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Semi-Natural and Synthetic
Chiral Cycloketo-Porphyrin
Approaching Novel Photosensitizers

Der naturwissenschaftlichen Fakultät
der Friedrich-Alexander-Universität Erlangen-Nürnberg


Erlangung des Doktorgrades

vorgelegt von

Stefan Jasinski

aus Nürnberg

Als Dissertation genehmigt von der naturwissenschaftlichen Fakultät der Universität

Tag der mündlichen Prüfung: 17. April 2009
Vorsitzender der Promotionskommision: Prof. Dr. Eberhard Bänsch
Erstberichterstatter: Priv.-Doz. Dr. Norbert Jux
Zweitberichterstatter: Prof. Dr. Andreas Hirsch
Drittberichterstatterin: Prof. Dr. Beate Röder

Die vorliegende Arbeit entstand in der Zeit von August 2004 bis Dezember 2008 am Institut
für Organische Chemie der Friedrich-Alexander-Universität Erlangen-Nürnberg.
Mein besonderer Dank gilt hierbei meinen Doktorvätern Prof. Dr. Andreas Hirsch und P. D.
Dr. Norbert Jux für die gewährte Unterstützung und das rege Interesse am Fortgang der
Arbeiten. In diesem Zusammenhang danke ich auch herzlich meinen Kooperationspartnern
Prof. Dr. Gerhard Bringmann (Julius-Maximilians-Universität Würzburg), Prof. Dr. Klaus
Schomäcker (Universität zu Köln) und vor allem Prof. Dr. Beate Röder (Humboldt-Universität
zu Berlin) und Dr. Eugeny Ermilov (Berlin) für die hervorragende Zusammenarbeit.

Phantasie ist wichtiger als Wissen, denn Wissen ist begrenzt.


Table of Contents
1 Introduction 1
1.1 Porphyrins – A General Survey 4
1.2 Photodynamic Therapy (PDT) 14

2 State of the Art & Aims 21
2.1 State of the Art 21
2.2 Aim of the Work 24
3 Discussion and Results 25
3.1 Semi-Natural Cycloketo-Porphyrins 25
3.2 Synthetic Cycloketo-Porphyrin Systems 31
3.2.1 o-(Bromomethyl) Substituted Porphyrin Building Blocks Revisited 31
3.2.2 Setup of a Synthetic Pathway to Novel Cycloketo-Porphyrins 34
3.2.3 Mono-Exocyclic Cycloketo-Porphyrin 53 - Characterization Data and
Photophysical & Electrochemical Investigations 43
3.2.4 Chemical Reactivity of Mono-Exocyclic Cycloketo-Porphyrin 53 61
3.2.5 Inherent Chirality and Resolution of Cycloketo-Porphyrin 53 70
3.2.6 Studying the Structure-Properties-Relations 75
3.2.7 Approaching Polyexocyclic Cycloketo-Porphyrin Systems 92
3.2.8 Cycloketo-Porphyrin Systems with Additional Functionality 109
3.2.9 Potential Strategies for the Development of Novel Photosensitizers 124

4 Summary 131
5 Zusammenfassung 134
6 Experimental Section 137
6.1 Chemicals, Methods and Equipment 137
6.2 Studied Compounds – Syntheses & Characterization 140
6.2.1 Preliminaries 140
6.2.2 Semi-Natural Cycloketo-Porphyrin Systems 141
6.2.3 General Procedures (GPs) 143
6.2.4 AB -Type Mono-Exocyclic Cycloketo-Porphyrins and Their Precursors 1463
6.2.5 A B -Type Poly-Annulated Cycloketo-Porphyrin Systems and Precursors 1622 2
6.2.6 ABC-Type Mono-Exocyclic Cycloketo-Porphyrins, Precursors & 2
Derivatives 178

7 References 189
Appendix 197
Publications, Acknowledgements (Danksagung), Curriculum Vitae

List of Abbreviations
Ac acetyl
acac acetylacetonate
aq. aqueous
Ar aryl
ATR attenuated total reflection
BCKP bis-cycloketo-porphyrin
BOC t-butoxycarbonyl
Bu butyl
COSY correlation spectroscopy
δ chemical shift
DAFS decay associated fluorescence spectroscopy
DCTB trans-2-(3-(4-t-butylphenyl)-2-methyl-2-propenylidene)malononitrile
DDQ 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
DFT density functional theory
DMAP N,N-dimethyl-4-aminopyridine
DMF N,Nylformamide
DMSO dimethylsulfoxide
e electron
E energy
E (E ) (half-wave) potential ½
ε molar extinction coefficient
EA elemental analysis
EDC 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide
EN (EN) (group) electronegativity G
E ,E anodic (cathodic) peak potential pa pc
eq. equivalent(s)
ET energy transfer / electron transfer
Et (EtOH) ethyl (ethanol)
exc. excess(ive)
FAB+ fast atom bombardment, positive detection mode
FC flash column chromatography
+Fc / Fc ferrocene / ferrocinium
FRET FÖRSTER resonance energy transfer
fl fluorescence
GP general procedure
+[H] protic or LEWIS acid catalyst
hν photonic/light energy
HOMO highest occupied molecular orbital
Hp (HpD) hematoporphyrin (derivative)
IC internal conversion
IR infra-red
ISC intersystem crossing
IUPAC international union of pure and applied chemistry

