Singlet Oxygen Quantum Yield ΦΔ Research Articles

Silicon phthalocyanines functionalized withaxial substituents targeting PSMA: synthesisand preliminary assessment of their potential for PhotoDynamic Therapy of prostate cancer.

Photodynamic therapy (PDT) is a clinical modality based on the irradiation of different diseases, mostly tumours, with light following the selective uptake of a photosensitiser by the pathological tissue. In this study, two new silicon(IV)phtalocyanines (SiPcs) functionalized at both axial positions with a PSMA inhibitors are reported as candidate photosensitizers for PDT of prostate cancer, namely compounds SiPc-PQ(PSMAi)2 and SiPc-OSi(PSMAi)2. These compounds share the same PSMA-binding motif, but differ in the linker that connects the inhibitor moiety to the Si(IV) atom: an alkoxy (Si-O-C) bond for SiPc-PQ(PSMAi)2, and a silyloxy (Si-O-Si) bond for SiPc-OSi(PSMAi)2. Both compounds were synthesized by a facile synthetic route and fully characterized by 2D NMR, mass spectrometry and absorption/fluorescence spectrophotometry. The PDT agents showed a suitable solubility in water, where they essentially exist in monomeric form. SiPc-PQ(PSMAi)2 showed a higher singlet oxygen quantum yield ΦΔ, higher fluorescence quantum yields ФF and better photostability than SiPc-OSi(PSMAi)2. Both compounds were efficiently taken up by PSMA(+) PC3-PIP cells, but not by PSMA(-) PC3-FLU cells. However, SiPc-PQ(PSMAi)2 showed a more specific photoinduced cytotoxicity in vitro, which is likely attributable to a better stability of its water solutions.

Charge Separation and Intersystem Crossing in Homo- and Hetero-Compact Naphthalimide Dimers.

Naphthalimide (NI) homo- and hetero-dimers adopting orthogonal geometry were prepared to study photo-induced symmetry-breaking charge transfer (SBCT) and charge recombination (CR)-induced intersystem crossing (ISC). The two moieties in the dimer are connected either at the 3-C or 4-C position of the NI unit. The photophysical properties of the dimers were studied with steady-state and transient absorption spectroscopic methods. Significant CT only occurs for the hetero-dimer, in which one NI unit has a 4-amino substituent and the other NI unit is without it. The CR-induced ISC is most efficient for this dimer (singlet oxygen quantum yield ΦΔ = 50.3%). For the homo-dimer, in which both NI units did not present amino substitution, SBCT was not observed. Based on the electrochemical studies, we propose that the absence of SBCT for the homo-dimer is attributed to its high oxidation potential and low reduction potential. Femtosecond transient absorption (fs TA) spectra show that there is no charge separation (CS) for the homo-dimer. Nanosecond transient absorption spectroscopy indicate the formation of a triplet state with electron delocalization for the homo dimer, with a lifetime of 72.0 μs, while for the hetero dimer a triplet state with an intrinsic lifetime of 206.4 μs is observed. CS (11.6 ps) and slow CR-induced ISC (>1.5 ns) were observed for the hetero-dimer. Time-resolved electron paramagnetic resonance spectra give the zero-field splitting parameters (|D| = 1894 MHz and |E| = 111 MHz) and electron spin polarization patterns (e, e, e, a, a, a) for the triplet state of the hetero-dimer, inferring that the triplet state of the hetero-dimer is confined on the amino-substituted NI moiety.

