Degradation Of Natural Products Research Articles

Effects of interactions between natural organic matter and aquatic organism degradation products on the transformation and dissolution of cobalt and nickel-based nanoparticles in synthetic freshwater

Expanding applications and production of engineered nanoparticles lead to an increased risk for their environmental dispersion. Systematic knowledge of surface transformation and dissolution of nanoparticles is essential for risk assessment and regulation establishment. Such aspects of Co- and Ni-based nanoparticles including metals, oxides, and solution combustion synthesized metal nanoparticles (metal cores with carbon shells) were investigated upon environmental interaction with organic matter, simulated by natural organic matter (NOM) and degradation products from zooplankton and algae (eco-corona biomolecules, EC) in freshwater (FW). The presence of NOM and EC in FW results in negative surface charges of the nanoparticles reduces the extent of nanoparticles agglomeration, and increases concentration, mainly due to the surface adsorption of carboxylate groups of the organic matter. The dissolution of the Co-based nanoparticles was for all conditions (FW, FW with NOM or EC) higher than the Ni-based, except for Co3O4 being nearly non-soluble. The surface transformation and dissolution of nanoparticles are highly exposure and time-dependent, and surface- and environment specific. Therefore, no general correlation was observed between dissolution and, particle types, surface conditions, or EC/NOM adsorption. This underlines the importance of thorough investigations of nanoparticles adsorption/desorption, degradation, and exposure scenarios for developing regulatory relevant protocols and guidelines.

Building comprehensive glucosinolate profiles for brassica varieties

Brassica plants play an important role in common agricultural practices, such as livestock feed or biofumigation, due to the bioactivity of the natural degradation products of glucosinolate metabolites. Therefore, the ability to survey comprehensive glucosinolate profiles for individual brassicas is essential for informing proper species selection for the intended application. Current methods for glucosinolate identification and quantification involve complex or unconventional procedures, and proper reference materials are not readily available. Therefore, researchers with limited resources that require glucosinolate profiles are at an extreme disadvantage. In this work, a simple and accurate HPLC-MS method was developed and validated to build preliminary glucosinolate profiles for three agriculturally relevant forage brassica varieties [turnip (B. rapa L.), canola (B. napus L.), and rapeseed (B. napus L.)]. The average glucosinolate content across three herbage collection dates for canola, rapeseed and turnip were 2.9 ± 0.9 mg g−1, 6.4 ± 1.3 mg g−1, and 14 ± 3.4 mg g−1, respectively. GLS concentrations are reported in milligrams of glucosinolate, calculated as sinigrin equivalents, per gram of dry plant material. This semi-quantitative approach for reporting total GLS content in brassicas is accurate within 15%. Several minor individual glucosinolates were identified that have not been previously reported in canola, rapeseed and turnip species, including glucotropaeolin and 4-hydroxyglucobrassicin (canola), glucoraphanin and glucoberteroin (rapeseed), and glucosinalbin and glucobarbarin (turnip). This non-targeted screen of several forage brassica varieties demonstrates the inherent variation in both the individual glucosinolate content and the total glucosinolate profile among brassicas, and highlights the importance of such glucosinolate characterization in agricultural practices. Additionally, the method developed in this study can be used as a tool for researchers with limited resources to build accurate glucosinolate profiles of brassica plants.

Synthesis of naturally occurring β-l-arabinofuranosyl-l-arabinofuranoside structures towards the substrate specificity evaluation of β-l-arabinofuranosidase

