Synthesis and immobilisation of biologically active substances [Elektronische Ressource] / vorgelegt von Thomas Walenzyk

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Synthesis and immobilisation of biologically active substances Dissertation Zur Erlangung des Doktorgrades der Naturwissenschaften (Dr. rer. nat.) der naturwissenschaftlichen Fakultät IV – Chemie und Pharmazie – der Universität Regensburg vorgelegt von Thomas Walenzyk aus Rüsselsheim 2005 Synthesis and immobilisation of biologically active substances Dissertation Zur Erlangung des Doktorgrades der Naturwissenschaften (Dr. rer. nat.) der naturwissenschaftlichen Fakultät IV – Chemie und Pharmazie – der Universität Regensburg vorgelegt von Thomas Walenzyk aus Rüsselsheim 2005 The experimental part of this work was carried out between October 2001 and November 2004 at the Institute for Organic Chemistry at the University of Regensburg, under the supervision of Prof. Dr. B. König. The PhD thesis was submitted on: 16.02.2005 The colloqium took place on: 24.03.2005 Board of Examiners: Prof. Dr. G. Schmeer (Chairman) Prof. Dr. B. König (1st Referee) Prof. Dr. W. Kunz (2nd Referee) Prof. Dr. A. Göpferich (3rd Referee) Acknowledgements I would like to express my sincere gratitude to Prof. Dr. B. König, for his continued guidance, advice and encouragement throughout this work. I would also like to thank Merck KGaA in Darmstadt for financing my research, especially Dr. H.

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• Published by: universitat_regensburg
• Published: 01 January 2006
• Reads: 6
• Language: English
• Document size: 6 MB

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Synthesis and immobilisation of
biologically active substances

Dissertation

Zur Erlangung des Doktorgrades der Naturwissenschaften
(Dr. rer. nat.)
der naturwissenschaftlichen Fakultät IV
– Chemie und Pharmazie –
der Universität Regensburg














vorgelegt von
Thomas Walenzyk
aus Rüsselsheim

2005
Synthesis and immobilisation of
biologically active substances


Dissertation
Zur Erlangung des Doktorgrades der Naturwissenschaften
(Dr. rer. nat.)
der naturwissenschaftlichen Fakultät IV
– Chemie und Pharmazie –
der Universität Regensburg





vorgelegt von
Thomas Walenzyk
aus Rüsselsheim

2005
The experimental part of this work was carried out between October 2001 and November
2004 at the Institute for Organic Chemistry at the University of Regensburg, under the
supervision of Prof. Dr. B. König.

















The PhD thesis was submitted on: 16.02.2005

The colloqium took place on: 24.03.2005

Board of Examiners: Prof. Dr. G. Schmeer (Chairman)
Prof. Dr. B. König (1st Referee)
Prof. Dr. W. Kunz (2nd Referee)
Prof. Dr. A. Göpferich (3rd Referee) Acknowledgements

I would like to express my sincere gratitude to Prof. Dr. B. König, for his continued
guidance, advice and encouragement throughout this work.

I would also like to thank Merck KGaA in Darmstadt for financing my research, especially
Dr. H. Buchholz who allowed me to conduct my research in his laboratory. I also thank all
my coworkers in the department Pigments R&D Cosmetics, for assisting me in my efforts.

Thanks are extended to the analytical departments of Merck KGaA for the prompt and
accurate measurement of my numerous, often difficult samples. Special thanks to Mr. H.
Opfermann (SEM images), Ms. J. Donath and Ms. N. Blatt (UV samples), Dr. F. Pfluecker
and Ms. G. Witte (photostability tests), Mr. T. Stein (ICP-OES), Dr. H. Ackermann (DPPH
tests) and Dr. B. Schubach (MALDI-MS). Thanks are also extended to the analytical
departments of the Faculty of Chemistry and Pharmacy at the University of Regensburg.
Special thanks to Dr. T. Burgemeister, Mr. F. Kastner, Ms. N. Pustet, Ms. A. Schramm and
Ms. G. Stühler (NMR), Dr. K. K. Mayer, Mr. J. Kiermaier and Herrn W. Söllner (MS), Mr.
G. Wandinger, Ms. S. Stempfhuber and Mr. H. Schüller (elemental analysis) and Dr. M.
Zabel (X-ray crystallography).

My special thanks go to:
All collegues, past and present, both at Merck KGaA and at the University of Regensburg,
for making the working environment positive, constructive, as well as relaxed.
Dr. C. Carola for giving me advice, guidance and always an open ear for discussions.
Dr. T. Mujica for making sure that the day was always lively and never ordinary. Thanks
for the long discussions and many great laughs. Mr. M. Kruppa for being my partner in
crime. The willingness to help and give advice was only outdone by the many great
experiences we had outside of the laboratory. Mr. R. Rosskopf for always having an
answer to any problem or task I threw at him. Thanks for your persistence and
thoroughness, and always with a smile. Mr. M. Subat for the good cooperation on one of
the projects. For the long and interesting discussions and showing me there are always two
ways to tackle a problem.









