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. 2020 Oct 12;5(42):27702–27708. doi: 10.1021/acsomega.0c04303

Photooxidation Activity Control of Dimethylaminophenyl-tris-(N-methyl-4-pridinio)porphyrin by pH

Kazutaka Hirakawa §,†,*, Syunsuke Takai §, Hiroaki Horiuchi ∥, Shigetoshi Okazaki ‡
PMCID: PMC7594313  PMID: 33134734

Abstract

graphic file with name ao0c04303_0008.jpg

To control the activity of photodynamic agents by pH, an electron donor-connecting cationic porphyrin, meso-(N′,N′-dimethyl-4-aminophenyl)-tris(N-methyl-p-pyridinio)porphyrin (DMATMPyP), was designed and synthesized. The photoexcited state (singlet excited state) of DMATMPyP was deactivated through intramolecular electron transfer under a neutral condition. The pKa of the protonated DMATMPyP was 4.5, and the fluorescence intensity and singlet oxygen-generating activity increased under an acidic condition. Furthermore, the protonation of DMATMPyP enhanced the biomolecule photooxidative activity through electron extraction. Photodamage of human serum albumin (HSA) was observed under a neutral condition because a hydrophobic HSA environment can reverse the deactivation of photoexcited DMATMPyP. However, an HSA-damaging mechanism of DMATMPyP under a neutral condition was explained by singlet oxygen production. Therefore, it is indicated that the protein photodamaging activity of DMATMPyP goes into an OFF state under a neutral hypoxic condition. Under an acidic condition, the HSA photodamaging quantum yield by DMATMPyP through electron extraction could be preserved in the presence of a singlet oxygen quencher. Photooxidation of nicotinamide adenine dinucleotide by DMATMPyP was also enhanced under an acidic condition. This study demonstrated the concept of using pH to control photosensitizer activity via inhibition of the intramolecular electron transfer deactivation and enhancement of the oxidative activity through the electron extraction mechanism. Specifically, biomolecule oxidation through electron extraction may play an important role in photodynamic therapy to treat tumors under a hypoxic condition.

Introduction

Electron transfer is the key factor in controlling the photochemical process of photoexcited molecules.1−6 Fluorescence sensing,7−9 bioimaging,10−14 singlet oxygen (1O2) production,15−21 and photooxidative activities22 of photoexcited molecules can be controlled through intramolecular electron transfer. Changes in the redox potential of a molecule by its surroundings, for example, pH,9,18−22 metal ion concentration,7,8 and interaction with macromolecules, such as DNA,15−17 can inhibit the electron-transfer quenching, leading to an active (ON) state. One important application of the OFF → ON control is in the photomedicinal property of molecules. For example, cancer-selective photodynamic therapy (PDT) can be realized by controlling the activity of photosensitizing molecules (photosensitizers). PDT is a less-invasive treatment for cancer and other nonmalignant conditions.5,23−27 Administered photosensitizers are illuminated by nonthermal visible light, resulting in biomolecule damage through photochemical reactions. In general, 1O2 production through energy transfer from the excited photosensitizer to oxygen molecules is considered to be an important mechanism in biomolecule damage.28,29 Electron transfer from biomolecules to the photoexcited photosensitizers can be an alternate mechanism of PDT.30−32 It has been reported that the pH of cancer cells is slightly acidic because of the enhancement of glycolysis.33−35 As mentioned above, electron transfer can be controlled by pH. Furthermore, in general, a protonated cationic compound becomes a stronger electron acceptor than its nonprotonated form.36 Therefore, the pH-induced change in the intramolecular electron transfer can be applied to cancer-selective PDT.18−22 The aim of this study is to examine the concept of using pH to control the activity of a cationic water-soluble porphyrin photosensitizer. Tetrakis(N-methyl-p-pyridinio)porphyrin (TMPyP) has been studied as the model compound for PDT.17,29 Because the water-solubility of previously reported porphyrins was relatively low,18−20,22 the use of TMPyP-based porphyrin may be advantageous for the application. To control the photosensitizing activity of TMPyP, meso-(N′,N′-dimethyl-4-aminophenyl)-tris(N-methyl-p-pyridinio)porphyrin (DMATMPyP, Figure 1) was designed and synthesized. The dimethylaniline (DMA) moiety was used as a pH-dependent electron donor. The photochemical property and biomolecule-damaging activity of DMATMPyP were examined.

Figure 1.

Figure 1

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Molecular structure and the proposed relaxation schemes of DMATMPyP and the protonated form (H+-DMATMPyP).

Results

Energy Level of the Intramolecular Charge Transfer State

The structures of DMATMPyP and its protonated form (H+-DMATMPyP) were optimized using density functional theory (DFT) calculation at the ωB97X-D/6-31G* level (Supporting Information). Their orbital energies were also calculated. These calculations showed that the highest occupied molecular orbital (HOMO) of DMATMPyP is located on the DMA moiety (Supporting Information). Consequently, it is speculated that the photoexcited state of DMATMPyP can be deactivated via intramolecular electron transfer from the DMA moiety to the porphyrin ring, forming a charge-transfer (CT) state (Figure 1). In the case of H+-DMATMPyP, the HOMO is located on the porphyrin ring, suggesting that the electron transfer-mediated quenching can be suppressed under an acidic condition. In addition, the highest molecular orbital energy of the porphyrin ring of H+-DMATMPyP (−17.4 eV, in vacuum, calculated using the DFT method) became lower than that of DMATMPyP (−12.9 eV).