Methyl β-l-arabinofuranosyl-(1 → 2)-, -(1 → 3)-, and -(1 → 5)-α-l-arabinofuranosides have been stereoselectively synthesized through 2-naphthylmethyl ether-mediated intramolecular aglycon delivery (NAP-IAD), whose β-linkages were confirmed by NMR analysis on the 3JH1–H2 coupling constant and 13C chemical shift of C1. The NAP-IAD approach was simply extended for the synthesis of trisaccharide motifs possessing β-l-arabinofuranosyl-(1 → 5)-l-arabinofuranosyl non-reducing terminal structure with the branched β-l-arabinofuranosyl-(1 → 5)-[α-l-arabinofuranosyl-(1 → 3)]-α-l-arabinofuranosyl and the liner β-l-arabinofuranosyl-(1 → 5)-β-l-arabinofuranosyl-(1 → 5)-β-l-arabinofuranosyl structures in olive arabinan and dinoflagellate polyethers, respectively. The results on the substrate specificity of a bifidobacterial β-l-arabinofuranosidase HypBA1 using the regioisomers indicated that HypBA1 could hydrolyze all three linkages however behaved clearly less active to β-(1 → 5)-linked disaccharide than other two regioisomers including the proposed natural degradation product, β-(1 → 2)-linked one from plant extracellular matrix such as extensin. On the other hand, Xanthomonas XeHypBA1 was found to hydrolyze all three disaccharides as the substrate with higher specificity to β-(1 → 2)-linkage than bifidobacterial HypBA1.

Adsorption of bio-organic eco-corona molecules reduces the toxic response to metallic nanoparticles in Daphnia magna

As the use of engineered nanomaterials increases, so does the risk of them spreading to natural ecosystems. Hitherto, knowledge regarding the toxic properties of nanoparticles (NP’s) and their potential interactions with natural bio-organic molecules adsorbed to them, and thereby forming surface coronas, is limited. However, we show here that the toxic effect of NPs of tungsten carbide cobalt (WC–Co) and cobalt (Co) on the crustacean Daphnia magna is postponed in the presence of natural biological degradation products (eco-corona biomolecules). For Daphnia exposed to WC–Co NPs the survival time increased with 20–25% and for Co NPs with 30–47% after mixing the particles with a solution of eco-corona biomolecules before exposure. This suggests that an eco-corona, composed of biomolecules always present in natural ecosystems, reduces the toxic potency of both studied NPs. Further, the eco-coronas did not affect the particle uptake, suggesting that the reduction in toxicity was related to the particle-organism interaction after eco-corona formation. In a broader context, this implies that although the increasing use and production of NPs may constitute a novel, global environmental threat, the acute toxicity and long-term effects of some NPs will, at least under certain conditions, be reduced as they enter natural ecosystems.

Visualization of vermilion degradation using pump-probe microscopy

Here, we demonstrate the use of pump-probe microscopy for high-resolution studies of vermilion degradation. Vermilion (mostly α-HgS), an important red pigment used in historical paintings, blackens over time, and metallic Hg and β-HgS have been implicated as possible degradation products. Conventional analysis techniques have trouble differentiating α- and β-HgS with sufficiently high spatial resolution. However, pump-probe microscopy can differentiate metallic mercury, α- and β-HgS, and map each distribution on the microscopic scale. We studied artificial degradation of α-HgS; femtosecond-pulsed laser irradiation induces an irreversible phase shift of α- to β-HgS, in which the initial presence of β-HgS grains can increase the rate of conversion in their vicinity. Continuous ultraviolet exposure instead generates both liquid Hg and β-HgS, with a conversion rate that increases with elevated temperatures. Last, we reveal the presence of β-HgS as a natural degradation product in discolored vermilion layers in a 14th century Italian painting.

The neuroprotective effects and probable mechanisms of Ligustilide and its degradative products on intracerebral hemorrhage in mice

BackgroundIntracerebral hemorrhage (ICH) is a common neurological emergency with higher mortality and disability rate than cerebral ischemia. Although diverse therapeutic interventions have been explored for potential neuroprotection from ICH, no effective drugs until now are available for improvement of survival rate or the life quality of survivors after ICH. Just like cerebral ischemia, inflammatory mechanism is highly thought to play a vital role in hemorrhagic brain injury. Ligustilide (LIG) has potent anti-inflammatory effects, which were shown to be closely related to its neuroprotective effects against ischemic brain injury. Senkyunolide H (SH) and senkyunolide I (SI) are natural degradation products of LIG, which contain the mother nucleus structure of LIG as that of phthalide. However, no reports have been retrieved about the neuroprotective effects of the three phthalide compounds on ICH, especially from the perspectives of inflammatory pathways. Accordingly, this study investigated the neuroprotective potentials and mechanisms of LIG, SH and SI on experimental ICH in mice. MethodsICH was induced in adult male CD-1 mice by intracerebral injection of autologous blood. LIG, SH and SI, respectively, was administrated after ICH induction. Neurological deficits, brain edema, injury volume, the number of surviving/dying neurons and inflammatory gene expression were evaluated at 3 days after ICH. ResultsNeurological deficits, brain edema, neuronal injury, microglia and astrocytes activation as well as peripheral immune cells infiltration were all significantly improved by LIG and SH, yet SI not. Moreover, the expression of TLR4, p-NF-kB p65, TNF-α and IL-6, was significantly downregulated by LIG and SH treatment. So was Prx1 expression and release. ConclusionsLIG and SH provide the potent neuroprotective effects against hemorrhagic stroke by inhibiting Prx1/TLR4/NF-kB signaling and the subsequent immune and neuroinflammation lesions.

