatial resolution afforded by irradiation with a focused laser beam).     

DNA-programmed control of photosensitized singlet oxygen production

DNA sequence-controlled on-and-off switching of a singlet oxygen sensitizer has been developed and demonstrated. The singlet oxygen photosensitizer pyropheophorbide-a (P) was attached to a 15-mer nucleotide sequence. A molecule that could quench the sensitizer, the so-called "black hole quencher 3" (Q), was attached to a complementary nucleotide strand. Upon hybridization of the two conjugates, singlet oxygen production from P was completely shut down. Upon the addition of a third DNA sequence that can displace and release the P-DNA conjugate from the P-Q pair, up to 85% of the singlet oxygen production was recovered. This system is a model for a benign drug that becomes active only in the presence of a specific targeted nucleotide sequence.     

Two-photon photosensitized production of singlet oxygen in water

Singlet molecular oxygen (a(1)Delta(g)) has been produced and optically detected in time-resolved experiments upon nonlinear two-photon excitation of a photosensitizer dissolved in water. For a given sensitizer, specific functional groups that impart water solubility and that give rise to larger two-photon absorption cross sections are, in many cases, not conducive to the production of singlet oxygen in high yield. This issue involves the competing influence of intramolecular charge transfer that can be pronounced in aqueous systems; more charge transfer in the chromophore facilitates two-photon absorption but decreases the singlet oxygen yield. This phenomenon is examined in a series of porphyrins and vinyl benzenes.     

The microenvironment of DNA switches the activity of singlet oxygen generation photosensitized by berberine and palmatine

The effect of the interaction between DNA and the photosensitizer on photosensitized singlet oxygen (1O2) generation was investigated using DNA-binding alkaloids, berberine and palmatine. These photosensitizers were bound to DNA by electrostatic force. Near-infrared luminescence measurement demonstrated that the photoexcited alkaloids can generate 1O2 only when the photosensitizers are bound to DNA. A fluorescence decay study showed significant enhancement of the lifetime of their photoexcited state with the DNA binding. A calculation study suggested that the electrostatic interaction with DNA inhibits the quenching of the photoexcited state of these alkaloids via intramolecular electron transfer, leading to the prolongation of the lifetime of their excited state. This effect should enhance their intersystem crossing and the yield of energy transfer to molecular oxygen. The results show that the electrostatic interaction with DNA significantly affects the 1O2 generation activity of a photosensitizer. In addition, this interaction may be applied to the control and the design of photosensitizers for medical applications such as photodynamic therapy.     

Singlet oxygen generation by novel NIR BODIPY dyes

Five novel near-infrared BODIPY dyes were prepared for improved singlet oxygen generation using thiophene and bromine. Theoretical, optical, photostable, and singlet oxygen generation characteristics of these dyes were assessed. Predicted excitation energies by TDDFT calculations were in good agreement (ΔE ≈ 0.06 eV) with experimental data. All five dyes showed both excitation and emission in the NIR range. In particular, two dyes having sulfur and bromine atoms showed efficient singlet oxygen generation with high photostability.     

Photosensitized generation of singlet oxygen

This work gives an overview of what is currently known about the mechanisms of the photosensitized production of singlet oxygen. Quenching of pi pi* excited triplet states by O2 proceeds via internal conversion of excited encounter complexes and exciplexes of sensitizer and O2. Both deactivation channels lead with different efficiencies to singlet oxygen generation. The balance between the deactivation channels depends on the triplet-state energy and oxidation potential of the sensitizer, and on the solvent polarity. A model has been developed that reproduces rate constants and efficiencies of the competing processes quantitatively. Sensitization by excited singlet states is much more complex and hence only qualitative rules could be elaborated, despite serious efforts of many groups. However, the most important deactivation paths of fluorescence quenching by O2 are again directed by excess energies and charge-transfer interactions similar to triplet-state quenching by O2. Finally, two recent developments in photosensitization of singlet oxygen are reviewed: Two-photon sensitizers with particular application potential for photodynamic therapy and fluorescence imaging of biological samples and singlet oxygen sensitization by nanocrystalline porous silicon, a material with very different photophysics compared to molecular sensitizers.     

