Identifying degradation products responsible for increased toxicity of UV-degraded insensitive munitions

Degradation of insensitive munitions (IMs) by ultraviolet (UV) light has become a concern following observations that some UV-degradation products have increased toxicity relative to parent compounds in aquatic organisms. This investigation focused on the Army's IM formulation, IMX-101, composed of three IM constituents: 2,4-dinitroanisole (DNAN), 3-nitro-1,2,4-triazol-5-one (NTO), and nitroguanidine (NQ). The IM constituents and IMX-101 were irradiated in a UV photo-reactor and then administered to Daphnia pulex in acute (48 h) exposures comparing toxicities relative to the parent materials. UV-degradation of DNAN had little effect on mortality whereas mortality for UV-degraded NTO and NQ increased by factors of 40.3 and 1240, making UV-degraded NQ the principle driver of toxicity when IMX-101 is UV-degraded. Toxicity investigations for specific products formed during UV-degradation of NQ, confirmed greater toxicity than the parent NQ for degradation products. Summation of the individual toxic units for the complete set of individually measured UV-degradation products identified for NQ only accounted for 25% of the overall toxicity measured in the exposures to the UV-degraded NQ product mixture. Given the underestimation of toxicity using the sum toxic units for the individually measured UV-degradation products of NQ, we conclude that: (1) other unidentified NQ degradation products contributed principally to toxicity and/or (2) synergistic toxicological interactions occurred among the NQ degradation product mixture that exacerbated toxicity.

Synergistic Neuroprotective Effects of a Natural Product Mixture against AD Hallmarks and Cognitive Decline in Caenorhabditis elegans and an SAMP8 Mice Model

The study of different natural products can provide a wealth of bioactive compounds, and more interestingly, their combination can exert a new strategy for several neurodegenerative diseases with major public health importance, such as Alzheimer’s disease (AD). Here, we investigated the synergistic neuroprotective effects of a mixed extract composed of docosahexaenoic acid, Ginkgo biloba, D-pinitol, and ursolic acid in several transgenic Caenorhabditis elegans (C. elegans) and a senescence-accelerated prone mice 8 (SAMP8) model. First, we found a significantly higher survival percentage in the C. elegans group treated with the natural product mixture compared to the single extract-treated groups. Likewise, we found a significantly increased lifespan in group of C. elegans treated with the natural product mixture compared to the other groups, suggesting synergistic effects. Remarkably, we determined a significant reduction in Aβ plaque accumulation in the group of C. elegans treated with the natural product mixture compared to the other groups, confirming synergy. Finally, we demonstrated better cognitive performance in the group treated with the natural product mixture in both AD models (neuronal Aβ C. elegans strain CL2355 and the SAMP8 mice model), confirming the molecular results and unraveling the synergist effects of this combination. Therefore, our results proved the potential of this new natural product mixture for AD therapeutic strategies.

The β-Carotene-Oxygen Copolymer: its Relationship to Apocarotenoids and β‑Carotene Function

β-Carotene spontaneously copolymerizes with molecular oxygen to form a β-carotene-oxygen copolymer compound (“copolymer”) as the main product, together with small amounts of many apocarotenoids. Both the addition and scission products are interpreted as being formed during progression through successive free radical β-carotene-oxygen adduct intermediates. The product mixture from full oxidation of β-carotene, lacking both vitamin A and β-carotene, has immunological activities, some of which derive from the copolymer. However, the copolymer’s chemical makeup is unknown. A chemical breakdown study shows the compound to be moderately stable but nevertheless the latent source of many small apocarotenoids. GC-MS analysis with mass-spectral library matching identified a minimum of 45 structures, while more than 90 others remain unassigned. Newly identified products include various small keto carboxylic acids and dicarboxylic acids, several of which are central metabolic intermediates. Also present are glyoxal and methyl glyoxal dialdehydes, recently reported as β-carotene metabolites in plants. Although both compounds at higher concentrations are known to be toxic, at low concentration methyl glyoxal has been reported to be potentially capable of activating an immune response against microbial infection. In plants, advantage is taken of the electrophilic reactivity of specific apocarotenoids derived from β-carotene oxidation to activate protective defenses. Given the copolymer occurs naturally and is a major product of non-enzymatic β-carotene oxidation in stored plants, by partially sequestering apocarotenoid metabolites the copolymer may serve to limit potential toxicity and maintain low cellular apocarotenoid concentrations for signaling purposes. In animals the copolymer may serve as a systemic source of apocarotenoids.

The β-Carotene-Oxygen Copolymer: its Relationship to Apocarotenoids and β-Carotene Function

