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Understanding, identifying and influencing the biological systems are the primary objectives of chemical biology. From this perspective, metal complexes have always been of great assistance to chemical biologists, for example, in structural identification and purification of essential biomolecules, for visualizing cellular organelles or to inhibit specific enzymes. This inorganic side of chemical biology, which continues to receive considerable attention, is referred to as inorganic chemical biology. Inorganic Chemical Biology: Principles, Techniques and Applications provides a comprehensive…mehr
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- Produktdetails
- Verlag: John Wiley & Sons
- Seitenzahl: 432
- Erscheinungstermin: 14. April 2014
- Englisch
- ISBN-13: 9781118684252
- Artikelnr.: 41096768
- Verlag: John Wiley & Sons
- Seitenzahl: 432
- Erscheinungstermin: 14. April 2014
- Englisch
- ISBN-13: 9781118684252
- Artikelnr.: 41096768
xxi 1. New Applications of Immobilized Metal Ion Affinity Chromatography in
Chemical Biology 1 Rachel Codd, Jiesi Gu, Najwa Ejje and Tulip Lifa 1.1
Introduction 1 1.2 Principles and Traditional Use 2 1.3 A Brief History 4
1.4 New Application 1: Non-protein Based Low Molecular Weight Compounds 5
1.4.1 Siderophores 6 1.4.2 Anticancer Agent: Trichostatin A 10 1.4.3
Anticancer Agent: Bleomycin 12 1.4.4 Anti-infective Agents 13 1.4.5 Other
Agents 14 1.4.6 Selecting a Viable Target 15 1.5 New Application 2:
Multi-dimensional Immobilized Metal Ion Affinity Chromatography 17 1.6 New
Application 3: Metabolomics 20 1.7 New Application 4: Coordinate-bond
Dependent Solid-phase Organic Synthesis 20 1.8 Green Chemistry Technology
21 1.9 Conclusion 23 Acknowledgments 24 References 24 2. Metal Complexes as
Tools for Structural Biology 37 Michael D. Lee, Bim Graham and James D.
Swarbrick 2.1 Structural Biological Studies and the Major Techniques
Employed 37 2.2 What do Metal Complexes have to Offer the Field of
Structural Biology? 38 2.3 Metal Complexes for Phasing in X-ray
Crystallography 39 2.4 Metal Complexes for Derivation of Structural
Restraints via Paramagnetic NMR Spectroscopy 41 2.4.1 Paramagnetic
Relaxation Enhancement (PRE) 42 2.4.2 Residual Dipolar Coupling (RDC) 43
2.4.3 Pseudo-Contact Shifts (PCS) 43 2.4.4 Strategies for Introducing
Lanthanide Ions into Bio-Macromolecules 44 2.5 Metal Complexes as Spin
Labels for Distance Measurements via EPR Spectroscopy 53 2.6 Metal
Complexes as Donors for Distance Measurements via Luminescence Resonance
Energy Transfer (LRET) 54 2.7 Concluding Statements and Future Outlook 56
References 56 3. AAS, XRF, and MS Methods in Chemical Biology of Metal
Complexes 63 Ingo Ott, Christophe Biot and Christian Hartinger 3.1
Introduction 63 3.2 Atomic Absorption Spectroscopy (AAS) 64 3.2.1
Fundamentals and Basic Principles of AAS 64 3.2.2 Instrumental and
Technical Aspects of AAS 65 3.2.3 Method Development and Aspects of
Practical Application 67 3.2.4 Selected Application Examples 69 3.3 Total
Reflection X-Ray Fluorescence Spectroscopy (TXRF) 72 3.3.1 Fundamentals and
