The Experts below are selected from a list of 30867 Experts worldwide ranked by ideXlab platform
Erin E. Carlson - One of the best experts on this subject based on the ideXlab platform.
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Structure Elucidation of macrolide antibiotics using msn analysis and deuterium labelling
Journal of the American Society for Mass Spectrometry, 2019Co-Authors: Andrew R Johnson, Erin E. CarlsonAbstract:: The 14- and 16-membered macrolide antibiotics are an important structural class. Ubiquitously produced by a number of bacterial strains, namely actinomycetes, purification and Structure Elucidation of the wide array of analogs is challenging, both for discovery efforts and methodologies to monitor for byproducts, metabolites, and contaminants. Collision-induced dissociation mass spectrometry offers an attractive solution, enabling characterization of mixtures, and providing a wealth of structural information. However, interpretation of these spectra can be difficult. We present a study of 14- and 16-membered macrolide antibiotics, including MSn analysis for unprecedented depth of coverage, and complimentary analysis with D2O and H218O labeling to elucidate fragmentation mechanisms. These analyses contrast the behaviors of varying classes of macrolides and highlight how analogues can be identified in relation to similar Structures, which will provide utility for future studies of novel macrolides, as well as impurities, metabolites, and degradation products of pharmaceuticals. Graphical Abstract.
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collision induced dissociation mass spectrometry a powerful tool for natural product Structure Elucidation
Analytical Chemistry, 2015Co-Authors: Andrew R Johnson, Erin E. CarlsonAbstract:Mass spectrometry is a powerful tool in natural product Structure Elucidation, but our ability to directly correlate fragmentation spectra to these Structures lags far behind similar efforts in pep...
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collision induced dissociation mass spectrometry a powerful tool for natural product Structure Elucidation
Analytical Chemistry, 2015Co-Authors: Andrew R Johnson, Erin E. CarlsonAbstract:Abstract Mass spectrometry is a powerful tool in natural product Structure Elucidation, but our ability to directly correlate fragmentation spectra to these Structures lags far behind similar efforts in peptide sequencing and proteomics. Often, manual data interpretation is required and our knowledge of the expected fragmentation patterns for many scaffolds is limited, further complicating analysis. Here, we summarize advances in natural product Structure Elucidation based upon the application of collision induced dissociation fragmentation mechanisms.
Kirill A Blinov - One of the best experts on this subject based on the ideXlab platform.
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application of 1 n adequate and modified variants to Structure Elucidation and spectral assignment problems
ChemInform, 2016Co-Authors: Gary E Martin, Kirill A Blinov, Mikhail Reibarkh, Alexei V Buevich, Thomas R WilliamsonAbstract:This article has no abstract. Keywords: 1,n-ADEQUATE; inverted 1JCC 1,n-ADEQUATE; dual optimization; Structure Elucidation; long-range correlation; cryogenic NMR probes; small volume probes
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the impact of lr hsqmbc very long range heteronuclear correlation data on computer assisted Structure Elucidation
Organic and Biomolecular Chemistry, 2014Co-Authors: Kirill A Blinov, Alexei V Buevich, R T Williamson, Gary E MartinAbstract:The impact of LR-HSQMBC very long-range nJCH heteronuclear shift correlation data as a supplement to HMBC data as input for the computer-assisted Structure Elucidation program, Structure Elucidator®, is assessed for the first time. The severely proton-deficient xanthone antibiotic cervinomycin A2 and the alkaloid staurosporine were employed as a model compounds.
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structural revisions of natural products by computer assisted Structure Elucidation case systems
Natural Product Reports, 2010Co-Authors: Mikhail E Elyashberg, Antony J Williams, Kirill A BlinovAbstract:Covering: up to the end of 2009 It is shown in this review that the application of an expert system for the purpose of computer-assisted Structure Elucidation allows the researcher to avoid the production of incorrect structural hypotheses, and also to evaluate the reliability of suggested Structures. Many examples of Structure revision using CASE methods are given.
