Granzhan, Anton: Synthesis and studies of annelated quinolizinium derivatives as versatile constructs for fluorescent probes and ligands for triple-helical and abasic DNA [...]. 2006
Inhalt
- ACKNOWLEDGEMENTS
- LIST OF PUBLICATIONS
- GENERAL REMARKS
- SUMMARY
- ZUSAMMENFASSUNG
- 1 INTRODUCTION AND LITERATURE SURVEY
- 1.1 Annelated Quinolizinium Derivatives as DNA Binders
- 1.2 Fluorescence Probes for Detection of Biomacromolecules
- 1.3 Triplex-DNA Binders
- 1.4 Ligands Associating with DNA Abasic Sites
- 1.5 Methods for Study of DNA–Ligand Interactions
- 2 9-SUBSTITUTED ACRIDIZINIUM SALTS AS FLUORESCENT PROBES
- 2.1 Objective
- 2.2 Results
- 2.2.1 Synthesis of 9-Substituted Acridizinium Salts
- 2.2.1.1 Synthesis of 9-Amino-Substituted Acridizinium Salts
- 2.2.1.2 Synthesis of 9-(Methylthio)acridizinium
- 2.2.2 Photophysical Properties of 9-Substituted Acridizinium Derivatives
- 2.2.2.1 Absorption and Fluorescence Properties of 9-Amino-substitued Acridizinium Salts
- 2.2.2.2 Absorption and Fluorescence Properties of 9 (Methylthio)acridizinium
- 2.2.2.3 Viscosity Dependence of the Fluorescence of N-Aryl-9-aminoacridizinium Derivatives
- 2.2.3 Interaction of 9-Substituted Acridizinium Derivatives with DNA
- 2.2.3.1 Spectrophotometric Titrations
- 2.2.3.2 Spectrofluorimetric Titrations
- 2.2.3.3 Linear Dichroism Spectroscopy
- 2.2.4 Interaction of N-Aryl-9-aminoacridizinium Derivatives with Proteins
- 2.3 Discussion
- 3 TARGETING TRIPLE-HELICAL DNA WITH DIAZONIAPOLYCYCLIC INTERCALATORS
- 3.1 Objective
- 3.2 Results
- 3.2.1 Synthesis of Diazoniapolycyclic Salts
- 3.2.1.1 Synthesis of Unsubstituted Diazoniapentaphenes
- 3.2.1.2 Synthesis of Substituted Diazoniapentaphenes
- 3.2.1.3 Synthesis of Hexacyclic Diazoniaarenes
- 3.2.2 X-Ray Structure Analysis of Diazoniapolycyclic Salts
- 3.2.2.1 Structure of 42a in the Solid State
- 3.2.2.2 Structure of 44 in the Solid State
- 3.2.2.3 Structure of 38c in the Solid State
- 3.2.3 Photophysical Properties of Diazoniapolycyclic Salts
- 3.2.4 Binding of Diazoniapolycyclic Salts to Double-Stranded DNA
- 3.2.5 Binding of Diazoniapolycyclic Salts to Triple-Helical DNA
- 3.3 Discussion
- 4 TARGETING DNA ABASIC SITES WITH ACRIDIZINIUM–NUCLEIC BASE CONJUGATES
- 4.1 Objective
- 4.2 Results
- 4.2.1 Synthesis of the Model Compounds and Acridizinium–Adenine Conjugates
- 4.2.1.1 Synthesis of Acridizinium-9-carboxamides
- 4.2.1.2 Synthesis of Acridizinium-3-carboxylic Acid
- 4.2.1.3 Synthesis of the Acridizinium–Adenine Conjugates
- 4.2.2 Photophysical Properties of Acridizinium-9-carboxamides and Acridizinium–Adenine Conjugates
- 4.2.3 DNA-Binding Properties of Acridizinium-9-carboxamides and Acridizinium–Adenine Conjugates
- 4.2.3.1 Binding to Regular and Abasic Oligonucleotides
- 4.2.3.2 Binding to Double-Stranded Polynucleotides
- 4.2.4 Photoinduced DNA Cleavage by Acridizinium-9-carboxamides and Acridizinium–Adenine Conjugates
- 4.3 Discussion
- 5 EXPERIMENTAL PART
- 5.1 General Remarks
- 5.2 Syntheses
- 5.2.1 Synthesis of 9-Substituted Acridizinium Derivatives
- 5.2.2 Synthesis of Diazoniapolycyclic Salts
- 5.2.3 Synthesis of Acridizinium-9-carboxamides and Acridizinium–Nucleic Base Conjugates
- 5.3 Single Crystal X-Ray Diffraction Analysis
- 5.4 Investigations of the Photophysical Properties
- 5.4.1 UV/Visible Absorption and Fluorescence Spectroscopy
- 5.4.2 Acid–Base Spectrophotometric Titrations of Compound 27d
- 5.4.3 Viscosity Dependence of Fluorescence
- 5.4.3.1 Fluorescence Spectroscopy using Water–Glycerol Mixtures
- 5.4.3.2 Fluorescence Spectroscopy at Different Temperatures
- 5.4.4 Photodegradation of Diazoniapolycyclic Salts 38c and 51 in Solution
- 5.5 Nucleic Acids Binding Studies
- 5.5.1 Buffer Solutions
- 5.5.2 Nucleic Acids
- 5.5.3 Spectrophotometric and Spectrofluorimetric Titrations
- 5.5.3.1 Sample Preparation and Experimental Conditions
- 5.5.3.2 Data Evaluation and Determination of Binding Constants
- 5.5.4 DNA Thermal Denaturation Studies
- 5.5.4.1 Sample Preparation
- 5.5.4.2 Experimental Conditions
- 5.5.4.3 Data Evaluation and Determination of Melting Temperatures
- 5.5.4.4 Salt Dependence of Melting Temperatures
- 5.5.4.5 Thermal Denaturation of Oligonucleotide–Ligand Complexes
- 5.5.5 Competition Dialysis Assay
- 5.5.6 Linear Dichroism Spectroscopy[ ]
- 5.6 Protein Binding Studies
- 5.7 Photocleavage of Plasmid DNA
- 5.7.1 Preparation of Abasic Plasmid DNA
- 5.7.2 Sample Preparation and Irradiation
- 5.7.3 Gel Electrophoresis and Data Evaluation
- 5.8 Quantum Chemical Calculations
- 6 REFERENCES
- APPENDIX A STRUCTURE CHART
- CURRICULUM VITÆ