Interactions of chiral ions and molecules in gas phase Towards an understanding of chiral recognition mechanism Oleksii Rebrov Academic dissertation for the Degree of Doctor of Philosophy in Physics at Stockholm University to be publicly defended on Tuesday 16 October 2018 at 10.00 in sal FB54, AlbaNova universitetscentrum, Roslagstullsbacken 21. Abstract This thesis comprises the research related to interactions of enantiopure amino acids with chiral and achiral molecules in gas phase. The investigation of the mechanism responsible for chiral discrimination is of the special interest in this work. An electrospray ion source platform (Stockholm University), quadrupole time-of-flight mass spectrometer (University of Oslo) and Fourier-transform ion cyclotron resonance mass spectrometer in combination with OPO laser (Centre Laser Infrarouge d'Orsay (CLIO), France) have been used in our studies. Results of experiments on collisions of enantiopure amino acids, namely phenylalanine (Phe), tryptophan (Trp), and methionine (Met) with chiral and achiral targets in high and low energy regimes are presented. The fragmentation process is discussed in detail and compared with generally accepted models of amino acid fragmentation. Formation of proton bound diastereomeric adducts of amino acid and chiral alcohols (2-butanol and 1-phenylethanol) in single collisions is reported. The emphasis was given to reveal stereochemical effects in above mentioned reactions. The structure and vibrational properties of diastereomeric dimers of tryptophan studied using infrared multiphoton dissociation (IRMPD) spectrometry are presented. Structures and energies of most stable conformers obtained with quantum chemical calculations are described and compared to the experimental data. The stereo-dependent features are underlined and the chiral discrimination using IRMPD is addressed. Stockholm 2018 http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-159310 ISBN 978-91-7797-354-6 ISBN 978-91-7797-355-3 Department of Physics Stockholm University, 106 91 Stockholm INTERACTIONS OF CHIRAL IONS AND MOLECULES IN GAS PHASE Oleksii Rebrov Interactions of chiral ions and molecules in gas phase Towards an understanding of chiral recognition mechanism Oleksii Rebrov ©Oleksii Rebrov, Stockholm University 2018 ISBN print 978-91-7797-354-6 ISBN PDF 978-91-7797-355-3 Printed in Sweden by Universitetsservice US-AB, Stockholm 2018 I dedicate this work to my family Abstract This thesis comprises the research related to interactions of enantiopure amino acids with chiral and achiral molecules in gas phase. The investigation of the mechanism responsible for chiral discrimination is of the special interest in this work. An electrospray ion source platform (Stockholm University), quadrupole time-of-flight mass spectrometer (University of Oslo) and Fourier-transform ion cyclotron resonance mass spectrometer in combination with OPO laser (Centre Laser Infrarouge d'Orsay (CLIO), France) have been used in our studies. Results of experiments on collisions of enantiopure amino acids, namely phenylalanine (Phe), tryptophan (Trp), and methionine (Met) with chiral and achiral targets in high- and low-energy regimes are presented. The fragmentation process is discussed in detail and compared with generally accepted models of amino acid fragmentation. Formation of proton bound diastereomeric adducts of amino acid and chiral alcohols (2-butanol and 1-phenylethanol) in single collisions is reported. The emphasis was given to reveal stereochemical effects in above mentioned reactions. The structure and vibrational properties of diastereomeric dimers of tryptophan studied using infrared resonant multiple photon dissociation (IRMPD) spectrometry are presented. Structures and energies of most stable conformers obtained with quantum chemical calculations are described and compared to the experimental data. The stereo-dependent features are underlined and the chiral discrimination using IRMPD is addressed. i Sammanfattning Avhandlingen omfattar forskning relaterad till interaktioner mellan enantiomera, kirala aminosyror och kirala och akirala molekyler i gasfas. Undersökningen av mekanismen som är ansvarig för kiral diskriminering är av särskilt intresse för detta arbete. En elektrosprajjonkälleplattform (Stockholms universitet), löptidsmasspektrometer (University of Oslo), och en Fourier-transformbaserad joncyklotronresonansmasspektrometer i kombination med OPO-laser (Center Laser Infrarouge d'Orsay (CLIO), Frankrike) har använts i våra studier. Resultat av experiment på hög- och lågenergikollisioner av enantiomera aminosyror, nämligen fenylalanin (Phe), tryptofan (Trp) och metionin (Met), med kirala och akirala mål presenteras. Fragmenteringsprocessen diskuteras i detalj och jämförs