Pyridone-containing phenalenone-based photosensitizer working both under light and in the dark for photodynamic therapy.

Photosensitizer attracts great attentions and has potential applications in cancer treatment. We developed here a novel pyridone-containing phenalenone-based (PPN-PYR) photosensitizer with excellent singlet oxygen generating ability. Upon light irradiation, PPN-PYR can produce singlet oxygen and transform to its endoperoxide form which in turn release singlet oxygen via thermal cycloreversion at dark. The ability of PPN-PYR to generate reactive oxygen species (ROS) in cell culture and induce corresponding apoptosis both at dark and under light was demonstrated. The efficient PDT performance of PPN-PYR was further verified on cancer cell in vitro. Our study indicate that PPN-PYR can alleviate tumor hypoxia problem and enhance the availability of intermittent photodynamic therapy.

Photochemical fate and photocatalysis of 3,5,6-trichloro-2-pyridinol, degradation product of chlorpyrifos.

In this study we have focused on 3,5,6-trichloro-2-pyridinol (TCP), degradation product of chlorpyrifos. Photolysis experiments were conducted in order to elucidate its degradation mechanism. Identification of products was performed using the LC-MS technique. To evaluate the mineralization efficiency, TiO2 photocatalytic study was performed. Under photolytic experimental conditions, the concentration of TCP after 120 min of irradiation reached 5.9 ± 1.5% of the initial concentration, while chloride concentration reached approximately 73% of total chloride concentration. The TOC measurements after 120 min of photocatalytic degradation experiment revealed high mineralization rate, i.e. 53.6 ± 1.9%, while chloride concentration reached 26.6 mg L(-1) what means almost quantitative transformation of organic chlorine into chloride. TIC chromatogram (ESI, negative ion mode) of the reaction mixture after 30 min of irradiation revealed the presence of several peaks. One of them has already been reported previously. Two other products have been identified in this study for the first time. They have been formed by radical attack of the reactive OH(•) species on the carbonyl group followed by the corresponding N-C or C-C bond cleavages and recyclization with formation of the pyrrol structures substituted with carboxylic groups. Both deprotonated molecules easily lose CO2 in ESI conditions.

The hydroxypyridinone iron chelator CP94 can enhance PpIX-induced PDT of cultured human glioma cells.

Photodynamic therapy (PDT) with the pro-drugs 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) utilizes the combined interaction of a photosensitizer, light and molecular oxygen to ablate tumor tissue. To potentially increase accumulation of the photosensitizer, protoporphyrin IX (PpIX), within tumor cells an iron chelator can be employed. This study analyzed the effects of ALA/MAL-induced PDT combined with the iron chelator 1, 2-diethyl-3-hydroxypyridin-4-one hydrochloride (CP94) on the accumulation of PpIX in human glioma cells in vitro. Cells were incubated for 0, 3 and 6h with various concentrations of ALA/MAL with or without CP94 and the resulting accumulations of PpIX, which naturally fluoresces, were quantified prior to and following light irradiation. In addition, counts of viable cells were recorded. The use of CP94 in combination with ALA/MAL produced significant enhancements of PpIX fluorescence in human glioma cells. At the highest concentrations of each prodrug, CP94 enhanced PpIX fluorescence significantly at 3h for ALA and by more than 50% at 6h for MAL. Cells subsequently treated with ALA/MAL-induced PDT in combination with CP94 produced the greatest cytotoxicity. It is therefore concluded that with further study CP94 may be a useful adjuvant to photodiagnosis and/or PpIX-induced PDT treatment of glioma.

Green chemistry: a facile synthesis of polyfunctionally substituted thieno[3,4-c]pyridinones and thieno[3,4-d]pyridazinones under neat reaction conditions.

A facile, solvent free, ecofriendly approach for the synthesis of pyridine-2,6-diones 4a-d, pyridazinone derivatives 8a-c and thienoazines 6 and 9 is herein described employing neat reaction conditions under both microwave and ultrasound irradiations. This solventless methodology is environmentally benign as it completely eliminates the use of solvent from the reaction procedure.

Photolytic (UVC) and photocatalyic (UVC/TiO2) decomposition of pyridines.

