Shangjie Xu

Active oxygen species (1O2, O2⋅−) generation in the system of TiO2 colloid sensitized by hypocrellin B

TiO2 semiconductor colloids have been successfully employed in environmental clean-up, antibacterial and bactericidal action under ultraviolet light due to its strong redox ability and high yield of active oxygen species (1O2, O2*-), *OOH) generation. Hypocrellin B, isolated from Hypocrella bambusae (B.et.Br) Sacc, a natural pigment with strong and broad absorption over the visible light region, was used in our work in an attempt to extend the photoresponse of TiO2 to visible light and maintain the high generation of active oxygen under visible light illumination. The formation of the HB-TiO2 chelate was characterized by UV-Vis and surface enhanced raman spectroscopy (SERS) and it was found that the chelate still had high efficiency of active oxygen generation. The possible generation mechanism was explored by Electron Paramagnetic Resonance (EPR) and time-resolved transient spectra techniques, showing that singlet oxygen (1O2) and superoxide radical anion (O2*-)) were produced via energy transfer and electron transfer, respectively. The application of HB-TiO2 chelate in environment protection and bacteria sterilization was implied.

Active oxygen generation and photo-oxygenation involving temporfin (m-THPC)

Abstract The active oxygen generating ability of m -THPC, including the formation of singlet oxygen and superoxide anion radical species, was studied via spin trapping ESR spectroscopy. The mechanisms and the products associated with the self-sensitized photo-oxygenation of m -THPC in different solvents were also characterised with the aid of quenching experiments in tandem with UV–visible and HPLC analyses.

Photosensitization of TiO2 colloid by hypocrellin B in ethanol

Abstract Hypocrellin B (HB), a natural pigment, when adsorbed on colloidal TiO 2 can participate in the sensitization process by injecting electrons from its excited singlet and triplet states into the conduction band of the semiconductor. Upon excitation in its absorption band, 80% of the fluorescence emission of HB could be quenched by colloidal TiO 2 . Lifetime measurements and time-resolved absorption spectra gave the rate constant for the electron injection process from the excited singlet and triplet states of HB into the conduction band of the semiconductor as 6×10 8 and 1.3×10 6 s −1 , respectively. Analysis of the electron paramagnetic resonance spectra confirmed the generation of the cation radical of HB.

A novel method for the preparation of amino-substituted hypocrellin B

A series of amino-substituted hypocrellins derived from hypocrellin B (HB) were synthesized by a novel mild method, in which the peri-hydroxylated perylenequinone structure of hypocrellin was preserved by the reaction of HB with an amine. The red absorption of the resulting products was significantly enhanced relative to the parent hypocrellins, which will significantly improve its photodynamic therapy effectiveness.

Investigation of photobleaching of hypocrellin B in non-polar organic solvent and in liposome suspension.

Hypocrellin B (HB) is a natural pigment with a promising application in the photodynamic therapy (PDT) for anticancer treatment. The photobleaching of HB in non-polar organic solvents and in liposomes in aqueous solution were investigated by the measurements of absorption spectra, quenching experiments and determination of photoproducts. Control experiments indicated that the sensitizer, oxygen and light were all essential for the photobleaching of HB, which suggested that it was mainly self-sensitized photooxidation. The illumination of HB with visible light in aerobic non-polar solvent generated singlet oxygen efficiently [Phi(1O(2))=0.76] which then attacked the sensitizer HB with formation of an endoperoxide product. The endoperoxide of HB was unstable at room temperature and underwent predominantly loss of singlet oxygen with regeneration of parent HB. The singlet oxygen released from the endoperoxide of HB was detected with chemical trapping experiments. When HB was embedded in EPC liposomes, no endoperoxide product and no singlet oxygen release from the photobleaching process of HB were detected. The quenching experiments indicated that the singlet oxygen mechanism (type II) played an important role in the non-polar solvent and the free radical mechanism (type I) was predominant in liposomal aqueous solution for the photobleaching of HB.

Butylamino-demethoxy-hypocrellins and photodynamic therapy decreases human cancer in vitro and in vivo

2-Butylamino-2-demethoxy-hypocrellin A (BAHA) and B (BAHB) are new photosensitizers synthesized by a mild reaction of hypocrellins and butylamine. In BAHA and BAHB, the peri-hydroxylated perylenequinone structure of the parent hypocrellins is preserved and the red absorption is enhanced distinctly. Electron paramagnetic resonance spin trapping measurements and 9,10-diphenylanthracene bleaching studies were used to investigate the photodynamic action of BAHA and BAHB in the presence of oxygen. Singlet oxygen (1O2) and superoxide anion radical (O2(*-)) produced by illuminating BAHA and BAHB in aerobic solution have been observed. Compared with hypocrellin A and B, BAHA and BAHB primarily remained able to generate 1O2 and enhanced distinctly the O2(*-)-generating abilities. The photodynamic action of BAHA and BAHB in the therapy of cancer was investigated in vitro and in vivo. Both in vitro and in vivo results revealed a significant decrease in cancer cell growth. Laser or dye alone had no effect, indicating that intratumor BAHA and laser therapy may prove useful in unresectable cancer.