Gibbs Energy of the Intramolecular Electron Transfer

The Gibbs energy (ΔGiet) of the intramolecular electron transfer from the DMA moiety to the porphyrin ring was roughly calculated using the redox potentials and excitation energy of DMATMPyP (Supporting Information). The obtained value (ΔGiet = −0.73 eV) supports the possibility of quenching through intramolecular electron transfer.

pKa of the Protonated DMATMPyP

The UV–Vis absorption spectra of DMATMPyP shifted depending on pH (Figure 2A). This absorption spectral change of DMATMPyP by pH could be explained by the protonation of the DMA moiety and the central pyrrole nitrogen atoms.37 Analysis of the relationship between absorbance and pH (Figure 3) was performed using a method similar to that in previous reports (Supporting Information).22 The obtained pKa values were 4.5 and 2.1. These values could be explained by the fact that the pKa of H+-DMATMPyP is 4.5 and that of the central nitrogen atoms is 2.1. Indeed, a similar pKa value of the central nitrogen atoms has been reported in the case of a similar porphyrin.37

Figure 2.

Figure 2

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(A) Absorption and (B) fluorescence spectra of DMATMPyP. The sample solution contained 5 μM DMATMPyP in a 10 mM sodium phosphate buffer (indicated pH). The excitation wavelength was 550 nm.

Figure 3.

Figure 3

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Relationship between the photochemical parameters of DMATMPyP (absorbance at 440 nm and fluorescence quantum yield) and the pH of the solvent. The sample solution contained 5 μM DMATMPyP in a 10 mM sodium phosphate buffer (indicated pH). The excitation wavelength was 550 nm. The method of analysis is described in the Supporting Information.

pH-Dependent Fluorescence Change

The fluorescence intensity was also changed by pH, and a relationship similar to that with the absorbance change was observed (Figure 3). A relatively small fluorescence quantum yield (Φf) value (0.037 at pH 7.6 and pH 6.4) under neutral conditions suggests the quenching of the singlet excited (S1) state of the porphyrin ring through intramolecular electron transfer. The observed Φf value at pH 3.2 (0.12) was significantly larger than that under the neutral condition and suggests the inhibition of electron transfer-mediated quenching.

Triplet Excited-State Formation and 1O2 Production

Transient absorption measurements showed the typical peak at around 470 nm,38 which was assigned to the absorption spectrum of the triplet excited (T1) state (Supporting Information). Enhancement of the T1-state formation under an acidic condition was qualitatively demonstrated. 1O2 production photosensitized by DMATMPyP was confirmed by near-infrared emission measurement, as previously reported (Supporting Information).39 The calculated values of 1O2 production quantum yield (ΦΔ) are listed in Table 1. The analyzed time constant of 1O2 emission showed that the lifetimes of 1O2 were 3.8 μs (pH 7.6) and 3.9 μs (pH 3.2). These values were similar to the reported values for the 1O2 lifetime in an aqueous solution.17 Furthermore, these results showed that the lifetime of 1O2 in an aqueous solution is barely affected by pH in this experimental region (pH 7.6–3.2). Indeed, the previous reports demonstrated that 1O2 lifetime in deuterium oxide (72–78 μs)40 is independent of acid concentration (72–77 μs in the presence of 5 mM trifluoroacetic acid).36 The T1 lifetime was also estimated from these emissions using the equation in the literature41 (Supporting Information). The obtained values of T1-state lifetimes were 1.6 μs (pH 7.6) and 1.3 μs (pH 3.2). These values were almost the same as the decay time of the T1 transient absorption (about 1 μs, Supporting Information). The T1-state lifetime is mostly determined by the quenching by oxygen molecules and becomes about 1–2 μs in an aqueous solution.17,30

Table 1. Quantum Yields of Biomolecule Damage and 1O2 Production Photosensitized by DMATMPyPa.

pH ΦHSA(T) ΦHSA(ET) ΦHSA(Δ) ΦNADH(T) ΦNADH (ET) ΦNADH(Δ) ΦΔ
7.6 4.4 × 10–4 ∼0 4.4 × 10–4 0.03 0.023 0.007 0.18
3.2 1.6 × 10–4 1.4 × 10–4 0.2 × 10–4 0.18 0.14 0.044 0.36
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a

ΦHSA(T): total quantum yields of HSA damage; ΦHSA(ET): quantum yield of HSA damage through electron transfer; ΦHSA(Δ): quantum yield of HSA damage through 1O2 production; ΦNADH(T): total quantum yields of NADH decomposition; ΦNADH (ET): quantum yield of NADH decomposition through electron transfer; ΦNADH(Δ): quantum yield of NADH decomposition through 1O2 production.

