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Assay and Drug Development Technologies Apr 2016Nonspecific bioactivity and assay artifacts have gained increasing attention in recent years. This focus has arisen primarily from the publication of a set of chemical...
Nonspecific bioactivity and assay artifacts have gained increasing attention in recent years. This focus has arisen primarily from the publication of a set of chemical substructures, termed pan assay interference compounds (PAINS), which are associated with promiscuous bioactivity and assay interference in real and virtual high-throughput screening (HTS) campaigns. Despite an increasing awareness in the HTS and medicinal chemistry communities about the liabilities of these compounds, articles featuring PAINS and PAINS-like compounds are still being published. In this perspective, we describe some of the factors we believe are driving this resource-sapping trend. We also provide what we hope are helpful insights that may lead to the earlier recognition of these generally nontranslatable compounds, thus preventing the propagation of PAINS-full costly research.
Topics: Artifacts; Chemistry, Pharmaceutical; Drug Discovery; High-Throughput Screening Assays; Humans; Molecular Structure; Organic Chemicals
PubMed: 26496388
DOI: 10.1089/adt.2015.674 -
Chemical Reviews Jan 2018The review compiles artificial cascades involving enzymes with a focus on the last 10 years. A cascade is defined as the combination of at least two reaction steps in a... (Review)
Review
The review compiles artificial cascades involving enzymes with a focus on the last 10 years. A cascade is defined as the combination of at least two reaction steps in a single reaction vessel without isolation of the intermediates, whereby at least one step is catalyzed by an enzyme. Additionally, cascades performed in vivo and in vitro are discussed separately, whereby in vivo cascades are defined here as cascades relying on cofactor recycling by the metabolism or on a metabolite from the living organism. The review introduces a systematic classification of the cascades according to the number of enzymes in the linear sequence and differentiates between cascades involving exclusively enzymes and combinations of enzymes with non-natural catalysts or chemical steps. Since the number of examples involving two enzymes is predominant, the two enzyme cascades are further subdivided according to the number, order, and type of redox steps. Furthermore, this classification differentiates between cascades where all reaction steps are performed simultaneously, sequentially, or in flow.
Topics: Bacteria; Biocatalysis; Enzymes; Epoxide Hydrolases; Laccase; Metals; Organic Chemicals; Oxidation-Reduction
PubMed: 28481088
DOI: 10.1021/acs.chemrev.7b00033 -
Environmental Research Apr 2017Current exposure assessment research does not sufficiently address multi-pollutant exposure and their correlations in human media. Understanding the extent of chemical...
BACKGROUND
Current exposure assessment research does not sufficiently address multi-pollutant exposure and their correlations in human media. Understanding the extent of chemical exposure in reproductive-aged women is of particular concern due to the potential for in utero exposure and fetal susceptibility.
OBJECTIVES
The objectives of this study were to characterize concentrations of chemical biomarkers during preconception and examine correlations between and within chemical classes.
METHODS
We examined concentrations of 135 biomarkers from 16 chemical classes in blood and urine from 73 women aged 18-40 enrolled in Snart Foraeldre/Milieu, a prospective cohort study of pregnancy planners in Denmark (2011-2014). We compared biomarker concentrations with United States similarly-aged, non-pregnant women who participated in the National Health and Nutrition Environmental Survey (NHANES) and with other international biomonitoring studies. We performed principal component analysis to examine biomarker correlations.
RESULTS
The mean number of biomarkers detected in the population was 92 (range: 60-108). The most commonly detected chemical classes were phthalates, metals, phytoestrogens and polycyclic aromatic hydrocarbons. Except blood mercury, urinary barium and enterolactone, geometric means were higher in women from NHANES. Chemical classes measured in urine generally did not load on a single component, suggesting high between-class correlation among urinary biomarkers, while there is high within-class correlation for biomarkers measured in serum and blood.
CONCLUSIONS
We identified ubiquitous exposure to multiple chemical classes in reproductive-aged Danish women, supporting the need for more research on chemical mixtures during preconception and early pregnancy. Inter- and intra-class correlation between measured biomarkers may reflect common exposure sources, specific lifestyle factors or shared metabolism pathways.