The degradation of 2-chloropyridine (2-CPY) and its degradation primary product 2-hydroxypyridine (2-HPY) was studied by means of ultraviolet (UV) irradiation at 254nm. Photolytic and photocatalytic experiments were conducted on 2-CPY and 2-HPY aqueous solutions in a batch reactor with internal recycle in laminar and turbulent conditions at 50 degrees C in a closed but not airtight system with and without additional aeration, at solution ambient pH and at controlled pH conditions, with use and in the absence of radical scavenger. The solution volume was 0.4L and initial substrate concentrations were approximately 2.6mmol/L (0.25-0.3g/L depending on the substrate). Where applicable 1g/L TiO(2) (P-25) was used, suspended in the liquid in a form of turbulent slurry or using a glass tube around the UV-lamp on which a fixed TiO(2) catalytic layer had been deposited. At the aforementioned conditions 2-CPY readily degrades photolytically, the catalytic path having very little influence. In all cases 2-CPY produces 2-HPY which further degrades to other products. Aeration, pH and the presence of catalyst and/or radical scavengers do not affect the rate of decomposition of 2-CPY, but have a strong influence on the further decomposition of the produced 2-HPY. 2-HPY decomposition proceeds both catalytically and photolytically following oxygen dependent and oxygen independent pathways.

Microwave-assisted synthesis of new polysubstituted dienaminoesters and their cyclization to 3-bromo-2(1H)-pyridinones.

A microwave-assisted, telescoped synthesis, involving a Michael-type addition followed by intramolecular cyclization, provides an effective entry to the polysubstituted 3-bromo-2(1H)-pyridinone core.

Photocycloaddition of four-carbon-tethered pyridones. Intramolecular hydrogen bonding and facilitated amide hydrolysis by a proximal secondary alcohol.

Four-carbon-tethered pyridones undergo photocycloaddition to give exclusively trans-[4 + 4] products. The presence of a tether alcohol engenders a solvent-dependent diastereoselectivity for the cycloaddition by intramolecular hydrogen bonding to the adjacent pyridone. Following cycloaddition, the alcohol can deliver a carbonyl group to the proximal, hindered amide nitrogen, leading to a very facile amide hydrolysis.

2'-Deoxyguanosine (DG) oxidation and strand-break formation in DNA by the radicals released in the photolysis of N-tert-butoxy-2-pyridone. Are tert-butoxyl or methyl radicals responsible for the photooxidative damage in aqueous media?

[reaction: see text] The photolysis of pyridone 3b (photo-Fenton reagent) in benzene releases tert-butoxyl radicals, which have been trapped by DMPO and EPR-spectrally identified. In aqueous solution, however, the fragmentation of the tert-butoxyl into methyl radicals prevails and the former radicals are of no direct consequence in the photooxidation of 2'-deoxyguanosine (dG) and pBR 322 DNA. The photooxidative damage of nucleic acids is caused by the oxyl radical species generated from the methyl radicals with oxygen.

The [2+2]-photocycloaddition of aromatic aldehydes and ketones to 3,4-dihydro-2-pyridones: regioselectivity, diastereoselectivity, and reductive ring opening of the product oxetanes.

3,4-Dihydro-2-pyridones [3,4-Dihydropyridin-2(1H)-ones] 6 were evaluated with respect to their use as alkene components in stereoselective Paternò-Büchi reactions. The parent compound 6a was shown to be a versatile synthetic building block that reacted with various photoexcited aromatic carbonyl compounds (benzaldehyde, benzophenone, acetophenone, methyl phenylglyoxylate, 3-pivaloyloxybenzaldehyde) with high regio- and diastereo-selectivity (51-63% yield). The products can be subjected to hydrogenolysis, opening a new and efficient route for the synthesis of 2-arylmethyl-3-piperidinols. As examples, the oxetanes 7a and 8a were hydrogenolytically cleaved and yielded the products 12 (88%) and 13 (93%). The ability of compound 6a to bind to a chiral lactam host through two hydrogen bonds was used favorably to differentiate the enantiotopic faces of its double bond. In the photocycloaddition to the chiral aldehyde 15, which was conducted at -10 degrees C in toluene, a high facial diastereoselectivity (>90% de. 56% yield) was recorded. The stereoselectivity results from a 1:1 association of dihydropyridone 6a to the aldehyde. The 4-substituted dihydropyridones 6b-6d (R = methyl, isopropyl, phenyl) were found to be less suited for potential use in photochemistry. The yields and facial diastereoselectivities recorded in their photocycloaddition to benzophenone remained low.

Solvent-dependent stereoselectivity of bis-2-pyridone [4 + 4] photocycloaddition is due to H-bonded dimers.

[formula: see text] A solvent-dependent stereoselectivity found for intramolecular [4 + 4] photocycloaddition of tethered 2-pyridones is concentration dependent, indicating that a dimeric structure with four hydrogen bonds plays a critical role in the observed cis selectivity found for nonpolar solvents.