Inorganic Chemical Biology

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

overview of the current and emerging role of metal complexes in
chemical biology. Throughout all

of the chapters there is a strong emphasis on fundamental
theoretical chemistry and experiments

that have been carried out in living cells or organisms. Outlooks
for the future applications of

metal complexes in chemical biology are also discussed.

Topics covered include:

• Metal complexes as tools for structural biology

• IMAC, AAS, XRF and MS as detection techniques for metals in
  chemical biology

• Cell and organism imaging and probing DNA using metal and
  metal carbonyl complexes

• Detection of metal ions, anions and small molecules using
  metal complexes

• Photo-release of metal ions in living cells

• Metal complexes as enzyme inhibitors and catalysts in
  living cells

Written by a team of international experts, Inorganic Chemical
Biology: Principles, Techniques and

Applications is a must-have for bioinorganic,
bioorganometallic and medicinal chemists as well as

chemical biologists working in both academia and industry.

Auteur
Editor
Gilles Gasser, Department of Chemistry, University of Zurich, Switzerland

Résumé

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
overview of the current and emerging role of metal complexes in chemical biology. Throughout all
of the chapters there is a strong emphasis on fundamental theoretical chemistry and experiments
that have been carried out in living cells or organisms. Outlooks for the future applications of
metal complexes in chemical biology are also discussed.

Topics covered include:

• Metal complexes as tools for structural biology

• IMAC, AAS, XRF and MS as detection techniques for metals in chemical biology

• Cell and organism imaging and probing DNA using metal and metal carbonyl complexes

• Detection of metal ions, anions and small molecules using metal complexes

• Photo-release of metal ions in living cells

• Metal complexes as enzyme inhibitors and catalysts in living cells

Written by a team of international experts, Inorganic Chemical Biology: Principles, Techniques and
Applications is a must-have for bioinorganic, bioorganometallic and medicinal chemists as well as
chemical biologists working in both academia and industry.

Contenu

About the Editor xiii

List of Contributors xv

Preface xix

Acknowledgements 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</...