Visible-light Photochemistry and Phototoxicity of Thiarubrines (original) (raw)
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Phototoxicity of (1H-INDENYL)THIOPHENES
Photochemistry and Photobiology, 1993
The (1 H-indeny1)thiophene derivatives 2 and 3 were recently reported to be excellent singlet oxygen sensitizers. comparable to a-terthienyl (1). The phototoxicity of these compounds was compared, using human erythrocytes, Aedes aegypti mosquito larvae. Daphnia rnagna. and fish (fathead minnows, Pimephales promelas). The known ranking of the photooxidation properties was found to be a good predictor of phototoxic properties in erythrocytes and mosquito larvae but not in daphnias. All three compounds photosensitized the cleavage ofsupercoiled pBR322 DNA to the same extent.
Photochemical properties and degradation by-products of triasulphuron and thifensulphuron-methyl
International Journal of Environmental Analytical Chemistry, 2006
The effect of light on two sulphonylurea herbicides, triasulphuron and thifensulphuron methyl, was studied under both UV and solar simulator irradiation (Suntest). Energies of first singlet and triplet state transitions were calculated from fluorescence and phosphorescence spectra. Experiments were performed in the presence of either a singlet or a triplet quencher showing that photodegradation of both herbicides begins from a triplet state, T 1 . The photolysis process of both herbicides occurred through first-order kinetics. The investigation stressed the relevance of the light exposition on the degradation rate of both herbicides. Half-lives of photolysis reactions (Suntest) in the organic solvent used in the experiments (22 and 54 h for triasulphuron and thifensulphuron methyl, respectively) are comparable with the hydrolysis rate in aqueous environment. With UV irradiation, the degradation time of both herbicides can be greatly reduced to several minutes, thus suggesting that this technique can be adopted as an efficient method of detoxification. The main photoproducts, identified by LC-ESI-MS, were: (4-methoxy-6-methyl-1,3,5-triazin-2-yl)urea and 4-methoxy-6-methyl-1,3,5-triazin-2-amine, common to triasulphuron and thifensulphuron-methyl; 2-(2-chloroethoxy) benzenesulphonamide and (2-chloroethoxy) benzene, arising from triasulphuron degradation; 4-sulphamoylthiophene-3-carboxilic acid methyl ester and thiophene-3-carboxilic acid methyl ester, occurring from thifensulphuron-methyl transformation. The presence of minor by-products was also ascertained.
The phototoxicity of phenothiazinium-based photosensitizers to bacterial membranes
FEMS Immunology & Medical Microbiology, 2006
The ability of phenothiazinium-based photosensitizers to induce photodamage to Escherichia coli membranes is investigated. Phenothiazinium-based photosensitizers were found to be somewhat lipophilic (log P 4 0.7) and to induce surfacepressure changes (3-12 mN m À 1 ) in lipid monolayers mimetic of bacterial membranes, implying that these molecules are able to penetrate biological membranes. Under dark and light conditions (3.15 J cm À 1 for 30 min), phenothiazinium-based photosensitizers were incubated with E. coli cells. These cells showed levels of dark bacteriolysis that ranged between 6% and 13%, with light conditions leading to no significant increase in these levels. Gas chromatographybased analyses showed such incubations to produce no significant changes in the levels of C 16 and C 18 fatty acid chain saturation found in E. coli whole lipidextracts. It is concluded that the phenothiazinium-based photosensitizers studied may not use E. coli membranes as their primary photodynamic target, but may inflict photodamage on cytoplasmic targets, possibly DNA.
Journal of Photochemistry and Photobiology A: Chemistry, 2018
This work demonstrates that the fungicide thiophanate-methyl generates a sensitizing photoproduct upon irradiation in solar light and explains how the reaction proceeds. The degradation profileof aqueous thiophanatemethyl in simulated solar light showed an autoaccelerated shape indicating the formation of some photodegrading compounds. Among the detected photoproducts, I (λ max = 340 nm), a quinoxaline derivative generated in the very beginning of the reaction seemed to be the molecule responsible for this autoacceleration. Further experiments were conducted to confirm this hypothesis. The laser flash photolysis (λ exc = 355 nm) of I generated a transient species reminiscent to the triplet excited state of unsubstituted quinoxaline. The two triplets reacted with the phenolic probe, 2,4,6-trimethylphenol, with k = 2 × 10 9 M −1 s −1. Steady-state irradiations showed that thiophanate-methyl drastically accelerated the photolysis of the probe in an auto-accelerated reaction confirming the production of a sensitizing photoproduct. Moreover, unsubstituted quinoxaline sensitized the degradation of thiophanate-methyl showing that this latter contains labile H atoms. All these data confirmed that I was the sensitizer responsible for the auto-accelerated light induced transformation of thiophanate-methyl. The mechanism of formation of I was studied by quantum calculations. It proceeds through photocyclisation to form a SeS bridge, followed by intra and intermolecular H abstractions and finally departure of HSS. The sensitizing properties of micropollutants photoproducts open a large array of investigations. Our study provides a reliable approach to investigate the overlooked photosensitizing effect of photoproducts during photochemical reactions in water and opens the way to a vast array of research.