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computer assisted methods for molecular Structure Elucidation realizing a spectroscopist s dream
ChemInform, 2010Co-Authors: Mikhail E Elyashberg, Kirill A Blinov, Antony J Williams, Sergey G Molodtsov, Yegor D Smurnyy, Tatiana S ChuranovaAbstract:This article coincides with the 40 year anniversary of the first published works devoted to the creation of algorithms for computer-aided Structure Elucidation (CASE). The general principles on which CASE methods are based will be reviewed and the present state of the art in this field will be described using, as an example, the expert system Structure Elucidator. The developers of CASE systems have been forced to overcome many obstacles hindering the development of a software application capable of drastically reducing the time and effort required to determine the Structures of newly isolated organic compounds. Large complex molecules of up to 100 or more skeletal atoms with topological peculiarity can be quickly identified using the expert system Structure Elucidator based on spectral data. Logical analysis of 2D NMR data frequently allows for the detection of the presence of COSY and HMBC correlations of "nonstandard" length. Fuzzy Structure generation provides a possibility to obtain the correct solution even in those cases when an unknown number of nonstandard correlations of unknown length are present in the spectra. The relative stereochemistry of big rigid molecules containing many stereocenters can be determined using the StrucEluc system and NOESY/ROESY 2D NMR data for this purpose. The StrucEluc system continues to be developed in order to expand the general applicability, provide improved workflows, usability of the system and increased reliability of the results. It is expected that expert systems similar to that described in this paper will receive increasing acceptance in the next decade and will ultimately be integrated directly to analytical instruments for the purpose of organic analysis. Work in this direction is in progress. In spite of the fact that many difficulties have already been overcome to deliver on the spectroscopist's dream of "fully automated Structure Elucidation" there is still work to do. Nevertheless, as the efficiency of expert systems is enhanced the solution of increasingly complex structural problems will be achievable.
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are deterministic expert systems for computer assisted Structure Elucidation obsolete
Journal of Chemical Information and Modeling, 2006Co-Authors: Mikhail E Elyashberg, Kirill A Blinov, Antony J Williams, Sergey G Molodtsov, Gary E MartinAbstract:Expert systems for spectroscopic molecular Structure Elucidation have been developed since the mid-1960s. Algorithms associated with the Structure generation process within these systems are deterministic; that is, they are based on graph theory and combinatorial analysis. A series of expert systems utilizing 2D NMR spectra have been described in the literature and are capable of determining the molecular Structures of large organic molecules including complex natural products. Recently, an opinion was expressed in the literature that these systems would fail when elucidating Structures containing more than 30 heavy atoms. A suggestion was put forward that stochastic algorithms for Structure generation would be necessary to overcome this shortcoming. In this article, we describe a comprehensive investigation of the capabilities of the deterministic expert system Structure Elucidator. The results of performing the Structure Elucidation of 250 complex natural products with this program were studied and generalized. The conclusion is that 2D NMR deterministic expert systems are certainly capable of elucidating large Structures (up to about 100 heavy atoms) and can deal with the complexities associated with both poor and contradictory spectral data.
Juliane Hollender - One of the best experts on this subject based on the ideXlab platform.
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biotransformation pathways of biocides and pharmaceuticals in freshwater crustaceans based on Structure Elucidation of metabolites using high resolution mass spectrometry
Chemical Research in Toxicology, 2013Co-Authors: Junho Jeon, Denise Kurth, Juliane HollenderAbstract:So far, there is limited information on biotransformation mechanisms and products of polar contaminants in freshwater crustaceans. In the present study, metabolites of biocides and pharmaceuticals formed in Gammarus pulex and Daphnia magna were identified using liquid chromatography–high resolution mass spectrometry. Different confidence levels were assigned to the identification of metabolites without reference standards using a framework based on the background evidence used for Structure Elucidation. Twenty-five metabolites were tentatively identified for irgarol, terbutryn, tramadol, and venlafaxine in G. pulex (21 via oxidation and 4 via conjugation reactions) and 11 metabolites in D. magna (7 via oxidation and 4 via conjugation reactions), while no evidence of metabolites for clarithromycin and valsartan was found. Of the 360 metabolites predicted for the four parent compounds using pathway prediction systems and expert knowledge, 23 products were true positives, while 2 identified metabolites were ...
