Detection, identification and occurrence of thiotetronic acids in drinking water from underground sources by ESI-FAIMS-QTOF-MS

This paper demonstrates that electrospray ionization (ESI) with differential ion mobility spectroscopy (FAIMS) and \u201csoft\u201d mass spectrometry (MS) provide unique analytical capabilities that led to the discovery of sulfur-containing polar congeners of thiotetronic acid (TA) in drinking water from underground sources in Canada and the United States. Polar TAs accumulate in underground aquifers and appear to be the most abundant class of organic compounds in bottled water, but cannot be detected by conventional mass spectrometry methods. We show that normally stable TAs are converted into very reactive ions in ESI which have to be analyzed using special conditions in ESI-FAIMS-MS to avoid extensive dissociation and ion/molecule reactions. De novo identification of 10 TAs was accomplished by the comparative tandem mass spectrometry analysis of authentic TA derivatives from groundwater samples and synthetic TA analogues prepared for this study. We present highlights of gas phase ion chemistry of polar TAs to explain their unique properties and reactivity. TA derivatives were originally isolated from soil bacteria and are of interest in the pharmaceutical industry due to their potent activity against a broad spectrum of pathogenic bacteria and negligible toxicity to mammals. We suspect that TAs are natural disinfection agents protecting groundwater from bacterial contamination, but these compound undergo modifications or decompose during an ozonation water treatment.Peer reviewed: YesNRC publication: Ye

Detection, Identification, and Occurrence of Thiotetronic Acids in Drinking Water from Underground Sources by Electrospray Ionization-High Field Asymmetric Waveform Ion Mobility Spectrometry-Quadrupole Time-of-Flight-Mass Spectrometry

This paper demonstrates that electrospray ionization (ESI) with differential ion mobility spectroscopy (FAIMS) and “soft” mass spectrometry (MS) provide unique analytical capabilities that led to the discovery of sulfur-containing polar congeners of thiotetronic acid (TA) in drinking water from underground sources in Canada and the United States. Polar TAs accumulate in underground aquifers and appear to be the most abundant class of organic compounds in bottled water but cannot be detected by conventional mass spectrometry methods. We show that normally stable TAs are converted into very reactive ions in ESI which have to be analyzed using special conditions in ESI-FAIMS-MS to avoid extensive dissociation and ion/molecule reactions. <i>De novo</i> identification of 10 TAs was accomplished by the comparative tandem mass spectrometry analysis of authentic TA derivatives from groundwater samples and synthetic TA analogues prepared for this study. We present highlights of gas phase ion chemistry of polar TAs to explain their unique properties and reactivity. TA derivatives were originally isolated from soil bacteria and are of interest in the pharmaceutical industry due to their potent activity against a broad spectrum of pathogenic bacteria and negligible toxicity to mammals. We suspect that TAs are natural disinfection agents protecting groundwater from bacterial contamination, but these compound undergo modifications or decompose during an ozonation water treatment

Synthesis of Tumor-Associated Le^aLe^x Hexasaccharides: Instability of a Thiol-Containing Oligosaccharide in Mass Spectrometry and Hypermetalation Detected by ESI FAIMS

We report the efficient synthesis of three analogues of the tumor-associated carbohydrate antigen Le^aLe^x. This hexasaccharide was prepared as a soluble inhibitor hexyl glycoside, as a 6-aminohexyl glycoside for conjugation to proteins, and as a 6-thiohexyl glycoside for immobilization to a gold surface. These three analogues were obtained from a common hexasaccharide intermediate and isolated pure following efficient deprotection reactions that involved metal-dissolving conditions. While all other intermediates and analogues gave the expected molecular ions in ESI HRMS, the 6-thiohexyl glycoside final compound gave a complex spectrum in which no signal matched the molecular ion. Using ESI FAIMS HRMS, we were able to prevent ion dissociation reactions and obtained high quality spectral data. The ions detected could be characterized unambiguously from their accurate masses and gave insight into the behavior of the thiohexyl analogue in the gas phase. These results indicate that the 6-thiohexyl glycoside lost water and led to the formation of “hypermetalated” species which we propose are cyclic

Hydroxyl Radical-Induced Oxidation of a Phenolic C-Linked 2′-Deoxyguanosine Adduct Yields a Reactive Catechol

Phenolic toxins stimulate oxidative stress and generate C-linked adducts at the C8-site of 2′-deoxyguanosine (dG). We previously reported that the C-linked adduct 8-(4″-hydroxyphenyl)-dG (<i>p</i>-PhOH-dG) undergoes oxidation in the presence of Na₂IrCl₆ or horseradish peroxidase (HRP)/H₂O₂ to generate polymeric adducts through phenoxyl radical production [Weishar (2008) Org. Lett. 10, 1839−1842]. We now report on reaction of <i>p</i>-PhOH-dG with two radical-generating systems, Cu^II/H₂O₂ or Fe^II-EDTA/H₂O₂, which were utilized to study the fate of the C-linked adduct in the presence of hydroxyl radical (HO^•). The radical-generating systems facilitate (i) hydroxylation of the phenolic ring to afford the catechol adduct 8-(3″,4″-dihydroxyphenyl)-dG (3″,4″-DHPh-dG) and (ii) H-atom abstraction from the sugar moiety to generate the deglycosylated base <i>p</i>-PhOH-G. The ratios of 3″,4″-DHPh-dG to <i>p</i>-PhOH-G were ∼1 for Cu^II/H₂O₂ and ∼0.13 for Fe^II-EDTA/H₂O₂. The formation of 3″,4″-DHPh-dG was found to have important consequences in terms of reactivity. The catechol adduct has a lower oxidation potential than <i>p</i>-PhOH-dG and is sensitive to aqueous basic media, undergoing decomposition to generate a dicarboxylic acid derivative. In the presence of excess <i>N</i>-acetylcysteine (NAC), oxidation of 3″,4″-DHPh-dG produced mono-NAC and di-NAC conjugates. Our results imply that secondary oxidative pathways of phenolic-dG lesions are likely to contribute to toxicity