Jing-Yi An

Studies of the sulfonation of hypocrellin A and the photodynamic actions of the product

Abstract Hypocrellin A (HA), a perylenoquinone derivative, is an efficient phototherapeutic agent. The reaction of HA with Na2SO3 in alkaline solution under reflux led to the formation of the sodium salt of 14-dehydroxy-15-deacetyl-hypocrellin A-13-sulfonate (13-SO3Na-DDHA). ESR studies in combination with chemical methods showed that 13-SO3Na-DDHA was an active photosensitizer. An ESR spectrum, assigned to the semiquinone radical anion of 13-SO3Na-DDHA was generated by illumination of a DMF buffer (1:1 by volume) solution of 13-SO3Na-DDHA in the presence of a series of reductive biomaterials. Using 13-SO3Na-DDHA as photosensitizer and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap, the ESR spectra of DMPO/SO3− radical adduct, ascorbyl radical and DMPO/O2·− radical adduct were obtained. Singlet oxygen formed from 13-SO3Na-DDHA photosensitization was detected by means of the 13-SO3Na-DDHA photosensitized oxidation of anthracene and ESR spectroscopy. It was therefore concluded that the photodynamic actions of 13-SO3Na-DDHA proceeded via both Type 1 and Type 2 reactions.

Studies on the chelation of hypocrellin a with aluminium ion and the photodynamic action of the resulting complex

Hypocrellin A (HA), a perylenoquinone derivative, is an efficient phototherapeutic agent. The chelation of HA with aluminium ion (Al3+) results in the formation of a 1:1 complex (Al(3+)-HA). The probable structure for this complex has been proposed. Compared with HA, this complex has a much higher solubility in water. In addition, Al(3+)-HA preserves the 1O2-generating function of HA as demonstrated by diphenylanthracene photo-bleaching experiments. In irradiated oxygen-saturated solutions of Al(3+)-HA superoxide radical anion and hydroxyl radical are formed as verified using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the electron spin resonance (ESR) spin trapping agent. The production of superoxide radical anion is enhanced significantly in the presence of electron donors such as 1-benzyl-1,4-dihydronicotinamide (BNAH). These results suggest that the photodynamic action of Al(3+)-HA proceeds via both type 1 and type 2 reactions.

Photoreactions of hypocrellin B with thiol compounds

Abstract The photoreactions of hypocrellin B (HB) with thiol compounds (RSH) in ethanol buffer solutions have been investigated by electron spin resonance (ESR), α-phenyl-N-tert-butyl nitrone (PBN) spin trapping and quenching experiments. The mechanism of photothiylation of HB is proposed to involve a nucleophilic anion (RS−) addition of Michael type at the 5 or/and 8 positions followed by oxidation. The effects of oxygen and pH value have been studied. The photoreaction and thermal reaction have been compared.

Spectroscopic study on the photoreduction of hypocrellin A : generation of semiquinone radical anion and hydroquinone

Abstract Hypocrellin A (HA) is an efficient phototherapeutic agent. Illumination of HA in dimethylsulphoxide (DMSO) or DMSO-buffer (1:1 by volume, pH > 6.7) generated a strong electron paramagnetic resonance (EPR) signal. This EPR signal was intensified in the presence of reductants. The EPR spectrum obtained was assigned to the semiquinone radical anion of HA (HA .− ) based on a series of experimental results. Decay of HA .− , attributed to a radical-radical reaction, follows second-order kinetics. In acidic DMSO-buffer (1:1 by volume) solution, no EPR signal of HA .− was detected in the absence or presence of reductant. This was explained by a fast disproportionation of radicals, facilitated by protonation of radicals. The spectrophotometric measurements indicated that on illumination HA was directly reduced to its two-electron reduction product, i.e. hydroquinone, in acidic solution. The absorption maximum of the hydroquinone of HA which is at 496 nm at pH 5.8 shifts bathochromically with increase in pH of the medium. In DMSO or DMSO-buffer (1:1 by volume, pH > 6.7) solutions the semiquinone radical anion of HA was also observed spectrophotometrically. The absorption maximum of HA .− is at around 628 nm. Strong intramolecular hydrogen bonding was considered to exist in the chromophore of HA .− .

