Research Collection Doctoral Thesis Photochemical transformations in continuous flow devices Author(s): Laurino, Paola Publication Date: 2011 Permanent Link: https://doi.org/10.3929/ethz-a-006682166 Rights / License: In Copyright - Non-Commercial Use Permitted This page was generated automatically upon download from the ETH Zurich Research Collection. For more information please consult the Terms of use. ETH Library DISS. ETH NO. 19754 PHOTOCHEMICAL TRANSFORMATIONS IN CONTINUOUS FLOW DEVICES A dissertation submitted to ETH ZURICH for the degree of Doctor of Sciences presented by PAOLA LAURINO Dipl. Pharm. Chem., Universitá degli Studi di Milano Date of birth 1.4.1981 citizen of Italy accepted on the recommendation of Professor Dr. Hansjörg Grützmacher Professor Dr. Peter H. Seeberger Professor Dr. Dieter A. Schlüter 2011 A Maria Emilia, Silvia e Antonio I II “The fun of chemistry is in its unexpectedness. There are times when you come to face-to- face with an unexpected phenomenon while carrying out experiments. You simply have to be sufficiently aware and open to accept the seemingly unbelievable. There are still many more valuable ideas remaining to be discovered. The question is how to find them and how to develop them into new possibilities.” (Mukaiyama, Angew. Chem. Int. Ed. 2004, 43, 5590) III IV Acknowledgements I would first like to thank Professor Peter H. Seeberger for his support and encouragement during my entire stay in his group. The enthusiasm and scientific freedom that he provided were strong driving forces for me to develop new ideas, and his belief in my abilities helped me to be more confident and successfully carry on my research. I am grateful to Professor Hansjörg Grützmacher, his discussions which helped me to better understand the problems encountered in the polymerization project and improved the quality of my work and our collaboration. Thanks to Professor Dieter A. Schlüter who accepted to be my co-examiner. I thank Dr. Klaus Tauer, who patiently explained and taught me a lot about polymerization, helped me evaluate my data and supported me to develop the polymerization project. I especially want to thank Dr. Kikkeri Raghavendra to help me develop the QD projects. His creativity and imagination taught me a lot about a different way of pursuing science. Thanks to Dr Nahid Azzouz to carry most of the bioassays of my projects. I am grateful to Dr. Riccardo Castelli who was always available to help me with chemical mechanisms and reactions. Thanks to Dr. Hugo Hernandez who helped me understand the polymerization mechanism and scientifically supported me in the first period in Berlin. Thanks to Dr. Bastien Castagner who initially contributed to develop the flow reactor. I would like to thank the microreactor team, the former members who introduced me in the micro world and also the present members. V Thanks to Dr. Farhan Bou Hamdan and Dr. Alexander O´Brien to proof read the first versions of the thesis. I am grateful to Dr. Xiao Yin Mak, Dr. Mattan Hurevich, Dr. Hugo Hernandez and Dr. Klaus Tauer to correct and help me organize different parts of this thesis. Thanks to Mr. Bopanna Monnanda Ponnapa to proof read my thesis. Finally a special acknowledgement to Dr. Claney Lebev Pereira for going carefully through my entire thesis and helping me improve it with critical suggestions and corrections. I would like to thank Herr Mario Kessinger and Frau Dorothee Böhme their help in the administrative issues was fundamental. Thanks to My parents for supporting me consistently during these years. Silvia my sister who taught me a lot about life, without her advices I would have often felt lost. My Italian friends who were always there for me, and the friends that I met in Leiden, Zürich and Berlin, even if spread around the world, I bring part of them always with me. Professor Ad IJzerman and Dr. Laura Fumagalli without them I would have never been able to start my PhD in ETH. My boyfriend who endured me during this last period, his support was endless. VI TABLE OF CONTENTS Abstract 1 Riassunto 4 1. Microreactors for Continuous Flow Organic Synthesis 7 1.1 Concepts and Definition 8 1.2 Continuous Flow Microreactor Design 10 1.3 Particle Synthesis in Continuous Flow 16 1.4 Continuous Flow Photochemistry 22 1.5 Advantages and Limitations 31 1.6 Conclusions 33 1.7 References 34 2. Synthesis and Functionalization of Quantum Dots 41 2.1 Introduction 42 2.2 QDs Batch Synthesis 48 2.3 Continuous Flow QD Synthesis and Functionalization 53 2.4 Photophysical Properties of QDs Produced in Continuous Flow 58 2.5 Biological Studies Using Carbohydrate-Capped QDs 63 2.6 Conclusions 67 2.7 Experimental Part 68 2.8 References 83 3. Continuous Flow Microreactors and Phosphine Oxide Initiators: an Unique Combination 