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biotransformation pathways of biocides and pharmaceuticals in freshwater crustaceans based on Structure Elucidation of metabolites using high resolution mass spectrometry
Chemical Research in Toxicology, 2013Co-Authors: Junho Jeon, Denise Kurth, Juliane HollenderAbstract:So far, there is limited information on biotransformation mechanisms and products of polar contaminants in freshwater crustaceans. In the present study, metabolites of biocides and pharmaceuticals formed in Gammarus pulex and Daphnia magna were identified using liquid chromatography-high resolution mass spectrometry. Different confidence levels were assigned to the identification of metabolites without reference standards using a framework based on the background evidence used for Structure Elucidation. Twenty-five metabolites were tentatively identified for irgarol, terbutryn, tramadol, and venlafaxine in G. pulex (21 via oxidation and 4 via conjugation reactions) and 11 metabolites in D. magna (7 via oxidation and 4 via conjugation reactions), while no evidence of metabolites for clarithromycin and valsartan was found. Of the 360 metabolites predicted for the four parent compounds using pathway prediction systems and expert knowledge, 23 products were true positives, while 2 identified metabolites were unexpected products. Observed oxidative reactions included N- and O-demethylation, hydroxylation, and N-oxidation. Glutathione conjugation of selected biocides followed by subsequent reactions forming cysteine conjugates was described for the first time in freshwater invertebrates.
Gary E Martin - One of the best experts on this subject based on the ideXlab platform.
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application of 1 n adequate and modified variants to Structure Elucidation and spectral assignment problems
ChemInform, 2016Co-Authors: Gary E Martin, Kirill A Blinov, Mikhail Reibarkh, Alexei V Buevich, Thomas R WilliamsonAbstract:This article has no abstract. Keywords: 1,n-ADEQUATE; inverted 1JCC 1,n-ADEQUATE; dual optimization; Structure Elucidation; long-range correlation; cryogenic NMR probes; small volume probes
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carbon multiplicity editing in long range heteronuclear correlation nmr experiments a valuable tool for the Structure Elucidation of natural products
Journal of Natural Products, 2015Co-Authors: Josep Sauri, Thomas R Williamson, Michel Frederich, Alembert T Tchinda, Teodor Parella, Gary E MartinAbstract:A recently developed NMR method to simultaneously obtain both long-range heteronuclear correlations and carbon multiplicity information in a single experiment, ME-selHSQMBC, is demonstrated as a potentially useful technique for chemical shift assignment and Structure Elucidation of natural products presenting complicated NMR spectra. Carbon multiplicities, even for C/CH2 and odd for CH/CH3 resonances, can be distinguished directly from the relative positive/negative phase of cross-peaks. In addition, connectivity networks can be further extended by incorporating a TOCSY propagation step. Staurosporine (1) and sungucine (2) are utilized as model compounds to demonstrate these techniques.
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the impact of lr hsqmbc very long range heteronuclear correlation data on computer assisted Structure Elucidation
Organic and Biomolecular Chemistry, 2014Co-Authors: Kirill A Blinov, Alexei V Buevich, R T Williamson, Gary E MartinAbstract:The impact of LR-HSQMBC very long-range nJCH heteronuclear shift correlation data as a supplement to HMBC data as input for the computer-assisted Structure Elucidation program, Structure Elucidator®, is assessed for the first time. The severely proton-deficient xanthone antibiotic cervinomycin A2 and the alkaloid staurosporine were employed as a model compounds.