Ambient-air ozonolysis of triglycerides in aged fingerprint residues.

In forensic science, reconstructing the timing of events occurring during a criminal offense is of great importance. In some cases, the time when particular evidence was left on a crime scene is a critical matter. The ability to estimate the fingerprint age would raise the evidentiary value of fingerprints tremendously. For this purpose the most promising approach is the analysis of changes in the chemical compositions of fingerprint residues in the course of aging. The focus of our study is the identification of human specific compounds in fingerprint residues, characterized by a significant aging behavior that could analytically be used for the age determination of fingerprints in future. The first challenge is the sensitive detection of trace amounts of relevant human specific fingerprint compounds. Highly sensitive LC-MS methods were developed for the reliable structure identification of unsaturated triglycerides and their natural degradation products in order to proof the aging mechanism that takes place in fingerprint residues. Thus our results build the fundamental basis for further forensic method development and potential application in forensic investigation. Ozonolysis was found to be one of the major lipid degradation pathways in fingerprint residues in ambient air. High-resolution tandem mass spectrometry (HRMS2) was carried out to identify the ozonolysis products (TG48:0-monoozonide) formed under exposure to the highly reactive ozone in atmospheric air. The obtained products were confirmed by matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Despite several challenges and limitations in the age estimation of fingerprints, the identification of individual degradation products of specific unsaturated lipids in aged fingerprint samples represents a significant analytical progress, resulting in a strong increase in the validity of chemical analysis of fingerprints.

Exploring Natural Product Fragments for Drug and Probe Discovery.

Fragment-based ligand discovery is a key technology to develop lead structures for drug discovery. The majority of the fragments employed so far is aromatic and sp2-configured, and there is a high demand of fragments with stereogenic centers. Natural products (NPs) are evolutionary selected ligands for a range of diverse macromolecular targets. Small-sized molecules - fragments - based on NPs may inherit the biological relevance of nature's treasure and could offer novel opportunities to engage challenging protein targets. An overview of this emerging research area is presented. The deconstruction of a complex NP into small fragments marks the beginning of this journey that is facilitated by the synthesis of NP-based 3D fragments. The emerging strategies in organic synthesis for either degradation of NPs to access fragments or de novo construction of fragments and their further combinations to chart novel biologically relevant chemical space is discussed.

A relevant IgE-reactive 28 kDa protein identified from Salsola kali pollen extract by proteomics is a natural degradation product of an integral 47 kDa polygalaturonase

A highly prevalent IgE-binding protein band of 28kDa is observed when Salsola kali pollen extract is incubated with individual sera from Amaranthaceae pollen sensitized patients. By an immunoproteomic analysis of S. kali pollen extract, we identified this protein band as an allergenic polygalacturonase enzyme. The allergen, named Sal k 6, exhibits a pI of 7.14 and a molecular mass of 39,554.2Da. It presents similarities to Platanaceae, Poaceae, and Cupressaceae allergenic polygalacturonases. cDNA-encoding sequence was subcloned into the pET41b vector and produced in bacteria as a His-tag fusion recombinant protein. The far-UV CD spectrum determined that rSal k 6 was folded. Immunostaining of the S. kali pollen protein extract with a rSal k 6-specific pAb and LC-MS/MS proteomic analyses confirmed the co-existence of the 28kDa band together with an allergenic band of about 47kDa in the pollen extract. Therefore, the 28kDa was assigned as a natural degradation product of the 47kDa integral polygalacturonase. The IgE-binding inhibition to S. kali pollen extract using rSal k 6 as inhibitor showed that signals directed to both protein bands of 28 and 47kDa were completely abrogated. The average prevalence of rSal k 6 among the three populations analyzed was 30%, with values correlating well with the levels of grains/m3 of Amaranthaceae pollen. Sal k 6 shares IgE epitopes with Oleaceae members (Fraxinus excelsior, Olea europaea and Syringa vulgaris), with IgE-inhibition values ranging from 20% to 60%, respectively. No IgE-inhibition was observed with plant-derived food extracts.