Interaction between Human Serum Albumin and DMATMPyP

To investigate the protein photodamage by DMATMPyP using human serum albumin (HSA), their interaction was studied. The absorption spectra of DMATMPyP in the visible region were changed by the addition of HSA (Supporting Information). Since HSA has no absorption in the visible region, the absorption change can be explained by the binding interaction.30−32 Analysis of the absorbance change by the previously reported method30−32 showed that the binding constant (Kbc) under a neutral condition (3.3 × 106 M–1, pH 7.6) was larger than that under an acidic condition (2.1 × 105 M–1, pH 3.2). The distance between the binding DMATMPyP molecule and the tryptophan residue of HSA, which is located almost at the center of HSA, was estimated based on an analysis using the Förster resonance energy transfer (FRET) method based on the energy transfer theory42 (Supporting Information). The obtained values were 57 and 55 Å under pH 7.6 and 3.2, respectively.

Photosensitized Protein Oxidation by DMATMPyP

The photosensitized protein oxidation activity of DMATMPyP was examined by a fluorescence intensity of HSA, as previously reported.30−32 The abovementioned Kbc values showed that the binding ratios of DMATMPyP to HSA were 95% (pH 7.6) and 60% (pH 3.2) in this experimental condition (10 μM HSA and 5 μM DMATMPyP). The tryptophan residue of HSA can be an important indicator of protein oxidation. HSA has one tryptophan,43 which is easily oxidized through electron transfer and 1O2 generation, leading to the diminishment of its intrinsic fluorescence.30−32 We observed that HSA photooxidation was irradiation-dose dependent (Figure 4). The extent of photosensitized HSA oxidation caused by DMATMPyP increased under a neutral condition. The quantum yields of HSA photodamage through 1O2 generation and the electron transfer-mediated mechanism were examined in light of the scavenger effect of NaN3, a strong physical quencher of 1O2,44 as in previous reports.30−32 The photosensitized HSA damage increased linearly within 30 min. Therefore, the amount of HSA damage by DMATMPyP with NaN3 for 30 min of photoirradiation was compared with that without NaN3. The estimated quantum yields are listed in Table 1.

Figure 4.

Figure 4

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(A) Time profile of HSA damage photosensitized by DMATMPyP and (B) the effect of a 1O2 quencher. The sample solution containing 10 μM HSA and 5 μM DMATMPyP with or without 10 mM NaN3 in a 10 mM sodium phosphate buffer (indicated pH) was irradiated with an LED (585 nm, 2.0 mW cm–2). The effect of NaN3 was examined for 30 min photoirradiation. Data are presented as mean ± standard error (SE) (n = 3).

Photosensitized NADH Oxidation by DMATMPyP

Nicotinamide adenine dinucleotide (NADH) was used as the target biomolecule to examine the photosensitizing activity of DMATMPyP. NADH can be oxidized by 1O2 production and electron transfer reactions.22 Because NADH is a relatively small molecule and the binding interaction with DMATMPyP is considered to be negligibly small, an environmental effect such as the case of HSA does not occur. Therefore, relatively high concentration of NADH (100 μM) against DMATMPyP (5 μM) was used. The typical absorption spectrum of NADH, around 340 nm, was decreased by photoirradiation with DMATMPyP. The NADH photooxidation was increased under an acidic condition (Figure 5). Similar to the analysis of HSA damage, the NADH photooxidation by DMATMPyP with NaN3 for 5 min of photoirradiation was compared with that without NaN3. The estimated quantum yields of NADH oxidation photosensitized by DMATMPyP are listed in Table 1.

Figure 5.

Figure 5

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(A) Time profile of NADH oxidation photosensitized by DMATMPyP and (B) the effect of a 1O2 quencher. The sample solution containing 100 μM NADH and 5 μM DMATMPyP with or without 10 mM NaN3 in a 10 mM sodium phosphate buffer (indicated pH) was irradiated with an LED (585 nm, 2.0 mW cm–2). The effect of NaN3 was examined for 5 min photoirradiation. Data are presented as mean ± SE (n = 3).

Discussion

The photoexcited state (S1 state) of DMATMPyP was deactivated through intramolecular electron transfer from the DMA moiety, the electron-donating moiety, in an aqueous solution. DFT calculation and the observed redox potentials supported this intramolecular electron transfer. The pKa of the protonated DMA moiety of H+-DMATMPyP was 4.5, and the fluorescence intensity was recovered in an acidic solution. DFT calculation predicted that the intramolecular electron transfer in H+-DMATMPyP is suppressed because the highest occupied orbital energy of the DMA moiety becomes lower than that of the porphyrin ring. These results indicated that the relaxation process of the DMATMPyP S1 state could be controlled by pH through protonation of the electron-donating moiety, as proposed in Figure 1. The photosensitized 1O2-generating activity of DMATMPyP was increased under an acidic condition. Transient absorption spectrum measurements verified that T1-state formation is enhanced under an acidic condition (Supporting Information). Inhibition of the S1-state quenching leads to the increase in intersystem crossing efficiency to the T1 state and 1O2 generation.

