Visible Light Promoted, Catalyst-Free Radical Carbohydroxylation and Carboetherification under Mild Biomimetic Conditions.

Metal and catalyst-free carbohydroxylations and carboetherifications at room temperature have been achieved by a combination of beneficial factors including high aryl diazonium concentration and visible light irradiation. The acceleration of the reaction by visible light irradiation is particularly remarkable against the background that neither the aryldiazonium salt nor the alkene show absorptions in the respective range of wavelength. These observations point to weak charge transfer interactions between diazonium salt and alkene, which are nevertheless able to considerably influence the reaction course. As highly promising perspective, many more aryldiazonium-based radical arylations might benefit from simple light irradiation without requiring a photocatalyst or particular additive.

Photo(geno)toxicity changes associated with hydroxylation of the aromatic chromophores during diclofenac metabolism.

Diclofenac (DCF) can cause adverse reactions such as gastrointestinal, renal and cardiovascular disorders; therefore, topical administration may be an attractive alternative to the management of local pain in order to avoid these side effects. However, previous studies have shown that DCF, in combination with sunlight, displays capability to induce photosensitivity disorders. In humans, DCF is biotransformed into hydroxylated metabolites at positions 4' and 5 (4'OH-DCF and 5OH-DCF), and this chemical change produces non negligible alterations of the drug chromophore, resulting in a significant modification of its light-absorbing properties. In the present work, 5OH-DCF exhibited higher photo(geno)toxic potential than the parent drug, as shown by several in vitro assays (3T3 NRU phototoxicity, DNA ssb gel electrophoresis and COMET), whereas 4'OH-DCF did not display significant photo(geno)toxicity. This could be associated, at least partially with their more efficient UV-light absorption by 5OH-DCF metabolite and with a higher photoreactivity. Interestingly, most of the cellular DNA damage photosensitized by DCF and 5OH-DCF was repaired by the cells after several hours, although this effect was not complete in the case of 5OH-DCF.

Photochemistry of tetra- through hexa-brominated dioxins/furans, hydroxylated and native BDEs in different media.

The aim of this study was to investigate (i) the behavior of native PBDEs during UV irradiation in different media, (ii) the possibility of their transformation into hydroxylated PBDEs in aqueous media, and (iii) the photochemistry/levels of brominated dioxins/furans formed from hydroxylated PBDEs. Debromination leading to the formation of a wide range of low-brominated congeners was the main path of photocatalyzed transformations of PBDEs. In organic solvents other than toluene, BDEs degraded in line with the pseudo first order kinetics (10-20 min half-life, depending on congener type and reaction medium). Irradiated BDE 209 congener behaved quite differently than lower-brominated BDEs: detectable amounts of various bromo-benzenes were found. That suggests that UV irradiation of BDE 209 leads to cleavage of the ether bound between the congener's aromatic rings. Formation of bromophenyl bromo-methyl-biphenyl ethers or benzyl-bromophenoxybenzenes was observed in irradiated PBDE toluene-based solutions. The total concentration of OH-BDEs found in the reaction medium did not exceed 0.2% of the initial precursor mass. Moreover, lower-brominated congeners detected in the reaction medium indicate subsequent debromination of OH-BDEs or hydro-debromination of the degraded congeners. Brominated dioxins and low levels of furans were observed in samples containing OH-BDEs. The total mass of dioxins did not exceed 3.5% of the initial precursor mass.

Reduction of hydroxylated fullerene (fullerol) in water by zinc: reaction and hemiketal product characterization.

Water-soluble, hydroxylated fullerene (fullerol) materials have recently gained increasing attention as they have been identified as the primary product(s) during the exposure of fullerenes (as water stable, nanoscale aggregated C60) to UV light in water. The physical properties and chemical reactivity of resulting fullerols, however, have not been thoroughly studied. In this paper, we identified and characterized the reductive transformation of fullerol (C60(OH)x(ONa)y) by solid zinc metal (Zn(0)) through a series of batch reaction experiments and product characterization, including (13)C NMR, FTIR, XPS, UV-vis, DLS, and TEM. Results indicated the facile formation of water stable, pH sensitive hemiketal functionality as part of a relatively reduced fullerol product. Further, aqueous physical behavior of the product fullerol, as measured by octanol partitioning and surface deposition rates, was observed to significantly differ from the parent material and is consistent with a relative increase in molecular (product) hydrophobicity.