Direct 1270 nm irradiation as an alternative to photosensitized generation of singlet oxygen to induce cell death

This article is a highlight of the paper by Anquez et al. in this issue of Photochemistry and Photobiology and describes the potential benefits of direct excitation of molecular oxygen to produce singlet oxygen ((1)O(2)) rather than using a photosensitizer. Due to its simplicity, the direct excitation of molecular oxygen can potentially overcome problems associated with systemic administration of dyes, such as skin photosensitivity and the clearance of free sensitizer from the body. However, concerns associated with the technique include indiscriminate generation of extracellular and intracellular (1)O(2), the difficulty of controlling necrotic vs apoptotic cell death and the possible consequences of thermal effects.     

Two-photon photosensitized production of singlet oxygen: sensitizers with phenylene-ethynylene-based chromophores

[reaction: see text] Singlet molecular oxygen (a(1)Delta(g)) has been produced and optically monitored in time-resolved experiments upon nonlinear two-photon excitation of photosensitizers that contain triple bonds as an integral part of the chromophore. Both experiments and ab initio computations indicate that the photophysical properties of alkyne-containing sensitizers are similar to those in the alkene-containing analogues. Most importantly, however, in comparison to the analogue that contains double bonds, the sensitizer containing alkyne moieties is more stable against singlet-oxygen-mediated photooxygenation reactions. This increased stability can be advantageous, particularly with respect to two-photon singlet oxygen imaging experiments in which data are collected over comparatively long time periods.     

Photophysical behaviors of N-methylthioacridone triplet and efficiency of singlet oxygen generation from its quenching by oxygen

Kinetic and absorption-spectral behaviors of N-methylthioacridone triplet suggest its utility as a reference and a sensitizer under photoexcitation in the visible. The efficiency of singlet oxygen production as a result of triplet quenching by oxygen is essentially unity in polar and non-polar solvents.     

Single cell responses to spatially controlled photosensitized production of extracellular singlet oxygen

The response of individual HeLa cells to extracellularly produced singlet oxygen was examined. The spatial domain of singlet oxygen production was controlled using the combination of a membrane-impermeable Pd porphyrin-dendrimer, which served as a photosensitizer, and a focused laser, which served to localize the sensitized production of singlet oxygen. Cells in close proximity to the domain of singlet oxygen production showed morphological changes commonly associated with necrotic cell death. The elapsed postirradiation "waiting period" before necrosis became apparent depended on: (1) the distance between the cell membrane and the domain irradiated, (2) the incident laser fluence and, as such, the initial concentration of singlet oxygen produced and (3) the lifetime of singlet oxygen. The data imply that singlet oxygen plays a key role in this process of light-induced cell death. The approach of using extracellularly generated singlet oxygen to induce cell death can provide a solution to a problem that often limits mechanistic studies of intracellularly photosensitized cell death: it can be difficult to quantify the effective light dose, and hence singlet oxygen concentration, when using an intracellular photosensitizer.     

Tuning the singlet oxygen quantum yield of near-IR-absorbing porphyrazines

We report the quantum yields for singlet oxygen production by a series of porphyrazines (pz) of the form M[pz(An;B4-n)] (Scheme 1), where the peripheral substituent A is [S-R]2 with R = (CH2CH2O)3H, B is a fused alpha,alpha'-dialkoxybenzo group and M = 2H, Mg or Zn. These compounds show intense near-IR absorbance/emission (longest wavelength emission, approximately 830 nm). Their solubilities vary with R, whereas their optical properties do not. We show that singlet oxygen sensitization by these luminescent compounds can be "tuned" from essentially off to on by varying n and selection among M = 2H, Mg or Zn. The quantum yields vary ca 60-fold within the set of compounds studied, from phidelta = 0.007 for compound 3 to phidelta = approximately 0.4 for compound 11.     

A novel sensitized chemiluminescence: Infrared emissions from thiazine dyes sensitized by singlet oxygen

An unusual infrared chemiluminescence emission (8130Å) of methylene blue, and other thiazine dyes, sensitized by singlet molecular oxygen is reported. This chemiluminescence does not correspond to the ordinary fluorescence of the dye and cannot be explained by previously proposed mechanisms for singlet oxygen sensitized emissions of dyes. From energetic considerations singlet molecular oxygen in its ¹Σ_g⁺ state is postulated as the sensitizing agent for the thiazine dye chemiluminescences. Schemes in which ¹Σ_g⁺ oxygen transfers electronic excitation energy (a) to the lowest triplet state of the dye, (b) to a combined multiplicity state of the lowest triplet state of the dye, and triplet molecular oxygen, or (c) to a charge-transfer state between the dye and oxygen, are compared. The chemiluminescence of methylene blue in aqueous solution may be used as a luminescent probe for ¹Σ_g⁺ oxygen.     