The absorption spectral change showed that DMATMPyP bound to HSA. The tryptophan residue is located near the center of HSA,43 and HSA has pockets as drug-binding sites (Sudlow’s site I and site II).45 The FRET method suggests that the distance between DMATMPyP and the tryptophan residue is almost 55 Å. Since the size of HSA is almost 100 Å,43 this result suggests that DMATMPyP binds mostly to the surface of HSA pockets. The estimated binding constants between DMATMPyP and HSA under neutral (pH 7.6) and acidic (pH 3.2) conditions are 3.3 × 106 M–1 and 2.1 × 105 M–1, respectively. HSA that is positively charged by the amino acid protonation under an acidic condition should inhibit the interaction with H+-DMATMPyP.

Photoirradiation of DMATMPyP induced tryptophan residue damage. The estimated quantum yield of HSA damage at pH 7.6 was larger than that at pH 3.2. As mentioned above, a suppression of the interaction under an acidic condition may decrease the HSA damage by H+-DMATMPyP at pH 3.2. Furthermore, a hydrophobic environment of protein is not appropriate for the intramolecular electron transfer because the CT-state energy level depends on the surrounding dielectric constant and increases in a less-polar environment.46 The environment of HSA may lead to recovery of the photosensitizing activity of porphyrin. Therefore, the total HSA damage was decreased under an acidic condition. However, electron transfer-mediated HSA damage could be enhanced under an acidic condition. Analysis of the HSA-damaging quantum yield showed that the mechanism of HSA damage photosensitized by DMATMPyP at pH 7.6 is mainly explained by 1O2 generation. The protein damage through 1O2 production is suppressed under hypoxia in both cases of acidic and neutral conditions. However, the oxidative activity of DMATMPyP through the electron-transfer mechanism was enhanced under an acidic condition. DFT calculation showed that the molecular orbital energy level of the porphyrin ring becomes lower in the protonated state, H+-DMATMPyP (Supporting Information). Consequently, photosensitized HSA damage by DMATMPyP through electron transfer could be preserved at pH 3.2 in the presence of a 1O2 quencher. It is speculated that DMATMPyP can selectively oxidize proteins under an acidic hypoxic condition (Figure 6). NADH photooxidation was also induced by DMATMPyP. NADH is a relatively small biomolecule and does not form a binding complex with DMATMPyP. The results of NADH oxidation showed that the photooxidative activity of DMATMPyP can be increased under an acidic condition in a simple aqueous solution. Because NADH is easily oxidized, the observed quantum yield through the electron-transfer mechanism was not significantly increased under an acidic condition.

Figure 6.

Figure 6

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Diagram of the pH-controlled activity of the DMATMPyP photosensitizer and the relative energy levels of the highest occupied orbitals for the porphyrin moiety, DMA moiety, and targeting biomolecule.

In summary, the relaxation process of DMATMPyP can be controlled by pH through the protonation of the DMA moiety. Fluorescence intensity, T1-state formation, and the resulting ΦΔ are increased in the H+-DMATMPyP state. The total quantum yield of HSA photodamage was decreased under an acidic condition because the interaction between protonated HSA and H+-DMATMPyP is weaker than that under a neutral condition and a hydrophobic environment reverses the photodamaging activity of DMATMPyP. However, under a hypoxic condition, DMATMPyP can selectively photosensitize protein damage through the electron transfer-mediated mechanism under an acidic condition since 1O2-mediated biomolecule damage is not effective, whereas the electron transfer-mediated mechanism is enhanced by the protonation. Although the pKa 4.5 of H+-DMATMPyP is smaller than the physiological pH (around 7)35 and not an ideal value for clinical use, this study demonstrated the concept of activity control based on inhibition of the intramolecular electron-transfer deactivation and enhancement of the oxidative activity through protonation of the photosensitizer. Specifically, electron transfer-mediated biomolecule oxidation can become an important PDT mechanism to treat tumors under a hypoxic condition.

Experimental Section

Materials

DMATMPyP was obtained by the methylation of meso-(N,N-dimethyl-4-aminophenyl)-tris(p-pyridyl)porphyrin (DMATPyP). Synthesis of DMATPyP was according to the previously reported method.47 To obtain DMATMPyP, the methylation of DMATPyP was carried out according to the literature.48,49 Details about the synthesis and characterization of DMATMPyP are described in the Supporting Information. The spectroscopic-grade distilled water was purchased from Dojin Chemicals Co. (Kumamoto, Japan). Sodium phosphate buffer (pH 7.6) and NADH were from Nakalai Tesque Inc. (Kyoto, Japan). Dimethyl sulfoxide-d6 and sodium azide were from FUJIFILM Wako Pure Chemical Co. (Osaka, Japan). Methyl iodide and diethyl ether were from Kanto Chemical Co., Inc. (Tokyo, Japan). HSA was purchased from Sigma-Aldrich Co. LLC. (St. Louis, MO, USA). These reagents were used as received. A sodium phosphate buffer (pH 6.4) was prepared from disodium hydrogen phosphate dodecahydrate and sodium dihydrogen phosphate dihydrate (Nacalai Tesque, Inc., Kyoto, Japan). Sodium phosphate buffers (pH 4.4 and 3.2) were prepared from sodium dihydrogen phosphate dihydrate (Nacalai Tesque, Inc.) and 0.05 M phosphoric acid (Kanto Chemical, Co. Inc., Tokyo. Japan). An acidic solution (pH 2.0) was prepared from 0.1 M hydrochloric acid solution (FUJIFILM Wako Pure Chemical Co.) and distilled water (FUJIFILM Wako Pure Chemical Co.).