Basic Principles of TXRF 72 3.3.2 Instrumental/Methodical Aspects of TXRF
and Applications 73 3.4 Subcellular X-ray Fluorescence Imaging of a
Ruthenium Analogue of the Malaria Drug Candidate Ferroquine Using
Synchrotron Radiation 74 3.4.1 Application of X-ray Fluorescence in Drug
Development Using Ferroquine as an Example 75 3.5 Mass Spectrometric
Methods in Inorganic Chemical Biology 80 3.5.1 Mass Spectrometry and
Inorganic Chemical Biology: Selected Applications 83 3.6 Conclusions 90
Acknowledgements 90 References 90 4. Metal Complexes for Cell and Organism
Imaging 99 Kenneth Yin Zhang and Kenneth Kam-Wing Lo 4.1 Introduction 99
4.2 Photophysical Properties 100 4.2.1 Fluorescence and Phosphorescence 100
4.2.2 Two-photon Absorption 101 4.2.3 Upconversion Luminescence 102 4.3
Detection of Luminescent Metal Complexes in an Intracellular Environment
104 4.3.1 Confocal Laser-scanning Microscopy 104 4.3.2 Fluorescence
Lifetime Imaging Microscopy 105 4.3.3 Flow Cytometry 106 4.4 Cell and
Organism Imaging 107 4.4.1 Factors Affecting Cellular Uptake 107 4.4.2
Organelle Imaging 116 4.4.3 Two-photon and Upconversion Emission Imaging
for Cells and Organisms 133 4.4.4 Intracellular Sensing and Labeling 136
4.5 Conclusion 143 Acknowledgements 143 References 143 5. Cellular Imaging
with Metal Carbonyl Complexes 149 Luca Quaroni and Fabio Zobi 5.1
Introduction 149 5.2 Vibrational Spectroscopy of Metal Carbonyl Complexes
151 5.3 Microscopy and Imaging of Cellular Systems 154 5.3.1 Techniques of
Vibrational Microscopy 155 5.4 Infrared Microscopy 155 5.4.1 Concentration
Measurements with IR Spectroscopy and Spectromicroscopy 157 5.4.2 Water
Absorption 158 5.4.3 Metal Carbonyls as IR Probes for Cellular Imaging 158
5.4.4 In Vivo Uptake and Reactivity of Metal Carbonyl Complexes 162 5.5
Raman Microscopy 167 5.5.1 Concentration Measurements with Raman
Spectroscopy and Spectromicroscopy 169 5.5.2 Metal Carbonyls as Raman
Probes for Cellular Imaging 169 5.6 Near-field Techniques 171 5.6.1
Concentration Measurements with Near-field Techniques 172 5.6.2
High-resolution Measurement of Intracellular Metal-Carbonyl Accumulation by
Photothermal Induced Resonance 173 5.7 Comparison of Techniques 175 5.8
Conclusions and Outlook 176 Acknowledgements 177 References 178 6. Probing
DNA Using Metal Complexes 183 Lionel Marcélis, Willem Vanderlinden and
Andrée Kirsch-De Mesmaeker 6.1 General Introduction 183 6.2 Photophysics of
Ru(II) Complexes 184 6.2.1 The First Ru(II) Complex Studied in the
Literature: [Ru(bpy)3]2+ 184 6.2.2 Homoleptic Complexes 186 6.2.3
Heteroleptic Complexes 186 6.2.4 Photoinduced Electron Transfer (PET) and
Energy Transfer Processes 188 6.3 State-of-the-art on the Interactions of
Mononuclear Ru(II) Complexes with Simple Double-stranded DNA 190 6.3.1
Studies on Simple Double-stranded DNAs 191 6.3.2 Influence of DNA on the
Emission Properties 193 6.4 Structural Diversity of the Genetic Material
194 6.4.1 Mechanical Properties of DNA 195 6.4.2 DNA Topology 195 6.4.3 SMF
Study with [Ru(phen)2(PHEHAT)]2+ and [Ru(TAP)2(PHEHAT)]2+ 198 6.5 Unusual