Elucidation of the relative and absolute stereochemistry of the kalimantacin/batumin antibiotics.

Kalimantacin A and batumin exhibit potent and selective antibiotic activity against Staphylococcus species including MRSA. Both compounds are formed via a hybrid polyketide synthase/non-ribosomal peptide synthetase (PKS-NRPS) biosynthetic pathway and from comparison of the gene clusters it is apparent that batumin from Pseudomonas batumici and kalimantacin from P. fluorescens are the same compound. The linear structure of this unsaturated acid was assigned by spectroscopic methods, but the relative and absolute stereochemistry of the five stereocentres remained unknown. Herein we describe isolation of kalimantacin A and two further metabolites 17,19-diol 2 and 27-descarbomyl hydroxyketone 3 from cultures of P. fluorescens. Their absolute and relative stereochemistries are rigorously determined using a multidisciplinary approach combining natural product degradation and fragment synthesis with bioinformatics and NMR spectroscopy. Diol 2 has the 5R, 15S, 17S, 19R, 26R, 27R configuration and is the immediate biosynthetic precursor of the bioactive kalimantacin A formed by oxidation of the 17-alcohol to the ketone.

Construction of a 3D-shaped, natural product like fragment library by fragmentation and diversification of natural products

A fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of 3D-shaped, natural product like fragments available from commercial sources. In addition, during the course of these studies, novel rearrangements were discovered for Massarigenin C and Cytochalasin E. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering a novel, unexplored and underrepresented chemical space in fragment based drug discovery (FBDD).

Direct Reduction of Legacy Pesticides at Silver Cathodes in Dimethylformamide and Dimethylformamide–Water Mixtures

Mirex and its oxidized derivative decachloropentacyclo[5.3.0.02.6.03.9.04.8]decan-5-one (kepone) are both still widely used in much of the developing world, despite many dangers to the environment. Although its global use is severely restricted, DDT and its natural degradation product, 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (DDE), are still persistent in the environment. Because these pesticides exhibit low solubility in water, they accumulate in sediment layers in waterways and are often found in soils. Stockpiles of these and other halogenated legacy pesticides have been accumulating around the world since their phase-out from use; Mexico, for example, had over 100,000 kg of DDT sequestered in 2009.1 In previous work, our laboratory investigated the direct and metal salen-catalyzed reduction of DDT at carbon cathodes; it was determined that all aliphatic chlorines can be cleaved, resulting in 4,4′-(ethene-1,1-diyl)bis(chlorobenzene) as the principal product.2 Up to the present time, little work has been conducted to show electrochemical reduction of the natural degradation product, DDE. Furthermore, only one electrochemical study of mirex and kepone has been reported, which reveals partial dechlorination of both molecules at lead cathodes in a methanol solution.3 Electrochemical literature contains examples in which other persistent organohalogen pollutants are electrocatalytically reducible at silver cathodes, often with significant positive shifts in potentials in comparison with reductions at other electrodes.4 Recent work in our laboratory revealed that reduction of DDT at a silver cathode in dimethylformamide (DMF) results in the completely dechlorinated products, 1,1′-ethylidenebisbenzene and 1,1-diphenylethene. In the work to be reported in this presentation, we expand upon these previous results by examining the direct reduction of DDE, mirex, and kepone at silver cathodes in DMF as well as in DMF–water mixtures. Our laboratory has previously characterized the cyclic voltammetric behavior of DDT at silver cathodes, and it has found that DDT undergoes a sequence of five reductions in DMF. Similarly, it has recently been determined that DDE shows only four cathodic peaks when reduced at silver in DMF. Preliminary cyclic voltammetric investigations of the reduction of kepone (shown in Figure 1) and mirex have focused on a comparison of their behavior at silver cathodes in DMF with their behavior in DMF–water mixtures. Cyclic voltammograms for reduction of mirex and kepone show similar trends: reductions in DMF are characterized by a multitude of small peaks, whereas fewer well-defined peaks are seen in 9:1 DMF–water mixtures. We conclude that scission of carbon–chlorine bonds proceeds more readily in the presence of an excess of proton donor.Controlled-potential (bulk) electrolyses at silver mesh cathodes have been employed to study the extent of dechlorination of these persistant pollutants. Catholytes from bulk electrolyses of DDT and DDE analyzed by means of GC and GC–MS contain mainly mixtures of completely dechlorinated products (1,1′-ethylidenebisbenzene and 1,1-diphenylethene). Bulk electrolyses of mirex and kepone have also been conducted at potentials corresponding to their most negative cyclic voltammetric peaks, and product distributions have been determined with the aid of GC–MS. A procedure based on the use of stripping analysis has been used to determine the extent of dechlorination of kepone and mirex.