Measurements

The absorption spectra of DMATMPyP were measured with a UV–Vis spectrophotometer UV-1650PC (Shimadzu, Kyoto, Japan). The fluorescence spectra of samples were measured with an F-4500 fluorescence spectrophotometer (Hitachi, Tokyo, Japan). The Φf was measured with an absolute photo-luminescence quantum yield measurement system (C9920-02, Hamamatsu Photonics KK, Hamamatsu, Japan). The 1O2 formation photosensitized by DMATMPyP was directly measured by near-infrared luminescence around at 1270 nm from deactivated 1O2, which corresponds to the 1O2 (1Δg)-3O2(3Σg–) transition as previously reported.39 The ΦΔ was determined from the comparison of the 1O2 emission intensities by DMATMPyP solution and methylene blue (ΦΔ = 0.52 in water).50A cyclic voltammogram was measured with a potentiostat/galvanostat (HA-301, Hokuto Denko Co., Tokyo, Japan), a function generator (DF1906, NF Co., Yokohama, Japan), and a data logger (midi LOGGER, GL900-4, Graphtec Co., Yokohama, Japan) using a platinum working electrode (ALS Co., Ltd., Tokyo, Japan), a platinum counterelectrode (ALS Co., Ltd), and saturated calomel electrode (SCE, ALS Co., Ltd).

Calculations

The optimized structure and energy of DMATMPyP and H+-DMATMPyP were calculated by the DFT method at the ωB97X-D/6-31G* level utilizing the Spartan 18′ (Wavefunction Inc., CA, USA).

Acknowledgments

The authors wish to thank Dr. Hirohiko Watanabe and Dr. Kiyotada Hosokawa (Hamamatsu Photonics K.K.) for transient absorption measurement. The presented work was partially supported by Grants-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science (JSPS KAKENHI 17H03086) and Futaba Electronics Memorial Foundation (10407).

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c04303.

  • Synthesis of DMATPyP and DMATMPyP, DFT calculation, calculation of the driving force of electron transfer, analysis of the pKa values of DMATMPyP, transient absorption spectra of DMATMPyP, photosensitized singlet oxygen production by DMATMPyP, analysis of the interaction between DMATMPyP and HSA, and analysis of the binding position by the FRET method (PDF)

The authors declare no competing financial interest.

Supplementary Material

ao0c04303_si_001.pdf (1MB, pdf)

