Cover

Title Page

Copyright

Dedication

Contents

About the Editors

Preface

Acknowledgments

Section I Introduction

Chapter 1 Karen J. Brewer (1961–2014): A Bright Star that Burned Out Far Too Soon

1.1 Introduction

1.2 Early Years

1.3 Graduate Studies and Clemson University

1.4 Postdoctoral Research and the University of California, Berkeley

1.5 Washington State University: Beginning an Independent Career

1.6 Move to Virginia Tech

1.7 Collaboration with Brenda Winkel and the Study of Metal‐DNA Interactions

1.8 A Return to Where It All Started: Photochemical H2 Production

1.9 A Career Cut Tragically Short

1.10 Karen's Legacy

Acknowledgments

References

Chapter 2 Basic Coordination Chemistry of Ruthenium

2.1 Coordination Chemistry of Ruthenium

2.1.1 The Element

2.1.2 Stereochemistry and Common Oxidation States

2.1.2.1 Ruthenium in Low Oxidation States

2.1.2.2 Chemistry of Ruthenium(II) and (III)

2.1.2.3 Higher Oxidation States of Ruthenium

2.1.3 Conclusion

References

Section II Artificial Photosynthesis

Chapter 3 Water Oxidation Catalysis with Ruthenium

3.1 Introduction

3.1.1 Energy Issue and Energy from the Sun

3.1.2 Photosynthesis and Solar Fuels

3.1.3 Water Oxidation

3.1.4 Artificial Water Oxidation

3.2 Ruthenium in Water Oxidation Catalyst

3.2.1 Ruthenium Oxide

3.2.2 Molecular Ruthenium WOC

3.2.2.1 Meyer's Blue Dimer

3.2.2.2 The Ru‐Hbpp Catalyst

3.2.2.3 Single‐Site Ru‐WOCs

3.2.2.4 Heptacoordinated Ru Intermediates

3.2.3 Polyoxometalates: The Bridge Between Metal Oxides and Coordination Complexes

3.3 Conclusions and Perspectives

References

Chapter 4 Ruthenium‐ and Cobalt‐Containing Complexes and Hydrogenases for Hydrogen Production

4.1 Introduction

4.2 (A) Ruthenium‐ and Cobalt‐Containing Complexes for Hydrogen Production

4.2.1 Nonbridged Systems

4.2.2 Bridged Systems

4.3 (B) Ruthenium(II)‐Containing Complexes and Hydrogenases for Hydrogen Generation in Aqueous Solution

4.3.1 Hydrogenases

4.3.2 Hydrogenases with Ruthenium(II) Complexes

4.4 Conclusions

References

Section III Applications in Medicine

Chapter 5 Ligand Photosubstitution Reactions with Ruthenium Compounds: Applications in Chemical Biology and Medicinal Chemistry

5.1 Introduction

5.2 Caging and Uncaging Biologically Active Ligands with a Nontoxic Ruthenium Complex

5.3 Caging Cytotoxic Ruthenium Complexes with Organic Ligands

5.4 Low‐Energy Photosubstitution

5.4.1 Introduction

5.4.2 Modulating Ru Photophysics by Ligand Modulation

5.4.3 Upconversion (UC)

5.4.3.1 Triplet–Triplet Annihilation Upconversion

5.4.3.2 Upconverting Nanoparticles (UCNPs)

5.4.3.3 Two‐Photon Absorption (TPA) Photosubstitution

5.5 Conclusions

References

Chapter 6 Use of Ruthenium Complexes as Photosensitizers in Photodynamic Therapy

6.1 Introduction

6.2 The Basics of Photodynamic Therapy

6.2.1 Singlet Oxygen Production

6.2.2 Other Radical Production

6.2.3 PDT Dose Definition

6.2.3.1 PDT Dosimetry In Vitro

6.2.3.2 PDT Dosimetry In Vivo

6.2.3.3 Oxygen Consumption Model

6.2.3.4 In Vivo Tissue Response Models

6.2.4 PDT and Immunology

6.3 Status of Ru Photosensitizing Complexes

6.3.1 Photostability for Ru‐PS Complexes

6.3.2 Long Wavelength Activation of Ru(II)‐PS Complexes

6.4 Issues to Be Considered to Further Develop Ru‐Based Photosensitizers

6.4.1 Subcellular Localization

6.4.2 Ruthenium Complex Photosensitizers and the Immune Response

6.5 Future Directions for Ru‐PS Research

6.6 Conclusion

References

Chapter 7 Photodynamic Therapy in Medicine with Mixed‐Metal/Supramolecular Complexes

