Synthesis of Amphiphilic Porphyrins and Porphyrin Arrays

321 Pages·2017·9.74 MB·English

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2016
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Nicholas Roach
University of Wollongong, [email protected]
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Roach, Nicholas, Synthesis of Amphiphilic Porphyrins and Porphyrin Arrays, Doctor of Philosophy thesis,
School of Chemistry, University of Wollongong, 2016. https://ro.uow.edu.au/theses/4941
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Synthesis of Amphiphilic Porphyrins
and Porphyrin Arrays

A Thesis Presented in Partial Fulfilment of the Requirements
for the Degree of Doctor of Philosophy in Chemistry at The University of Wollongong,
Wollongong, Australia

Nicholas John Lambeth Roach
November 2016
Acknowledgements
I want to thank David, Pawel, Chris, Rhys and Dan for their assistance and friendship, and
Les Dutton and the group at UPenn for their hospitality and high quality work. I also want to
thank my family for their support, and everyone at IPRI and elsewhere who assisted me in
completing my studies.
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Abstract
The natural photosynthetic systems utilise protein scaffolds to hold their components,
which self assemble to form complex structures. Artificial protein maquettes offer the
possibility of producing similarly sophisticated molecular assemblies, containing light-
harvesting pigments and catalysts for charge separation and energy storage, with a potential
application in fuel production using solar energy.
The production of such an assembly requires the binding of light harvesting pigments to
the designed binding sites of a protein maquette, but it is not known what functionality on a
light harvesting pigment is required for optimal binding. In order to investigate these binding
requirements, a variety of single porphyrins with a range of hydrophilic and hydrophobic
properties were synthesised, and preliminary investigations into their binding to maquettes
were undertaken.
Mixed-aldehyde condensation was used to generate a large variety of porphyrins, which
were subsequently metalated with zinc or iron and then converted to their final amphiphilic
forms. A porphyrin bearing a ferrocene group and two porphyrins bearing electron-
withdrawing pentafluorobenzene groups were also produced in order to explore the
modification of the porphyrins’ electronic properties. HPLC was used to solve the problem of
determining the isomeric purity of ABAB and AABB porphyrins isolated from mixed-aldehyde
condensations.
Porphyrin dyads with a phenylene linkage were produced using similar mixed-aldehyde
condensations. Two amphiphilic dyads of this type were produced, bearing carboxylic acid and
quaternary ammonium salt hydrophilic substituents. Amphiphilic porphyrin dyads with vinyl
linkages were also produced using Wittig and Knoevenagel condensations.
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Methods of using bound metal ions to facilitate controlled differential metalation of a
phenylene-linked porphyrin dyad were investigated. A method of tagging porphyrins with
manganese was developed in order to facilitate the isolation of porphyrin arrays bearing ester
groups. This technique allowed the isolation of a porphyrin triad.
A preliminary investigation into the maquette-binding properties of the amphiphilic
porphyrins and porphyrin arrays was carried out, and the compounds that bound quickly and
strongly were identified. It was found that extremes of hydrophobicity and hydrophilicity were
not conducive to maquette binding, and that amphiphilic molecules bound the best. The
maquettes were able to accommodate a variety of porphyrins bearing from one to three
hydrophilic groups, and porphyrins bearing both carboxylic acids and quaternary ammonium
salts were found to be tolerated by the maquette. The best-binding of these porphyrin
materials have already formed the foundation of future research into light harvesting
porphyrin maquette ensembles.