References

  1. Wasielewski M. R. Photoinduced Electron Transfer in Supramolecular Systems for Artificial Photosynthesis. Chem. Rev. 1992, 92, 435–461. 10.1021/cr00011a005. [DOI] [Google Scholar]
  2. Zhang R.; Wu Y.; Wang Z.; Xue W.; Fu H.; Yao J. Effects of Photoinduced Electron Transfer on the Rational Design of Molecular Fluorescence Switch. J. Phys. Chem. C 2009, 113, 2594–2602. 10.1021/jp809135j. [DOI] [Google Scholar]
  3. Dadashi-Silab S.; Doran S.; Yagci Y. Photoinduced Electron Transfer Reactions for Macromolecular Syntheses. Chem. Rev. 2016, 116, 10212–10275. 10.1021/acs.chemrev.5b00586. [DOI] [PubMed] [Google Scholar]
  4. Fujitsuka M.; Majima T. Reaction Dynamics of Excited Radical Ions Revealed by Femtosecond Laser Flash Photolysis. J. Photochem. Photobiol., C 2018, 35, 25–37. 10.1016/j.jphotochemrev.2017.12.003. [DOI] [Google Scholar]
  5. Roy I.; Bobbala S.; Young R. M.; Beldjoudi Y.; Nguyen M. T.; Cetin M. M.; Cooper J. A.; Allen S.; Anamimoghadam O.; Scott E. A.; Wasielewski M. R.; Stoddart J. F. A Supramolecular Approach for Modulated Photoprotection, Lysosomal Delivery, and Photodynamic Activity of a Photosensitizer. J. Am. Chem. Soc. 2019, 141, 12296–12304. 10.1021/jacs.9b03990. [DOI] [PubMed] [Google Scholar]
  6. Kim J.; Oh J.; Park S.; Zafra J. L.; DeFrancisco J. R.; Casanova D.; Lim M.; Tovar J. D.; Casado J.; Kim D. Two-electron Transfer Stabilized by Excited-state Aromatization. Nat. Commun. 2019, 10, 4983. 10.1038/s41467-019-12986-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. de Silva A. P.; Moody T. S.; Wright G. D. Fluorescent PET (Photoinduced Electron Transfer) Sensors as Potent Analytical Tools. Analyst 2009, 134, 2385–2393. 10.1039/b912527m. [DOI] [PubMed] [Google Scholar]
  8. Daly B.; Ling J.; de Silva A. P. Current Developments in Fluorescent PET (photoinduced electron transfer) Sensors and Switches. Chem. Soc. Rev. 2015, 44, 4203–4211. 10.1039/C4CS00334A. [DOI] [PubMed] [Google Scholar]
  9. Rosenberg M.; Junker A. K. R.; Sørensen T. J.; Laursen B. W. Fluorescence pH Probes Based on Photoinduced Electron Transfer Quenching of Long Fluorescence Lifetime Triangulenium Dyes. ChemPhotoChem 2019, 3, 233–242. 10.1002/cptc.201800266. [DOI] [Google Scholar]
  10. Urano Y.; Asanuma D.; Hama Y.; Koyama Y.; Barrett T.; Kamiya M.; Nagano T.; Watanabe T.; Hasegawa A.; Choyke P. L.; Kobayashi H. Selective Molecular Imaging of Vable Cancer Cells with pH-activatable Fluorescence Probes. Nat. Med. 2009, 15, 104–109. 10.1038/nm.1854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sakabe M.; Asanuma D.; Kamiya M.; Iwatate R. J.; Hanaoka K.; Terai T.; Nagano T.; Urano Y. Rational Design of Highly Sensitive Fluorescence Probes for Protease and Glycosidase Based on Precisely Controlled Spirocyclization. J. Am. Chem. Soc. 2013, 135, 409–414. 10.1021/ja309688m. [DOI] [PubMed] [Google Scholar]
  12. Piao W.; Hanaoka K.; Fujisawa T.; Takeuchi S.; Komatsu T.; Ueno T.; Terai T.; Tahara T.; Nagano T.; Urano Y. Development of an Azo-Based Photosensitizer Activated under Mild Hypoxia for Photodynamic Therapy. J. Am. Chem. Soc. 2017, 139, 13713–13719. 10.1021/jacs.7b05019. [DOI] [PubMed] [Google Scholar]
  13. Yoshihara T.; Hirakawa Y.; Hosaka M.; Nangaku M.; Tobita S. Oxygen Imaging of Living Cells and Tissues Using Luminescent Molecular Probes. J. Photochem. Photobiol., C 2017, 30, 71–95. 10.1016/j.jphotochemrev.2017.01.001. [DOI] [Google Scholar]
  14. Zhu H.; Hamachi I.. Fluorescence Imaging of Drug Target Proteins Using Chemical Probes. J. Pharm. Anal. in press, 2020, DOI: 10.1016/j.jpha.2020.05.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cló E.; Snyder J. W.; Ogilby P. R.; Gothelf K. V. Control and Selectivity of Photosensitized Singlet Oxygen Production: Challenges in Complex Biological Systems. ChemBioChem 2007, 8, 475–481. 10.1002/cbic.200600454. [DOI] [PubMed] [Google Scholar]
  16. Tørring T.; Toftegaard R.; Arnbjerg J.; Ogilby P. R.; Gothelf K. V. Reversible pH-regulated Control of Photosensitized Singlet Oxygen Production Using a DNA i-Motif. Angew. Chem. Int. Ed. Engl. 2010, 49, 7923–7925. 10.1002/anie.201003612. [DOI] [PubMed] [Google Scholar]
