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Modeling the Interaction Between Light and Complex Molecular Systems Hugo Gattuso

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Modeling the Interaction Between Light and Complex Molecular Systems Hugo Gattuso DNA photosensitization : modeling the interaction between light and complex molecular systems Hugo Gattuso To cite this version: Hugo Gattuso. DNA photosensitization : modeling the interaction between light and complex molec- ular systems. Theoretical and/or physical chemistry. Université de Lorraine, 2017. English. NNT : 2017LORR0101. tel-01735331 HAL Id: tel-01735331 https://tel.archives-ouvertes.fr/tel-01735331 Submitted on 15 Mar 2018 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. AVERTISSEMENT Ce document est le fruit d'un long travail approuvé par le jury de soutenance et mis à disposition de l'ensemble de la communauté universitaire élargie. Il est soumis à la propriété intellectuelle de l'auteur. Ceci implique une obligation de citation et de référencement lors de l’utilisation de ce document. D'autre part, toute contrefaçon, plagiat, reproduction illicite encourt une poursuite pénale. Contact : [email protected] LIENS Code de la Propriété Intellectuelle. articles L 122. 4 Code de la Propriété Intellectuelle. articles L 335.2- L 335.10 http://www.cfcopies.com/V2/leg/leg_droi.php http://www.culture.gouv.fr/culture/infos-pratiques/droits/protection.htm Thèse présentée en vue de l’obtention du grade de Docteur de l’Université de Lorraine Spécialité Chimie Photosensibilisation de l’ADN: modélisation des interactions entre la lumière et les systèmes moléculaires complexes DNA photosensitization: modeling the interaction between light and complex molecular systems Hugo Gattuso Soutenue publiquement le 6 juillet 2017, Faculté des Sciences et Technologies de Vandœuvre-lès-Nancy, France Membres du jury: Rapporteurs: Mme. Célia Fonseca Guerra Professeure Vrije Universiteit, Amsterdam Mr. Mathieu Linares Professeur Royal Institute of Technology, Stockholm Examinateurs: Mr. Richard Lavery Directeur de Recherche CNRS/Université de Lyon I Mme. Elise Dumont Maître de conférence Ecole Normale Supérieure de Lyon Mr. Antonio Monari Maître de conférence Université de Lorraine Directeur de thèse: Mr. Xavier Assfeld Professeur Université de Lorraine Laboratoire : Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC) Equipe : Théorie-Modélisation-Simulation (TMS) Ecole doctorale : Synthèse, Expérience, Simulations, Applications: de la Molécule aux Edifices Supramoléculaires (SESAMES) Contents I Acknowledgments/Remerciements ii II Outreach activities iv 0.1 Introduction ................................ v 0.2 Pretexte .................................. v 0.3 Esperluette ................................ vi 0.4 MT180 ................................... viii III List of publications xii IV Introduction générale 1 V General introduction 6 VI Main concepts and systems 11 1 Photochemical and photophysical processes 12 1.1 Photochemistry .............................. 12 1.2 Spectroscopies ............................... 15 1.2.1 UV-visible absorption ....................... 15 1.2.2 Circular dichroism ........................ 18 1.2.3 Fluorescence ............................ 18 1.3 Photosensitization ............................. 19 1.4 Photodynamic therapy .......................... 20 2 DNA 23 2.1 Introduction ................................ 23 2.2 Fundamental building blocks of DNA .................. 24 2.3 Double helix ................................ 25 2.4 DNA structural parameters ....................... 27 ii CONTENTS iii 2.5 DNA photosensitivity........................... 27 2.6 DNA photolesions ............................. 28 2.7 Repair processes .............................. 29 VII Methods 31 3 Molecular Mechanics 32 4 Molecular Dynamics 34 4.1 Integration of equations of motion .................... 34 4.2 Periodic Boundary Conditions (PBC) .................. 35 4.3 Ewald summation and Particule Mesh Ewald (PME) ......... 37 4.4 Biased Molecular Dynamics ....................... 38 4.5 Alchemical simulations .......................... 39 5 Quantum chemistry 41 5.1 The six postulates of quantum mechanics ................ 41 5.1.1 Postulate 1: the wave function Ψ ................ 41 5.1.2 Postulate 2: Hermitian operators ................ 42 5.1.3 Postulate 3: eigenstates and eigenvalues ............ 42 5.1.4 Postulate 4: expectation of the wave function ......... 42 5.1.5 Postulate 5: Time dependent Schrödinger equation ...... 43 5.1.6 Postulate 6: wave function collapse ............... 43 5.2 The Schrödinger equation in quantum chemistry ............ 