Schweitzer Fachinformationen
Wenn es um professionelles Wissen geht, ist Schweitzer Fachinformationen wegweisend. Kunden aus Recht und Beratung sowie Unternehmen, öffentliche Verwaltungen und Bibliotheken erhalten komplette Lösungen zum Beschaffen, Verwalten und Nutzen von digitalen und gedruckten Medien.
About the Editor xiii
List of Contributors xv
Preface xix
Acknowledgements xxi
1. New Applications of Immobilized Metal Ion Affinity Chromatography in Chemical Biology 1Rachel 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 37Michael 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 63Ingo 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 99Kenneth 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 149Luca 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 183Lionel 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 215Danielle 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 233Qin 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 275Celina 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 309Peter 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 341Julien 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 373Tanmaya 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
Rachel Codd, Jiesi Gu, Najwa Ejje and Tulip Lifa
School of Medical Sciences (Pharmacology) and Bosch Institute, The University of Sydney, Australia
Immobilized metal ion affinity chromatography (IMAC) was first introduced as a method for resolving native proteins with surface exposed histidine residues from a complex mixture of human serum [1]. IMAC has since become a routine method used in molecular biology for purifying recombinant proteins with histidine tags engineered at the N- or C-terminus. The success of IMAC for protein purification may have obscured its potential utility in other applications in biomolecular chemistry and chemical biology. Since there exists in nature a multitude of non-protein based low molecular weight compounds that have an inherent affinity towards metal ions, or that have a fundamental requirement for metal ion binding for activity, IMAC could be used to capture these targets from complex mixtures. This highly selective affinity-based separation method could facilitate the discovery of new anti-infective and anticancer compounds from bacteria, fungi, plants, and sponges. A recent body of work highlights new applications of IMAC for the isolation of known drugs and for drug discovery, metabolome profiling, and for preparing metal-specific molecular probes for chemical proteomics-based drug discovery. At its core, IMAC is a method underpinned by the fundamental tenets of coordination chemistry. This chapter will briefly focus on these aspects, before moving on to describe a number of recent innovations in IMAC. The ultimate intent of this chapter is to seed interest in other research groups for expanding the use of IMAC across chemical biology.
An IMAC system comprises three variable elements (Fig. 1.1): the insoluble matrix (green), the immobilized chelate (depicted as iminodiacetic acid, IDA, red), and the metal ion (commonly Ni(II), blue). Critical to the veracity of IMAC as a separation technique is that the coordination sphere of the immobilized metal–chelate complex is unsaturated, which allows target compounds to reversibly bind to the resin via the formation and dissociation of coordinate bonds. Each element of the IMAC system can be varied independently or in combination, which, together with basic experimental conditions (buffer selection, pH value), will influence the outcome of a separation experiment. This modular type of experimental system allows a high level of control for optimization.
Figure 1.1 The elements of an immobilized metal ion affinity chromatography (IMAC) experiment. The system (left-hand side) comprises an insoluble matrix (green) with a covalently bound chelate (iminodiacetic acid, IDA, red) which coordinates in a 1:1 fashion a metal ion (Ni(II), blue) to give a complex with vacant coordination sites available for the reversible binding of targets with metal binding groups. Traditional IMAC targets (right-hand side) include native proteins with surface exposed histidine residues, histidine-tagged proteins, and phosphorylated proteins
In accord with its original intended use, the majority of IMAC targets are proteins, which even as native molecules can bind to the immobilized metal–chelate complex with variable affinities, as determined by the presence of surface exposed histidine residues and, in some cases, more weakly binding cysteine residues (Fig. 1.1, protein shown at left). Compared with native proteins, recombinant proteins, which feature a hexameric histidine repeat unit (His-tag) engineered at the C- or N-terminus, are higher affinity IMAC targets (Fig. 1.1, protein shown at middle). In this case, the C-terminal histidine residues of the recombinant protein displace the three water ligands in the immobilized Ni(II)–IDA coordination sphere, with the majority of the components in the protein expression mixture not retained on the resin (Fig. 1.2). After washing the resin to remove these unbound components, the coordinate bonds between the Ni(II)–IDA complex and the C-terminal histidine residues are dissociated by competition upon washing the resin with a buffer containing a high concentration of imidazole.
Figure 1.2 The traditional use of IMAC for the purification of His-tagged recombinant proteins. The recombinant protein binds to the immobilized coordination complex upon the displacement of water ligands by the histidine residues engineered at the N- or C- (as shown) terminus. The resin is washed to remove unbound components from the expression mixture, and the purified protein is eluted from the resin by competition upon washing with a high concentration of imidazole buffer
Phosphorylated proteins (Fig. 1.1, protein at right) as studied in phosphoproteomics [2–4], are also isolable using an IMAC format, based upon the affinity between Fe(III) and phosphorylated proteins (Fe(III)–phosphoserine, log K ∼ 13 [5]). The IMAC-compatible metal ions most suited for phosphoproteomics include Fe(III), Ga(III), or Zr(IV), with these hard acids having preferential binding affinities towards the hard base phosphate groups. This highlights that the IMAC technique is governed by key principles of coordination chemistry, including the hard and soft acids and bases (HSAB) theory [6], coordination number and geometry preferences, and thermodynamic and kinetic factors.