Thienyl/phenyl bay-substituted perylenebisimides: Intersystem crossing and application as heavy atom-free triplet photosensitizers

Different perylene-3,4:9,10-bis(dicarboximide) (abbreviated as perylenebisimides, or simply PBI) compounds (MT-PBI, DT-PBI, MP-PBI and DP-PBI) with thienyl and phenyl substituents at the bay position were prepared to study the effect of substitution on the photophysical properties, especially the intersystem crossing (ISC) efficacy. We found that the derivative with a monothienyl substituent (MT-PBI) shows efficient ISC (singlet oxygen quantum yield ΦΔ = 72%) and longer triplet state lifetime (τT = 64.4 μs) as compared to reference compounds (derivative with monophenyl substituent at bay position, MP-PBI, ΦΔ = 23% and τT = 48.5 μs). Theoretical computations reveal that the ISC efficiency is dependent on the magnitude of the spin orbit couplings (SOC) between the singlet and triplet excited states, and the SOC matrix element is up to 2 cm−1 for compound showing the highest ISC efficiency. Femtosecond transient absorption spectra show the ISC rate constant of 8 × 109 s−1 for MT-PBI, and no charge transfer exists. Photo-driven electron transfer was observed with the PBI derivatives in the presence of sacrificial electron donor triethanolamine (TEOA), and reversible formation of PBI radical anion (PBI−•) was observed, which shows absorption in the range of 600 nm–800 nm and 900 nm–1000 nm. Delayed fluorescence (P-type) in MT-PBI was also observed (τT = 31.0 μs). These finding are useful for the design of PBI-derived heavy atom-free compounds to be used as triplet photosensitizers.

Twisted Bodipy Derivative as a Heavy-Atom-Free Triplet Photosensitizer Showing Strong Absorption of Yellow Light, Intersystem Crossing, and a High-Energy Long-Lived Triplet State.

A Bodipy derivative with twisted π-conjugation system is demonstrated that shows efficient intersystem crossing (ISC) (singlet oxygen quantum yield ΦΔ = 55%) and a long-lived triplet state (τT = 197.5 μs) with high energy (ET1 = 1.44-1.53 eV). This is superior to the conventional heavy-atom-enhanced ISC in a reference Bodipy compound, which results in much shorter triplet state lifetime (3.3 μs) and lower triplet-state energy (1.2 eV).

Photophysical properties and singlet oxygen generation of meso-iodinated free-base corroles.

In order to study the effect of meso-iodination of free-base corroles on their photophysical character, we designed and synthesized a series of free-base corrole derivatives F10–OH (iodine-free), F10–OH–I (mono-iodo) and F10–OH–2I (di-iodo), with different substitution patterns at the meso-position as candidates for photodynamic therapy (PDT). We employed several optical spectroscopic techniques, including time-resolved spectroscopy from a femtosecond to microsecond and singlet oxygen luminescence to study the properties of excited singlet and triplet states, as well as the singlet oxygen quantum yields. The sub-picosecond internal conversion, ∼1 ps intramolecular vibrational energy redistribution, tens of ps vibrational cooling, are similar across the three corroles. The addition of one (F10–OH–I) and two iodine (F10–OH–2I) atoms to the remote aryl ring of triarylcorroles induces a 4.6-fold and 6.2-fold decrease in fluorescence quantum yields Φfl and a 2.2-fold and 4.9-fold increase in the time constant of intersystem crossing kISC. In addition, a slight increase in intersystem crossing quantum yields ΦT was also observed from F10–OH to F10–OH–2I. It means the intersystem crossing is improved by the iodination, from F10–OH to F10–OH–2I, because of the heavy atom effect. However, the sample F10–OH–I, instead of F10–OH–2I, shows the highest singlet oxygen quantum yield ΦΔ.

DiiodoBodipy-perylenebisimide dyad/triad: preparation and study of the intramolecular and intermolecular electron/energy transfer.

