Vida Alinezhad, Yuen Ki Ng, Sanvid Mehta, Lars Konermann
{"title":"Uncovering the Pathway of Serine Octamer Magic Number Cluster Formation during Electrospray Ionization: Experiments and Simulations","authors":"Vida Alinezhad, Yuen Ki Ng, Sanvid Mehta, Lars Konermann","doi":"10.1021/jacs.4c05760","DOIUrl":null,"url":null,"abstract":"Electrospray ionization (ESI) of serine (Ser) solution generates Ser<sub>8</sub>H<sup>+</sup> as an abundant magic number cluster. ESI clustering of most other solutes yields nonspecific stoichiometries. It is unclear why Ser<sub>8</sub>H<sup>+</sup> dominates in the case of Ser, and how Ser<sub>8</sub>H<sup>+</sup> forms during ESI. Even the location of Ser<sub>8</sub>H<sup>+</sup> formation is contentious (in solution, in ESI droplets, or elsewhere). Here we unravel key aspects of the <span>l</span>-Ser<sub>8</sub>H<sup>+</sup> formation pathway. Harsh ion sampling conditions promote the collision-induced dissociation (CID) of regular ESI analytes. Unexpectedly, Ser<sub>8</sub>H<sup>+</sup> was seemingly resistant against CID during ion sampling, despite its extremely low tandem mass spectrometry (MS/MS) stability. This unusual behavior reveals that Ser<sub>8</sub>H<sup>+</sup> forms during ion sampling. We propose the following pathway: (1) Nonspecific Ser clusters are released when ESI droplets evaporate to dryness. These initial clusters cover a wide size range, from a few Ser to hundreds or thousands of monomers. (2) The clusters undergo dissociation during ion sampling, mostly via successive loss of neutral monomers. For any source activation voltage, there is a subpopulation of clusters for which this CID cascade tends to terminate at the octamer level, culminating in Ser<sub>8</sub>H<sup>+</sup>-dominated product distributions. Mobile proton molecular dynamics simulations were used to model the entire pathway. Ser<sub>8</sub>H<sup>+</sup> structures formed in these simulations were consistent with ion mobility experiments. The most compact structures resembled the model of [<contrib-group><span>Scutelnic, V.</span></contrib-group> <cite><i>J. Am. Chem. Soc.</i></cite> <span>2018</span>, <em>140</em>, 7554–7560], with numerous intermolecular salt bridges and H-bonds. Our findings illustrate how the interplay of association and dissociation reactions across phase boundaries can culminate in magic number clusters.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":14.4000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/jacs.4c05760","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Electrospray ionization (ESI) of serine (Ser) solution generates Ser8H+ as an abundant magic number cluster. ESI clustering of most other solutes yields nonspecific stoichiometries. It is unclear why Ser8H+ dominates in the case of Ser, and how Ser8H+ forms during ESI. Even the location of Ser8H+ formation is contentious (in solution, in ESI droplets, or elsewhere). Here we unravel key aspects of the l-Ser8H+ formation pathway. Harsh ion sampling conditions promote the collision-induced dissociation (CID) of regular ESI analytes. Unexpectedly, Ser8H+ was seemingly resistant against CID during ion sampling, despite its extremely low tandem mass spectrometry (MS/MS) stability. This unusual behavior reveals that Ser8H+ forms during ion sampling. We propose the following pathway: (1) Nonspecific Ser clusters are released when ESI droplets evaporate to dryness. These initial clusters cover a wide size range, from a few Ser to hundreds or thousands of monomers. (2) The clusters undergo dissociation during ion sampling, mostly via successive loss of neutral monomers. For any source activation voltage, there is a subpopulation of clusters for which this CID cascade tends to terminate at the octamer level, culminating in Ser8H+-dominated product distributions. Mobile proton molecular dynamics simulations were used to model the entire pathway. Ser8H+ structures formed in these simulations were consistent with ion mobility experiments. The most compact structures resembled the model of [Scutelnic, V.J. Am. Chem. Soc.2018, 140, 7554–7560], with numerous intermolecular salt bridges and H-bonds. Our findings illustrate how the interplay of association and dissociation reactions across phase boundaries can culminate in magic number clusters.
期刊介绍:
The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.