Interaction of Dinuclear Ru(II) Complexes with Different DNA Types 200
6.5.1 Reversible Interaction of [{(Ru(phen)2}2HAT]4+ with Denatured DNA 201
6.5.2 Targeting G-quadruplexes with Photoreactive [{Ru(TAP)2}2TPAC]4+ 204
6.5.3 Threading Intercalation 205 6.6 Conclusions 207 Acknowledgement 208
References 208 7. Visualization of Proteins and Cells Using
Dithiol-reactive Metal Complexes 215 Danielle Park, Ivan Ho Shon, Minh Hua,
Vivien M. Chen and Philip J. Hogg 7.1 The Chemistry of As(III) and Sb(III)
215 7.2 Cysteine Dithiols in Protein Function 217 7.3 Visualization of
Dithiols in Isolated Proteins with As(III) 218 7.4 Visualization of
Dithiols on the Mammalian Cell Surface with As(III) 218 7.5 Visualization
of Dithiols in Intracellular Proteins with As(III) 219 7.6 Visualization of
Tetracysteine-tagged Recombinant Proteins in Cells with As(III) 219 7.7
Visualization of Cell Death in the Mouse with Optically Labelled As(III)
220 7.7.1 Cell Death in Health and Disease 220 7.7.2 Cell Death Imaging
Agents 222 7.7.3 Visualization of Cell Death in Mouse Tumours, Brain and
Thrombi with Optically Labelled As(III) 223 7.8 Visualization of Cell Death
in Mouse Tumours with Radio-labelled As(III) 225 7.9 Summary and
Perspectives 227 References 227 8. Detection of Metal Ions, Anions and
Small Molecules Using Metal Complexes 233 Qin Wang and Katherine J. Franz
8.1 How Do We See What's in a Cell? 233 8.1.1 Why Metal Complexes as
Sensors? 234 8.1.2 Design Strategies for Sensors Built with Metal Complexes
234 8.1.3 General Criteria of Metal-based Sensors for Bioimaging 236 8.2
Metal Complexes for Detection of Metal Ions 236 8.2.1 Tethered Sensors for
Detecting Metal Ions 237 8.2.2 Displacement Sensors for Detecting Metal
Ions 240 8.2.3 MRI Contrast Agents for Detecting Metal Ions 240 8.2.4
Chemodosimeters for Metal Ions 249 8.3 Metal Complexes for Detection of
Anions and Neutral Molecules 252 8.3.1 Tethered Approach: Metal Complex as
Recognition Unit 255 8.3.2 Displacement Approach: Metal Complex as Quencher
258 8.3.3 Dosimeter Approach 262 8.4 Conclusions 268 Acknowledgements 268
Abbreviations 268 References 269 9. Photo-release of Metal Ions in Living
Cells 275 Celina Gwizdala and Shawn C. Burdette 9.1 Introduction to
Photochemical Tools Including Photocaged Complexes 275 9.2 Calcium
Biochemistry and Photocaged Complexes 278 9.2.1 Strategies for Designing
Photocaged Complexes for Ca2+ 278 9.2.2 Biological Applications of
Photocaged Ca2+ Complexes 282 9.3 Zinc Biochemistry and Photocaged
Complexes 284 9.3.1 Biochemical Targets for Photocaged Zn2+ Complexes 284
9.3.2 Strategies for Designing Photocaged Complexes for Zn2+ 286 9.4
Photocaged Complexes for Other Metal Ions 291 9.4.1 Photocaged Complexes
for Copper 291 9.4.2 Photocaged Complexes for Iron 295 9.4.3 Photocaged
Complexes for Other Metal Ions 297 9.5 Conclusions 298 Acknowledgment 298
References 298 10. Release of Bioactive Molecules Using Metal Complexes 309
Peter V. Simpson and Ulrich Schatzschneider 10.1 Introduction 309 10.2
Small-molecule Messengers 310 10.2.1 Biological Generation and Delivery of
