Quantitative High-Field NMR- and Mass Spectrometry-Based Fatty Acid Sequencing Reveals Internal Structure in Ru-Catalyzed Deuteration of Docosahexaenoic Acid.

Autor: Wang DH; Dell Pediatric Research Institute, Departments of Pediatrics, of Chemistry, and of Nutrition, University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, Texas 78723, United States.; Division of Nutritional Sciences and Department of Food Science, Cornell University, Ithaca, New York 14850, United States., Vidovic D; School of Chemistry, Monash University, Clayton, Victoria 3800 Australia., McKay AI; School of Chemistry, Monash University, Clayton, Victoria 3800 Australia., Darwish T; National Deuteration Facility-ANSTO, Sydney, New Illawarra Rd, Lucas Heights, NSW 2234, Australia., Park HG; Dell Pediatric Research Institute, Departments of Pediatrics, of Chemistry, and of Nutrition, University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, Texas 78723, United States.; Division of Nutritional Sciences and Department of Food Science, Cornell University, Ithaca, New York 14850, United States., Garza SM; Dell Pediatric Research Institute, Departments of Pediatrics, of Chemistry, and of Nutrition, University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, Texas 78723, United States.; Department of Chemistry, University of Texas at Austin, Austin, Texas 78712 United States., Shields SW; Department of Chemistry, University of Texas at Austin, Austin, Texas 78712 United States., Brodbelt JS; Department of Chemistry, University of Texas at Austin, Austin, Texas 78712 United States., Wang Z; Dell Pediatric Research Institute, Departments of Pediatrics, of Chemistry, and of Nutrition, University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, Texas 78723, United States.; Division of Nutritional Sciences and Department of Food Science, Cornell University, Ithaca, New York 14850, United States., Lacombe RJS; Dell Pediatric Research Institute, Departments of Pediatrics, of Chemistry, and of Nutrition, University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, Texas 78723, United States., Shmanai VV; Institute of Physical Organic Chemistry, National Academy of Science of Belarus, 13 Surganova Street, Minsk 220072, Belarus., Lysenko IL; Institute of Physical Organic Chemistry, National Academy of Science of Belarus, 13 Surganova Street, Minsk 220072, Belarus., Bekish AV; Institute of Physical Organic Chemistry, National Academy of Science of Belarus, 13 Surganova Street, Minsk 220072, Belarus., Schmidt K; BioJiva Inc, Los Altos, California 94022, United States., Redfield C; Dept of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, U.K., Brenna JT; Dell Pediatric Research Institute, Departments of Pediatrics, of Chemistry, and of Nutrition, University of Texas at Austin, 1400 Barbara Jordan Blvd, Austin, Texas 78723, United States.; Division of Nutritional Sciences and Department of Food Science, Cornell University, Ithaca, New York 14850, United States.; Department of Chemistry, University of Texas at Austin, Austin, Texas 78712 United States., Shchepinov MS; BioJiva Inc, Los Altos, California 94022, United States.
Jazyk: angličtina
Zdroj: Analytical chemistry [Anal Chem] 2022 Sep 27; Vol. 94 (38), pp. 12971-12980. Date of Electronic Publication: 2022 Sep 13.
DOI: 10.1021/acs.analchem.2c00923
Abstrakt: Ru-based catalysis results in highly unsaturated fatty acid (HUFA) ethyl esters (EE) deuterated to various extents. The products carry 2 H (D) mainly at their bis -allylic positions, where they are resistant to autoxidation compared to natural HUFA and are promising as neurological and retinal drugs. We characterized the extent of deuteration at each allylic position of docosa-4,7,10,13,16,19-hexaenoic acid deuterated to completion at bis -allylic and allylic positions (D-DHA) by two-dimensional (2D) and high-field (600 and 950 MHz) NMR. In separate experiments, the kinetics of docosahexaenoic acid (DHA) EE deuteration was evaluated using Paternò-Büchi (PB) reaction tandem mass spectrometry (MS/MS) analysis, enabling deuteration to be quantitatively characterized for isotopologues (D0-D14 DHA) at each internal allylic position. NMR analysis shows that the net deuteration of the isotopologue mixture is about 94% at the bis -allylic positions, and less than 1% remained as the protiated -CH 2 -. MS analysis shows that deuteration kinetics follow an increasing curve at bis -allylic positions with higher rate for internal bis -allylic positions. Percent D of bis -allylic positions increases linearly from D1 to D9 in which all internal bis -allylic positions (C9, C12, C15) deuterate uniformly and more rapidly than external bis -allylic positions (C6, C18). The mono -allylic positions near the methyl end (C21) show a steep increase of D only after the D10 isotopologue has been deuterated to >90%, while the mono -allylic position near the carboxyl position, C3, deuterates last and least. These data establish detailed methods for the characterization of Ru-catalyzed deuteration of HUFA as well as the phenomenological reaction kinetics as net product is formed.
Databáze: MEDLINE