2,6-diiodoBodipy-perylenebisimide (PBI) dyad and triad were prepared, with the iodoBodipy moiety as the singlet/triplet energy donor and the PBI moiety as the singlet/triplet energy acceptor. IodoBodipy undergoes intersystem crossing (ISC), but PBI is devoid of ISC, and a competition of intramolecular resonance energy transfer (RET) with ISC of the diiodoBodipy moiety is established. The photophysical properties of the compounds were studied with steady-state and femtosecond/nanosecond transient absorption and emission spectroscopy. RET and photoinduced electron transfer (PET) were confirmed. The production of the triplet state is high for the iodinated dyad and the triad (singlet oxygen quantum yield ΦΔ = 80%). The Gibbs free energy changes of the electron transfer (ΔGCS) and the energy level of the charge transfer state (CTS) were analyzed. With nanosecond transient absorption spectroscopy, we confirmed that the triplet state is localized on the PBI moiety in the iodinated dyad and the triad. An exceptionally long lived triplet excited state was observed (τT = 150 μs) for PBI. With the uniodinated reference dyad and triad, we demonstrated that the triplet state localized on the PBI moiety in the iodinated dyad and triad is not produced by charge recombination. These information are useful for the design and study of the fundamental photochemistry of multichromophore organic triplet photosensitizers.

Improving photodynamic inactivation of bacteria in dentistry: highly effective and fast killing of oral key pathogens with novel tooth-colored type-II photosensitizers.

Increasing antibiotic resistances in microorganisms create serious problems in public health. This demands alternative approaches for killing pathogens to supplement standard treatment methods. Photodynamic inactivation of bacteria (PIB) uses light activated photosensitizers (PS) to generate reactive oxygen species immediately upon illumination, inducing lethal phototoxicity. Positively charged phenalen-1-one derivatives are a new generation of PS for light-mediated killing of pathogens with outstanding singlet oxygen quantum yield ΦΔ of >97%. Upon irradiation with a standard photopolymerizer light (bluephase C8, 1260 ± 50 mW/cm(2)) the PS showed high activity against the oral key pathogens Enterococcus faecalis, Actinomyces naeslundii, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans. At a concentration of 10 μM, a maximum efficacy of more than 6 log10 steps (≥ 99.9999%) of bacteria killing is reached in less than 1 min (light dose 50 J/cm(2)) after one single treatment. The pyridinium substituent as positively charged moiety is especially advantageous for antimicrobial action.

Photodynamic biofilm inactivation by SAPYR—An exclusive singlet oxygen photosensitizer

Prevention and control of biofilm-growing microorganisms are serious problems in public health due to increasing resistances of some pathogens against antimicrobial drugs and the potential of these microorganisms to cause severe infections in patients. Therefore, alternative approaches that are capable of killing pathogens are needed to supplement standard treatment modalities. One alternative is the photodynamic inactivation of bacteria (PIB). The lethal effect of PIB is based on the principle that visible light activates a photosensitizer, leading to the formation of reactive oxygen species, e.g., singlet oxygen, which induces phototoxicity immediately during illumination. SAPYR is a new generation of photosensitizers. Based on a 7-perinaphthenone structure, it shows a singlet oxygen quantum yield ΦΔ of 99% and is water soluble and photostable. Moreover, it contains a positive charge for good adherence to cell walls of pathogens. In this study, the PIB properties of SAPYR were investigated against monospecies and polyspecies biofilms formed in vitro by oral key pathogens. SAPYR showed a dual mechanism of action against biofilms: (I) it disrupts the structure of the biofilm even without illumination; (II) when irradiated, it inactivates bacteria in a polymicrobial biofilm after one single treatment with an efficacy of ≥99.99%. These results encourage further investigation on the potential of PIB using SAPYR for the treatment of localized infectious diseases.

Observation of the room temperature phosphorescence of Bodipy in visible light-harvesting Ru(ii) polyimine complexes and application as triplet photosensitizers for triplet–triplet-annihilation upconversion and photocatalytic oxidation