CO, NO, and H2S 310 10.2.2 Metal-Nitrosyl Complexes for the Cellular
Delivery of Nitric Oxide 311 10.2.3 CO-releasing Molecules (CORMs) 314 10.3
"Photouncaging" of Neurotransmitters from Metal Complexes 321 10.3.1
"Caged" Compounds 321 10.3.2 "Uncaging" of Bioactive Molecules 322 10.4
Hypoxia Activated Cobalt Complexes 324 10.4.1 Bioreductive Activation of
Cobalt Complexes 324 10.4.2 Hypoxia-activated Cobalt Prodrugs of DNA
Alkylators 326 10.4.3 Hypoxia-activated Cobalt Prodrugs of MMP Inhibitors
329 10.5 Summary 333 Acknowledgments 333 References 323 11. Metal Complexes
as Enzyme Inhibitors and Catalysts in Living Cells 341 Julien Furrer,
Gregory S. Smith and Bruno Therrien 11.1 Introduction 341 11.2 Metal-based
Inhibitors: From Serendipity to Rational Design 342 11.2.1 Mimicking the
Structure of Known Enzyme Binders 342 11.2.2 Coordinating Known Enzymatic
Inhibitors to Metal Complexes 343 11.2.3 Exchanging Ligands to Inhibit
Enzymes 344 11.2.4 Controlling Conformation by Metal Coordination 344
11.2.5 Competing with Known Metallo-Enzymatic Processes 345 11.3 The Next
Generation: Polynuclear Metal Complexes as Enzyme Inhibitors 346 11.3.1
Polyoxometalates: Broad Spectrum Enzymatic Inhibitory Effects 347 11.3.2
Polynuclear G-quadruplex DNA Stabilizers: Potential Inhibitors of
Telomerase 349 11.3.3 Polynuclear Polypyridyl Ruthenium Complexes: DNA
Topoisomerase II Inhibitors 352 11.4 Metal Complexes as Catalysts in Living
Cells 355 11.4.1 Catalysis of NAD+/NADH 355 11.4.2 Oxidation of the Thiols
Cysteine and Glutathione 357 11.4.3 Cytotoxicity Controlled by Oxidation
361 11.5 Catalytic Conversion and Removal of Functional Groups 361 11.6
Catalytically Controlled Carbon-Carbon Bond Formation 362 11.7 Conclusion
364 References 364 12. Other Applications of Metal Complexes in Chemical
Biology 373 Tanmaya Joshi, Malay Patra and Gilles Gasser 12.1 Introduction
373 12.2 Surface Immobilization of Proteins and Enzymes 373 12.3 Metal
Complexes as Artificial Nucleases 378 12.3.1 Mono- and Multinuclear Cu(II)
and Zn(II) Complexes 380 12.3.2 Lanthanide Complexes 388 12.4 Cellular
Uptake Enhancement Using Metal Complexes 390 12.5 Conclusions 394
Acknowledgments 394 References 394 Index 403
xxi 1. New Applications of Immobilized Metal Ion Affinity Chromatography in
Chemical Biology 1 Rachel Codd, Jiesi Gu, Najwa Ejje and Tulip Lifa 1.1
Introduction 1 1.2 Principles and Traditional Use 2 1.3 A Brief History 4
1.4 New Application 1: Non-protein Based Low Molecular Weight Compounds 5
1.4.1 Siderophores 6 1.4.2 Anticancer Agent: Trichostatin A 10 1.4.3
Anticancer Agent: Bleomycin 12 1.4.4 Anti-infective Agents 13 1.4.5 Other
Agents 14 1.4.6 Selecting a Viable Target 15 1.5 New Application 2:
Multi-dimensional Immobilized Metal Ion Affinity Chromatography 17 1.6 New
Application 3: Metabolomics 20 1.7 New Application 4: Coordinate-bond
Dependent Solid-phase Organic Synthesis 20 1.8 Green Chemistry Technology
21 1.9 Conclusion 23 Acknowledgments 24 References 24 2. Metal Complexes as
Tools for Structural Biology 37 Michael D. Lee, Bim Graham and James D.