Topics: Adolescent; Adult; Biomarkers; Denmark; Environmental Exposure; Environmental Pollutants; Female; Humans; Organic Chemicals; Principal Component Analysis; Reproductive History; Socioeconomic Factors; Young Adult
PubMed: 28039828
DOI: 10.1016/j.envres.2016.12.011 -
Ecotoxicology and Environmental Safety Jan 2021The presence of xenobiotic compounds especially organic micro-pollutants in municipal wastewater treatment plant (MWWTP) is a major concern worldwide. The occurrence and...
The presence of xenobiotic compounds especially organic micro-pollutants in municipal wastewater treatment plant (MWWTP) is a major concern worldwide. The occurrence and removal of trace organic pollutants in a MWWTP by a combined analysis using GC-MS with spectral analysis and acute toxicity were studied in this work. Non-target screening and toxicity analysis of organic compounds were conducted to understand the types of toxic and refractory pollutants in municipal wastewater and evaluated the toxicity removal efficiency of MWWTP. The results showed that most of the effects were significantly reduced or completely eliminated during the wastewater treatment process, while some compounds, such as antioxidants, drugs, and organic plasticizers, had detection rates of up to 100% at each site, indicating that these harmful substances remained throughout wastewater treatment process. Based on Pearson correlation analysis, paired correlation analysis showed a positive correlation between UV, humification index, conventional parameters, and organic acute toxicity, while acute toxicity was negatively correlated with biological index and fluorescence index. The results indicated that the composition of MWWTP had a similar influence law in different locations, and the combination of spectral analysis provided a new insight to qualitatively and quantitatively showed the distribution of organic pollutants in the wastewater treatment system.
Topics: Environmental Monitoring; Gas Chromatography-Mass Spectrometry; Organic Chemicals; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical
PubMed: 32905934
DOI: 10.1016/j.ecoenv.2020.111237 -
Molecules (Basel, Switzerland) Sep 2022Predicting products of organic chemical reactions is useful in chemical sciences, especially when one or more reactants are new organics. However, the performance of...
Predicting products of organic chemical reactions is useful in chemical sciences, especially when one or more reactants are new organics. However, the performance of traditional learning models heavily relies on high-quality labeled data. In this work, to utilize unlabeled data for better prediction performance, we propose a method that combines semi-supervised learning with graph convolutional neural networks for chemical reaction prediction. First, we propose a Mean Teacher Weisfeiler-Lehman Network to find the reaction centers. Then, we construct the candidate product set. Finally, we use an Improved Weisfeiler-Lehman Difference Network to rank candidate products. Experimental results demonstrate that, with 400k labeled data, our framework can improve the top-5 accuracy by 0.7% using 35k unlabeled data. When the proportion of unlabeled data increases, the performance gain can be larger. For example, with 80k labeled data and 35k unlabeled data, the performance gain with our framework can be 1.8%.
Topics: Neural Networks, Computer; Organic Chemicals; Supervised Machine Learning
PubMed: 36144703
DOI: 10.3390/molecules27185967 -
Journal of Proteome Research Jun 2022Generating comprehensive and high-fidelity metabolomics data matrices from LC/HRMS data remains to be extremely challenging for population-scale large studies ( > 200)....
Generating comprehensive and high-fidelity metabolomics data matrices from LC/HRMS data remains to be extremely challenging for population-scale large studies ( > 200). Here, we present a new data processing pipeline, the Intrinsic Peak Analysis (IDSL.IPA) R package (https://ipa.idsl.me), to generate such data matrices specifically for organic compounds. The IDSL.IPA pipeline incorporates (1) identifying potential C and C ion pairs in individual mass spectra; (2) detecting and characterizing chromatographic peaks using a new sensitive and versatile approach to perform mass correction, peak smoothing, baseline development for local noise measurement, and peak quality determination; (3) correcting retention time and cross-referencing peaks from multiple samples by a dynamic retention index marker approach; (4) annotating peaks using a reference database of / and retention time; and (5) accelerating data processing using a parallel computation of the peak detection and alignment steps for larger studies. This pipeline has been successfully evaluated for studies ranging from 200 to 1600 samples. By specifically isolating high quality and reliable signals pertaining to carbon-containing compounds in untargeted LC/HRMS data sets from larger studies, IDSL.IPA opens new opportunities for discovering new biological insights in the population-scale metabolomics and exposomics projects. The package is available in the R CRAN repository at https://cran.r-project.org/package=IDSL.IPA.