  17. Hirakawa K.; Nishimura Y.; Arai T.; Okazaki S. Singlet Oxygen Generating Activity of an Electron Donor Connecting Porphyrin Photosensitizer Can Be Controlled by DNA. J. Phys. Chem. B 2013, 117, 13490–13496. 10.1021/jp4072444. [DOI] [PubMed] [Google Scholar]
  18. Horiuchi H.; Kuribara R.; Hirabara A.; Okutsu T. pH-Response Optimization of Amino-Substituted Tetraphenylporphyrin Derivatives as pH-Activatable Photosensitizers. J. Phys. Chem. A 2016, 120, 5554–5561. 10.1021/acs.jpca.6b05019. [DOI] [PubMed] [Google Scholar]
  19. Horiuchi H.; Hirabara A.; Okutsu T. Importance of the Orthogonal Structure between Porphyrin and Aniline Moieties on the pH-Activatable Porphyrin Derivative for Photodynamic Therapy. J. Photochem. Photobiol., A 2018, 365, 60–66. 10.1016/j.jphotochem.2018.07.034. [DOI] [Google Scholar]
  20. Horiuchi H.; Isogai M.; Hirakawa K.; Okutsu T. Improvement of the ON/OFF Switching Performance of a pH-Activatable Porphyrin Derivative by the Introduction of Phosphorus(V). ChemPhotoChem 2019, 3, 138–144. 10.1002/cptc.201800248. [DOI] [Google Scholar]
  21. Radunz S.; Wedepohl S.; Röhr M.; Calderón M.; Tschiche H. R.; Resch-Genger U. pH-Activatable Singlet Oxygen-Generating Boron-dipyrromethenes (BODIPYs) for Photodynamic Therapy and Bioimaging. J. Med. Chem. 2020, 63, 1699–1708. 10.1021/acs.jmedchem.9b01873. [DOI] [PubMed] [Google Scholar]
  22. Hirakawa K.; Onishi Y.; Ouyang D.; Horiuchi H.; Okazaki S. pH-Dependent Photodynamic Activity of Bis(6-methyl-3-pyridylmethoxy)P(V)tetrakis(p-methoxyphenyl)porphyrin. Chem. Phys. Lett. 2020, 746, 137315. 10.1016/j.cplett.2020.137315. [DOI] [Google Scholar]
  23. Dolmans D. E. J. G. J.; Fukumura D.; Jain R. K. Photodynamic Therapy for Cancer. Nat. Rev. Cancer 2003, 3, 380–387. 10.1038/nrc1071. [DOI] [PubMed] [Google Scholar]
  24. Castano A. P.; Mroz P.; Hamblin M. R. Photodynamic Therapy and Anti-tumour Immunity. Nat. Rev. Cancer 2006, 6, 535–545. 10.1038/nrc1894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Galstyan A.; Maurya Y. K.; Zhylitskaya H.; Bae Y. J.; Wu Y.-L.; Wasielewski M. R.; Lis T.; Dobrindt U.; Stępień M. p-Extended Donor–Acceptor Porphyrins and Metalloporphyrins for Antimicrobial Photodynamic Inactivation. Chem. – Eur. J. 2020, 26, 8262–8266. 10.1002/chem.201905372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ghorbani J.; Rahban D.; Aghamiri S.; Teymouri A.; Bahador A. Photosensitizers in Antibacterial Photodynamic Therapy: An Overview. Laser Ther. 2018, 27, 293–302. 10.5978/islsm.27_18-RA-01. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Cecatto R. B.; de Magalhães L. S.; Rodrigues M. F. S. D.; Pavani C.; Lino-dos-Santos-Franco A.; Gomes M. T.; Silva D. F. T. Methylene Blue Mediated Antimicrobial Photodynamic Therapy in Clinical Human Studies: The State of the Art. Photodiagn. Photodyn. Ther. 2020, 31, 101828. 10.1016/j.pdpdt.2020.101828. [DOI] [PubMed] [Google Scholar]
  28. DeRosa M. C.; Crutchley R. J. Photosensitized Singlet Oxygen And Its Applications. Coord. Chem. Rev. 2002, 233-234, 351–371. 10.1016/S0010-8545(02)00034-6. [DOI] [Google Scholar]
  29. Lang K.; Mosinger J.; Wagnerová D. M. Photophysical Properties of Porphyrinoid Sensitizers Non-covalently Bound to Host Molecules; Models for Photodynamic Therapy. Coord. Chem. Rev. 2004, 248, 321–350. 10.1016/j.ccr.2004.02.004. [DOI] [Google Scholar]
  30. Hirakawa K.; Umemoto H.; Kikuchi R.; Yamaguchi H.; Nishimura Y.; Arai T.; Okazaki S.; Segawa H. Determination of Singlet Oxygen and Electron Transfer Mediated Mechanisms of Photosensitized Protein Damage by Phosphorus(V)porphyrins. Chem. Res. Toxicol. 2015, 28, 262–267. 10.1021/tx500492w. [DOI] [PubMed] [Google Scholar]
  31. Hirakawa K.; Ouyang D.; Ibuki Y.; Hirohara S.; Okazaki S.; Kono E.; Kanayama N.; Nakazaki J.; Segawa H. Photosensitized Protein-damaging Activity, Cytotoxicity, and Antitumor Effects of P(V)porphyrins Using Long-Wavelength Visible-light through Electron Transfer. Chem. Res. Toxicol. 2018, 31, 371–379. 10.1021/acs.chemrestox.8b00059. [DOI] [PubMed] [Google Scholar]
  32. Hirakawa K.; Suzuki A.; Ouyang D.; Okazaki S.; Ibuki Y.; Nakazaki J.; Segawa H. Controlled Photodynamic Action of Axial Fluorinated DiethoxyP(V)tetrakis(p-methoxyphenyl)porphyrin through Self-Aggregation. Chem. Res. Toxicol. 2019, 32, 1638–1645. 10.1021/acs.chemrestox.9b00172. [DOI] [PubMed] [Google Scholar]