Swarbrick 2.1 Structural Biological Studies and the Major Techniques
Employed 37 2.2 What do Metal Complexes have to Offer the Field of
Structural Biology? 38 2.3 Metal Complexes for Phasing in X-ray
Crystallography 39 2.4 Metal Complexes for Derivation of Structural
Restraints via Paramagnetic NMR Spectroscopy 41 2.4.1 Paramagnetic
Relaxation Enhancement (PRE) 42 2.4.2 Residual Dipolar Coupling (RDC) 43
2.4.3 Pseudo-Contact Shifts (PCS) 43 2.4.4 Strategies for Introducing
Lanthanide Ions into Bio-Macromolecules 44 2.5 Metal Complexes as Spin
Labels for Distance Measurements via EPR Spectroscopy 53 2.6 Metal
Complexes as Donors for Distance Measurements via Luminescence Resonance
Energy Transfer (LRET) 54 2.7 Concluding Statements and Future Outlook 56
References 56 3. AAS, XRF, and MS Methods in Chemical Biology of Metal
Complexes 63 Ingo Ott, Christophe Biot and Christian Hartinger 3.1
Introduction 63 3.2 Atomic Absorption Spectroscopy (AAS) 64 3.2.1
Fundamentals and Basic Principles of AAS 64 3.2.2 Instrumental and
Technical Aspects of AAS 65 3.2.3 Method Development and Aspects of
Practical Application 67 3.2.4 Selected Application Examples 69 3.3 Total
Reflection X-Ray Fluorescence Spectroscopy (TXRF) 72 3.3.1 Fundamentals and
Basic Principles of TXRF 72 3.3.2 Instrumental/Methodical Aspects of TXRF
and Applications 73 3.4 Subcellular X-ray Fluorescence Imaging of a
Ruthenium Analogue of the Malaria Drug Candidate Ferroquine Using
Synchrotron Radiation 74 3.4.1 Application of X-ray Fluorescence in Drug
Development Using Ferroquine as an Example 75 3.5 Mass Spectrometric
Methods in Inorganic Chemical Biology 80 3.5.1 Mass Spectrometry and
Inorganic Chemical Biology: Selected Applications 83 3.6 Conclusions 90
Acknowledgements 90 References 90 4. Metal Complexes for Cell and Organism
Imaging 99 Kenneth Yin Zhang and Kenneth Kam-Wing Lo 4.1 Introduction 99
4.2 Photophysical Properties 100 4.2.1 Fluorescence and Phosphorescence 100
4.2.2 Two-photon Absorption 101 4.2.3 Upconversion Luminescence 102 4.3
Detection of Luminescent Metal Complexes in an Intracellular Environment
104 4.3.1 Confocal Laser-scanning Microscopy 104 4.3.2 Fluorescence
Lifetime Imaging Microscopy 105 4.3.3 Flow Cytometry 106 4.4 Cell and
Organism Imaging 107 4.4.1 Factors Affecting Cellular Uptake 107 4.4.2
Organelle Imaging 116 4.4.3 Two-photon and Upconversion Emission Imaging
for Cells and Organisms 133 4.4.4 Intracellular Sensing and Labeling 136
4.5 Conclusion 143 Acknowledgements 143 References 143 5. Cellular Imaging
with Metal Carbonyl Complexes 149 Luca Quaroni and Fabio Zobi 5.1
Introduction 149 5.2 Vibrational Spectroscopy of Metal Carbonyl Complexes
151 5.3 Microscopy and Imaging of Cellular Systems 154 5.3.1 Techniques of
Vibrational Microscopy 155 5.4 Infrared Microscopy 155 5.4.1 Concentration
Measurements with IR Spectroscopy and Spectromicroscopy 157 5.4.2 Water
Absorption 158 5.4.3 Metal Carbonyls as IR Probes for Cellular Imaging 158
5.4.4 In Vivo Uptake and Reactivity of Metal Carbonyl Complexes 162 5.5
Raman Microscopy 167 5.5.1 Concentration Measurements with Raman
Spectroscopy and Spectromicroscopy 169 5.5.2 Metal Carbonyls as Raman