med allmänt accepterade modeller av aminosyrafragmentation. Bildning av protonbundna diastereomera addukter av aminosyra och kirala alkoholer (2-butanol och 1-fenyletanol) vid enskilda kollisioner rapporteras. Tonvikten är för att avslöja stereokemiska effekter i ovan nämnda reaktioner. Strukturen och vibrationsegenskaperna hos diastereomera dimerer av tryptofan studerade med infraröd multifotondissociation-spektrometri presenteras. Strukturer och energier av de mest stabila konformatorerna som erhållits med kvantkemiska beräkningar beskrivs och jämförs med experimentella data. De stereo-beroende egenskaperna är poängterade och den kirala diskrimineringen med användning av IRMPD är adresserad. ii List of Papers THE FOLLOWING PAPERS ARE INCLUDED IN THIS THESIS PAPER I: High-Energy Collisions of Protonated Enantiopure Amino Acids With a Chiral Target Gas Kostiantyn Kulyk, Oleksii Rebrov, Mark H. Stockett, John D. Alexander, Henning Zettergren, Henning T. Schmidt, Richard D. Thomas, Henrik Cederquist, Mats Larsson, International Journal of Mass Spectrometry, 388, 2015, 59–64. DOI:10.1016/j.ijms.2015.08.010 PAPER II: Low-Energy Collisions of Protonated Enantiopure Amino Acids with Chiral Target Gases Kostiantyn Kulyk, Oleksii Rebrov, Mauritz Ryding, Richard D. Thomas, Einar Uggerud, Mats Larsson, Journal of The American Society for Mass Spectrometry, 28, 2017, 2686–2691. DOI: 10.1007/s13361-017-1796-7 PAPER III: Chirally Sensitive Collision Induced Dissociation of Proton- Bound Diastereomeric Complexes of Tryptophan and 2-Butanol Oleksii Rebrov, Kostiantyn Kulyk, Mauritz Ryding, Richard D. Thomas, Einar Uggerud, Mats Larsson, Chirality, 29, 2017, 115–119. DOI: 10.1002/chir.22679 PAPER IV: Non-covalently Bonded Diastereomeric Adducts of Amino Acids and (S)-1-Phenylethanol in Low-energy Dissociative Collisions Oleksii Rebrov, Mauritz Ryding, Richard D. Thomas, Einar Uggerud, Mats Larsson. Journal of The American Society for Mass Spectrometry. Submitted. PAPER V: IRMPD Spectroscopy of Protonated Tryptophan Diastereomers Oleksii Rebrov, Mathias Poline, Philippe Maitre, Estelle Loire, Vasyl Yatsyna, Mats Larsson, Vitali Zhaunerchyk. In manuscript. iii PUBLICATIONS NOT INCLUDED IN THIS THESIS PAPER A: Cooper Minimum Photoelectron Dynamics Beyond the One- Particle Picture in Chiral Molecules L. Schio, M. Alagia, D. Toffoli, P. Decleva, O. Rebrov, V. Zhaunerchyk, M. Larsson, S. Falcinelli, D. Catone, S. Turchini, N. Zema, F. Salvador, P. Bertoch, D. Benedetti, S. Stranges. In manuscript. PAPER B: Fragmentation of Positively-Charged Biological Ions Activated with a Beam of High-Energy Cations K. Chingin, A. Makarov, E. Denisov, O. Rebrov, R. A. Zubarev, Analytical Chemistry, 86 (1), 2014, 372–379. Reprints were made with permission from the publishers. iv Author’s contribution PAPER I: Major part of experiments and data processing. Part of the data analysis. Discussion of the results and manuscript. PAPER II: Major part of experiments, data processing and data analysis. Part of writing. PAPER III: Suggested and performed major part of experiments, data analysis and major part of the writing. PAPER IV: Major part of experiments and data processing, data analysis and theoretical calculations. Major part of the writing. PAPER V: Part of experiments and calculations. Major part of writing. v Contents Abstract i Sammanfattning ii List of Papers iii Author’s contribution v List of Abbreviations viii Declaration ix 1. Introduction ……………………………………..……………………………………………………..1 1.1. Chirality in life chemistry……………………………………………………………………1 1.2. Chiral recognition of ions in gas phase…....…………………………………………..3 1.3. Mass spectrometry based methods of chiral recognition………………………..4 1.3.1. Kinetic method……………………………………………………………………….5 1.3.2. Collision-induced dissociation of diastereomeric adducts…………..6 1.3.3. Host-guest diastereomeric adduct formation……………………………7 1.3.4. Ion-molecule reactions…………………………………………………………..7 1.3.5. Ion mobility spectrometry……………………………………………………...8 1.4. Infrared spectroscopy of chiral molecules…………………………………………...9 1.5. Aim of thesis…………………………………………………………………………………....10 2. Experimental and theoretical methods…………………………………………………11 2.1. Electrospray ionization (ESI)……………………………………………….…………...11 2.2. Experimental setup…………………………………………………………………………..12 2.2.1. ESI platform………………………………………………………………………….12 2.2.2. Time-of-flight mass spectrometry……………………………………………13 2.2.3. Fourier transform ion cyclotron resonance mass spectrometry….15 2.3. Theoretical methods…………………………………………………………………….…..17 2.3.1. Density functional theory (DFT)……… …………………………………....17 2.3.2. Self-consistent charge density functional tight binding (SCC-DFTB) molecular dynamics (MD)………………………….………..17 3. Summary of results……………………………………………….………………………………..19 3.1. High-energy