Because there is a significant market demand for IMAC-based separations, considerable research in the biotechnology sector has focused upon finding new and improved matrices and immobilized chelates. Common matrices include cross-linked agarose, cellulose, and sepharose. These polymers can be prepared with different degrees of cross-linking, branching, and different levels of activation, which affect the concentration of the immobilized chelate in the final matrix. There are several different types of immobilized chelates in use in IMAC applications (Fig. 1.3), with the most common being tridentate iminodiacetic acid (IDA, A) and tetradentate nitrilotriacetic acid (NTA, B). Immobilized tetradentate N-(carboxymethyl)aspartic acid (CM-Asp, C) and pentadentate N,N,N′-tris(carboxymethyl)ethylenediamine (TED, D) are used less frequently. These different N- and O-atom containing ligand types cover a range of degrees of coordinative unsaturation, which for a metal ion with an octahedral coordination preference would span: three available sites (M(N1O2(OH2)3) (IDA)), two available sites (M(N1O3(OH2)2) (NTA), M(N1O3(OH2)2) (CM-Asp)), and one available site (M(N2O3(OH2)) (TED)). A significant number of resins with non-traditional immobilized chelates, such as 1,4,7-triazocyclononane [7], 8-hydroxyquinoline [8] or N-(2-pyridylmethyl)aminoacetate [9] have been prepared, which have different performance characteristics with respect to protein purification, compared with the traditional IMAC resins.
Figure 1.3 Immobilized chelates used in IMAC applications. Chelates: iminodiacetic acid (IDA, a), nitrilotriacetic acid (NTA, b), N-(carboxymethyl)aspartic acid (CM-Asp, c) or N,N,N′-tris(carboxymethyl)ethylenediamine (TED, d). A range of metal ions, including Ni(II), Cu(II), Co(II) or Zn(II), are compatible with each type of immobilized chelate. The type of chelate and the coordination preferences of the metal ion will direct the degree of coordinative unsaturation of the immobilized complex
The nature of the immobilized coordination complex, in terms of both chelate and metal ion, has a major influence on the outcome of an IMAC procedure. An example of the influence of the chelate is found in early studies, which focused on the development of IMAC for phosphoproteomics. Fractions of phosphoserine-containing ovalbumin were retained on an immobilized Fe(III)–IDA resin, but were not retained on an immobilized Fe(III)–TED resin [2]. While an explanation for this observation was not provided in the original work, we posit that this is most likely due to the difference between the number of available coordination sites in the Fe(III)–IDA complex (three sites) and the Fe(III)–TED complex (one site) (Fig. 1.3). This would suggest that retention of ovalbumin fractions via phosphoserine residues involves at least a bidentate binding mode, and that the single coordination site at the Fe(III)–TED complex was insufficient for retaining the target.
As an enabling technology, IMAC has played a significant role in accelerating knowledge of molecular, cell, and human biology, through expediting access to significant quantities of pure proteins. For a technique that is conducted every day in many laboratories around the world, it is interesting to reflect briefly upon the history and acceptance of IMAC in its early phases of development. The many review articles available on the history of IMAC [10–14] warrants only a brief coverage of this topic here. The first description of IMAC for protein fractionation used Zn(II)- or Cu(II)-loaded IDA resins prepared in house, with the columns configured in series [1]. Processing of an aliquot of human serum showed that the Zn(II) column was enriched with transferrin, acid glycoprotein, and ceruloplasmin, while the Cu(II) column was...
Dateiformat: ePUBKopierschutz: Adobe-DRM (Digital Rights Management)
Systemvoraussetzungen:
Das Dateiformat ePUB ist sehr gut für Romane und Sachbücher geeignet – also für „fließenden” Text ohne komplexes Layout. Bei E-Readern oder Smartphones passt sich der Zeilen- und Seitenumbruch automatisch den kleinen Displays an. Mit Adobe-DRM wird hier ein „harter” Kopierschutz verwendet. Wenn die notwendigen Voraussetzungen nicht vorliegen, können Sie das E-Book leider nicht öffnen. Daher müssen Sie bereits vor dem Download Ihre Lese-Hardware vorbereiten.Bitte beachten Sie: Wir empfehlen Ihnen unbedingt nach Installation der Lese-Software diese mit Ihrer persönlichen Adobe-ID zu autorisieren!
Weitere Informationen finden Sie in unserer E-Book Hilfe.
Dateiformat: PDFKopierschutz: Adobe-DRM (Digital Rights Management)
Das Dateiformat PDF zeigt auf jeder Hardware eine Buchseite stets identisch an. Daher ist eine PDF auch für ein komplexes Layout geeignet, wie es bei Lehr- und Fachbüchern verwendet wird (Bilder, Tabellen, Spalten, Fußnoten). Bei kleinen Displays von E-Readern oder Smartphones sind PDF leider eher nervig, weil zu viel Scrollen notwendig ist. Mit Adobe-DRM wird hier ein „harter” Kopierschutz verwendet. Wenn die notwendigen Voraussetzungen nicht vorliegen, können Sie das E-Book leider nicht öffnen. Daher müssen Sie bereits vor dem Download Ihre Lese-Hardware vorbereiten.
Bitte beachten Sie: Wir empfehlen Ihnen unbedingt nach Installation der Lese-Software diese mit Ihrer persönlichen Adobe-ID zu autorisieren!
