Boris Ucur, Oisin J. Shiels, Alan T. Maccarone, Stephen J. Blanksby and Adam J. Trevitt*,
{"title":"What Drives the Vehicle Mechanism? Protonation Isomer Interconversion of Arylamine Derivatives Probed with Solvent-Mediated Kinetics","authors":"Boris Ucur, Oisin J. Shiels, Alan T. Maccarone, Stephen J. Blanksby and Adam J. Trevitt*, ","doi":"10.1021/jasms.4c0047010.1021/jasms.4c00470","DOIUrl":null,"url":null,"abstract":"<p >Reactions with mobile protons occur under electrospray ionization (ESI) in many applications of mass spectrometry. Understanding how protonation isomers (protomers) form and how molecular structure influences protomer interconversion provides fundamental insight into ESI mechanisms, which can then be exploited to rationalize ion mobility and ion activation processes for robust analyte detection. Using ten arylamine protomer systems, this paper establishes the key substrate properties that influence protomer isomerism. Protomers from ten arylamines are separated by differential ion mobility spectrometry (DMS) mass spectrometry and identified by characteristic collision-induced dissociation mass spectra. These assignments are further rationalized using quantum chemical calculations (M06-2X/6-31G(2df,p)). Based on these assignments, mobility-selected protomers are then allowed to react with methanol vapor under atmospheric and reduced pressure conditions (2.5 mTorr, 300 K). The latter enabled measurements of the second-order rate coefficients for methanol-catalyzed protomer isomerization, which span 3.9 × 10<sup>–11</sup>–2 × 10<sup>–13</sup> cm<sup>3</sup> molecule<sup>–1</sup> s<sup>–1</sup>. Double-hybrid quantum chemical calculations (DSD-PBEP86-D3(BJ)/aug-cc-pVDZ) show that the direction of proton transfer is controlled by protomer relative stability, whereas reaction rates are controlled by a key transition state that separates the protonation sites. Computational exploration of a larger substituted-arylamine test-set shows that the protomer proton affinity generally correlates with energy of the key transition state. Applying the Bell–Evans–Polanyi principle to this reaction set highlights that outliers in the predictive model correspond to transition states with significant displacements along the reaction coordinate. This archetype system of derivatized arylamines provides a foundation to understand how substrate functionalization influences protomer isomerism for ions during ESI and predicts protonation isomer distributions.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 3","pages":"601–612 601–612"},"PeriodicalIF":3.1000,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Society for Mass Spectrometry","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/jasms.4c00470","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Reactions with mobile protons occur under electrospray ionization (ESI) in many applications of mass spectrometry. Understanding how protonation isomers (protomers) form and how molecular structure influences protomer interconversion provides fundamental insight into ESI mechanisms, which can then be exploited to rationalize ion mobility and ion activation processes for robust analyte detection. Using ten arylamine protomer systems, this paper establishes the key substrate properties that influence protomer isomerism. Protomers from ten arylamines are separated by differential ion mobility spectrometry (DMS) mass spectrometry and identified by characteristic collision-induced dissociation mass spectra. These assignments are further rationalized using quantum chemical calculations (M06-2X/6-31G(2df,p)). Based on these assignments, mobility-selected protomers are then allowed to react with methanol vapor under atmospheric and reduced pressure conditions (2.5 mTorr, 300 K). The latter enabled measurements of the second-order rate coefficients for methanol-catalyzed protomer isomerization, which span 3.9 × 10–11–2 × 10–13 cm3 molecule–1 s–1. Double-hybrid quantum chemical calculations (DSD-PBEP86-D3(BJ)/aug-cc-pVDZ) show that the direction of proton transfer is controlled by protomer relative stability, whereas reaction rates are controlled by a key transition state that separates the protonation sites. Computational exploration of a larger substituted-arylamine test-set shows that the protomer proton affinity generally correlates with energy of the key transition state. Applying the Bell–Evans–Polanyi principle to this reaction set highlights that outliers in the predictive model correspond to transition states with significant displacements along the reaction coordinate. This archetype system of derivatized arylamines provides a foundation to understand how substrate functionalization influences protomer isomerism for ions during ESI and predicts protonation isomer distributions.
期刊介绍:
The Journal of the American Society for Mass Spectrometry presents research papers covering all aspects of mass spectrometry, incorporating coverage of fields of scientific inquiry in which mass spectrometry can play a role.
Comprehensive in scope, the journal publishes papers on both fundamentals and applications of mass spectrometry. Fundamental subjects include instrumentation principles, design, and demonstration, structures and chemical properties of gas-phase ions, studies of thermodynamic properties, ion spectroscopy, chemical kinetics, mechanisms of ionization, theories of ion fragmentation, cluster ions, and potential energy surfaces. In addition to full papers, the journal offers Communications, Application Notes, and Accounts and Perspectives