Articles & Third-Party References

Recent journal articles and third-party references about ACD/Labs from the last year

Qualitative screening for new psychoactive substances in wastewater collected during a city festival using liquid chromatography coupled to high-resolution mass spectrometry
Oct 01, 2017
A. Causanilles, J. Kinyua, C. Ruttkies, A.L.N. van Nuijs, E. Emke, A. Covaci, P. de Voogt
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The inclusion of new psychoactive substances (NPS) in the wastewater-based epidemiology approach presents challenges, such as the reduced number of users that translates into low concentrations of residues and the limited pharmacokinetics information available, which renders the choice of target biomarker difficult. The sampling during special social settings, the analysis with improved analytical techniques, and data processing with specific workflow to narrow the search, are required approaches for a successful monitoring. This work presents the application of a qualitative screening technique to wastewater samples collected during a city festival, where likely users of recreational substances gather and consequently higher residual concentrations of used NPS are expected. The analysis was performed using liquid chromatography coupled to high-resolution mass spectrometry. Data were processed using an algorithm that involves the extraction of accurate masses (calculated based on molecular formula) of expected m/z from an in-house database containing about 2,000 entries, including NPS and transformation products. We positively identified eight NPS belonging to the classes of synthetic cathinones, phenethylamines and opioids. In addition, the presence of benzodiazepine analogues, classical drugs and other licit substances with potential for abuse was confirmed. The screening workflow based on a database search was useful in the identification of NPS biomarkers in wastewater. The findings highlight the specific classical drugs and low NPS use in the Netherlands. Additionally, meta-chlorophenylpiperazine (mCPP), 2,5-dimethoxy-4-bromophenethylamine (2C-B), and 4-fluoroamphetamine (FA) were identified in wastewater for the first time.
Chemosphere, 184: 1186–93

Targeted Dereplication of Microbial Natural Products by High-Resolution MS and Predicted LC Retention Time
Apr 26, 2017
J. Chervin, M. Stierhof, M.H. Tong, D. Peace, K. Østnes Hansen, D.S. Urgast, J.H. Andersen, Y. Yu, R. Ebel, K. Kyeremeh, V. Paget, G. Cimpan, A. Van Wyk, H. Deng, M. Jaspars, and J.N. Tabudravu
Journal of Natural Products
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A new strategy for the identification of known compounds in Streptomyces extracts that can be applied in the discovery of natural products is presented. The strategy incorporates screening a database of 5555 natural products including 5098 structures from Streptomyces sp., using a high-throughput LCMS data processing algorithm that utilizes HRMS data and predicted LC retention times (tR) as filters for rapid identification of known compounds in the natural product extract. The database, named StrepDB, contains for each compound the structure, molecular formula, molecular mass, and predicted LC retention time. All identified compounds are annotated and color coded for easier visualization. It is an indirect approach to quickly assess masses (which are not annotated) that may potentially lead to the discovery of new or novel structures. In addition, a spectral database named MbcDB was generated using the ACD/Spectrus DB Platform. MbcDB contains 665 natural products, each with structure, experimental HRESIMS, MS/MS, UV, and NMR spectra. StrepDB was used to screen a mutant Streptomyces albus extract, which led to the identification and isolation of two new compounds, legonmaleimides A and B, the structures of which were elucidated with the aid of MbcDB and spectroscopic techniques. The structures were confirmed by computer-assisted structure elucidation (CASE) methods using ACD/Structure Elucidator Suite. The developed methodology suggests a pipeline approach to the dereplication of extracts and discovery of novel natural products.
J. Nat. Prod., 2017, 80 (5): 1370-1377

Relative toxicological ranking of eight polybrominated diphenyl ether congeners using cytotoxicity, chemical properties and exposure data
Feb 26, 2017
Sabrina Tait, Monia Perugini, Cinzia La Rocca
Food and Chemical Toxicology
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Polybrominated diphenyl ethers are widely used flame retardants which persist and diffuse in the environment thus entering the food chain. Eight congeners, most relevant for human exposure (BDE-28, 47, 99, 100, 153, 154, 183 and 209), were analyzed in vitro and in silico to derive a relative toxicological ranking.

Cytotoxicity was assessed on human liver (HepG2) and colon (DLD-1) cell lines, by three assays (MTS, ATP and DNA content) in a range of realistic concentration (1pM - 10 nM). Jejunum and Caco-2 passive absorptions were calculated in silico. Exposure estimates were calculated using EFSA database. By ToxPi we integrated the overall data.

No reduction of DNA content was observed, supporting absence of cytotoxicity. Otherwise, hormetic effects were exerted by all the congeners, except BDE-183. BDE-28, 47, 99, 100 differently affected the ATP content inducing a dose-related increase in HepG2 and depletion in DLD-1. Jejunum coefficients did not differ among congeners, whereas a higher Caco-2 coefficient indicates rapid absorption of BDE-28.

ToxPi relative rankings support the toxicological relevance of BDE-153 and 28 congeners for their potential hazard; the inclusion of exposure data in young and adult populations shifted BDE-209 and BDE-47 as top ranked due to their widespread occurrence in the diet.
Food and Chemical Toxicology. 108 (Part A): 74–84, 2017

Determination of acid dissociation constants (pKa) of cephalosporin antibiotics: Computational and experimental approaches
Nov 18, 2016
Alyson R. Ribeiro, Torsten C. Schmidt
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Cefapirin (CEPA) and ceftiofur (CEF) are two examples of widely used veterinarian cephalosporins presenting multiple ionization centers. However, the acid dissociation constants (pKa) of CEF are missing and experimental data about CEPA are rare. The same is true for many cephalosporins, where available data are either incomplete or even wrong. Environmentally relevant biotic and abiotic processes depend primordially on the antibiotic pH-dependent speciation. Consequently, this physicochemical parameter should be reliable, including the correct ionization center identification. In this direction, two experimental techniques, potentiometry and spectrophotometry, along with two well-known pKa predictors, Marvin and ACD/Percepta, were used to study the macro dissociation constants of CEPA and CEF. Additionally, the experimental dissociation constants of 14 cephalosporins available in the literature were revised, compiled and compared with data obtained in silico. Only one value was determined experimentally for CEF (2.68 ± 0.05), which was associated to the carboxylic acid group deprotonation. For CEPA two values were obtained experimentally: 2.74 ± 0.01 for the carboxylic acid deprotonation and 5.13 ± 0.01 for the pyridinium ring deprotonation. In general, experimentally obtained values agree with the in silico predicted data (ACD/Percepta RMSE: 0.552 and Marvin RMSE: 0.706, n = 88). However, for cephalosporins having imine and aminothiazole groups structurally close, Marvin presented problems in pKa predictions. For the biological and environmental fate and effect discussion, it is important to recognize that CEPA and CEF, as well as many other cephalosporins, are present as anionic species in the biologic and environmentally relevant pH values of 6–7.5.
Chemosphere. 169:524–533.

Facing a formidable challenge
Oct 31, 2016
S. Ktori (Scientific Computing World)
Scientific Computing World
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Andrew Anderson and Graham A. McGibbon discuss ACD/Labs' partnership with the Allotrope Foundation.
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