How Do Amino Acids Transport Electrons Through Peptides?

153 Pages·2008·1.89 MB·English

How Do Amino Acids Transport Electrons
Through Peptides?

Inaugural Dissertation
zur
Erlangung der Würde eines Doktors der Philosophie

vorgelegt der
Philosophisch-Naturwissenschaftlichen Fakultät
der Universität Basel

von

Meike Cordes
aus Mülheim an der Ruhr (Deutschland)

Basel 2008
Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel
auf Antrag von

Prof. Dr. Bernd Giese
Prof. Dr. Helma Wennemers

Basel, den 25.03.2008

Prof. Dr. Hans-Peter Hauri
Dekan

Cover Picture: Cordes, M., Köttgen, A., Jasper, C. Jacques, O., Boudebous, H., Giese, B.: Influence of Amino Acid Side
Chains on Long-Distance Electron Transfer in Peptides: Electron Hopping via "Stepping Stones", Angew. Chem. Int. Ed..
2008, 47, 3461.; Der Einfluss von Aminosäureseitenketten auf weitreichenden Elektronentransfer in Peptiden:
Elektronenhopping mit Zwischenstationen, Angew. Chem. 2008, 120, 3511., Copyright Wiley-VCH Verlag GmbH & Co.
KGaA. Reproduced with permission.
The work presented here was initiated and supervised by Prof. Bernd Giese at the Chemistry
Departement of the University of Basel, during the time period October 2004 to Februar 2008.

Excerpts from this work are published in:

Cordes, M., Jacques, O., Köttgen, A., Jasper, C., Boudebous, H., Giese, B.: Development of a Model
System for the Study of Long Distance Electron Transfer in Peptides, Adv. Synth. Cat., in press.
Cordes, M., Köttgen, A., Jasper, C. Jacques, O., Boudebous, H., Giese, B.: Influence of Amino Acid
Side Chains on Long-Distance Electron Transfer in Peptides: Electron Hopping via "Stepping
Stones", Angew. Chem. Int. Ed.. 2008, 47, 3461.; Der Einfluss von Aminosäureseitenketten auf
weitreichenden Elektronentransfer in Peptiden: Elektronenhopping mit Zwischenstationen,
Angew. Chem. 2008, 120, 3511.

The work was supported by:
Stiftung Stipendien Fonds, Verband der chemischen Industrie e.V.

Diese Arbeit ist meinem Freund Christian Wetter gewidmet.

einander zudrehen

einanderzudrehen und
aufeinandereinstellen

ineinandergreifen und
einandermitteilen

miteinanderdrehen und
voneinanderlösen

auseinanderkreisen und
einanderzudrehen

aufeinandereinstellen und
ineinandergreifen

einandermitteilen und
miteinanderdrehen

voneinanderlösen und
auseinanderkreisen

einanderzudrehen und

(Eugen Gomringer)
Ein Gleichnis

Wie wenn da einer, und er hielte
ein frühgereiftes Kind, das schielte,
hoch in den Himmel und er bäte:
„Du hörst jetzt auf den Namen Käthe!“ —
Wär dieser nicht dem Elch vergleichbar,
der tief im Sumpf und unerreichbar
nach Wurzeln, Halmen, Stauden sucht
und dabei stumm den Tag verflucht,
an dem er dieser Erde Licht …
Nein? Nicht vergleichbar? Na, dann nicht!

(Robert Gernhardt)
Acknowledgements

I want to thank my supervisor Prof. Dr. Bernd Giese for providing me with a fascinating research topic
and creating a work climate, which was governed by confidence, optimism and scientific curiosity. I
would also like to thank Prof. Dr. Helma Wennemers for helpful discussions and for co-refereeing this
thesis.

I am grateful to all former and present members of the Giese group, who contributed to this work: Dr.
Christian Jasper and Dr. Agnieszka Köttgen were a tremendous help in the development of the
syntheses of the building blocks. So was Dr. Olivier Jacques, who also had a patient ear and a helping
hand for all technical and synthetical questions. Dr. Hassen Boudebous introduced me to the field of
laser flash photolysis.
I would also like to thank Michael Kümin from the Wennemers group for his assistance with the
peptide synthesizer and the CD spectrometer.