Two Ru(II) polyimine complexes containing a boron-dipyrromethene (Bodipy) chromophore were prepared. The two complexes are different in the linker which connects the Bodipy part and the Ru(II) coordination centre. The Bodipy core and the Ru(II) centre are in π-conjugation in Ru-1, whereas in Ru-2 the Bodipy part is linked in a non-conjugated way to the Ru(II) centre. Ru(bpy)3[PF6]2 (Ru-3) was used as a reference complex. Both Ru-1 and Ru-2 show strong absorption in the visible region (e = 65 200 M−1 cm−1 at 528 nm for Ru-1 and e = 76 700 M−1 cm−1 at 499 nm for Ru-2). The fluorescence of the Bodipy ligands was almost completely quenched in Ru-1 and Ru-2. Ru-1 shows room temperature phosphorescence of the Bodipy chromophore, as well as the residual fluorescence of the Bodipy ligand. Ru-2 shows only the residual fluorescence of the Bodipy ligand. A long-lived Bodipy-localized triplet excited state was observed for both Ru-1 and Ru-2 upon visible light excitation (τT is up to 279.7 μs, the longest T1 state lifetime observed for the Bodipy moiety in the transition metal complex). Application of the complexes in triplet–triplet-annihilation upconversion and singlet oxygen (1O2)-mediated photo-oxidation proved that Ru-1 is more efficient (e.g. singlet oxygen quantum yield ΦΔ = 0.93) as a triplet photosensitizer than Ru-2 (ΦΔ = 0.64). Therefore, direct connection of the π-core of the Bodipy chromophore to the coordination centre, i.e. by establishing π-conjugation between the visible light-harvesting chromophore and the metal coordination centre is essential to enhance the effective visible light-harvesting of the Ru(II) complexes.

Singlet oxygen generation by 9-acetoxy-2,7,12,17-tetrakis-(β-methoxyethyl)-porphycene (ATMPn) in solution

Despite the approval of Photofrin® in various countries, chemically pure sensitizers for photodynamic therapy (PDT) are still needed. Based on numerous experiments in vitro, singlet oxygen is considered to play the major role in PDT. Therefore, the generation of singlet oxygen by the promising, hydrophobic photosensitizer 9-acetoxy-2,7,12,17-tetrakis-(β-methoxyethyl)-porphycene (ATMPn) in deuterated ethanol (EtOD) has been investigated in detail by time-resolved near-infrared spectroscopy. Using a new, highly sensitive infrared photomultiplier the complete time dependence of singlet oxygen luminescence was measured at 1270 nm. The respective relaxation rates and rate constants of the involved ATMPn triplet T1 state and oxygen 1Δg state were determined, in particular at different oxygen concentrations. Therefore, the oxygen concentration dependence of the proportion PT of the ATMPn triplet T1 state population quenched by oxygen, which is proportional to the singlet oxygen quantum yield ΦΔ, could be calculated. The result shows that PT decreased significantly with decreasing oxygen concentration. The completely different oxygen concentrations in vitro and in vivo lead therefore to a different quantum yield of singlet oxygen generation in both situations. Thus, one has to be careful when transferring results from in vitro experiments to photodynamic therapy in vivo, in particular regarding the role of singlet oxygen (type-II reaction) as compared to the type-I reaction.

Singlet Oxygen Generation by 8-Methoxypsoralen in Deuterium Oxide: Relaxation Rate Constants and Dependence of the Generation Efficacy on the Oxygen Partial Pressure

The photoactivation of 8-methoxypsoralen (8-MOP) by ultraviolet light is widely used for the treatment of several skin diseases. The major mechanism is the intercalation of 8-MOP into nuclear DNA in the dark and subsequently the formation of monoadducts and potential cross links under UVA irradiation. In addition, the irradiation of 8-MOP leads to the generation of singlet oxygen by means of photodynamic action which has been shown to induce a critical oxidative damage of the DNA in vitro. To assess the role of singlet oxygen generated by photoactivated 8-MOP, its relaxation in solutions of deuterium oxide was studied in detail. Relaxation rates and rate constants of the involved 8-MOP triplet T1 state and oxygen 1Δg state were determined by analyzing the rise and decay rates of the luminescence of singlet oxygen at 1.27 μm. The efficacy of singlet oxygen generation is described by the singlet oxygen quantum yield ΦΔ, which depends on the efficacy of 8-MOP T1 state deactivation by oxygen, PT([O2]). PT([O2...