nJ j-coupling (constant) with n indicating the number of involved bonds
λ wavelength
LUMO lowest unoccupied molecular orbital
M molecular weight
M(X)-1 metal complex of 1, X represents the metal’s oxidation state
M molar, mol·L
m/z mass per charge
MALDI-TOF matrix assisted laser desorption ionization – time of flight
Me (MeOH) methyl (methanol)
+ MM molecular mechanics
MRCI multireference configuration interaction
MS mass spectrometry
NBA m-nitrobenzyl alcohol
NHS N-hydroxysuccinimide
NMR nuclear magnetic resonance
NOE nuclear OVERHAUSER effect
Nu nucleophile
1 3O ( O ) singlet (triplet) oxygen 2 2
o/m/p ortho / meta / para
Ox oxidation
P(x) portion of compound x
1 3P ( P) singlet (triplet) state of a photosensitizer
PDT photodynamic therapy
PEG polyethylene glycol
Φ (Φ ) quantum yield (of singlet oxygen generation)
PM3 parameterized method No. 3
ppm parts per million
r radius
R substituent
Red reduction
rt room temperature
S singlet state, x = 0, 1, 2… (singlet ground state, first excited singlet state…) x
S nucleophilic substitution N
SCE standard calomel electrode
SPR structure-properties-relations
Sub (organic) substrate
t tertiary
T / K thermodynamic temperature in degrees KELVIN
T triplet state, x = 0, 1, 2… (triplet ground state, first excited triplet state…) x
τ fluorescence decay time
TCSPC time-correlated single photon counting
TFA 2,2,2-trifluoroacetic acid
θ / °C temperature in degrees CELSIUS
THF tetrahydrofuran
TLC thin layer chromatography
TPP tetraphenylporphyrin
UV/Vis ultra violet / visual
VT various temperature
wt% weight percent

Introduction 1
1 Introduction
When we just take a look around, we find ourselves in a fast moving society affected by a
highly mobile, interdependent and interconnected world offering a myriad of opportunities.
But this situation represents a mixed blessing since besides the prodigious progress there
are several problems we have to face. These not only grab the headlines but also receive
particular attention in several reports of prestigious organizations like the WHO (World
1 2Health Organization) or the Shell Group in the context of the Global Reporting Initiative
(GRI). Concerning health care, still many serious illnesses like AIDS (Acquired
Immunodeficiency Syndrome) or cancer in its various types lack a reliable and effective
treatment. In the technical field, the impending shortage of fuel and energy has to be fought
necessitating e.g. efficient light-harvesting devices. Furthermore, environmental pollution
and the hence accruing problems call for solutions.

1,2Figure 1. Reports pointing out global problems.
These needs represent an incentive for many scientists working in different fields comprising
materials science, physics, medicine and chemistry. Special targets of interest in scope of
those researchers are photoactive and redoxactive materials as they exhibit versatile
1 1 Introduction
characteristics. For medicinal purposes, they would pave a path to a highly efficient non-
3,4,5,6invasive treatment of cancer in terms of e. g. photodynamic therapy (PDT) or they could
7be used to remove pollutants from air, water or food. In the technical field, photoinduced
charge separation or electron transfer processes could give rise to novel optoelectronic
8devices like switches or solar cells.
In their aiming for suitable compounds or materials, researchers can often rely on naturally
occurring systems since there are many highly developed concepts which may serve as an
example. By studying those, principles may be deduced, important structural elements
identified and this way, novel systems can be established.
In the case of organic photoactive materials, like the ones being subject of this work, the
corresponding natural principle to be considered is photosynthesis – the process that
enables green plants, several algae and some bacteria to convert solar energy into chemical
9energy in a highly efficient way. Being perhaps the most important biochemical pathway
and essential for life, it has represented – and still does – a matter of interest for lots of
th 10scientists since the end of the 18 century.
Modern methods and the ongoing development of chemistry itself have provided deep
11insights into what the complex “natural photovoltaic device” in plants is looking like and
12how it works. As an example, structural details for photosystem II are depicted in Figure 2.

Figure 2. Structure of photosystem II: Cofactors embedded in the protein matrix (left) and
13arrangement of the chlorophyll cofactors (right).