Chromatography and high-resolution mass spectrometry for the characterization of the degradation products of the photodegradation of amidosulfuron: an analytical approach.

Simulated sunlight irradiation causing degradation of amidosulfuron, a pyrimidinylsulfonylurea herbicide, has been investigated in aqueous solution. The main degradation products were followed up by ultrahigh-pressure liquid chromatography with a UV detector (UHPLC-UV) and identified by combining ultrahigh-pressure liquid chromatography-mass spectrometry (UHPLC-MS) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). On the basis of the retrosynthetic analysis, the most identified degradation products were mainly due to the losses of methylsulfamic acid (CH5NO3S), sulfocarbamic acid (CH3NO5S), carbamic acid (CH3NO2), methyl(methylsulfonyl)sulfamic acid (C2H7NO5S2), N-methylmethanesulfonamide (C2H7NO2S), and sulfonic acid (H2SO4) molecules. Accordingly, O and S-demethylation as well as hydroxylation processes were also observed. Sum formulas of the main degradation products were assigned, and a mechanical pathway is proposed.

T box RNA decodes both the information content and geometry of tRNA to affect gene expression.

The T box leader sequence is an RNA element that controls gene expression by binding directly to a specific tRNA and sensing its aminoacylation state. This interaction controls expression of amino acid-related genes in a negative feedback loop. The T box RNA structure is highly conserved, but its tRNA binding mechanism is only partially understood. Known sequence elements are the specifier sequence, which recognizes the tRNA anticodon, and the antiterminator bulge, which base pairs with the tRNA acceptor end. Here, we reveal the crucial function of the highly conserved stem I distal region in tRNA recognition and report its 2.65-Å crystal structure. The apex of this region contains an intricately woven loop-loop interaction between two conserved motifs, the Adenine-guanine (AG) bulge and the distal loop. This loop-loop structure presents a base triple on its surface that is optimally positioned for base-stacking interactions. Mutagenesis, cross-linking, and small-angle X-ray scattering data demonstrate that the apical base triple serves as a binding platform to dock the tRNA D- and T-loops. Strikingly, the binding platform strongly resembles the D- and T-loop binding elements from RNase P and the ribosome exit site, suggesting that this loop-loop structure may represent a widespread tRNA recognition platform. We propose a two-checkpoint molecular ruler model for tRNA decoding in which the information content of tRNA is first examined through specifier sequence-anticodon interaction, and the length of the tRNA anticodon arm is then measured by the distal loop-loop platform. When both conditions are met, tRNA is secured, and its aminoacylation state is sensed.

Light-driven cytochrome p450 hydroxylations.

Plants are light-driven "green" factories able to synthesize more than 200,000 different bioactive natural products, many of which are high-value products used as drugs (e.g., artemisinin, taxol, and thapsigargin). In the formation of natural products, cytochrome P450 (P450) monooxygenases play a key role in catalyzing regio- and stereospecific hydroxylations that are often difficult to achieve using the approaches of chemical synthesis. P450-catalyzed monooxygenations are dependent on electron donation typically from NADPH catalyzed by NADPH-cytochrome P450 oxidoreductase (CPR). The consumption of the costly cofactor NADPH constitutes an economical obstacle for biotechnological in vitro applications of P450s. This bottleneck has been overcome by the design of an in vitro system able to carry out light-driven P450 hydroxylations using photosystem I (PSI) for light harvesting and generation of reducing equivalents necessary to drive the P450 catalytic cycle. The in vitro system is based on the use of isolated PSI and P450 membrane complexes using ferredoxin as an electron carrier. The turnover rate of the P450 in the light-driven system was 413 min(-1) compared to 228 min(-1) in the native CPR-catalyzed system. The use of light as a substitute for costly NADPH offers a new avenue for P450-mediated synthesis of complex bioactive natural products using in vitro synthetic biology approaches.

Photodimerizations of hydroxy- and benzoylated 4-azachalcones and quantum chemical investigation of the reactions.