  33. Casey J. R.; Grinstein S.; Orlowski J. Sensors and Regulators of Intracellular pH. Nat. Rev. Mol. Cell Biol. 2010, 11, 50–61. 10.1038/nrm2820. [DOI] [PubMed] [Google Scholar]
  34. Webb B. A.; Chimenti M.; Jacobson M. P.; Barber D. L. Dysregulated pH: a Aerfect Storm for Cancer Progression. Nat. Rev. Cancer 2011, 11, 671–677. 10.1038/nrc3110. [DOI] [PubMed] [Google Scholar]
  35. Persi E.; Duran-Frigola M.; Damaghi M.; Roush W. R.; Aloy P.; Cleveland J. L.; Gillies R. J.; Ruppin E. Systems Analysis of Intracellular pH Vulnerabilities for Cancer Therapy. Nat. Commun. 2018, 9, 2997. 10.1038/s41467-018-05261-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Hirakawa K.; Hirano T.; Nishimura Y.; Arai T.; Nosaka Y. Control of Singlet Oxygen Generation Photosensitized by meso-Anthrylporphyrin through Interaction with DNA. Photochem. Photobiol. 2011, 87, 833–839. 10.1111/j.1751-1097.2011.00929.x. [DOI] [PubMed] [Google Scholar]
  37. Fujimura T.; Aoyama Y.-H.; Sasai R. Unique Protonation Behavior of Cationic Free-base Porphyrins in the Interlayer Space of Transparent Solid Films Comprising Layered A-zirconium Phosphate. Tetrahedron Lett. 2019, 60, 150912. 10.1016/j.tetlet.2019.07.003. [DOI] [Google Scholar]
  38. Hirakawa K.; Hosokawa Y.; Nishimura Y.; Okazaki S. Relaxation Process of S2 Excited Zinc Porphyrin through Interaction with a Directly Connected Phenanthryl Group. Chem. Phys. Lett. 2019, 732, 136652. 10.1016/j.cplett.2019.136652. [DOI] [Google Scholar]
  39. Hirakawa K.; Taguchi M.; Okazaki S. Relaxation Process of Photoexcited meso-Naphthylporphyrins while Interacting with DNA and Singlet Oxygen Generation. J. Phys. Chem. B 2015, 119, 13071–13078. 10.1021/acs.jpcb.5b08025. [DOI] [PubMed] [Google Scholar]
  40. Hirakawa K.; Hirano T.; Nishimura Y.; Arai T.; Nosaka Y. Dynamics of Singlet Oxygen Generation by DNA-Binding Photosensitizers. J. Phys. Chem. B 2012, 116, 3037–3044. 10.1021/jp300142e. [DOI] [PubMed] [Google Scholar]
  41. Krasnovsky A. A. Jr. Luminescence and Photochemical Studies of Singlet Oxygen Photonics. J. Photochem. Photobiol., A 2008, 196, 210–218. 10.1016/j.jphotochem.2007.12.015. [DOI] [Google Scholar]
  42. Förster T. Zwischenmolekulare Energiewanderung und Fluoreszenz. Ann. Phys. 1948, 437, 55–75. 10.1002/andp.19484370105. [DOI] [Google Scholar]
  43. He X. M.; Carter D. C. Atomic Structure and Chemistry of Human Serum Albumin. Nature 1992, 358, 209–215. 10.1038/358209a0. [DOI] [PubMed] [Google Scholar]
  44. Li M. Y.; Cline C. S.; Koker E. B.; Carmichael H. H.; Chignell C. F.; Bilski P. Quenching of Singlet Molecular Oxygen (1O2) by Azide Anion in Solvent Mixtures. Photochem. Photobiol. 2001, 74, 760–764. . [DOI] [PubMed] [Google Scholar]
  45. Sudlow G.; Birkett D. J.; Wade D. N. The Characterization of Two Specific Drug Binding Sites on Human Serum Albumin. Mol. Pharmacol. 1975, 11, 824–832. [PubMed] [Google Scholar]
  46. Weller A. Photoinduced Electron Transfer in Solution: Exciplex and Radical Ion Pair Formation Free Enthalpies and their Solvent Dependence. Z. Phys. Chem. Neue Folge 1982, 133, 93–98. 10.1524/zpch.1982.133.1.093. [DOI] [Google Scholar]
  47. Khan T. A.; Hriljac J. A. Hydrothermal Synthesis of Microporous Materials with the Direct Incorporation odf Porphyrin Molecules. Inorg. Chim. Acta 1999, 294, 179–182. 10.1016/S0020-1693(99)00247-9. [DOI] [Google Scholar]
  48. Hambright P.; Fleischer E. B. The Acid-Base Equilibria, Kinetics of Copper Ion Incorporation, and Acid-Catalyzed Zinc Ion Displacement from the Water-Soluble Porphyrin α,β,γ,δ-Tetra(4-N-methylpyridyl)porphyrin. Inorg. Chem. 1970, 9, 1757–1761. 10.1021/ic50089a030. [DOI] [Google Scholar]
  49. Ishikawa Y.; Yamashita A.; Uno T. Efficient Photocleavage of DNA by Cationic Porphyrin-Acridine Hybrids with the Effective Length of Diamino Alkyl Linkage. Chem. Pharm. Bull. 2001, 49, 287–293. 10.1248/cpb.49.287. [DOI] [PubMed] [Google Scholar]
  50. Usui Y.; Kamogawa K. A Standard System to Determine the Quantum Yield of Singlet Oxygen Formation in Aqueous Solution. Photochem. Photobiol. 1974, 19, 245–247. 10.1111/j.1751-1097.1974.tb06506.x. [DOI] [Google Scholar]

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