THE USE OF DOPANTS IN ATMOSPHERIC PRESSURE IONIZATION SOURCES OF MASS SPECTROMETERS by Faezeh Dousty M.Sc, The University of Tehran, 2009 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Doctor of Philosophy in THE COLLEGE OF GRADUATE STUDIES (Chemistry) THE UNIVERSITY OF BRITISH COLUMBIA (Okanagan) May 2015 © Faezeh Dousty, 2015 Abstract Dopants, as ―ionization assisting‖ chemicals, have been used in different ionization techniques. However, they have been used most frequently in the field of Atmospheric Pressure Photoionization (APPI). These chemicals that have high photoabsorption and photoionization cross sections easily get photoionized and ―preserve‖ to a certain extent the energy of the photon flux, which otherwise is significantly lost due to the absorption by matrix components. Subsequently, these photo-dopant ions ionize analyte molecules through ion-molecule chemical reactions. Obtaining a profound understanding of ion formation mechanisms is a crucial step in successful applications of mass spectrometry. The first part of this thesis focuses on comprehensively describing ionization mechanisms and specifically the role of dopants. With the understanding obtained from in depth research on ion formation mechanisms, two novel dopants for APPI are proposed, i.e., carbon disulfide and isoprene. The potential of these chemicals as dopants, alongside their underlying ionization mechanisms, were investigated with a commercial APPI source coupled to a liquid chromatograph and a custom-built APPI source coupled to a gas chromatograph. Carbon disulfide was proven to be an effective charge transfer reagent for the positive ion APPI (PI-APPI) and promoted the ionization of non-polar compounds, for which the proton transfer route was not possible. The advantage of carbon disulfide over commonly used dopants is its high ionization energy (10 eV), which enables the ionization of analytes with high IEs through a charge transfer route, when other commonly used dopants with less IEs suppressed their ionization. Isoprene, which is considered a green chemical, gave effective results in the negative ion APPI (NI-APPI). In contrast to LC, in which mobile phases can interfere with the ionization of analytes and complicate the ionization matrix, GC provides a very simple matrix for photoionization. Thus, underlying ion formation mechanisms can be more reliably studied and interpreted. The investigation of ionization mechanisms in both LC- and GC-based/MS analyses in parallel contributed to better formulating the role of all chemicals present in the source. Last but not least, the role of dopants in enhancing ionization responses in Atmospheric Pressure Laser Ionization (APLI) for GC/MS applications was investigated. In APLI, instead of a one-step VUV ionization event used in APPI, a two-step UV ionization event is ii employed. APLI has only been recently introduced; thus, the utilization of dopants in this technique has not been explored as extensively as for APPI. The potential of carbon disulfide and isoprene as dopants were also examined for this technique. The short lifetime of the excited transition states of carbon disulfide suppressed its laser ionization. Therefore, laser ionization of carbon disulfide did not increase the total ion production in order to assist the ionization in the PI mode. Positive electron affinity of carbon disulfide disqualifies its applications for negative ionization. Therefore, dopant-assisted studies in PI-APLI were limited to using toluene as dopant, which produced an abundant intensity of toluene radical cations. Laser ionization of isoprene produced a range of radical cations. Thus, the elevated chemical noise and the presence of many ions at the low m/z range of the isoprene spectrum can interfere with ion products of small molecules, which render its application as a dopant for PI-APLI problematic, similar as for PI-APPI. In NI APLI, toluene offered more effective results than isoprene. Therefore, toluene was chosen to investigate the role of dopants in enhancing the ionization responses and to study the corresponding ionization mechanisms in PI/NI APLI. iii Preface The author has performed all experiments and data analysis in this thesis. The research project presented in Chapter 2 and 3 have been previously published as follows: (i) Dousty, F., O’Brien, R., Gahler, R., Kersten, H., & Benter, T. Carbon disulfide as a dopant in photon-induced chemical ionization mass spectrometry. Rapid Commun. Mass Spectrom. 2013, 27, 1969. (ii) Dousty, F., O’Brien, R. The use of isoprene as a novel dopant in negative ion atmospheric pressure photoionization mass spectrometry coupled to high- performance liquid chromatography. Rapid Commun. Mass Spectrom. 