Photodimerization reactions of compounds 4-6 gave four new cyclobutane-containing compounds (7-9) with full control over the stereochemistry at the four stereogenic centers. These new cyclobutane-containing compounds had beta-truxinic (7a), delta-truxinic (7b and 9), and epsilon-truxillic (8) structures. However, o-, m-, and p-hydroxy 4-azachalcones (1-3) did not give photochemical cyclization products under any conditions (in solvent or in their solid or molten states). Experimental data suggested the possibility of frontier orbital control over stereochemical behavior, so some theoretical calculations were performed. Full geometrical optimization of compounds 1-9 was performed via DFT B3LYP/6-31(+)G**, and their electronic structures were also investigated. The geometries of the singlet and triplet states were initially optimized by density functional theory (DFT) and the configuration interaction singles (CIS) B3LYP/3-21(+)G** level. An additional calculation was performed for the triplet state using the ground-state geometry. The possible photochemical dimerization products of compounds 7-9 (a-g) and the intrinsic reaction coordinates (IRCs) of the reactions of compounds 4-6 were calculated theoretically by the DFT/3-21(+)G** method. The configurations (reactant, transition state, product, and reaction pathway) corresponding to the stationary points (minima or saddle points) were determined. The intrinsic reaction coordinates were followed to verify the energy profiles that connect each TS to the appropriate local minimum. The dimeric products expected from the calculations coincided with the dimers produced experimentally.

Hydroxylation of 3-nitrotyrosine and its derivatives by gamma irradiation.

Radiation-induced hydroxylation of 3-nitrotyrosine (3-NY) and its derivatives in aqueous solution were investigated as a function of gamma-radiation dose. Irradiated 3-NY, 3-nitrotyrosine ethyl ester (3-NYE) and 3-NY containing peptide Gly-nitroTyr-Gly were separated and analyzed with reverse-phase HPLC and UV-Vis absorption spectroscopy. The structures of the hydroxylated products were confirmed by electrospray ionization mass spectrometry and (1)H-NMR spectrometry. The amounts of the hydroxylated products in irradiated 3-NY and Gly-nitroTyr-Gly solutions increased with increasing radiation dose. Tandem electrospray ionization mass spectrometry (ESI-Mass(2)) was performed to investigate the hydroxylation of peptide Gly-nitroTyr-Gly. These studies showed that the hydroxylation occurred at 3-NY residue. We also found that the identification of 3-NY hydroxylation in peptide could be identified by ion scanning for the specific immonium ion at m/z 197.0.

Mechanism of hydroxyl radical scavenging by rebamipide: identification of mono-hydroxylated rebamipide as a major reaction product.

Rebamipide, an antiulcer agent, is known as a potent hydroxyl radical (*OH) scavenger. In the present study, we further characterized the scavenging effect of rebamipide against *OH generated by ultraviolet (UV) irradiation of hydrogen peroxide (H2O2), and identified the reaction products to elucidate the mechanism of the reaction. Scavenging effect of rebamipide was accessed by ESR using DMPO as a *OH-trapping agent after UVB exposure (305 nm) to H2O2 for 1 min in the presence of rebamipide. The signal intensity of *OH adduct of DMPO (DMPO-OH) was markedly reduced by rebamipide in a concentration-dependent fashion as well as by dimethyl sulfoxide and glutathione as reference radical scavengers. Their second order rate constant values were 5.62 x 10(10), 8.16 x 10(9) and 1.65 x 10(10) M(-1) s(-1), respectively. As the rebamipide absorption spectrum disappeared during the reaction, a new spectrum grew due to generation of rather specific reaction product. The reaction product was characterized by LC-MS/MS and NMR measurements. Finally, a hydroxylated rebamipide at the 3-position of the 2(1H)-quinolinone nucleus was newly identified as the major product exclusively formed in the reaction between rebamipide and the *OH generated by UVB/H2O2. Specific formation of this product explained the molecular characteristics of rebamipide as a potential *OH scavenger.

[An EPR study of the joint action of sodium nitrite and whole-body irradiation on animal tissues]. / Issledovanie metodom EPR sovmestnogo deistviia nitrita natriia i obshchego oblucheniia na tkani zhivotnykh.

Changes in metabolic paramagnetic centers of the liver, kidney, spleen, brain and heart tissues, and blood after sodium nitrite intraperitoneal administration irradiation, or combined action of sodium nitrite and irradiation on mice, were studied using the EPR method. It was shown that irradiation of mice after sodium nitrite administration enhanced the effects induced by sodium nitrite alone: the levels of nitrosyl complexes Heme-NO in the tissues, cytochrome P-450 inhibition, and MetHb were higher.