Extended Arm Polyphenylene Dendrimers: Synthesis and Characterization Dissertation zur Erlangung des Grades ‚‚Doktor der Naturwissenschaften’’ am Fachbereich Chemie und Pharmazie der Johannes Gutenberg-Universität in Mainz vorgelegt von Ekaterina Vladimirovna Andreitchenko geb. in Sankt-Petersburg, Russland Mainz, 2006 Die vorliegende Arbeit wurde in der Zeit von Mai 2002 bis November 2005 am Max-Planck- Institut für Polymerforschung in Mainz unter der Leitung von Prof. Dr. K. Müllen durchgeführt. Herrn Professor Dr. K. Müllen danke ich für die sehr interessante Themenstellung and für seine wissenschaftliche Förderung. Contents 1 Introduction 1.1 The dendrimer concept 1 1.2 Chemical synthesis of dendrimers 2 1.3 Flexible dendrimers 5 1.4 Molecular structure 5 1.5 Properties of dendritic macromolecules compared to linear polymers 7 1.6 Rigid dendrimers 8 1.7 Synthesis of polyphenylene dendrimers through Diels-Alder cycloaddition 10 1.7.1 Divergent synthesis 12 1.7.2 Convergent synthesis 12 1.8 The influence of the cores and the branching units on the shape of the polyphe- nylene dendrimers 15 1.9 Functionalization of polyphenylene dendrimers 16 a) Prior group introduction, the cyclopentadienone route 17 b) Posteriori Group Introduction 19 c) Electrophilic Aromatic Substitution 19 1.10 Practical applications of dendrimers 20 1.11 Motivation 21 1.12 Literature for Chapter 1 24 2 Extended Arm Polyphenylene Dendrimers 2.1 Introduction 28 2.2 Synthesis of the new branching unit 2.1 bearing tris-(para -phenylene ethynylene)arms 28 2.3 Synthesis of the new extended arm branching unit 3.1 30 2.4 The synthesis of ''exploded'' dendrimers up to the sixth generation 35 2.5 MALDI-TOF MS applied to the extended dendrimers 38 2.6 1H NMR analysis of exploded dendrimers 49 2.7 Size exclusion chromatography (SEC) 52 2.8 Multi-angle laser light scattering size exclusion chromatography (MALLS-SEC) 62 2.9 Vibrational spectroscopy (IR/Raman) 63 2.10 Visualisation of the exploded dendrimers by structural simulation 64 2.11 Dynamic light scattering (DLS) 65 2.12 Transmission electron microscopy (TEM) 68 2.13 Atomic Force Microscopy (AFM) 74 2.14 Guest molecules and their monitoring by the quartz microbalance (QMB) technique 81 2.15 Shortening the arms slightly: ‘‘semi-extended’’ dendrimers bearing a biphenyl - instead of a terphenyl spacer 87 2.16 Characterization of the dendrimers with biphenyl spacer 90 2.17 Outlook: dendrimers with biphenyl spacers for future application 92 2.18 Literature for Chapter 2 95 3 Synthesis and Hydrogenation of Dendrimers possessing internal -C≡C- Triple bonds 3.1 Introduction 101 3.2 Synthesis of new cyclopentadienone branching unit bearing the para-phenylene ethynylene arms ( 5.1 ) 101 3.3 Synthesis of the first-generation dendrimer with branching unit 5.1 104 3.4 Synthesis of the second- and third-generation dendrimers bearing eight internal triple bonds 108 3.5 Heterogeneous catalysis of hydrogenation: some principal considerations 110 3.6 Hydrogenation of the second-generation dendrimer 5.6 113 3.7 Hydrogenation of the third-generation dendrimer 5.7 116 3.8 Further effects caused by hydrogenation of internal -C≡C- triple bond 3.8.1 UV-Vis absorption of the second- and third-generation dendrimers 118 3.8.2 Raman spectroscopy of the third-generation dendrimers 5.7 and 5.9 119 3.8.3 Diffusion-ordered 2D NMR (DOSY) of the third-generation dendrimers 5.7 and 5.9 120 3.8.4 Incorporation of guest molecules 122 3.9 Literature for Chapter 3 123 4 Dendronization of a Chromophore Core by means of the New Extended Arm 3.1 4.1 Introduction 125 4.2 Synthesis of dendronized perylene dyes using the branching unit 3.1 127 4.3 Characterization of dendronized chromophore dendrimers 6.5 -6.10 130 4.4 Optical properties 4.4.1 Absorption and emission 132 4.4.2 Fluorescence quenching experiment 135 4.4.3 Fluorescence correlation spectroscopy (FCS) 137 4.5 Literature for Chapter 4 145 5 Summary 147 6 Experimental Part 6.1 Reagents and solvents 158 6.2 Instruments and analysis 159 6.3 General procedures 161 6.4 Synthesis of the extended arm polyphenylene dendrimers (for Chapter 2) 162 6.5 Synthesis of the semi-extended arm polyphenylene dendrimers (for Chapter 2) 178 6.6 Synthesis of the dendrimers possessing eight inner -C≡C- triple bonds and their hydrogenation (for Chapter 3) 185 6.7 Synthesis of the extended arm polyphenylene dendrimers with perylenedimide core (for Chapter 4) 195 6.8 Literature for Chapter 6 200 Abbreviations AFM atomic force microscopy Calcd. calculated Da Dalton DLS dynamic light scattering DOSY diffusion-ordered (NMR spectrum) EDA ethylenediamine FD MS field desorption mass spectrometry G1-G6 first-sixth generation number HPLC high performance liquid chromatography IR infrared MALDI-TOF matrix assisted laser desorption ionization time of flight (MS) MALLS multiple angle laser light scattering MS mass spectrometry Mn number average molecular weight Mw weight average molecular weight M molecular weight (calculated molecular mass) NMR nuclear magnetic