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Tandem Mass Spectrometry for Investigation of Binding Energies of Host-Guest Complexes and Structural Elucidation of Oligosaccharides Parisa Bayat

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Tandem Mass Spectrometry for Investigation of Binding Energies of Host-Guest Complexes and Structural Elucidation of Oligosaccharides Parisa Bayat Tandem mass spectrometry for investigation of binding energies of host-guest complexes and structural elucidation of oligosaccharides Parisa Bayat To cite this version: Parisa Bayat. Tandem mass spectrometry for investigation of binding energies of host-guest complexes and structural elucidation of oligosaccharides. Theoretical and/or physical chemistry. Sorbonne Uni- versité, 2018. English. NNT : 2018SORUS108. tel-02953259 HAL Id: tel-02953259 https://tel.archives-ouvertes.fr/tel-02953259 Submitted on 30 Sep 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Sorbonne Université Ecole doctorale 406 Institut Parisien de Chimie Moléculaire (IPCM) / Chimie Structurale Organique et Biologique (CSOB) Spectrométrie de masse en tandem pour l'étude des énergies de liaison de complexes "hôte-invité" et l'élucidation structurale d'oligosaccharides Par Parisa Bayat Thèse de doctorat de Chimie moléculaire Directeur de thèse : Prof. Richard B. Cole Encadrant : Dr. Denis Lesage Présentée et soutenue publiquement le 28 septembre 2018 Devant un jury composé de : Pr. David RONDEAU Rapporteur Pr. László DRAHOS Rapporteur Pr. Guillaume VAN DER REST Examinateur Dr. Sandrine SAGAN Examinatrice Pr. Richard B COLE Directeur de thèse Dr. Denis LESAGE Encadrant Résumé En faisant progresser la chimie hôte-invité (H-G), des efforts importants ont été déployés pour synthétiser des molécules hôtes avec des caractéristiques de reconnaissance moléculaire spécifiques et bien définies, y compris de sélectivité et d’affinité ajustable. Une étape importante dans le processus est la caractérisation des forces de liaison des complexes H-G. Cette caractérisation est typiquement réalisée en solution en utilisant la RMN ou la fluorescence. L'étude en phase gazeuse de l'énergétique des systèmes H-G est très importante pour fournir des informations concernant leurs propriétés intrinsèques de liaison. La majeure partie de cette thèse est consacrée à l'étude de l'énergétique des complexes H-G formés par trois hôtes en cage d'hémicryptophane avec diverses molécules invitées biologiquement pertinentes. Parmi les techniques basées sur la spectrométrie de masse en tandem, nous utilisons ici la dissociation radiative infrarouge de corps noir (BIRD), la dissociation induite par collision basse énergie (CID à basse énergie), la dissociation de collision de plus haute énergie (HCD) et la CID haute pression pour les mesures énergétiques des complexes HG. Ces techniques ont été utilisées soit seules, soit en combinaison les unes avec les autres, soit avec la modélisation Rice-Ramsperger-Kassel-Marcus (RRKM). Ce travail nous a permis de développer la CID à basse énergie, technique prometteuse mais jusqu’à présent peu employée. En plus des études de chimie H-G, nous avons comparé l’énergie de dissociation de la - cyclodextrine lithiée et du maltoheptaose lithiée à l’aide de la CID basse énergie. Ces deux espèces sont relativement similaires à l’exception du fait que la première est cyclique et la seconde est un oligosaccharide linéaire. Enfin, nous avons utilisé les propriétés des différentes techniques de CID à basse énergie, de CID et du HCD pour l'analyse structurale des sucres, et aussi pour explorer le mécanisme de dissolution des oligosaccharides dans N,N-diméthylacétamide/chlorure de lithium (DMAc/LiCl). Mots-clés: BIRD, CID à basse énergie, modélisation RRKM, CID, HCD, chimie hôte-invité, caractérisation structurale des oligosaccharides, DMAc/LiCl Summary Subject: Tandem mass spectrometry for investigation of binding energies of host-guest complexes and structural elucidation of oligosaccharides In advancing host-guest (H-G) chemistry, considerable effort has been spent to synthesize host molecules with specific and well-defined molecular recognition characteristics including selectivity and adjustable affinity. An important step in the process is the characterization of binding strengths of the H-G complexes. This characterization is typically performed in solution using NMR or fluorescence. Gas-phase investigation of energetics of H-G systems is of great importance in providing information regarding their intrinsic binding properties. The major portion of this thesis is devoted to the study of the energetics of H-G complexes formed by three hemicryptophane cage hosts with various biologically-relevant guest molecules. Among the existing