7.1 Introduction

7.2 Platinum and Rhodium Centers as Bioactive Sites

7.2.1 Platinum(II)‐Based Chemotherapeutics

7.2.2 Rhodium(III) as a Bioactive Site

7.3 Supramolecular Complexes as DNA Photomodification Agents

7.4 Mixed‐Metal Complexes as Photodynamic Therapeutic Agents

7.4.1 Photosensitizers with a Ru(II) Metal Center Coupled to Pt(II) Bioactive Sites

7.4.1.1 Binuclear Complexes with Ru(II) and Pt(II) Metal Centers with Bidentate Ligands

7.4.1.2 Binuclear and Trinuclear Complexes with Ru, Pt with Tridentate Ligands

7.4.2 Photosensitizers with a Ru(II) Metal Center Coupled to Rh(III) Bioactive Sites

7.4.2.1 Trinuclear Complexes with Ru(II), Rh(III), and Ru(II) Metal Centers

7.4.2.2 Binuclear Complexes with Ru(II) and Rh(III) Metal Centers

7.4.3 Photosensitizers with a Ru(II) Metal Cenetr Coupled to Other Bioactive Sites

7.4.3.1 Binuclear Complexes with Ru(II) and Cu

7.4.3.2 Binuclear Complexes with Ru(II) and Co(III) Metal Centers

7.4.3.3 Binuclear Complexes with Ru (II) and V(IV) Metal Centers

7.4.3.4 Applications of Ru(II) Metal Centers in Nanomedicine

7.5 Summary and Conclusions

Abbreviations

References

Chapter 8 Ruthenium Anticancer Agents En Route to the Tumor: From Plasma Protein Binding Agents to Targeted Delivery

8.1 Introduction

8.2 Protein Binding RuIII Anticancer Drug Candidates

8.2.1 RuIII Anticancer Drug Candidates Targeting Primary Tumors

8.2.2 Antimetastatic RuIII Compounds

8.3 Functionalization of Macromolecular Carrier Systems with Ru Anticancer Agents

8.3.1 Proteins as Delivery Vectors for Organometallic Compounds

8.3.2 Polymers and Liposomes as Delivery Systems for Bioactive Ruthenium Complexes

8.3.3 Dendrimers

8.4 Hormones, Vitamins, and Sugars: Ruthenium Complexes Targeting Small Molecule Receptors

8.5 Peptides as Transporters for Ruthenium Complexes into Tumor Cells and Cell Compartments

8.6 Polynuclear Ruthenium Complexes for the Delivery of a Cytotoxic Payload

8.7 Summary and Conclusions

Acknowledgments

References

Chapter 9 Design Aspects of Ruthenium Complexes as DNA Probes and Therapeutic Agents

9.1 Introduction

9.2 Physical Interaction to Disrupt DNA Structure

9.2.1 Irreversible Covalent Binding

9.2.2 Intercalation

9.2.3 Additional Noncovalent Binding Interactions

9.3 Biological Consequences of Ru‐Complex/DNA Interactions

9.4 Effects of Ru Complexes on Topoisomerases and Telomerase

9.5 Summary and Conclusions

References

Chapter 10 Ruthenium‐Based Anticancer Compounds: Insights into Their Cellular Targeting and Mechanism of Action

10.1 Introduction

10.2 Cellular Uptake

10.3 DNA and DNA‐Related Cellular Targets

10.4 Targeting Signaling Pathways

10.5 Targeting Enzymes of Specific Cell Functions

10.6 Targeting Glycolytic Pathways

10.7 Macromolecular Ruthenium Conjugates: A New Approach to Targeting

10.8 Conclusions

References

Chapter 11 Targeting cellular DNA with Luminescent Ruthenium(II) Polypyridyl Complexes