resonance PAMAM poly-(amino amine) PDI 1) poly-dispersity index, 2) perylene-3,4,9,10-tetracarboxdimides PDs polyphenylene dendrimers PS poly-(styrene) RI refractive index RF retention factor r.t. room temperature SEC size exclusion chromatography TBAF tetrabutylammoniumfluoride trihyrate Td tetraphenylmethane core TEM transmission electron microscopy THF tetrahydrofuran TiPS triisopropylsilyl group UV-Vis ultraviolet-visible (light) QMB quartz microbalance Introduction Chapter 1 1 Introduction 1.1 The dendrimer concept Traditional polymers, according to Staudinger, 1-3] may be divided into three major macromolecular architectures: (I) linear (plexiglass, nylon), (II) cross-linked (rubber, expoxies), and (III) branched (low density polyethylene). As the fourth major of macromolecular architecture dendritic polymers have evolved; they consist of four sub- categories: random hyperbranched, [3-4] dendigraftes, [3] dendrons, [3] and dendrimers. [3,5] The present dissertation is concerned with the last category, namely that of dendrimers, exclusively. A dendrimer is generally described as a macromolecule, which is characterized by its extensively branched 3D structure that provides a high degree of surface functionality and versatility. Its structure is always built around a central multi-functional core molecule, with branches and end-groups. Dendrimers are synthesised in a stepwise manner, i.e. each successive shell, known as a generation, is formed in an individual step. In 1978 Vögtle and co-workers reported the first preparation, separation and mass spectrometric characterization of a basic dendrimer structure. [5-6] These authors produced a cascade in an iterative sequence of reaction steps, in which each additional reaction gave a higher generation material (Scheme 1.1). The reaction of a monoamine 1.1 , as a starting material, with acrylonitrile via Michael addition led to the synthesis of desired dinitrile 1.2-A which was reduced to the terminal diamine 1.2-B, serving as a branching unit. Then the molecule 1.2-B was subjected to the same reaction sequence to generate a heptaamine. This was the first synthesis of a cascade molecule and during the 1980’s only a handful of [5] additional research papers on cascade molecules were published. CN CN CN CH NH CN 2 2 CN N N Red. Red. R NH R N R N 2 R N CN R N CN CN CH2NH2 1.1 1.2 - A 1.2 - B N N CN CN NC NC Scheme 1.1: First synthesis of a cascade molecular architecture. 1 Introduction Chapter 1 Subsequently, Denkewalter et. al. obtained patents on the first divergent preparation of dendritic polypeptidies based on amino acids as the monomeric building block. [7] The term ‘’dendrimer’’ was first offered by Tomalia in 1984. The word ‘‘dendrimer’’ derives from the Greek word ‘‘dendron’’ meaning ‘‘tree’’ and ‘‘meros’’ meaning ‘‘part’’. Other names for dendrimers are ‘‘arborols’’ from Latin also referring to a tree, and ‘‘cascade polymers’’. Although the earlier name ‘‘cascade molecule’’ is connected more directly to nomenclature, the expression ‘‘dendrimer’’ has now been generally accepted. [8] Since the 1990’s after significant advances in analytical methods the field blossoms. 1.2 Chemical synthesis of dendrimers Dendrimer synthesis can be achieved through different methods. [6-18] However, divergent (a) and convergent (b) syntheses are the most common and extended methods (Scheme 1.2). In the divergent approach the dendrimer is prepared from the core as the starting point and built up generation by generation. However the high number of reactions which have to be performed on a single molecule demands very effective transformations (99 + % yield) to avoid defects. In the divergent way problems occur from an incomplete reaction of the end groups, since these structure defects accumulate with the build up of further generation. [8] As the side products possess similar physical properties, chromatographic separation is not always possible. Therefore the higher generations of divergently constructed dendrimers always contain certain structural defects. To prevent side reactions and to force reactions to completion a large excess of reagents is required, however this causes some difficulties in the purification of the final product. The convergent approach starts from the surface and ends up at the core, where the dendrimer segments (dendrons) are coupled together. In this way only a small number of reactive sites are functionalized in each step, giving a small number of possible side-reactions per step. Therefore each synthesized generation of dendrimers can be purified, although purification of the high-generation dendrons becomes more cumbersome because of increasing similarity between reactants and formed product. [9-10] But with proper purification after each step dendrimers without defects can be obtained by the convergent approach. On the other side, the convergent approach does not allow the formation of high generations because steric problems occur in the reactions of the dendrons and the core molecule.