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the impact of long range 1h 15n heteronuclear shift correlation data on computer assisted Structure Elucidation posaconazole
Journal of Heterocyclic Chemistry, 2012Co-Authors: Bruce D Hilton, Gary E MartinAbstract:Considerable work has been invested in the area of computer-assisted Structure Elucidation (CASE) methods. As NMR techniques have been developed that provide more effective atom-to-atom connectivity information, it has become theoretically possible to do de novo Structure Elucidation based on 2D NMR datasets recorded for an unknown molecule. However, as annular (ring) nitrogen atoms become more prevalent in complex chemical Structures, the ability to rely solely on 1H and 13C homo- and hetero-nuclear direct and long-range connectivity information to solve a Structure correspondingly diminishes. Hence, we now wish to report the results of an investigation into the application of CASE methods with and without long-range 1H-15N data using posaconazole as a model compound, which has eight annular nitrogens in its Structure. With the inclusion of 1H-15N data long-range data, the Structure could be successfully determined in a few hours. Excluding the 1H-15N data caused the program to generate millions of candidate Structures, none of which fit the data well enough to be stored.
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are deterministic expert systems for computer assisted Structure Elucidation obsolete
Journal of Chemical Information and Modeling, 2006Co-Authors: Mikhail E Elyashberg, Kirill A Blinov, Antony J Williams, Sergey G Molodtsov, Gary E MartinAbstract:Expert systems for spectroscopic molecular Structure Elucidation have been developed since the mid-1960s. Algorithms associated with the Structure generation process within these systems are deterministic; that is, they are based on graph theory and combinatorial analysis. A series of expert systems utilizing 2D NMR spectra have been described in the literature and are capable of determining the molecular Structures of large organic molecules including complex natural products. Recently, an opinion was expressed in the literature that these systems would fail when elucidating Structures containing more than 30 heavy atoms. A suggestion was put forward that stochastic algorithms for Structure generation would be necessary to overcome this shortcoming. In this article, we describe a comprehensive investigation of the capabilities of the deterministic expert system Structure Elucidator. The results of performing the Structure Elucidation of 250 complex natural products with this program were studied and generalized. The conclusion is that 2D NMR deterministic expert systems are certainly capable of elucidating large Structures (up to about 100 heavy atoms) and can deal with the complexities associated with both poor and contradictory spectral data.
Andrew R Johnson - One of the best experts on this subject based on the ideXlab platform.
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Structure Elucidation of macrolide antibiotics using msn analysis and deuterium labelling
Journal of the American Society for Mass Spectrometry, 2019Co-Authors: Andrew R Johnson, Erin E. CarlsonAbstract:: The 14- and 16-membered macrolide antibiotics are an important structural class. Ubiquitously produced by a number of bacterial strains, namely actinomycetes, purification and Structure Elucidation of the wide array of analogs is challenging, both for discovery efforts and methodologies to monitor for byproducts, metabolites, and contaminants. Collision-induced dissociation mass spectrometry offers an attractive solution, enabling characterization of mixtures, and providing a wealth of structural information. However, interpretation of these spectra can be difficult. We present a study of 14- and 16-membered macrolide antibiotics, including MSn analysis for unprecedented depth of coverage, and complimentary analysis with D2O and H218O labeling to elucidate fragmentation mechanisms. These analyses contrast the behaviors of varying classes of macrolides and highlight how analogues can be identified in relation to similar Structures, which will provide utility for future studies of novel macrolides, as well as impurities, metabolites, and degradation products of pharmaceuticals. Graphical Abstract.
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collision induced dissociation mass spectrometry a powerful tool for natural product Structure Elucidation
Analytical Chemistry, 2015Co-Authors: Andrew R Johnson, Erin E. CarlsonAbstract:Mass spectrometry is a powerful tool in natural product Structure Elucidation, but our ability to directly correlate fragmentation spectra to these Structures lags far behind similar efforts in pep...
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collision induced dissociation mass spectrometry a powerful tool for natural product Structure Elucidation
Analytical Chemistry, 2015Co-Authors: Andrew R Johnson, Erin E. CarlsonAbstract:Abstract Mass spectrometry is a powerful tool in natural product Structure Elucidation, but our ability to directly correlate fragmentation spectra to these Structures lags far behind similar efforts in peptide sequencing and proteomics. Often, manual data interpretation is required and our knowledge of the expected fragmentation patterns for many scaffolds is limited, further complicating analysis. Here, we summarize advances in natural product Structure Elucidation based upon the application of collision induced dissociation fragmentation mechanisms.