DNA and chromosomal damage induced in fish (Anguilla anguilla L.) by aminomethylphosphonic acid (AMPA)—the major environmental breakdown product of glyphosate

The assessment of the direct impact of breakdown products of pesticide components on aquatic wildlife is ecotoxicologically relevant, but frequently disregarded. In this context, the evaluation of the genotoxic hazard posed by aminomethylphosphonic acid (AMPA--the major natural degradation product of glyphosate) to fish emerges as a critical but unexplored issue. Hence, the main goal of the present research was to assess the AMPA genotoxic potential to fish following short-term exposures (1 and 3 days) to environmentally realistic concentrations (11.8 and 23.6 μg L(-1)), using the comet and erythrocytic nuclear abnormalities (ENA) assays, as reflecting different levels of damage, i.e. DNA and chromosomal damage, respectively. Overall, the present findings pointed out the genotoxic hazard of AMPA to fish and, subsequently, the importance of including it in future studies concerning the risk assessment of glyphosate-based herbicides in the water systems.

Blue transition metal complexes of a natural bilin-type chlorophyll catabolite

Natural pink degradation products of chlorophyll occur in de-greened leaves. They form blue transition metal complexes, some of which show intensive red fluorescence and may serve as highly sensitive reporters of transition metals in plants.

Chlorinated Solvent Source‐Zone Remediation via ZVI‐Clay Soil Mixing: 1‐Year Results

ZVI‐Clay is an emerging remediation approach that combines zero‐valent iron (ZVI)‐mediated degradation and in situ stabilization of chlorinated solvents. Through use of in situ soil mixing to deliver reagents, reagent‐contaminant contact issues associated with natural subsurface heterogeneity are overcome. This article describes implementation, treatment performance, and reaction kinetics during the first year after application of the ZVI‐Clay remediation approach at Marine Corps Base Camp Lejeune, North Carolina. Primary contaminants included trichloroethylene, 1,1,2,2‐tetrachloroethane, and related natural degradation products. For the field application, 22,900 m3 of soils were treated to an average depth of 7.6 m with 2% ZVI and 3% sodium bentonite (dry weight basis). Performance monitoring included analysis of soil and water samples. After 1 year, total concentrations of chlorinated volatile organic compounds (CVOCs) in soil samples were decreased by site‐wide average and median values of 97% and >99%, respectively. Total CVOC concentrations in groundwater were reduced by average and median values of 81% and >99%, respectively. In several of the soil and groundwater monitoring locations, reductions in total CVOC concentrations of greater than 99.9% were apparent. Further reduction in concentrations of chlorinated solvents is expected with time. Pre‐ and post‐mixing average hydraulic conductivity values were 1.7 × 10−5 and 5.2 × 10−8 m/s, respectively, indicating a reduction of about 2.5 orders of magnitude. By achieving simultaneous contaminant mass depletion and hydraulic conductivity reduction, contaminant flux reductions of several orders of magnitude are predicted.