My family & Daniela Table of Contents
1. MOLECULAR RECOGNITION OF AZAMACROCYCLES.......................................................... 1
1.1 INTRODUCTION................................................................................................................................1
1.1.1 General Properties of metal complexes of azamacrocycles....................................................... 1
1.1.2 Scope.......................................................................................................................................... 2
1.2 STRUCTURES OF 1,4,7,10-TETRAAZA-CYCLODODECANE ([12]ANEN OR CYCLEN) COMPLEXES IN 4
SOLID STATE................... 4
1.2.1 Co(III) complexes ...................................................................................................................... 4
1.2.2 Cu(II) complexes........................................................................................................................ 6
1.2.3 Ni(II) complexes.......... 6
1.2.4 Zn(II) complexes......... 8
1.3 STRUCTURES OF 1,4,7,10-TETRAAZA-CYCLODODECANE ([12]ANEN OR CYCLEN) COMPLEXES IN 4
SOLID STATE (TABULATED) ......................................................................................................................... 12
1.4 MOLECULAR RECOGNITION OF 1,4,7,10-TETRAAZA-CYCLODODECANE ([12]ANEN OR CYCLEN) 4
COMPLEXES IN SOLUTION............................................................................................................................. 18
1.4.1 Co(III) complexes .................................................................................................................... 18
1.4.2 Cd(II) complexes...................................................................................................................... 18
1.4.3 Zn(II) complexes....... 19
1.5 IMMOBILISED 1,4,7,10-TETRAAZA-CYCLODODECANE ([12]ANEN OR CYCLEN) COMPLEXES ........ 25 4
1.5.1 Zn(II) complexes....... 25
1.6 STRUCTURES OF 1,4,8,11-TETRAAZA-CYCLOTETRADECANE ([14]ANEN OR CYCLAM) COMPLEXES 4
IN SOLID STATE ............................................................................................................................................ 28
1.6.1 Zn(II) complexes....... 28
1.6.2 Ni(II)es........ 29
1.7 STRUCTURES OF 1,4,8,11-TETRAAZA-CYCLOTETRADECANE ([14]ANEN OR CYCLAM) COMPLEXES 4
IN SOLID STATE (TABULATED)...................................................................................................................... 31
1.8 MOLECULAR RECOGNITION OF 1,4,8,11-TETRAAZA-CYCLOTETRADECANE ([14]ANEN OR CYCLAM) 4
COMPLEXES IN SOLUTION............................................................................................................................. 37
1.8.1 Zn(II) complexes ...................................................................................................................... 37
1.8.2 Ni(II)es........ 39
1.8.3 Hg(II) complexes....... 40
1.9 IMMOBILISED 1,4,8,11-TETRAAZA-CYCLOTETRADECANE ([14]ANEN OR CYCLAM) COMPLEXES.. 41 4
1.9.1 Ni(II) complexes........ 41
1.10 STRUCTURES OF 1,5,9-TRIAZA-CYCLODODECANE ([12]ANEN ) COMPLEXES IN SOLID STATE........ 42 3
1.10.1 Zn(II) complexes ................................................................................................................. 42
1.11 MOLECULAR RECOGNITION OF 1,5,9-TRIAZA-CYCLODODECANE ([12]ANEN ) COMPLEXES IN 3
SOLUTION .................................................................................................................................................... 42
1.11.1 Zn(II) complexes.. 42
1.12 IMMOBILISED 1,5,9-TRIAZA-CYCLODODECANE ([12]ANEN ) COMPLEXES..................................... 43 3
1.13 STRUCTURES OF 1,4,7-TRIAZONANE ([9]ANEN OR TACN) COMPLEXES IN SOLID STATE.............. 43 31.13.1 Cu(II) complexes ................................................................................................................. 43
1.14 STRUCTURES OF 1,4,7-TRIAZONANE ([9]ANEN OR TACN) COMPLEXES IN SOLID STATE 3
(TABULATED) .............................................................................................................................................. 44
1.15 MOLECULAR RECOGNITION OF 1,4,7-TRIAZONANE ([9]ANEN OR TACN) COMPLEXES IN SOLUTION3
49
1.15.1 Cu(II) complexes ................................................................................................................. 49
1.16 IMMOBILISED 1,4,7-TRIAZONANE ([9]ANEN OR TACN) COMPLEXES........................................... 49 3
1.16.1 Cu(II) complexes.. 49
1.17 CONCLUSION ................................................................................................................................. 51
1.18 REFERENCES... 52
2. IMMOBILISED ZN (II) CYCLEN COMPLEXES AS CATALYTIC REAGENTS FOR
PHOSPHODIESTER HYDROLYSIS ......................................................................................................... 63
2.1 INTRODUCTION.............................................................................................................................. 64
2.1.1 Metalloenzymes........................................................................................................................ 64
2.1.2 Models...................................................................................................................................... 65
2.1.3 Synzymes - Synthetic polymers with enzyme like activities ...................................................... 67
2.2 RESULTS AND DISCUSSION............................................................................................................. 68
2.2.1 Synthesis of mono-Zn(II)Cyc polymer...................................................................................... 68
2.2.2 Kinetic measurements for the phosphodiester cleavage reaction with mono-Zn(II)Cyc
complexes bound to a solid support ....................................................................................................... 71
2.2.2.1 Calculation of the molar extinction coefficient for para-nitrophenolate........................................71
2.2.2.2 Non-catalysed hydrolysis of bis-(4-nitrophenyl)phosphate (BNPP) ..............................................74
2.2.2.3 Hydrolysis of BNPP with immobilised mononuclear Zn(II)Cyc complexes (batch reaction)........75
2.2.2.4 Hydrolysis of BNmobilised mononuclear Zn(II)Cyc complexes (PBR Reactor) .........78
2.2.3 Synthesis of bis-Zn(II)Cyc Polymer ......................................................................................... 80
2.2.4 Kinetic measurements for the phosphodiester cleavage reaction with bis-Zn(II)Cyc complexes
bound to a solid support......................................................................................................................... 82
2.3 CONCLUSION ................................................................................................................................. 83
2.4 EXPERIMENTAL ............................................................................................................................. 84