Probes for Cellular Imaging 169 5.6 Near-field Techniques 171 5.6.1
Concentration Measurements with Near-field Techniques 172 5.6.2
High-resolution Measurement of Intracellular Metal-Carbonyl Accumulation by
Photothermal Induced Resonance 173 5.7 Comparison of Techniques 175 5.8
Conclusions and Outlook 176 Acknowledgements 177 References 178 6. Probing
DNA Using Metal Complexes 183 Lionel Marcélis, Willem Vanderlinden and
Andrée Kirsch-De Mesmaeker 6.1 General Introduction 183 6.2 Photophysics of
Ru(II) Complexes 184 6.2.1 The First Ru(II) Complex Studied in the
Literature: [Ru(bpy)3]2+ 184 6.2.2 Homoleptic Complexes 186 6.2.3
Heteroleptic Complexes 186 6.2.4 Photoinduced Electron Transfer (PET) and
Energy Transfer Processes 188 6.3 State-of-the-art on the Interactions of
Mononuclear Ru(II) Complexes with Simple Double-stranded DNA 190 6.3.1
Studies on Simple Double-stranded DNAs 191 6.3.2 Influence of DNA on the
Emission Properties 193 6.4 Structural Diversity of the Genetic Material
194 6.4.1 Mechanical Properties of DNA 195 6.4.2 DNA Topology 195 6.4.3 SMF
Study with [Ru(phen)2(PHEHAT)]2+ and [Ru(TAP)2(PHEHAT)]2+ 198 6.5 Unusual
Interaction of Dinuclear Ru(II) Complexes with Different DNA Types 200
6.5.1 Reversible Interaction of [{(Ru(phen)2}2HAT]4+ with Denatured DNA 201
6.5.2 Targeting G-quadruplexes with Photoreactive [{Ru(TAP)2}2TPAC]4+ 204
6.5.3 Threading Intercalation 205 6.6 Conclusions 207 Acknowledgement 208
References 208 7. Visualization of Proteins and Cells Using
Dithiol-reactive Metal Complexes 215 Danielle Park, Ivan Ho Shon, Minh Hua,
Vivien M. Chen and Philip J. Hogg 7.1 The Chemistry of As(III) and Sb(III)
215 7.2 Cysteine Dithiols in Protein Function 217 7.3 Visualization of
Dithiols in Isolated Proteins with As(III) 218 7.4 Visualization of
Dithiols on the Mammalian Cell Surface with As(III) 218 7.5 Visualization
of Dithiols in Intracellular Proteins with As(III) 219 7.6 Visualization of
Tetracysteine-tagged Recombinant Proteins in Cells with As(III) 219 7.7
Visualization of Cell Death in the Mouse with Optically Labelled As(III)
220 7.7.1 Cell Death in Health and Disease 220 7.7.2 Cell Death Imaging
Agents 222 7.7.3 Visualization of Cell Death in Mouse Tumours, Brain and
Thrombi with Optically Labelled As(III) 223 7.8 Visualization of Cell Death
in Mouse Tumours with Radio-labelled As(III) 225 7.9 Summary and
Perspectives 227 References 227 8. Detection of Metal Ions, Anions and
Small Molecules Using Metal Complexes 233 Qin Wang and Katherine J. Franz
8.1 How Do We See What's in a Cell? 233 8.1.1 Why Metal Complexes as
Sensors? 234 8.1.2 Design Strategies for Sensors Built with Metal Complexes
234 8.1.3 General Criteria of Metal-based Sensors for Bioimaging 236 8.2
Metal Complexes for Detection of Metal Ions 236 8.2.1 Tethered Sensors for
Detecting Metal Ions 237 8.2.2 Displacement Sensors for Detecting Metal
Ions 240 8.2.3 MRI Contrast Agents for Detecting Metal Ions 240 8.2.4
Chemodosimeters for Metal Ions 249 8.3 Metal Complexes for Detection of
Anions and Neutral Molecules 252 8.3.1 Tethered Approach: Metal Complex as
Recognition Unit 255 8.3.2 Displacement Approach: Metal Complex as Quencher
258 8.3.3 Dosimeter Approach 262 8.4 Conclusions 268 Acknowledgements 268
