LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4
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 charact...
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| Format: | Article |
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MDPI AG
2020-03-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/4/182 |
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| author | Fedor Kryuchkov Alison Robertson Christopher O. Miles Elizabeth M. Mudge Silvio Uhlig |
| author_facet | Fedor Kryuchkov Alison Robertson Christopher O. Miles Elizabeth M. Mudge Silvio Uhlig |
| author_sort | Fedor Kryuchkov |
| collection | DOAJ |
| description | 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 (<b>1</b> and <b>2</b>), using a sensitive UHPLC–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 (<b>3</b> and <b>4</b>), which we found to be reduced at C-56 relative to <b>1</b> and <b>2</b>. Furthermore, we tested and applied reduction and oxidation reactions, monitored by LC–HRMS, in order to confirm the structures of <b>3</b> and <b>4</b>. Reduction of <b>1</b> and <b>2</b> with NaBH<sub>4</sub> afforded <b>3</b> and <b>4</b>, thereby unambiguously confirming the identities of <b>3</b> and <b>4</b>. 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. |
| first_indexed | 2024-03-10T20:46:57Z |
| format | Article |
| id | doaj.art-80ac6f8b16a146058ce3d472bc51e34e |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T20:46:57Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-80ac6f8b16a146058ce3d472bc51e34e2023-11-19T20:13:41ZengMDPI AGMarine Drugs1660-33972020-03-0118418210.3390/md18040182LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4Fedor Kryuchkov0Alison Robertson1Christopher O. Miles2Elizabeth M. Mudge3Silvio Uhlig4Toxinology Research Group, Norwegian Veterinary Institute, P.O. Box 750 Sentrum, 0106 Oslo, NorwayDepartment of Marine Sciences, University of South Alabama, 5871 University Drive North, Mobile, AL 36688, USANational Research Council, 1411 Oxford Street, Halifax, NS B3H 3Z1, CanadaNational Research Council, 1411 Oxford Street, Halifax, NS B3H 3Z1, CanadaToxinology Research Group, Norwegian Veterinary Institute, P.O. Box 750 Sentrum, 0106 Oslo, NorwayCiguatera 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 (<b>1</b> and <b>2</b>), using a sensitive UHPLC–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 (<b>3</b> and <b>4</b>), which we found to be reduced at C-56 relative to <b>1</b> and <b>2</b>. Furthermore, we tested and applied reduction and oxidation reactions, monitored by LC–HRMS, in order to confirm the structures of <b>3</b> and <b>4</b>. Reduction of <b>1</b> and <b>2</b> with NaBH<sub>4</sub> afforded <b>3</b> and <b>4</b>, thereby unambiguously confirming the identities of <b>3</b> and <b>4</b>. 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.https://www.mdpi.com/1660-3397/18/4/182ciguateraciguatoxinHRMS<i>Gambierdiscus</i>polyether toxinLC–MS |
| spellingShingle | Fedor Kryuchkov Alison Robertson Christopher O. Miles Elizabeth M. Mudge Silvio Uhlig LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4 Marine Drugs ciguatera ciguatoxin HRMS <i>Gambierdiscus</i> polyether toxin LC–MS |
| title | LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4 |
| title_full | LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4 |
| title_fullStr | LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4 |
| title_full_unstemmed | LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4 |
| title_short | LC–HRMS and Chemical Derivatization Strategies for the Structure Elucidation of Caribbean Ciguatoxins: Identification of C-CTX-3 and -4 |
| title_sort | lc hrms and chemical derivatization strategies for the structure elucidation of caribbean ciguatoxins identification of c ctx 3 and 4 |
| topic | ciguatera ciguatoxin HRMS <i>Gambierdiscus</i> polyether toxin LC–MS |
| url | https://www.mdpi.com/1660-3397/18/4/182 |
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