Abstractβ-Carotene spontaneously copolymerizes with molecular oxygen to form a β-carotene-oxygen copolymer compound (“copolymer”) as the main product, together with small amounts of many apocarotenoids. Both the addition and scission products are interpreted as being formed during progression through successive free radical β-carotene-oxygen adduct intermediates. The product mixture from full oxidation of β-carotene, lacking both vitamin A and β-carotene, has immunological activities, some of which derive from the copolymer. However, the copolymer’s chemical makeup is unknown. A chemical breakdown study shows the compound to be moderately stable but nevertheless the latent source of many small apocarotenoids. Although the copolymer alone is only slightly affected by heating at 100°C for 4 h, in methanol solution it is significantly degraded by hydrochloric acid or sodium hydroxide, liberating many apocarotenoids. GC-MS analysis with mass-spectral library matching identified a minimum of 45 structures, while more than 90 others remain unassigned. Thirteen products are Generally Recognized as Safe (GRAS) human flavor agents. Newly identified products include various small keto carboxylic acids and dicarboxylic acids, several of which are central metabolic intermediates. Also present are the dialdehydes glyoxal and methyl glyoxal, recently reported as β-carotene metabolites in plants. Although both compounds at higher concentrations are known to be toxic, at low concentration methyl glyoxal has been reported to be potentially capable of activating an immune response against microbial infection. In plants, advantage is taken of the electrophilic reactivity of specific apocarotenoids derived from β-carotene oxidation to activate protective defenses. Given the copolymer occurs naturally and is a major product of non-enzymatic β-carotene oxidation in stored plants, by partially sequestering apocarotenoid metabolites the copolymer may serve to limit potential toxicity and maintain low cellular apocarotenoid concentrations for signaling purposes. In animals the copolymer may serve as a systemic source of apocarotenoids.

Electrocoagulation with AC Electrical Current at Low Voltage for Separation of Crude Glycerol from Biodiesel Product Mixture

Electrocoagulation with AC electrical current at low voltage was implemented to remove crude glycerol from biodiesel which was produced via transesterification reaction of refined palm oil (RPO) as feedstock with methanol in the presence of sodium hydroxide derivative-catalyst at 60°C for 2 hr using the conventional heating in the water bath. Effects of point-to-point electrode configuration, electrode materials, inter-electrode distances, optimized AC low voltages, molar ratios of glycerol and biodiesel product mixture on the separation time and the separation efficiency were studied. Electrocoagulation process with applied AC at 96 V and using Al point-to-point electrodes at the inter-electrode distance of 0.1 cm could efficiently remove free glycerol more than the gravitation settling for the separation time of 120 s. The separation efficiency was over 99.99%. Even though the clear interface between biodiesel and glycerol was firstly observed after applying the electrocoagulation for 30 s, the separation time had to proceed for additional 90 s to eliminate unreacted catalyst. The methyl ester content of 98.56±0.47 wt% was obtained after purification with 2 times of water-washing. This process can be achieved by shortening the separation time and could significantly reduce the water consumption during the purification process.

Disinfection by-Products and Ecotoxic Risk Associated with Hypochlorite Treatment of Tramadol

In recent years, many studies have highlighted the consistent finding of tramadol (TRA) in the effluents from wastewater treatment plants (WTPs) and also in some rivers and lakes in both Europe and North America, suggesting that TRA is removed by no more than 36% by specific disinfection treatments. The extensive use of this drug has led to environmental pollution of both water and soil, up to its detection in growing plants. In order to expand the knowledge about TRA toxicity as well as the nature of its disinfection by-products (DBPs), a simulation of the waste treatment chlorination step has been reported herein. In particular, we found seven new by-products, that together with TRA, have been assayed on different living organisms (Aliivibrio fischeri, Raphidocelis subcapitata and Daphnia magna), to test their acute and chronic toxicity. The results reported that TRA may be classified as a harmful compound to some aquatic organisms whereas its chlorinated product mixture showed no effects on any of the organisms tested. All data suggest however that TRA chlorination treatment produces a variety of DBPs which can be more harmful than TRA and a risk for the aquatic environment and human health.

Taming Combinatorial Explosion of the Formose Reaction via Recursion within Mineral Environments

<p><i>One-pot reactions of simple precursors, such as those found in the formose reaction or formamide condensation, continuously lead to combinatorial explosions in which simple building blocks capable of function exist, but are in insufficient concentration to self-organize, adapt, and thus generate complexity. We set out to explore the effect of recursion on such complex mixtures by ‘seeding’ the product mixture into a fresh version of the reaction, with the inclusion of different mineral environments, over a number of reaction cycles. Through untargeted UPLC-HRMS analysis of the mixtures<a> we found that the overall number of products detected reduces as the number of cycles increases, as a result of recursively enhanced mineral environment selectivity, </a>thus limiting the combinatorial explosion. This discovery demonstrates how the involvement of mineral surfaces with simple reactions could lead to the emergence of some building blocks found in RNA, </i><i>Ribose and Uracil, under much simpler conditions that originally thought.</i><i> </i></p>

Taming Combinatorial Explosion of the Formose Reaction via Recursion within Mineral Environments

<p><i>One-pot reactions of simple precursors, such as those found in the formose reaction or formamide condensation, continuously lead to combinatorial explosions in which simple building blocks capable of function exist, but are in insufficient concentration to self-organize, adapt, and thus generate complexity. We set out to explore the effect of recursion on such complex mixtures by ‘seeding’ the product mixture into a fresh version of the reaction, with the inclusion of different mineral environments, over a number of reaction cycles. Through untargeted UPLC-HRMS analysis of the mixtures<a> we found that the overall number of products detected reduces as the number of cycles increases, as a result of recursively enhanced mineral environment selectivity, </a>thus limiting the combinatorial explosion. This discovery demonstrates how the involvement of mineral surfaces with simple reactions could lead to the emergence of some building blocks found in RNA, </i><i>Ribose and Uracil, under much simpler conditions that originally thought.</i><i> </i></p>