Abstract
ChEMBL is a large, open-access bioactivity database (https://www.ebi.ac.uk/chembl), previously described in the 2012, 2014 and 2017 Nucleic Acids Research Database Issues. In the last two ...years, several important improvements have been made to the database and are described here. These include more robust capture and representation of assay details; a new data deposition system, allowing updating of data sets and deposition of supplementary data; and a completely redesigned web interface, with enhanced search and filtering capabilities.
Background
The ChEMBL database is one of a number of public databases that contain bioactivity data on small molecule compounds curated from diverse sources. Incoming compounds are typically not ...standardised according to consistent rules. In order to maintain the quality of the final database and to easily compare and integrate data on the same compound from different sources it is necessary for the chemical structures in the database to be appropriately standardised.
Results
A chemical curation pipeline has been developed using the open source toolkit RDKit. It comprises three components: a
Checker
to test the validity of chemical structures and flag any serious errors; a
Standardizer
which formats compounds according to defined rules and conventions and a
GetParent
component that removes any salts and solvents from the compound to create its parent. This pipeline has been applied to the latest version of the ChEMBL database as well as uncurated datasets from other sources to test the robustness of the process and to identify common issues in database molecular structures.
Conclusion
All the components of the structure pipeline have been made freely available for other researchers to use and adapt for their own use. The code is available in a GitHub repository and it can also be accessed via the ChEMBL Beaker webservices. It has been used successfully to standardise the nearly 2 million compounds in the ChEMBL database and the compound validity checker has been used to identify compounds with the most serious issues so that they can be prioritised for manual curation.
In southeast Asia, the widespread high prevalence of counterfeits tablets of the vital antimalarial artesunate is of great public health concern. To assess the seriousness of this problem, we ...quantified the amount of active ingredient present in artesunate tablets by liquid chromatography coupled to mass spectrometry. This method, in conjunction with analysis of the packaging, classified tablets as genuine, substandard, or fake and validated results of the colorimetric Fast Red TR test. Eight (35%) of 23 fake artesunate samples contained the wrong active ingredients, which were identified as different erythromycins and paracetamol. Raman spectroscopy identified calcium carbonate as an excipient in 9 (39%) of 23 fake samples. Multivariate unsupervised pattern recognition results indicated two major clusters of artesunate counterfeits, those with counterfeit foil stickers and containing calcium carbonate, erythromycin, and paracetamol, and those with counterfeit holograms and containing starch but without evidence of erythromycin or paracetamol.
During the last few years, counterfeiters have become increasingly sophisticated by falsifying drugs and making them look identical to genuine tablets. In this paper, Raman spectroscopy is proposed ...as a fast and reliable method for the detection of counterfeit Viagra
® tablets. This technique can easily differentiate genuine from counterfeit tablets without the need of sample preparation. In total 18 tablets were analysed which all contained the active ingredient sildenafil, but different excipients were used, as could be observed in the Raman spectra between 1150 and 700
cm
−1. So, the spectra could be divided into genuine or counterfeit. Additionally, principal component analysis (PCA), combined with hierarchical cluster analysis (HCA), was used to establish an automated approach for the discrimination of counterfeit from genuine Viagra
® tablets. Raman spectroscopy, combined with principal components analysis, could be used in the future by customs or in the field to identify counterfeit tablets on the spot without involvement of trained chemists.
In general, the first overtone modes produce weak bands that appear at approximately twice the wavenumber value of the fundamental transitions in vibrational spectra. Here, we report the existence of ...a series of enhanced non-fundamental bands in resonance Raman (RR) spectra recorded for hemoglobin (Hb) inside the highly concentrated heme environment of the red blood cell (RBC) by exciting with a 514.5 nm laser line. Such bands are most intense when detecting parallel-polarized light. The enhancement is explained through excitonic theory invoking a type C scattering mechanism and bands have been assigned to overtone and combination bands based on symmetry arguments and polarization measurements. By using malaria diagnosis as an example, we demonstrate that combining the non-fundamental and fundamental regions of the RR spectrum improves the sensitivity and diagnostic capability of the technique. The discovery will have considerable implications for the ongoing development of Raman spectroscopy for blood disease diagnoses and monitoring heme perturbation in response to environmental stimuli.
In general, the first overtone modes produce weak bands that appear at approximately twice the wavenumber value of the fundamental transitions in vibrational spectra. Here, we report the existence of ...a series of enhanced non‐fundamental bands in resonance Raman (RR) spectra recorded for hemoglobin (Hb) inside the highly concentrated heme environment of the red blood cell (RBC) by exciting with a 514.5 nm laser line. Such bands are most intense when detecting parallel‐polarized light. The enhancement is explained through excitonic theory invoking a type C scattering mechanism and bands have been assigned to overtone and combination bands based on symmetry arguments and polarization measurements. By using malaria diagnosis as an example, we demonstrate that combining the non‐fundamental and fundamental regions of the RR spectrum improves the sensitivity and diagnostic capability of the technique. The discovery will have considerable implications for the ongoing development of Raman spectroscopy for blood disease diagnoses and monitoring heme perturbation in response to environmental stimuli.
Band aid: Red blood cells and solid‐state hemes give rise to intense overtone bands when excited with green laser light.
No disposal option exists for “mixed wastes” such as paint scrapings that are co-contaminated with polychlorinated biphenyls (PCBs) and radioactive metals. Either removal or destruction of the PCBs ...is required prior to disposal. Comparison of subcritical water dechlorination (350 °C, 1 h) of Aroclor 1254 in paint scrapings (180 ppm) and of standard Aroclor 1254 showed significantly enhanced dechlorination in the presence of paint. While no significant degradation was observed for standard Aroclor (no paint), the dechlorination of PCBs in paint was 99, 99, and 80% for the hepta-, hexa-, and pentachlorinated congeners, respectively, indicating that metals in the paint enhanced the dechlorination reactions. Adding metals to the standard Aroclor (no paint) reactions enhanced PCB dechlorination in subcritical water in descending order of activity: Pb ≈ Cu > Al > Zn > Fe. In the presence of both zerovalent and divalent lead and zerovalent copper in subcritical water (350 °C, 1 h), 99% of the Aroclor 1254 mixture (tetra- to heptachlorinated biphenyls) was dechlorinated. High dechlorination (ca. 95%) was also achieved with zerovalent aluminum. In contrast to other metals, lead retained its degradation ability at a lower temperature of 250 °C after 18 h. The high degradation efficiency achieved using metal additives in water at reasonable temperatures and pressures demonstrates the potential for subcritical water dechlorination of PCBs in paint scrapings and, potentially, in other solid and liquid wastes.
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