Dissociation of Nystatin and Amphotericin Analogues: Characterisation of Minor Anti-Fungal Macrolides

Tandem mass spectrometry combined with Fourier transform ion cyclotron resonance (FT-ICR) has been the basis for rationalizing the fragmentation mechanisms of anti-fungal macrolides nystatin A(1), amphotericin B and pimaricin. The positive ion mass spectra were not informative, however, the dissociation of deprotonated molecules led to structurally significant ring-opened fragments. Using this approach of tandem FT-ICR mass spectrometry and electrospray ionisation coupled with high-performance liquid -chromatography (HPLC), 11 macrolide natural analogues or degradation products were characterised in the nystatin mixture.

Electrochemical treatment of drainage water from toxic dump of pesticides and degradation products

Polluted drainage water from a dump of toxic chemical waste containing organophosphoric pesticides and their natural degradation products was treated with electrochemical oxidation in order to investigate the applicability of the technique in remediation of natural complex polluted water. The dump is located adjacent to the sea in sand dunes, the natural salinity of the investigated water was 0.7 w/w% and sodium chloride served as main electrolyte. A commercial available flow cell with a tubular design, Ti/Pt 90–Ir 10 anode, and 316 SS cathode was applied, and the electrolysis experiments were conducted in a batch recirculation experimental set-up. COD measurements showed that the overall oxidation of organic and inorganic substances followed first-order kinetics by the current densities investigated, 310–1131 mA cm −2, and the COD removal rate increased by increased current density and to a minor extent by increased salinity up to 2.0 w/w%. Evaluation of ICE and energy consumption showed that further optimization is possible and needed. The target organic pollutants parathion, methyl-parathion, malathion, ethylaminoparathion, paraoxon, and several phosphoric triesters were all degraded during the treatment except O,O,O-triethylphosphoric acid, a compound formed during the electrochemical process with a highly stable low energy structure, rendering it recalcitrant to participate in the oxidation reaction. The degradation of the subjected organics was found to be caused by indirect oxidation by the hypochlorous/hypochlorite pair as the main oxidizing agent, produced by the anodic oxidation of chloride. The study has showed that electrochemical chloride mediated indirect oxidation is a relevant, neat and possible solution for the remediation of organophosphoric pesticide polluted natural water.

Modification of Vimentin

In a recent study, we were able to show that the intermediate filament protein vimentin aggregates in human dermal fibroblasts because of modification by the advanced glycation endproduct carboxymethyllysine (CML). In this work, we investigated the formation of intracellular CML in relation to the concentration of glucose in the culture medium. The natural degradation product of glucose, methylglyoxal, was able to induce the aggregation of vimentin. This dicarbonyl leads to the formation of the modifications MG-H1 and carboxyethyllysine (CEL) as a result of the reaction with arginine and lysine residues of proteins. Furthermore, we found that the protein vimentin was modified, not only by CML and CEL, but also by pentosidine and pyrraline. These findings underline the special position of vimentin as a preferential target of the Maillard reaction in human skin.

Stereochemical Assignment of the C1—C6 Fragment of Psymberin (I) by Synthesis and Natural Product Degradation.

Stereochemical Assignment of the C₁—C₆ Fragment of Psymberin (I) by Synthesis and Natural Product Degradation.

Evaluation of HCH isomers and metabolites in soils, leachates, river water and sediments of a highly contaminated area

In this work we evaluate the contamination caused by HCH residues in the soil, leachates, river water and sediments of an industrial estate of the NW of Spain. We study the distribution of the isomers in the different matrices, analysing 37 soil samples, collected in eight points at several depths, six natural leachates, four river water samples and three river sediments. Soil and leachate samples present very high levels of HCH isomers, higher than the established by legislation, and some pesticides were also detected in the analysed river water whereas no pesticides were detected in the river sediments. The distribution of isomers was different depending on the matrix analysed. Some natural degradation products and also other organochlorine pesticides were detected in the samples analysed.