EPR studies of the photodynamic properties of a novel potential photodynamic therapeutic agent: photogeneration of semiquinone radical anion and active oxygen species (O2˙−, OH˙, H2O2 and 1O2)

Cyclohexylamino-substituted hypocrellin B (CHAHB) has been synthesized with the aim of improving the red absorption and specific affinity for malignant tumors over those of the parent compound. Irradiation of a deoxygenated DMSO solution of CHAHB generates a strong electron paramagnetic resonance (EPR) signal, which is assigned to the semiquinone radical anion of CHAHB with the aid of a series of experimental results. In the presence of oxygen, superoxide radical anions (O2*-) are generated via electron transfer from CHAHB*-, the precursor, to ground-state molecular oxygen. Hydroxyl radicals were detected by spin-trapping EPR when an oxygen-saturated aqueous solution containing CHAHB and DMPO was irradiated. Singlet oxygen (1O2) is produced via energy transfer from triplet CHAHB to ground-state oxygen molecules, with a sharply decreased quantum yield, i.e. 0.11. Furthermore, cell survival studies reveal CHAHB exhibits much higher photodynamic activities than its parent hypocrellins. The strongly enhanced photodynamic activities and sharply decreased quantum yield of 1O2 generation suggest that the type I (free radical) mechanism may play a significant role in CHAHB-PDT, rather than the type II (singlet oxygen) mechanism found in photofrin-PDT.

Synthesis and characterization of three novel amphiphilic aminated hypocrellins as photodynamic therapeutic agents.

Abstract To improve the amphiphilicities and red absorption of the hypocrellins, three novel 2-amino-2-demethoxy-hypocrellins were synthesized by the mild reactions of hypocrellin B with 4-(2-amino-ethyl)morpholine, N,N-dimethylethylenediamine and 1-(2-amino-ethyl)piperazine, respectively. The structures of these derivatives were characterized with proton nuclear magnetic resonance, infrared and mass spectra (MS). The ultraviolet–visible absorption and fluorescence spectra of the derivatives were measured and the new amino-substituted hypocrellins showed strong absorption in the domain of the phototherapeutic window (600–900 nm). Their amphiphilicities evaluated via the partition coefficients between n-octanol and phosphate-buffered saline buffer improved remarkably. Electron paramagnetic resonance spin-trapping measurements were used to investigate the photodynamic action of the three compounds in the presence of oxygen. Singlet oxygen (1O2) and superoxide anion radical (O2•−) generated by illuminating the hypocrellin derivatives in aerobic solution were observed.

Novel phototherapeutic agents: Investigation and progress of hypocrellin derivatives

Hypocrellins, as a kind of novel phototherapeutic agents, have several advantages over the clinically used hematoporphyrin derivatives, including high-excited triplet state yield, high phototoxicity, low dark toxicity, and rapid metabolism. However, they exhibit little absorption in the photodynamic window (600–900 nm) and are not water soluble, which limits their application in photodynamic therapy. Sulfonated and metal-ioned hypocrellins have been designed and synthesized to improve their water solubility. Unfortunately, the water-soluble derivatives obtained exhibit lower photodynamic activity than the parent hypocrellins. Thiolated and aminated hypocrellins have also been designed and synthesized to enlarge their photoresponse. Among them, the aminated hypocrellins possess the highest photodynamic activity. We recently have further designed and synthesized some amphiphilic aminated hypocrellin derivatives. Thus, not only the photoresponse but also the water solubility is enhanced. The experimentsin vitro andin vivo on the derivatives are under way at present.

The Fluorescence Properties of Hypocrellin B and its Amino-substituted Derivative: Photoinduced Intramolecular Proton Transfer and Photoinduced Intramolecular Electron Transfer¶

Abstract We report on the emission spectra and emission quantum yields of a newly synthesized hypocrellin dye, 2-demethoxy-2,3-ethylenediamino hypocrellin B (EDAHB), and its parent HB in different solvents of varying polarity. Our results demonstrate that EDAHB is one of the few dyes that exhibit highly solvent polarity–dependent fluorescence in the useful region (680–730 nm). Therefore, it offers some applications in the biomedical field as a fluorescent probe molecule. The solvatochromic effect of EDAHB is proposed to be due to a distinct change in the dipole moment of the dye on excitation. A photoinduced intramolecular proton transfer and a photoinduced intramolecular electron transfer process are considered relevant for the fluorescence properties of HB and EDAHB, respectively.