11.1 Introduction

11.1.1 DNA‐Binding Modes of Small Molecules

11.1.2 Metal Complexes and DNA

11.2 [Ru(bpy)2(dppz)]2+ and the DNA "Light‐Switch" Effect

11.3 Cellular Uptake of RPCs and Application as DNA‐Imaging Agents

11.3.1 Mononuclear Complexes

11.3.2 Dinuclear Complexes

11.3.3 Cyclometalated Systems

11.4 Alternative Techniques to Assess Cellular Uptake and Localization

11.5 Toward Theranostics: luminescent RPCs as Anticancer Therapeutics

11.6 Summary and Conclusions

References

Chapter 12 Biological Activity of Ruthenium Complexes With Quinoline Antibacterial and Antimalarial Drugs

12.1 Introduction

12.2 Antibacterial (Fluoro)quinolones

12.2.1 Quinolones and Their Interactions with Metal Ions

12.2.2 Ruthenium and Quinolones

12.2.3 Ruthenium and HIV Integrase Inhibitor Elvitegravir

12.3 Antibacterial 8‐Hydroxyquinolines

12.3.1 Mode of Action of 8‐Hydroxyquinoline Agents

12.3.2 Ruthenium and 8‐Hydroxyquinolines

12.4 Antimalarial 4‐Aminoquinolines

12.4.1 Mechanism of Action of Antimalarial Quinoline Agents

12.5 Metallocene Analogues of Chloroquine

12.6 Conclusions

References

Chapter 13 Ruthenium Complexes as NO Donors: Perspectives and Photobiological Applications

13.1 Introduction

13.2 Photochemical Processes of Some Nitrogen Oxide Derivative–Ruthenium Complexes

13.2.1 Metal‐Ligand Charge‐Transfer Photolysis of {Ru‐NO}6

13.2.2 Nitrosyl Ruthenium Complexes: Visible‐Light Stimulation

13.3 Photobiological Applications of Nitrogen Oxide Compounds

13.3.1 Photovasorelaxation

References

Chapter 14 Trends and Perspectives of Ruthenium Anticancer Compounds (Non‐PDT)

14.1 Introduction

14.2 Ruthenium(III) Compounds

14.2.1 NAMI‐A

14.2.1.1 Biotransformation

14.2.1.2 Antimetastatic Activity

14.2.1.3 Mode of Action

14.2.1.4 Clinical Studies and Perspectives

14.2.2 KP1019/NKP‐1339

14.2.2.1 Tumor Targeting Mediated by Plasma Proteins

14.2.2.2 Activation by Reduction

14.2.2.3 Mode of Action

14.2.2.4 Clinical Studies and Perspectives

14.3 Organoruthenium(II) Compounds

14.3.1 Ruthenium(II)–Arene Compounds in Preclinical Development

14.3.1.1 Organoruthenium Complexes Bearing Bioactive Ligand Scaffolds

14.3.1.2 Cytotoxic Organoruthenium Complexes without Activation by Aquation

References

Chapter 15 Ruthenium Complexes as Antifungal Agents

15.1 Introduction

15.2 Antifungal Activity Investigations of Ruthenium Complexes

15.2.1 Ruthenium Complexes with Activity against Several Pathogenic Fungi Species: Dinuclear, Trinuclear, and Tetranuclear ruthenium Polydentate Polypyridil ligands, Heterotrimetallic di‐Ruthenium‐Mono‐Palladium Complexes, Dinuclear bis‐&rmbeta;‐Diketones and Pentadithiocarbamate Ligands

15.2.2 Aromatic and Heteroaromatic Ligands in Ru Monometallic Centers (Pyridine, Phenantroline, Terpyridine, Quinoline, and Phenazine)

15.2.3 Schiff bases, Thiosemicarbazones, and Chalcones

15.2.3.1 Schiff bases (Tetradentate Salen Like, Tridentate, and bidentate)

15.2.3.2 Thiosemicarbazones

15.2.3.3 Chalcone Derivatives

15.2.4 Other ligands (Dithio‐Naphtyl‐Benzamide, Arylazo, Catecholamine, Organophosphorated, Hydridotris(pyrazolyl)borate and Bioactive Azole Ligands)

15.3 Conclusion

References

Index

EULA