LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4

Autor: Silvio Uhlig, Alison Robertson, Christopher O. Miles, Elizabeth M. Mudge, Fedor Kryuchkov
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Ciguatoxin
Ciguatera
Gambierdiscus
polyether toxin
Molecular Conformation
Pharmaceutical Science
Sphyraena barracuda
HRMS
Mass spectrometry
01 natural sciences
Redox
LC–MS
Article
Ciguatoxins
03 medical and health sciences
chemistry.chemical_compound
Fragmentation (mass spectrometry)
Scomberomorus cavalla
Liquid chromatography–mass spectrometry
Tandem Mass Spectrometry
Drug Discovery
medicine
Animals
Derivatization
Pharmacology
Toxicology and Pharmaceutics (miscellaneous)
lcsh:QH301-705.5
Chromatography
High Pressure Liquid
030304 developmental biology
ciguatera
0303 health sciences
Chromatography
010401 analytical chemistry
Fishes
Ciguatera Poisoning
fragmentation pathways
medicine.disease
0104 chemical sciences
LC-MS
chemistry
lcsh:Biology (General)
Caribbean Region
Seafood
ladder-frame molecule
ciguatoxin
Zdroj: Marine Drugs
Volume 18
Issue 4
Marine Drugs, Vol 18, Iss 182, p 182 (2020)
ISSN: 1660-3397
Popis: Ciguatera poisoning is linked to the ingestion of seafood that is contaminated with ciguatoxins (CTXs). The structural variability of these polyether toxins in nature remains poorly understood due to the low concentrations present even in highly toxic fish, which makes isolation and chemical characterization difficult. We studied the mass spectrometric fragmentation of Caribbean CTXs, i.e., the epimers C-CTX-1 and -2 (1 and 2), using a sensitive UHPLC&ndash
HRMS/MS approach in order to identify product ions of diagnostic value. We found that the fragmentation of the ladder-frame backbone follows a characteristic pattern and propose a generalized nomenclature for the ions formed. These data were applied to the structural characterization of a pair of so far poorly characterized isomers, C-CTX-3 and -4 (3 and 4), which we found to be reduced at C-56 relative to 1 and 2. Furthermore, we tested and applied reduction and oxidation reactions, monitored by LC&ndash
HRMS, in order to confirm the structures of 3 and 4. Reduction of 1 and 2 with NaBH4 afforded 3 and 4, thereby unambiguously confirming the identities of 3 and 4. In summary, this work provides a foundation for mass spectrometry-based characterization of new C-CTXs, including a suite of simple chemical reactions to assist the examination of structural modifications.
Databáze: OpenAIRE
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