Abbreviations 268 References 269 9. Photo-release of Metal Ions in Living
Cells 275 Celina Gwizdala and Shawn C. Burdette 9.1 Introduction to
Photochemical Tools Including Photocaged Complexes 275 9.2 Calcium
Biochemistry and Photocaged Complexes 278 9.2.1 Strategies for Designing
Photocaged Complexes for Ca2+ 278 9.2.2 Biological Applications of
Photocaged Ca2+ Complexes 282 9.3 Zinc Biochemistry and Photocaged
Complexes 284 9.3.1 Biochemical Targets for Photocaged Zn2+ Complexes 284
9.3.2 Strategies for Designing Photocaged Complexes for Zn2+ 286 9.4
Photocaged Complexes for Other Metal Ions 291 9.4.1 Photocaged Complexes
for Copper 291 9.4.2 Photocaged Complexes for Iron 295 9.4.3 Photocaged
Complexes for Other Metal Ions 297 9.5 Conclusions 298 Acknowledgment 298
References 298 10. Release of Bioactive Molecules Using Metal Complexes 309
Peter V. Simpson and Ulrich Schatzschneider 10.1 Introduction 309 10.2
Small-molecule Messengers 310 10.2.1 Biological Generation and Delivery of
CO, NO, and H2S 310 10.2.2 Metal-Nitrosyl Complexes for the Cellular
Delivery of Nitric Oxide 311 10.2.3 CO-releasing Molecules (CORMs) 314 10.3
"Photouncaging" of Neurotransmitters from Metal Complexes 321 10.3.1
"Caged" Compounds 321 10.3.2 "Uncaging" of Bioactive Molecules 322 10.4
Hypoxia Activated Cobalt Complexes 324 10.4.1 Bioreductive Activation of
Cobalt Complexes 324 10.4.2 Hypoxia-activated Cobalt Prodrugs of DNA
Alkylators 326 10.4.3 Hypoxia-activated Cobalt Prodrugs of MMP Inhibitors
329 10.5 Summary 333 Acknowledgments 333 References 323 11. Metal Complexes
as Enzyme Inhibitors and Catalysts in Living Cells 341 Julien Furrer,
Gregory S. Smith and Bruno Therrien 11.1 Introduction 341 11.2 Metal-based
Inhibitors: From Serendipity to Rational Design 342 11.2.1 Mimicking the
Structure of Known Enzyme Binders 342 11.2.2 Coordinating Known Enzymatic
Inhibitors to Metal Complexes 343 11.2.3 Exchanging Ligands to Inhibit
Enzymes 344 11.2.4 Controlling Conformation by Metal Coordination 344
11.2.5 Competing with Known Metallo-Enzymatic Processes 345 11.3 The Next
Generation: Polynuclear Metal Complexes as Enzyme Inhibitors 346 11.3.1
Polyoxometalates: Broad Spectrum Enzymatic Inhibitory Effects 347 11.3.2
Polynuclear G-quadruplex DNA Stabilizers: Potential Inhibitors of
Telomerase 349 11.3.3 Polynuclear Polypyridyl Ruthenium Complexes: DNA
Topoisomerase II Inhibitors 352 11.4 Metal Complexes as Catalysts in Living
Cells 355 11.4.1 Catalysis of NAD+/NADH 355 11.4.2 Oxidation of the Thiols
Cysteine and Glutathione 357 11.4.3 Cytotoxicity Controlled by Oxidation
361 11.5 Catalytic Conversion and Removal of Functional Groups 361 11.6
Catalytically Controlled Carbon-Carbon Bond Formation 362 11.7 Conclusion
364 References 364 12. Other Applications of Metal Complexes in Chemical
Biology 373 Tanmaya Joshi, Malay Patra and Gilles Gasser 12.1 Introduction
373 12.2 Surface Immobilization of Proteins and Enzymes 373 12.3 Metal
Complexes as Artificial Nucleases 378 12.3.1 Mono- and Multinuclear Cu(II)
and Zn(II) Complexes 380 12.3.2 Lanthanide Complexes 388 12.4 Cellular
Uptake Enhancement Using Metal Complexes 390 12.5 Conclusions 394
Acknowledgments 394 References 394 Index 403