tandem mass spectrometry-based techniques, here we employ blackbody infrared radiative dissociation (BIRD), low-energy collision induced dissociation (low-energy CID), higher-energy collision dissociation (HCD) and high-pressure CID for measurements of energetics of H-G complexes. These techniques were used either alone, or in combination with each other, or with Rice–Ramsperger–Kassel–Marcus (RRKM) modeling. This work has allowed us to develop the low-energy CID, a promising technique, but so far infrequently used. In addition to the H-G chemistry studies, a comparative investigation of dissociation energetics of lithiated -cyclodextrin and lithiated maltoheptaose which are relatively similar to each other except that the former is a cyclic and the latter is a linear oligosaccharide, were performed using low-energy CID. Finally, the capabilities of low-energy CID, CID and HCD for structural analysis of carbohydrates, and also for exploring the dissolution mechanism of oligosaccharides in N,N-dimethylacetamide/lithium chloride (DMAc/LiCl) were investigated. Keywords: BIRD, low-energy CID, RRKM modeling, CID, HCD, host-guest chemistry, structural characterization of oligosaccharides, DMAc/LiCl Dédicace شکر و سپاس خدا را هک زبر گرتین امید و یاور رد لحظه لحظه زندگی است پیشکش هب پدر و ماردم استوار رتین تکیه گاه و امن رتین پناه زندگانی ام حم هب دست اهی ز تکش پ ی نه بسته شان این رساهل ی دکتری مرهون حمایت سخاوتمنداهن و اعتماد شما رد تمام مراحل زندگی ام هست امروز، دلخوشی ام هب وجود شما و فردا کلید باغ بهشتم رضای شماست تقدیم هب همسرم هب سا هی سار زندگی ا م، پناه دل خستگی اهیم و همدم شادی اه و غم اهیم هب پاس مهربانی اه، صبوری اه و حمایت اهی بی ردیغش هب او هک زندگی سر شار از عشق و محبت و آرامش ربایم فراهم آورده است Remerciements First, I would like to express my sincere gratitude to my advisor Prof. Richard B. Cole for his continuous support of my Ph.D study, for his patience and encouragement. His advices always helped me during my research. I am extremely thankful and indebted to Dr. Denis Lesage for his great support, sincere and valuable supervision and encouragement. The door of Denis’s office was always open whenever I had a question. I also acknowledge all the jury members: Prof. David Rondeau, Prof. László Drahos, Prof. Guillaume van der Rest and Dr. Sandrine Sagan who were willing to participate in my defense committee. I place on record, my heartfelt thanks to Dr. David Gatineau for his excellent guidance, caring, patience and continuous support. I express my sense of gratitude to Dr. Cédric Przybylski for his help, encouragement and attention. I would like to thank Prof. Vincent Robert and Prof. Alexandre Martinez who were willing to collaborate with us in our host-guest chemistry projects. I take this opportunity to express gratitude to all of the CSOB, “plateforme de MS” and “protéomique de l'IBPS” members, who directly or indirectly assisted me through this period. I also thank my husband, Dr. Sina Marhabaie, for his sympathy, kindness and encouragement. He was always there cheering me up and stood by me through the good times and bad. Finally, I would like to thank my parents, my sisters and my brother for their attention, encouragement, and support throughout my life. BAYAT Parisa – Thèse de doctorat - 2018 Table of contents Table of contents ............................................................................................................... I List of Abbreviations ........................................................................................................ IV Introduction générale ....................................................................................................... 1 Chimie hôte-invité .................................................................................................................... 2 Hémicryptophanes ................................................................................................................... 4 Spectrométrie de masse en tandem .......................................................................................... 6 Ionisation par électronébulisation ........................................................................................... 11 Préface .................................................................................................................................... 17 Chapter 1: Fundamentals of unimolecular ion dissociation .......................................... 22 Lindemann mechanism ............................................................................................................ 23 Hinshelwood theory ................................................................................................................ 27 RRK
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