86 3.1 Introduction 87 3.2 Continuous Flow Microreactor Design 95 3.3 Emulsification 100 3.4 Extraordinarily High Molecular Weight Polymer in Small Particles 104 3.5 Ultrafast Polymerization of Styrene 110 3.6 Investigations on BAPO-AA 113 3.7 Studies on Different Phosphine Oxide Initiators 121 VII 3.8 Molecular Weight Distribution and Average Size of Polymer Particles 123 3.9 Snowballing Radical Generation Mechanism 125 3.10 Snowballing Radical Generation Simulation 133 3.11 Seed Polymerization of Polymer Particles 138 3.12 Applications of SRG Mechanism 140 3.13 Conclusions 145 3.14 Experimental Part 146 3.15 References 151 4. Final Conclusions and Outlook 155 Appendix 159 5. Glyco-dendronized Polylysine for Bacteria Detection 161 5.1 Indroduction 162 5.2 Synthesis of Glyco-dendrons 165 5.3 Photofunctionalization of Polylysine 166 5.4 Bacteria Detection with Glyco-dendronized Polylysine 168 5.5 Conclusions 170 5.6 Experimental Part 171 5.7 References 183 List of Abbreviations 185 Curriculum Vitae 187 VIII IX Abstract Microreactor enables precise and automated manipulation of reaction mixture in a defined volume of space. In recent times there has been an increasing interest in the miniaturization of chemical and biochemical reactors. The microreactor is an efficient and versatile alternative to the traditional batch reactor techniques and has facilitated the development of new methods for organic and polymer chemists. Microreactors, when used in continuous flow permit the precise control and screening of reaction parameters. This thesis emphasizes the benefits of using microreactor technology for the synthesis of nanoparticles and the study of photochemical reactions. Herein two successful applications were studied and described: 1) The use of continuous flow device for the synthesis and functionalization of quantum dots (QDs). 2) Discovery of a new mechanism for the reaction of phosphine oxide initiators during the emulsion polymerization in a continuous flow microreactor. Preliminary results regarding the synthesis of QDs in a round bottomed flask resulted in major limitations in the control of particle nucleation and growth, which were primarily due to the non-homogeneous mixing and heating of the reaction mixture. To overcome these limitations, a versatile new strategy was developed and applied for producing carbohydrate- or dihydrolipoic acid-capped CdSe/ZnS and CdTe/ZnS quantum 1 dots (QDs) for biological applications. This method involved a three-step flow synthesis in single-phase by using a continuous flow microreactor. The first step involved screening different reaction time and temperature conditions to produce QDs of different size with precise photophysical properties. The second and third step involved the shell formation (ZnS) to obtain QDs and functionalization of the same with thiol linked carbohydrate or dihydrolipic acid. The method described has the following advantages: 1) Production of QDs in the range of 2–4 nm with narrow particle size distribution. 2) Precise control of the nucleation and growth of QD cores in a single-phase flow and lower temperature than previous syntheses. 3) Easy screening of reaction parameters. 4) The procedure can be scaled up to produce large amounts of QDs. In the second part of this thesis a photo-initiated phosphine oxide mediated polymerization reaction accelerated by snowballing radical generation (SRG) in a continuous flow microreactor was described. This method afforded narrow size distributed particle in a scalable and reproducible manner. Surprisingly, high molecular weight polymer chains were detected in small particles generated at short residence times (36.5 s). The use of microreactor permitted an in-depth investigation of the reaction mechanism, screening parameters and conditions not obtainable in a batch reactor. The classical emulsion polymerization could not justify the 2 observed screening results. A new mechanism for the reaction was proposed whereby upon irradiation phosphine oxide was able to generate more radicals for particles than expected. The discovery of this new mechanism of reaction (Snowballing Radicals Generation) permitted to produce materials with defined morphologies that were difficult to synthesize previously. 3 Riassunto Il microreattore permette di manipolare in modo preciso e automatizzato miscele di reazione in un volume di spazio definito. Recentemente l´interesse per la miniaturizzazione di reattori chimici e biochimici è aumentato. L´uso del microreattore si presenta come un´alternativa efficiente e versatile ai tradizionali reattori e ha facilitato lo sviluppo di nuovi metodi in chimica organica e polimerica. I microreattori quando usati in flusso continuo, permettono il controllo preciso e lo screening di parametri