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Table of Contents
Certification ............................................................................................................................. i
Acknowledgements ............................................................................................................... iii
Abstract....... ............................................................................................................................ v
Table of Contents .................................................................................................................. vii
List of Figures ....................................................................................................................... xiii
List of Abbreviations ......................................................................................................... xxvii
Chapter 1: Introduction ...................................................................................................... 1
1.1 The photosynthetic mechanism ................................................................................ 2
1.2 Harvesting photons ................................................................................................... 2
1.2.1 Charge separation and energy storage ............................................................. 4
1.3 Porphyrinoid-protein conjugates .............................................................................. 6
1.3.1 Natural ensembles ............................................................................................ 6
1.3.2 Protein maquettes ............................................................................................ 8
1.4 The porphyrins ........................................................................................................ 12
1.4.1 Properties of porphyrins ................................................................................. 12
1.4.2 Laboratory synthesis of porphyrins ................................................................ 14
1.4.3 Water soluble and amphiphilic porphyrins ..................................................... 20
1.4.4 Porphyrin arrays .............................................................................................. 23
1.5 Thesis aims and structure ....................................................................................... 33
Chapter 2: Amphiphilic porphyrins from mixed-aldehyde condensations .................... 35
2.1 Introduction ............................................................................................................ 35
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2.2 Choosing hydrophilic and hydrophobic groups for mixed-aldehyde condensation 36
2.3 Synthesis of phenylporphyrin carboxylic acids ........................................................ 37
2.3.1 Porphyrin synthesis ......................................................................................... 37
2.3.2 Formation of porphyrin metal complexes ....................................................... 42
2.3.3 Hydrolysis of the ester groups ......................................................................... 46
2.4 Synthesis of butylporphyrin carboxylic acids .......................................................... 48
2.4.1 Butylporphyrin synthesis ................................................................................. 49
2.4.2 ABAB butylporphyrin diester via a dipyrromethane ....................................... 51
2.4.3 Zinc insertion ................................................................................................... 53
2.4.4 Hydrolysis of the ester groups ......................................................................... 54
2.5 Synthesis of phenylporphyrin quaternary ammonium salts ................................... 55
2.5.1 Porphyrin synthesis ......................................................................................... 56
2.5.2 Tetraamine via tetranitro TPP ......................................................................... 59
2.5.3 Zinc insertion ................................................................................................... 60
2.5.4 Methylation of dimethylaminophenylporphyrins ........................................... 62
2.5.5 Methylation of the tetra amino porphyrin ...................................................... 63
2.6 Synthesis of a ferrocene porphyrin carboxylic acid ................................................. 65
2.6.1 Porphyrin synthesis ......................................................................................... 66
2.6.2 Zinc insertion ................................................................................................... 68
2.6.3 Hydrolysis of the ester groups ......................................................................... 69
2.7 Synthesis of pentafluorophenylporphyrin esters .................................................... 70
2.7.1 Porphyrin synthesis ......................................................................................... 71
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2.7.2 Iron insertion ................................................................................................... 73
2.7.3 Hydrolysis ........................................................................................................ 74
2.7.4 Electrochemical analysis ................................................................................. 75
2.8 Chapter conclusion ................................................................................................. 78
Chapter 3: Analysis of ABAB and AABB isomers ............................................................. 81
3.1 Introduction ............................................................................................................ 81
3.2 HPLC analysis ........................................................................................................... 85
3.2.1 Reversed-phase HPLC ..................................................................................... 86
3.2.2 Normal-phase HPLC ........................................................................................ 89
3.3 Chapter conclusion ................................................................................................. 94
Chapter 4: Phenylene-linked porphyrin arrays ............................................................... 95
4.1 Introduction ............................................................................................................ 95
4.1.1 Porphyrin arrays from statistical mixtures ..................................................... 96
4.2 Synthesis of meso-aldehyde bearing porphyrins .................................................... 97
4.2.1 Porphyrin aldehydes via Bouveault formylation ............................................ 97
4.2.2 Porphyrin aldehydes via monoprotected phthalaldehyde ........................... 102
4.3 Synthesis of porphyrin arrays ............................................................................... 105
4.3.1 Ester porphyrin dyad formation in a statistical mixture ............................... 105
4.3.2 Dimethylamine porphyrin dyad .................................................................... 109
4.3.3 Zinc complexes of porphyrin dyads .............................................................. 112
4.3.4 Hydrolysis of zinc porphyrin ester dyad ........................................................ 114
4.3.5 Methylation of zinc porphyrin dimethylamine dyad .................................... 115
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4.3.6 Triad formation in statistical mixtures .......................................................... 115
4.4 Chapter conclusion ................................................................................................ 118
Chapter 5: Vinyl-linked porphyrin arrays ....................................................................... 119
5.1 Introduction ........................................................................................................... 119
5.1.1 Synthesis of starting materials ...................................................................... 121
5.1.2 Meso-disubstituted porphyrin aldehyde ....................................................... 121
5.2 Synthesis of vinyl-linked dyads .............................................................................. 123
5.2.1 Meso-free dyad .............................................................................................. 123
5.2.2 Fully meso-substituted arrays........................................................................ 124
5.2.3 Vinyl-linked dyad ........................................................................................... 125
5.2.4 Vinyl-linked ABAB triad syntheses ................................................................. 131
5.3 Knoevenagel condensation ................................................................................... 133
5.3.1 Preparation of cyanoporphyrins .................................................................... 136
5.3.2 Knoevenagel condensation ........................................................................... 147
5.4 Chapter conclusion ................................................................................................ 152
Chapter 6: Using porphyrin metalation to facilitate array synthesis and purification . 153
6.1 Differential dyad metalation of phenylene-linked dyad ....................................... 153
6.1.1 Silver protection of porphyrin aldehyde ....................................................... 155
6.1.2 Separation of partially-metalated dyads ....................................................... 161
6.2 Manganese tagging to produce phenylene-linked porphyrin triads ..................... 170
6.2.1 Mn tagged porphyrin aldehyde ..................................................................... 172
6.2.2 Triad synthesis ............................................................................................... 172
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6.2.3 Manganese removal...................................................................................... 173
6.3 Silver redox tagging chromatography ................................................................... 177
6.3.1 Development of oxidation conditions .......................................................... 178
6.3.2 Application in the isolation of Wittig-linked arrays ...................................... 180
6.4 Chapter conclusion ............................................................................................... 182
Chapter 7: Maquette binding of amphiphilic porphyrins and porphyrin arrays .......... 183
7.1 Introduction .......................................................................................................... 183
7.2 Formation of porphyrin-maquette complexes ..................................................... 184
7.2.1 Binding strength: K measurement ............................................................... 185
d
7.3 Maquette-binding of amphiphilic Zn porphyrins .................................................. 189
7.3.1 Zinc Phenylporphyrin benzoic acids 2.07, 2.17 – 2.21 .................................. 189
7.3.2 Zinc butylporphyrin benzoic acids 2.33, 2.39 – 2.42 ..................................... 200
7.3.3 Zinc phenylporphyrin QASs 2.56 – 2.60 ........................................................ 209
7.3.4 Ferrocene porphyrin triacid 2.63 .................................................................. 220
7.4 Binding of amphiphilic Fe porphyrins 2.23 – 2.25 ................................................ 222
7.5 Binding of porphyrin dyads ................................................................................... 227
7.6 Chapter conclusion ............................................................................................... 232
Future work ....................................................................................................................... 235
Experimental ...................................................................................................................... 237
References... ....................................................................................................................... 281

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