Photodynamic action of hypocrellin dyes: structure–activity relationships

Abstract Hypocrellin and its derivatives were compared for their photodynamic effects on human oral cavity epithelial carcinoma KB cell line. The amphiphilicity as well as the singlet oxygen generating quantum yield of the hypocrellin dyes affected their photodynamic activity. The most hydrophilic dyes exhibited the lowest phototoxic activity, whereas the hydrophobic and amphiphilic dyes with higher singlet oxygen-generating quantum yield, exhibited high photodynamic activity. Cysteamine mono- and di-substituted hypocrellin B and cysteine mono-substituted hypocrellin B, demonstrating strong red absorption in the domain of phototherapeutic window (600–900 nm), proper hydrophobic and amphiphilic properties and high photocytotoxicity to KB cells, might prove to be potential phototherapeutic agents.

pH Effect on the spectroscopic behavior and photoinduced generation of semiquinone anion radical of hypocrellin B

Abstract The spectroscopic behavior and photoinduced generation of the semiquinone anion radical (HB ·− ) of hypocrellin B (HB), a naturally occurred pigment, have been investigated in ethanol-buffer (1:1 by volume) in a wide range of pH from −0.6 to 14. The absorption and emission properties of HB are strongly affected by pH. Protonation and deprotonation induce a hypsochromic and a bathochromic shift of the spectra, respectively, and a decrease in the quantum yield of fluorescence. The protonation and deprotonation pKa values of HB in the ground and excited singlet states have been determined by means of spectrophotometric and spectrofluorometric titrations and Forster Cycle calculation. The generation of HB ·− is influenced strongly by pH; HB ·− could not be detected either by electron paramagnetic resonance (EPR) or by spectrophotometric measurements in anaerobic acidic or strong alkaline media, and is stable in anaerobic neutral and weak alkaline environment. ©

STUDIES OF THE TRIPLET STATE PROPERTIES OF HYPOCRELLIN A BY NANOSECOND FLASH PHOTOLYSIS

Abstract Hypocrellin A (HA) is an efficient phototherapeutic agent. Its triplet properties have been investigated in cyclohexane using the nanosecond flash photolysis technique. The triplet—triplet (T—T) absorption spectrum of HA gives three bands with absorption maxima at around 520, 555 and 600 nm. The triplet energy level for HA has been estimated to be about 42.5 kcal mol −1 by the energy transfer method. The extinction coefficients for the T—T absorption of HA have been determined by the ground state depletion method. The triplet quantum yield of HA is 0.78±0.04 (by reference to benzophenone).

Reactivity of semiquinone radical anions of hydroxyperylenequinone with oxygen

Abstract Hyprocrellin B (HB) could be regarded as a 4,9-perylenequinone derivative bearing two hydroxy group at the 3- and 10- two carbonyl groups. The product of demethylation of the 11-methoxy of HB, HB(11-OH), bears three hydroxy groups at the 3-, 10-positions peri to positions. Illumination of the HB (11-OH) in the presence of an electron donor led to accumulation of the semiquinone radical anion HB − (11-OH). The ESR hyperfine structure was recorded and the UV-visible spectum was investigated. HB − (11-OH) reacted with oxygen with generation of the conjugated mono base HB(11-O − ) and hydrogen peroxide. The effect of the position of the hydroxy groups on the reactivity of the semiquinone radical anion with oxygen was investigated by redox potential, acid dissociation constant and NMR measurements. It was indicated that the acidity of the 11-hydroxy group in HB (11-OH) was stronger than that of the groups at 3- and 10-positions. The reaction of HB − (11-OH) with oxygen yields at first the original quinone HB(11-OH) and O 2 − , and then HB (11-OH) transfers the phenolic hydroxy proton at the 11-position to O 2 to yield the conjugated base HB (11-O − ) and HO 2 which disproportionates rapidly to H 2 O 2 and O 2 .

SYNTHESIS AND ESR INVESTIGATION OF HYPOCRELLIN GLYCOSIDE

Abstract A glycoside derived from hypocrellin B was designed and synthesized using an improved Konigs-Knorr reaction. The water-solubility and red absorption of the resulting product was enhanced significantly over hypocrellin B. Electron spin resonance (ESR) measurements indicated that this glycoside remained photodynamically active in terms of Type I and Type 11 mechanisms.

Glycoconjugated hypocrellin: synthesis of [(β-d-glucosyl)ethylthiyl]hypocrellins and photosensitized generation of singlet oxygen

In order to improve the water solubility and specific affinity for malignant tumors of hypocrellin, glycoconjugated hypocrellins have been synthesized using an improved Königs-Knörr reaction from mercaptoethanol substituted hypocrellin B and 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide precursors. Deprotection of glucose moieties allows the production of derivatives which had improved solubility in neutral aqueous solution and covered a range of amphiphilic character. The structures of these new protected and unprotected compounds were characterized by UV-Vis, IR, 1H-NMR and MS data. The present strategy should prove applicable to the synthesis of other glycoconjugated perylenequinone compounds. In addition, the quantum yield of singlet oxygen generation photosensitized by these glycoconjugated hypocrellins has been determined.