Lanthanide complexes of bifunctional chelates as pH and Ca_1hn2_1hn+ sensitive contrast agents for MR imaging [Elektronische Ressource] : design, synthesis and characterization = Lanthanoidkomplexe von funktionalisierten Chelaten als pH- und Ca_1hn2_1hn+-abhängige Kontrastmittel für die Magnetresonanz-Bildgebung / vorgelegt von Ilgar Mammadov

Ilgar

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• Gesundheit

Informations

• Publié par: eberhard_karls_universitat_tubingen
• Publié le: 01 janvier 2006
• Nombre de lectures: 18
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Lanthanide Complexes of Bifunctional Chelates as pH
2+
and Ca Sensitive Contrast Agents for MR Imaging.
Design, Synthesis and Characterization


Lanthanoidkomplexe von funktionalisierten Chelaten
2+als pH- und Ca - abhängige Kontrastmittel für die
Magnetresonanz-Bildgebung.
Design, Synthese und Charakterisierung




D I S S E R T A T I O N


der Fakultät für Chemie und Pharmazie
der Eberhard-Karls-Universität Tübingen

zur Erlangung des Grades eines Doktors
der Naturwissenschaften

2006


vorgelegt von

Ilgar Mammadov
















Tag der mündliche Prüfung: 11. September 2006

Dekan: Prof. Dr. Stefan Laufer

1. Berichterstatter Prof. Dr. H.A. Mayer
2. Berichterstatter Prof. Dr. M. E. Maier



This work is a result from the
collaboration between the departments of
the Cognitive Processes of the Max
Planck Institute for Biological Cybernetic,
under the supervision of Prof. Dr. Nikos
K. Logothetis and the Institute for
Inorganic Chemistry, Eberhard-Karls
University of Tübingen, under the
supervision of Prof. Dr. Hermann A.
Mayer.

















I am thankful to the Hertie and Louis-Jeantet foundations for the financial
support of the project.

I
I am gratefully acknowledging my supervisors.
I thank Prof. Dr. Hermann A. Mayer for his supervision, advises and continuous
interest in my work. I thank him for his time, patience and his support during the
“hard times” of my work under the high pressure.
I thank Prof. Dr. Nikos Logothetis for the opportunity to work in his group on the
very exciting project, for his financial and intellectual support, his advises and
improvements during the work on this topic.
I thank Dr. Josef Pfeuffer for his help and advice during the work on this project.
I would like to thank all people of the chemistry groups of the departments
Logothetis and Ugurbil: Dr. Goran Angelovski for his advises and suggestions,
Dr. Jorn Engelmann for the helpful discussions, Anurag Mishra, Aneta Brud,
Kirti Dhingra, Deepti Jha and Wu Su for their help and a good working
atmosphere.
I am very thankful to Dr. Santiago Canals for his help in performing and design
of in vivo experiments and his advises in writing of the “biological” part of thesis.
I thank Michael Beyerlein for the performing of the T , T experiments at 7T and 1 2
for his help in the in vivo experiments. I also thank Mark Augath for the
performing experiments at 4.7T and Dr. Yusuke Murayama for his help in the
evaluation of data.
I also thank Prof. Dr. Robert Muller and his group from the University of Mons
Dr Sophie Laurent and Prof. Dr Luce Van der Elst for performing of the relaxivity
and NMRD measurements.
I thank Dr. Přemysl Lubal from the Masaryk University of Brno for the help in
establishing of the methods of potentiometric titrations and data evaluation.
I am thankful to the all people I worked with in the group of Prof. Dr. Hermann
A. Mayer for their help and support.
I thank Dr. Klaus Eichele for his help by the problems concerning the NMR
spectroscopy, his suggestions and helpful discussions.
I thank Prof. Dr. Lars Wesemann for the excellence working atmosphere.
I am also very grateful to Angelika Ehemann and Heike Dorn for the help in the
NMR experiments.
II
I thank Mr. W. Bock for performing of EL measurements, Mr. G. Nicholson for
performing of HRMS experiments, Mr H. Bartholomö and Mr R. Müller for
performing of FAB MS experiments.
I thank Prof. Dr. Martin Maier for agreeing to be a referee of this thesis.

My very special thanks to Dr. Susan Byron-Baumhauer. Susan, we will never
forget your help, optimism and energy.

I am very thankful to my parents, my brother and his family for the feeling of
permanent support during the whole period of my research work.
I especially thank my wife Sheyda, who helped me through difficult times,
making it possible to continue my work and our lovely daughters Narmina and
Naila for their understanding and support.



















III




























IV









To my wife Sheyda and
our cute daughters
V Abbreviations

Abbreviations


Abbreviation Name

AcCN acetonitrile

Ar aromatic

Anal analysis

ATN-4T manganese porphyrin

ACSF artificial cerebrospinal fluids

APP amino polyphosphonate

APC amino polycarboxylate

BBB blood brain barrier

BOLD blood-oxygen-level-dependent

Boc butoxycarbonyl

br broad

CBz chlorobenzoformate

Calcd calculated

CEST chemical exchange saturation transfer

CLIO cross- linked iron oxide

d doublet (NMR)

dd doublet of doublets (NMR)

DMC dichloromethane

DMF dimethylformamide

I Abbreviations



Abbreviation Name

DMSO dimethylsulfoxide

DTPA diethylenetriaminepentaacetic acid

DTPA-BMA diethylentriaminepentaacetic acide bis-
methylamide

DOPE dioleoyl phosphatidyl ethanolamine

DOTA 1,4,7,10-tetraazacyclododecane-
1,4,7,10-tetraacetic acid

DOTAM-Gly DOTA- tetraglycineamide

DPDP dipyridoxyl diphosphate

DPPE/PA dipalmitoyl phosphatidyl
ethanolamine/palmitic acid

DO3A 1,4,7,10-tetraazacyclododecane-1,4,7-
triaacetic acid

DO3AMP DO3A-methyl phosphonic acid

DO3AEP DO3A-ethyl phosphonic acid

EA elemental analysis

EDTA ethylenediaminetetraacetic acid

EGTA ethylene glycol bis(2-aminoethyl
ether)-N,N,N'N'-tetraacetic acid

EI electron impact

ESI-MS electrospray ionisation mass
spectrometry

Et ethyl

FAB fast atom bombarding

FT Fourier transformation
II