43 5.3 Born-Oppenheimer approximation .................... 44 5.3.1 Variational Principle ....................... 44 5.4 Ground state ............................... 44 5.4.1 Hartree-Fock approximation ................... 44 5.4.2 Density Functional theory (DFT) ................ 48 5.4.2.1 Principle ........................ 48 5.4.2.2 The electronic density ................. 48 5.4.2.3 The Hohenberg-Kohn theorems ............ 49 5.4.2.4 The Kohn-Sham equations ............... 50 5.4.2.5 LDA ........................... 51 5.4.2.6 GGA .......................... 52 5.4.2.7 meta-GGA ....................... 52 5.4.2.8 Hybrid GGA and hybrid meta-GGA ......... 52 5.4.2.9 Double hybrids ..................... 53 5.5 Excited states ............................... 54 CONTENTS iv 5.5.1 Time Dependent-Hartree Fock (TDHF) ............. 54 5.5.2 Time Dependent-Density Functional Theory (TDDFT) .... 55 5.5.2.1 The Runge-Gross theorem ............... 55 5.5.2.2 Time-Dependent Kohn-Sham equation ........ 55 5.5.3 Frenkel excitons theory ...................... 56 6 QM/MM 58 6.1 QM/MM energy .............................. 58 6.1.1 QM/MM embeddings ....................... 59 6.1.1.1 Mechanical Embedding (ME) ............. 60 6.1.1.2 Electrostatic Embedding (EE) ............. 60 6.1.1.3 Polarisable Embedding (PE) .............. 60 6.2 QM/MM boundary ............................ 60 6.2.1 Link Atom (LA) ......................... 60 VIII Results and discussions 62 7 Introduction 63 8 Electronic Circular Dichroism (ECD) modeling 64 8.1 ECD of B-DNA .............................. 64 8.2 ECD of G-quadruplexes ......................... 71 9 Binding free energy of Benzophenone 80 10 Photosensitization of DNA 91 10.1 Benzophenone: Hydrogen abstraction .................. 91 10.2 Nile Blue, Nile Red: Electron transfer .................. 101 10.3 BMEMC: Radical species ......................... 111 10.4 Pyo: Triplet-Triplet Energy Transfer (TTET) ............. 123 11 Damaged DNA: structure and recognition 134 11.1 Cluster abasic sites ............................ 134 11.1.1 Recognition by APE1 ....................... 147 11.2 64-PP and CPD .............................. 150 CONTENTS i IX Conclusion générale 162 X General conclusion 166 XI Appendices 170 A DNA structural parameters 171 B ECD of B-DNA 174 C ECD of G-quadruplexes 175 D Binding free energy of Benzophenone 179 E Benzophenone: Hydrogen abstraction 183 F Nile Blue, Nile Red: Electron transfer 186 G BMEMC: Radical reactive species 189 H Pyo: Triplet-Triplet Energy Transfer (TTET) 191 I Cluster abasic sites 195 J 6-4PP and CPD 199 Part I Acknowledgments/Remerciements ii iii First of all, I want to warmly thank Antonio and Xavier who are without doubt the pillars of the work accomplished during these three years. I feel privileged to have been supervised by both of you; being introduced to your scientific networks, the conferences, the beers together . Also, I want to thank everyone from the TMS team (now LPCT) for their kind- ness and our discussions about my scientific problems: Gerald, Mounir, Maria- Chiara, Fabien, Christian, and Severine (without who this lab would fall apart). And the volatiles (PhDs, postdocs and interns): Tony, Maura, Antoine, Ilke, Ma- rina, Maryline, Wanlei, Audrey, Elena, Tony, Elodie , Cecilia, Elodie, Saber, Houda and certainly more. Special mention to the team of Zozos for the entertainment they provided me: Francois, Chris, Andreea, Sebastien and Carole. Since I am leaving soon, they will be happy to know that I will stop disturbing their long "scientific" discussions in the coffee room of the 6th floor. Also, I would like to express my gratitude to the amazing people who spiced up my PhD: Benjamin for a 2 years long deskmate relationship, amazing times together and interesting discussions at the Quincaillerie (we were like two dogs sitting at the top of a hill, looking at the horizon); Thibaud aka the belgian for our great friendship and all the things that came with it, parties, trips and more parties; Marco for our great scientific collaboration and his unexpected help to sometimes put things in perspective; Angelo, the best guide of Sicily, first an amazing scientific match between us that soon became a strong friendship; to Fernanda for our adventures together, road trips and discoveries, especially for having initiated me to rollerblading; the Phi-Science team of course that was after all always here when I needed to relax from the first day of my PhD to the last, Delphine, Clara, Manon, Ismael, Belo, Greg, Nata . ; I also feel privileged having built such an amazing friendship with my dear PhD fellows, I definitely
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