Topics: Chromatography, Liquid; Mass Spectrometry; Metabolomics; Organic Chemicals; Software
PubMed: 35579321
DOI: 10.1021/acs.jproteome.2c00120 -
Environmental Science & Technology Jan 2016We reviewed compliance monitoring requirements in the European Union, the United States, and the Oslo-Paris Convention for the protection of the marine environment of... (Review)
Review
We reviewed compliance monitoring requirements in the European Union, the United States, and the Oslo-Paris Convention for the protection of the marine environment of the North-East Atlantic, and evaluated if these are met by passive sampling methods for nonpolar compounds. The strengths and shortcomings of passive sampling are assessed for water, sediments, and biota. Passive water sampling is a suitable technique for measuring concentrations of freely dissolved compounds. This method yields results that are incompatible with the EU's quality standard definition in terms of total concentrations in water, but this definition has little scientific basis. Insufficient quality control is a present weakness of passive sampling in water. Laboratory performance studies and the development of standardized methods are needed to improve data quality and to encourage the use of passive sampling by commercial laboratories and monitoring agencies. Successful prediction of bioaccumulation based on passive sampling is well documented for organisms at the lower trophic levels, but requires more research for higher levels. Despite the existence of several knowledge gaps, passive sampling presently is the best available technology for chemical monitoring of nonpolar organic compounds. Key issues to be addressed by scientists and environmental managers are outlined.
Topics: Biota; Environmental Monitoring; Geologic Sediments; Organic Chemicals; Water Pollutants, Chemical
PubMed: 26619247
DOI: 10.1021/acs.est.5b04050 -
Bioscience, Biotechnology, and... 2011Enzymes that catalyze the conversion of organohalogen compounds have been attracting a great deal of attention, partly because of their possible applications in... (Review)
Review
Enzymes that catalyze the conversion of organohalogen compounds have been attracting a great deal of attention, partly because of their possible applications in environmental technology and the chemical industry. We have studied the mechanisms of enzymatic degradation of various organic halo acids. In the reaction of L-2-haloacid dehalogenase and fluoroacetate dehalogenase, the carboxylate group of the catalytic aspartate residue nucleophilically attacked the α-carbon atom of the substrates to displace the halogen atom. In the reaction catalyzed by DL-2-haloacid dehalogenase, a water molecule directly attacked the substrate to displace the halogen atom. In the course of studies on the metabolism of 2-chloroacrylate, we discovered two new enzymes. 2-Haloacrylate reductase catalyzed the asymmetric reduction of 2-haloacrylate to produce L-2-haloalkanoic acid in an NADPH-dependent manner. 2-Haloacrylate hydratase catalyzed the hydration of 2-haloacrylate to produce pyruvate. The enzyme is unique in that it catalyzes the non-redox reaction in an FADH(2)-dependent manner.
Topics: Animals; Enzymes; Halogens; Hydro-Lyases; Hydrolases; Organic Chemicals; Oxidoreductases
PubMed: 21307570
DOI: 10.1271/bbb.100746 -
Molecules (Basel, Switzerland) Nov 2016To overcome the well-established drawbacks of conventional organic solvents (toxicity, non-biodegradability, flammability, accumulation in the atmosphere) remarkable...
To overcome the well-established drawbacks of conventional organic solvents (toxicity, non-biodegradability, flammability, accumulation in the atmosphere) remarkable research efforts have been recently devoted to the replacement of traditional organic reaction media by the so-called . In this sense, the choice of a safe, non-toxic, biorenewable and cheap reaction media is a crucial goal in organic synthesis. Thus, this Special Issue on "" has been aimed to showcase a series of stimulating contributions from international experts within different sub-areas of organic synthesis in (ranging from metal- to organo-catalyzed organic reactions).
Topics: Chemistry Techniques, Synthetic; Green Chemistry Technology; Organic Chemicals; Solvents
PubMed: 27854295
DOI: 10.3390/molecules21111527 -
Molecules (Basel, Switzerland) Aug 2018,-Dimethylformamide and ,-dimethylacetamide are multipurpose reagents which deliver their own H, C, N and O atoms for the synthesis of a variety of compounds under a... (Review)
Review
,-Dimethylformamide and ,-dimethylacetamide are multipurpose reagents which deliver their own H, C, N and O atoms for the synthesis of a variety of compounds under a number of different experimental conditions. The review mainly highlights the corresponding literature published over the last years.
Topics: Acetamides; Dimethylformamide; Indicators and Reagents; Molecular Structure; Organic Chemicals; Solvents
PubMed: 30081462
DOI: 10.3390/molecules23081939