2.4.1 General .................................................................................................................................... 84
2.4.1.1 Spectroscopy..................................................................................................................................84
2.4.1.2 Analysis .........................................................................................................................................85
2.4.1.3 Synthesis......................................................................................................................85
2.4.2 Synthesis of New Compounds .................................................................................................. 85
2.5 REFERENCES... 93
3. SYNTHESIS OF MONO-DISPERSED SPHERICAL SILICA PARTICLES CONTAINING
COVALENTLY BONDED CHROMOPHORES ....................................................................................... 97
3.1 INTRODUCTION.............................................................................................................................. 98
3.1.1 Background.............................................................................................................................. 98
3.1.2 Bioaccumulation and degradation of UV filters in humans..................................................... 98
3.1.3 Non-penetrating inorganic UV filters ...................................................................................... 99 3.1.4 New advances in non-penetrating UV filters ......................................................................... 100
3.2 RESULTS AND DISCUSSION.......................................................................................................... 101
3.2.1 Synthesis of Microspheres...................................................................................................... 101
3.2.2 Choice of UV filter................................................................................................................. 101
3.2.3 Synthesis of monomer ............................................................................................................102
3.2.4 Microspheres containing a chromophore (MSI).................................................................... 104
3.2.5 Microspheres with chromophores on the surface (MSS) ....................................................... 107
3.2.6 Microspheres containing chromophores in the core and on the surface (MSIG).................. 110
3.2.7 Photostability......................................................................................................................... 111
3.3 CONCLUSION............................................................................................................................... 113
3.4 EXPERIMENTAL ........................................................................................................................... 114
3.4.1 General .................................................................................................................................. 114
3.4.1.1 Spectroscopy................................................................................................................................114
3.4.1.2 Analysis.......................................................................................................................................114
3.4.1.3 Synthesis......................................................................................................................115
3.4.2 Synthesis of New Compounds ................................................................................................ 116
3.5 REFERENCES................................................................................................................................134
4. CHROMONE DERIVATIVES WHICH BIND TO HUMAN HAIR............................................ 139
4.1 INTRODUCTION............................................................................................................................ 140
4.1.1 Chromones....... 140
4.1.2 Biological Activity of Flavonoids........................................................................................... 140
4.1.3 Structure Activity Relationships............................................................................................. 141
4.1.4 Reactive Oxygen Species........................................................................................................ 141
4.1.5 Multifunctional Chromones ................................................................................................... 141
4.2 RESULTS AND DISCUSSION........................................................................................................... 142
4.2.1 Background............................................................................................................................ 142
4.2.2 Synthesis of Chromone Derivatives with Hair Substantivity.................................................. 142
4.2.3 Synthesis of substituted chromone derivatives....................................................................... 143
4.2.4 Hair Substantivity .................................................................................................................. 145
4.2.4.1 SEM Images of treated and untreated hair...................................................................................148
4.2.5 Antioxidant activities ............................................................................................................. 149
4.2.6 Cyclic Voltammetry... 150
4.2.7 UV absorption of substituted chromones ............................................................................... 151
4.3 CONCLUSION............................................................................................................................... 152
4.4 EXPERIMENTAL ........................................................................................................................... 153
4.4.1 General .................................................................................................................................. 153
4.4.1.1 Spectroscopy................................................................................................................................153
4.4.1.2 Analysis.......................................................................................................................................154
4.4.1.3 Synthesis......................................................................................................................155
4.4.1.4 Hair Substantitivity......................................................................................................................155
4.4.1.5 X-ray Crystallography .................................................................................................................156