Photochemical & Photobiological Sciences
The fast-emerging and multidrug-resistant Candida auris is the first fungal pathogen to be considered a threat to global public health. Thus, there is a high unmet medical need to develop new therapeutic strategies to control this species. Antimicrobial photodynamic therapy (APDT) is a promising alternative that simultaneously targets and damages numerous microbial biomolecules. Here, we investigated the in vitro and in vivo effects of APDT with four phenothiazinium photosensitizers: (i) methylene blue (MB), (ii) toluidine blue (TBO), and two MB derivatives, (iii) new methylene blue (NMBN) and (iv) the pentacyclic derivative S137, against C. auris. To measure the in vitro efficacy of each PS, minimal inhibitory concentrations (MICs) and survival fraction were determined. Also, the efficiency of APDT was evaluated in vivo with the Galleria mellonella insect model for infection and treatment. Although the C. auris strain used in our study was shown to be resistant to the most-commonly used clinical antifungals, it could not withstand the damages imposed by APDT with any of the four photosensitizers. However, for the in vivo model, only APDT performed with S137 allowed survival of infected G. mellonella larvae. Our results show that structural and chemical properties of the photosensitizers play a major role on the outcomes of in vivo APDT and underscore the need to synthesize and develop novel photosensitizing molecules against multidrug-resistant microorganisms.
Tetrahedron Letters, 2002
p-Hydroxyphenacyl bromide is described as a photoremovable thiol protecting group on three biomolecules containing a free thiol group. The protecting group is efficiently incorporated by chemical coupling to the biomolecule in an ethanol-buffer mixture. The photofragmentations (u=312 nm) were analyzed by UV, HPLC and MS methods, yielding over 70% of the free biomolecules. The concomitant formation of p-hydroxyphenylacetic thioesters derived from the corresponding thiols, as a sulfur-containing side-product, should not hinder the use of this protecting group for the caging of thiol-containing biomolecules.
Chemical Research in Toxicology, 2006
This paper reports the results of an in vitro evaluation of the phototoxic potential of stable photoproducts formed by UVA photolysis of three phenothiazines, perphenazine, fluphenazine, and thioridazine, in a water environment. Perphenazine gave a single product due to dechlorination. From thioridazine, the two major products formed; the endocyclic sulfoxide and the endocyclic N-oxide in which the 2-SCH 3 substituent was replaced by a hydroxy group were tested. From fluphenazine, two products have been examined as follows: an exocyclic N-piperazine oxide and a carboxylic acid arising from hydrolysis of the 2-CF 3 group. The phototoxicity of the isolated photoproducts has been studied in order to determine their possibile involvement in the photosensitizing effects exhibited by the parent drugs, using hemolysis and 3T3 fibroblasts viability as in vitro assays. As fluphenazine, perphenazine, and thioridazine did, some photoproducts proved phototoxic. In particular, the perphenazine dechlorinated photoproduct and the thioridazine N-oxide were found to exert phototoxic properties similar to the parent compounds. Therefore, our data suggest that some phenothiazine photoproducts may play a role in the mechanism of photosensitivity of these drugs. Because some of these photoproducts correspond to metabolic products of phenothiazines found in humans, it cannot be ruled out that metabolites of phenothiazines can be phototoxic in vivo.
Acute Toxicity of Thioarsenates to Vibrio Fischeri
Environmental Toxicology and Chemistry, 2008
Thioarsenic species often are the predominant arsenic species in sulfidic environments, yet little is known about their toxicity. We report to our knowledge the first determination of acute toxicity of mono-, di-, and trithioarsenate to the bioluminescent bacterium Vibrio fischeri, which increases with an increasing number of thio(SH)-groups. Whereas mono-and dithioarsenate are much less toxic (effective analyte concentration causing a 50% decrease in luminescence [EC50], 676 and 158 mg/L, respectively), the toxicity of trithioarsenate (EC50, 14.4 mg/L) is comparable to the toxicities of arsenate and arsenite (EC50, 9.1 and 26.1 mg/L, respectively). The low toxicity of monothioarsenate is remarkable, because it has chemical properties very similar to those of arsenate. In contrast to the toxicities of arsenite and arsenate, the toxicity of thioarsenates increases with exposure time, suggesting a lack of detoxification mechanisms or a conversion of thioarsenic species into arsenic oxyanions after uptake. We determined the acute toxicity of synthetic arsenite solutions with varying sulfide concentration to V. fischeri. Arsenic speciation in these solutions was measured by ion chromatography-inductively coupled plasma-mass spectrometry, and the observed toxicity was related to the different arsenic species present. High inhibition of luminescence was observed at low and high ratios of sulfur to arsenic, in which arsenite or a mixture of di-, tri-, and tetrathioarsenate dominated arsenic speciation. Acute toxicity decreased at sulfur to arsenic ratios of from 1 to 10, with a minimum luminescence inhibition of 30% at a ratio of 3.5, at which concentrations of 55 mg/L of arsenite and 30 mg/L of trithioarsenate were determined. The toxicity observed under these conditions is much lower than that anticipated from the individual dose-response curves that predict each species alone already should cause 70 to 80% inhibition. The low toxicity suggests an antagonistic toxicological interaction between arsenite and trithioarsenate.
The phototoxicity of phenothiazinium derivatives against Escherichia coli and Staphylococcus aureus
Fems Immunology and Medical Microbiology, 2003
Phenothiazinium dyes, and derivatives, were tested for toxicity to Escherichia coli and Staphylococcus aureus. The dyes were generally lipophilic (log P s 1) and showed inherent dark toxicity (minimum lethal concentrations: 3.1^1000 WM). Dye illumination (total light dose of 3.15 J cm 31 over 30 min) led to up to eight-fold reductions in minimum lethal concentrations. Most of the illuminated dyes showed significant relative singlet oxygen yields (xP v : 0.18^1.35) suggesting a type II mechanism of generating a phototoxic response. Although generally up to six-fold more effective against S. aureus, the dyes tested efficiently killed E. coli and may be of particular use in combating Gram-negative pathogens. ß