I want to thank the technical staff at the Departement of Chemistry, especially Dr. Klaus Kulicke for
NMR-analysis, Dr. Heinz Nadig, who recorded the EI and FAB mass spectra, Werner Kirsch, who
measured the elemental analyses and Dr. Sigmund Gunzenhauser for the tedious maintainenance of
the ESI mass spectrometer. I would like to thank the complete team of "Werkstatt" and
"Materialausgabe" and also the secretaries, for furnishing the infrastrucure of the departement.

My thanks go to the past members of the Giese group for leaving not only a tremendous amount of
chemicals, but also of scientific knowledge behind and building up a friendly and cooperative tradition
- and to the present members of the Giese group for keeping this tradition alive. It was a great pleasure
to work with you.

I am especially grateful to my lab colleagues Stephan Buergi and Michael Graber who made lab work
enjoyable and solved any upcoming problem, no matter if it concerned synthesis, office work or just
motivation.

To Christian Wetter:
not only the correct angles in my schemes would be missing in this work, if you had not been there to
help and support me during the last 3.5 years. Thank you.

Table of Contents
Table of Contents

1 Introduction.....................................................................................................................................3
2 Electron Transfer.............................................................................................................................4
2.1 Marcus Theory.......................................................................................................................4
2.2 Distance Dependence of Electron Transfer............................................................................5
2.3 Electron Transfer through Peptides........................................................................................6
2.3.1 Superexchange...................................................................................................................6
2.3.2 Hopping...........................................................................................................................10
3 Research Project............................................................................................................................17
4 Spectroscopic Sensors for the Observation of Transients in ET through peptides........................19
4.1 Introduction..........................................................................................................................19
4.2 Laser Flash Photolysis.........................................................................................................21
4.3 Amino Acids as Spectroscopic Sensors...............................................................................22
4.3.1 Synthesis and Properties of Methoxysubstituted Phenylalanine-Derivatives..................26
5 Stability of Radical Cations...........................................................................................................31
6 Occurence of Oxidized Intermediates in ET through peptides......................................................37
6.1 Introduction..........................................................................................................................37
6.2 Synthesis of Enantiopure Non-natural Amino Acids...........................................................38
6.3 Synthesis of Peptides...........................................................................................................39
6.4 Data Collection and Analysis...............................................................................................42
6.4.1 Limitations.......................................................................................................................43
6.4.2 Analysis of the Data........................................................................................................46
6.5 Results and Discussion........................................................................................................48
7 Improving Charge Injection..........................................................................................................57
7.1 Synthesis of a New Charge Injector.....................................................................................58
7.2 Synthesis of Peptides...........................................................................................................60
7.3 Results and Discussion........................................................................................................63
8 Influence of Amino-Acid Side Chains on ET...............................................................................67
8.1 Introduction..........................................................................................................................67
8.2 Structure...............................................................................................................................70
8.3 Results and Discussion........................................................................................................72
8.3.1 Mechanism of Electron Transfer.....................................................................................72
8.3.2 Electron Transfer Rates...................................................................................................79
9 The Phenylalanine Effect..............................................................................................................83
10 Summary and Outlook.............................................................................................................87
11 Experimental Part.....................................................................................................................89
1
Table of Contents
11.1 Conditions of Measurements...............................................................................................89
11.2 Synthesis..............................................................................................................................91
11.2.1 Materials, Solvents and Reagents................................................................................91
11.2.2 Notation.......................................................................................................................92
11.2.3 General Procedures (GP)............................................................................................93
11.2.4 Characterisation of Peptides........................................................................................95
11.3 Compounds..........................................................................................................................96
11.4 List of LFP Experiments....................................................................................................135
12 Abbreviations.........................................................................................................................140
13 References..............................................................................................................................144

2