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

Tron

et al. 2015

Chemistry A European J

Singlet oxygen ((1)O2) is an important reactive oxygen species in biology that has deleterious effects. Proteins constitute the main target of (1)O2 in cells. Several organisms are able to mount a transcriptional defense against (1)O2. ChrR and MBS are two proteins with Zn(Cys)2(His)2 zinc finger sites that are involved in the regulation of the defense against (1)O2. In this article, we investigate the reactivity of Zn⋅CPF, a Zn(Cys)2(His)2 classical ββα zinc finger, with (1)O2. We show that Zn⋅CPF interacts with (1)O2 mainly by physical quenching using a combination of (1)O2 luminescence quenching and kinetic competition experiments. The chemical reaction, which accounts for 5% of the interaction, leads to oxidation of cysteines but not histidines. Primary photooxidation products, identified by HPLC and mass spectrometry, are sulfinate (75±5%) and disulfides (25±5%). The peptides that have a single cysteine thiolate oxidized into a sulfinate are still able to bind one equivalent Zn(2+) but with a dramatic reduction of the binding constant compared to Zn⋅CPF despite the preservation of the ββα fold, as shown by NMR and CD titrations. Finally, Zn⋅CPF is compared to Zn⋅LTC, a treble clef Zn(Cys)4 zinc finger, to gain further insight into the behavior of zinc fingers toward (1)O2.

Section: Methodsmentioning

confidence: 99%

Reactivity of a Zn(Cys)₂(His)₂ Zinc Finger with Singlet Oxygen: Oxidation Directed toward Cysteines but not Histidines

Tron

et al. 2015

Chemistry A European J

“…The quantum yield for 1 O 2 photosensitization is Φ ∆ = 0.3 ± 0.1 for most free-base compounds in organic solvents [71,99,163,165,166,208].…”

Section: Non-radiative Decay Processesmentioning

confidence: 99%

“…The rate constant for This value is close to Φ T , reflecting the high efficiency of the energy-transfer process. The production of 1 O 2 by porphycenes has been studied also in liposomes [63,208] and in cell suspensions [209]. Suitable metal complexation, e.g., with palladium(II), increases Φ ∆ as a result of a more efficient intersystem crossing brought about by the heavyatom effect.…”

Section: Non-radiative Decay Processesmentioning

confidence: 99%

Porphycenes: Facts and Prospects in Photodynamic Therapy of Cancer

Stockert¹,

Cañete²,

Juarranz³

et al. 2007

CMC

177

130

The photodynamic process induces cell damage and death by the combined effect of a photosensitizer (PS), visible light, and molecular oxygen, which generate singlet oxygen ((1)O(2)) and other reactive oxygen species that are responsible for cytotoxicity. The most important application of this process with increasing biomedical interest is the photodynamic therapy (PDT) of cancer. In addition to hematoporphyrin-based drugs, 2nd generation PSs with better photochemical properties are now studied using cell cultures, experimental tumors and clinical trials. Porphycene is a structural isomer of porphyrin and constitutes an interesting new class of PS. Porphycene derivatives show higher absorption than porphyrins in the red spectral region (lambda > 600 nm, epsilon > 50000 M-(1)cm(-1)) owing to the lower molecular symmetry. Photophysical and photobiological properties of porphycenes make them excellent candidates as PSs, showing fast uptake and diverse subcellular localizations (mainly membranous organelles). Several tetraalkylporphycenes and the tetraphenyl derivative (TPPo) induce photodamage and cell death in vitro. Photodynamic treatments of cultured tumor cells with TPPo and its palladium(II) complex induce cytoskeletal changes, mitotic blockage, and dose-dependent apoptotic or necrotic cell death. Some pharmacokinetic and phototherapeutic studies on experimental tumors after intravenous or topical application of lipophilic alkyl-substituted porphycene derivatives are known. Taking into account all these features, porphycene PSs should be very useful for PDT of cancer and other biomedical applications.

“…The timeresolved technique yields the time course of luminescence and reflects the solution of a coupled differential equation system. This describes 25,26 the population of the photosensitizer triplet state T 1 and the first excited state of oxygen ͑singlet oxygen, 1…”

Section: Resultsmentioning

confidence: 99%

“…The rise rate ␤ 1 and decay rate ␤ 2 of the luminescence of singlet oxygen was measured for different ͓O 2 ͔ ͑0 to 280 M͒ by flowing the solution prior to irradiation with nitrogen. 25 During the variation of oxygen and the variation of the concentration of TMPyP the sum of rate constants ͑k T 1 O 2 + k T 1 ⌬ ͒ = 1.8± 0.2 s −1 mM −1 , k T 1 = 0.007± 0.001 s −1 , and k ⌬ = 0.29± 0.02 s −1 were determined. Our value for TMPyP triplet state quenching by oxygen is in good agreement with literature ͑1.6 s −1 mM −1 in Ref.…”

Section: Without Albuminmentioning

confidence: 99%

Time dependence of singlet oxygen luminescence provides an indication of oxygen concentration during oxygen consumption

et al. 2007

Singlet oxygen plays a major role in photodynamic inactivation of tumor cells or bacteria. Its efficacy depends critically on the oxygen concentration [O(2)], which can decrease in case oxygen is consumed caused by oxidative reactions. When detecting singlet oxygen directly by its luminescence at 1270 nm, the course of the luminescence signal is critically affected by [O(2)]. Thus, it should be feasible to monitor oxygen consumption during photo-oxidative processes. Singlet oxygen was generated by exciting a photosensitizer (TMPyP) in aqueous solution (H(2)O or D(2)O) of albumin. Chromatography shows that most of the TMPyP molecules are unbound, and therefore singlet oxygen molecules can diffuse in the solution. A sensor device for oxygen concentration revealed a rapid decrease of [O(2)] (oxygen depletion) in the solution during irradiation. The extent of oxygen depletion in aqueous albumin solution depends on the radiant exposure and the solvent. When detecting the luminescence signal of singlet oxygen, the shape of the luminescence signal significantly changed with irradiation time. Thus, local oxygen consumption could be monitored during photodynamic action by evaluating the course of singlet oxygen luminescence.