Guanine-specific DNA oxidation photosensitized by the tetraphenylporphyrin phosphorus(V) complex via singlet oxygen generation and electron transfer

The photosensitized DNA damage caused by dihydroxoP(V)tetraphenylporphyrin (P(V)TPP), a cationic water-soluble porphyrin, was examined. The study of near-infrared emission measurements demonstrated the photosensitized singlet oxygen ((1)O(2)) generation by P(V)TPP (quantum yield: 0.28 in ethanol). The fluorescence quenching of P(V)TPP by DNA showed the electron transfer (ET) from nucleobases to photoexcited P(V)TPP. These results have shown that P(V)TPP has ability to damage DNA through dual mechanisms, (1)O(2) generation and ET. Under aerobic conditions, P(V)TPP photosensitized damage was more severe for single-stranded DNA compared to its double-stranded counterpart. Photoexcited P(V)TPP damaged every guanine residue in single-stranded DNA. HPLC measurements confirmed the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), an oxidized product of 2'-deoxyguanosine, and showed that the yield of 8-oxodGuo in single-stranded DNA is larger than that in double-stranded DNA. The guanine-specific DNA damage and the enhancement in single-stranded DNA suggest that the (1)O(2) generation mainly contributes to the mechanism of DNA photodamage by P(V)TPP. Absorption spectrum measurements suggested the interaction between P(V)TPP and DNA. This interaction is expected to enhance the (1)O(2)-mediated DNA damage since the lifetime of (1)O(2) is very short. On the other hand, for double-stranded DNA, photosensitized damage at consecutive guanines was much less pronounced. Because the consecutive guanines act as a hole trap, this DNA-damaging pattern suggests the partial involvement of photoinduced ET. However, DNA damage by ET was not a main mechanism, possibly due to the reverse ET. In conclusion, P(V)TPP induces guanine specific photooxidation mainly via (1)O(2) generation. The interaction with DNA and the energy level of the photoexcited porphyrin may be advantageous for (1)O(2)-mediated DNA damage rather than ET mechanism.     

Influence of bromine substitution pattern on the singlet oxygen generation efficiency of two-photon absorbing chromophores

A molecular engineering strategy based on rational variations of the bromine substitution pattern in two-photon absorbing singlet oxygen sensitizers allows studying the relations that exist between the positioning of an inter-system crossing promoter on the charge-transfer chromophore and its ability to generate singlet oxygen.     

Impact of photosensitized oxidation and singlet oxygen on degradation of stabilized polymers

Photooxidation, an important component of polymer weathering, involves excited polymer-inherent chromophores and photoactive additives and impurities. Quenching of excited species by ground state molecular oxygen, the common component of air, results in the formation of singlet state molecular oxygen ¹O₂. This active form of oxygen is a strong oxygenation agent attacking stabilized polymers. Resulting transformations of the polymer matrix and additives have a negative effect on the service life of the material. The formation of ¹O₂, its properties, and reactions and products arising from stabilizers are outlined.     

Synthesis and characterization of near-infrared absorbing benzannulated aza-BODIPY dyes

A series of novel aza‐diisoindolmethine dyes 9 with six different aryl and heteroaryl groups at the indole moiety have been synthesized by the addition of aryl Grignard compounds to phthalodinitrile and subsequent reaction with formamide. A plausible reaction mechanism, through a Leuckart–Wallach‐type reduction has been confirmed by means of DFT calculations of the related transition and intermediate states. The corresponding boron difluoride complexes ( 10) of 9 were prepared in a subsequent reaction step and the spectroscopic and electrochemical properties of 9 and 10 have been investigated both experimentally and theoretically. The aza‐diisoindolmethines 9 exhibit an absorption maximum in the range from 615 to 720 nm, whereas the complexes 10 show a bathochromically shifted absorption maximum between 681 and 793 nm. Measurements of 9 and 10 by cyclic voltammetry display fully reversible redox waves for the reduction and oxidation with higher potentials for 10 . From the measured redox potentials, the HOMO and LUMO energy levels were calculated for 9 and 10 . The frontier orbital energies, the energies of the absorption bands, as well as the orbitals involved in the absorption process were calculated with DFT and compared to the measured results of 9 and 10 . The absorption maximum can be related to an intense HOMO–LUMO transition and the more‐pronounced stabilization of the LUMO upon complexation is the origin of the bathochromic shift of the absorption. Additionally, single‐crystal structures for two species, 10 d and 10 f , are reported.