2015, 29, 1–8. In addition, some of the findings of the research presented in Chapters 2 and 3 contributed to a multi-university, international collaboration publication as follows: (iii)S. Klee, V. Derpmann, W. Wißdorf, S. Klopotowski, H. Kersten, K. J. Brockmann, T. Benter, S. Albrecht, A. P. Bruins, F. Dousty, T. J. Kauppila, R. Kostiainen, R. O’Brien, D. B. Robb, et al. Are clusters important in understanding the mechanisms in atmospheric pressure ionization? Part 1: Reagent ion generation and chemical control of ion populations. J. Am. Soc. Mass Spectrom. 2014, 25, 1310. The following is a list of poster presentations related to the work presented in this thesis: (1) Kersten, H., Haberer, K., Kroll, K., Dousty F., Benter, T; ―Progress in the development of a GC-APPI source with femtogram sensitivity‖. Presented at 62nd ASMS Conference on MASS Spectrometry and Allied Topics, Baltimore, MD, June 4-9, 2014 iv (2) Dousty F.; O'Brien R.; "The Use of Isoprene as a New Dopant in Negative Ion Atmospheric Pressure Photo Ionization (NI-APPI) Mass Spectrometry" Presented at 61st ASMS Conference on Mass Spectrometry and Allied Topics, Minneapolis Convention Center, Minneapolis, MN, June 11, 2013. (3) Dousty F.; O'Brien R.; Benter T, Kersten H."The Use of Carbon Disulfide as a New Dopant in Atmospheric Pressure Photo Ionization Mass Spectrometry" Presented at 60th ASMS Conference on Mass Spectrometry and Allied Topics, Vancouver Convention Centre, Vancouver, Canada, June 23rd, 2012, WP 746. (4) Dousty F.; O'Brien R.; Benter T, Kersten H. "An atmospheric pressure photo-ionization source based on a window-less atmospheric pressure spark discharge" Presented at Vancouver Post- ASMS Mass Spectrometry Symposium, Vancouver, BC, Canada, September 29th, 2011. (5) Dousty F.; O'Brien R.; Benter T, Kersten H. "An atmospheric pressure photo-ionization source based on a window-less atmospheric pressure spark discharge" Presented at 59th ASMS Conference on Mass Spectrometry and Allied Topics, Colorado Convention Center, Denver, CO, June 08, 2011. v Table of Contents Abstract .................................................................................................................................... ii Preface ..................................................................................................................................... iv Table of Contents ................................................................................................................... vi List of Tables .......................................................................................................................... xi List of Figures ....................................................................................................................... xiii List of Abbreviations ........................................................................................................... xix Acknowledgements .............................................................................................................. xxi Dedication ........................................................................................................................... xxiii 1 Chapter: Introduction ...................................................................................................... 1 1.1 Atmospheric Pressure Photoionization (APPI) and Dopant Assisted-Atmospheric Pressure Photoionization (DA-APPI) ............................................................................................................. 11 1.2 Dopant-free APPI (Direct photoionization) Applications ................................................... 12 1.3 Methods of dopants introduction into the APPI source ...................................................... 13 1.4 Advantages of APPI over ESI and APCI ............................................................................ 14 1.5 Ionization mechanisms in APPI and DA-APPI .................................................................. 17 1.6 Chemicals utilized as dopants in dopant assisted positive ion- atmospheric pressure ionization sources. ............................................................................................................................ 18 1.6.1 Benzene .......................................................................................................................... 20 1.6.1.1 The ranges of application for benzene as a dopant ................................................ 20 1.6.1.2 Ionization mechanisms of analytes with benzene-Assisted APPI .......................... 20 1.6.1.3 Advantages of utilizing benzene as a dopant ......................................................... 21 1.6.1.4 Limitations of utilizing benzene as a dopant.........................................................