Ruthenium Complexes: Photochemical and Biomedical Applications

Edited by a team of highly respected researchers combining their expertise in chemistry, physics, and medicine, this book focuses on the use of ruthenium–containing complexes in artificial photosynthesis and medicine. Following a brief introduction to the basic coordination chemistry of ruthenium–containing complexes and their synthesis, as well as their photophysical and photochemical properties, the authors discuss in detail the major concepts of artificial photosynthesis and mechanisms of hydrogen production and water oxidation with ruthenium. The second part of the text covers biological properties and important medical applications of ruthenium–containing complexes as therapeutic agents or in diagnostic imaging. Aimed at stimulating research in this active field, this is an invaluable information source for researchers in academia, health research institutes, and governmental departments working in the field of organometallic chemistry, green and sustainable chemistry as well as medicine/drug discovery, while equally serving as a useful reference also for scientists in industry. INDICE:   .About the Editors xv .Preface xvii .Acknowledgments xix .Section I Introduction 1 .1 Karen J. Brewer (1961 2014): A Bright Star that Burned Out Far Too Soon 3Seth C. Rasmussen .1.1 Introduction 3 .1.2 Early Years 4 .1.3 Graduate Studies and Clemson University 6 .1.4 Postdoctoral Research and the University of California, Berkeley 11 .1.5 Washington State University: Beginning an Independent Career 13 .1.6 Move to Virginia Tech 15 .1.7 Collaboration with BrendaWinkel and the Study of Metal–DNA Interactions 16 .1.8 A Return to Where It All Started: Photochemical H2 Production 18 .1.9 A Career Cut Tragically Short 19 .1.10 Karen s Legacy 20 .Acknowledgments 20 .References 20 .2 Basic Coordination Chemistry of Ruthenium 25Mark A.W. Lawrence, Jimmie L. Bullock, and Alvin A. Holder .2.1 Coordination Chemistry of Ruthenium 25 .2.1.1 The Element 25 .2.1.2 Stereochemistry and Common Oxidation States 26 .2.1.2.1 Ruthenium in Low Oxidation States 27 .2.1.2.2 Chemistry of Ruthenium(II) and (III) 31 .2.1.2.3 Higher Oxidation States of Ruthenium 36 .2.1.3 Conclusion 37 .References 37 .Section II Artificial Photosynthesis 43 .3 Water Oxidation Catalysis with Ruthenium 45Andrea Sartorel .3.1 Introduction 45 .3.1.1 Energy Issue and Energy from the Sun 45 .3.1.2 Photosynthesis and Solar Fuels 46 .3.1.3 Water Oxidation 48 .3.1.4 ArtificialWater Oxidation 49 .3.2 Ruthenium inWater Oxidation Catalyst 50 .3.2.1 Ruthenium Oxide 50 .3.2.2 Molecular Ruthenium WOC 52 .3.2.2.1 Meyer s Blue Dimer 53 .3.2.2.2 The Ru–Hbpp Catalyst 54 .3.2.2.3 Single–Site Ru–WOCs 55 .3.2.2.4 Heptacoordinated Ru Intermediates 56 .3.2.3 Polyoxometalates: The Bridge Between Metal Oxides and Coordination Complexes 57 .3.3 Conclusions and Perspectives 60 .References 61 .4 Ruthenium– and Cobalt–Containing Complexes and Hydrogenases for Hydrogen Production 67Michael J. Celestine, Raj K. Gurung, and Alvin A. Holder .4.1 Introduction 67 .4.2 (A) Ruthenium– and Cobalt–Containing Complexes for Hydrogen Production 68 .4.2.1 Nonbridged Systems 68 .4.2.2 Bridged Systems 70 .4.3 (B) Ruthenium(II)–Containing Complexes and Hydrogenases for Hydrogen Generation in Aqueous Solution 77 .4.3.1 Hydrogenases 77 .4.3.2 Hydrogenases with Ruthenium(II) Complexes 78 .4.4 Conclusions 84 .References 85 .Section III Applications in Medicine 89 .5 Ligand Photosubstitution Reactions with Ruthenium Compounds: Applications in Chemical Biology and Medicinal Chemistry 91Samantha L. Hopkins and Sylvestre Bonnet .5.1 Introduction 91 .5.2 Caging and Uncaging Biologically Active Ligands with a Nontoxic Ruthenium Complex 92 .5.3 Caging Cytotoxic Ruthenium Complexes with Organic Ligands 96 .5.4 Low–Energy Photosubstitution 100 .5.4.1 Introduction 100 .5.4.2 Modulating Ru Photophysics by Ligand Modulation 100 .5.4.3 Upconversion (UC) 105 .5.4.3.1 Triplet Triplet Annihilation Upconversion 105 .5.4.3.2 Upconverting Nanoparticles (UCNPs) 106 .5.4.3.3 Two–Photon Absorption (TPA) Photosubstitution 109 .5.5 Conclusions 110 .References 111 .6 Use of Ruthenium Complexes as Photosensitizers in Photodynamic Therapy 117Lothar Lilge .6.1 Introduction 117 .6.2 The Basics of PhotodynamicTherapy 118 .6.2.1 Singlet Oxygen Production 120 .6.2.2 Other Radical Production 120 .6.2.3 PDT Dose Definition 120 .6.2.3.1 PDT Dosimetry In Vitro 122 .6.2.3.2 PDT Dosimetry In Vivo 124 .6.2.3.3 Oxygen Consumption Model 125 .6.2.3.4 In Vivo Tissue Response Models 125 .6.2.4 PDT and Immunology 126 .6.3 Status of Ru Photosensitizing Complexes 126 .6.3.1 Photostability for Ru–PS Complexes 128 .6.3.2 LongWavelength Activation of Ru(II)–PS Complexes 128 .6.4 Issues to Be Considered to Further Develop Ru–Based Photosensitizers 129 .6.4.1 Subcellular Localization 130 .6.4.2 Ruthenium Complex Photosensitizers and the Immune Response 131 .6.5 Future Directions for Ru–PS Research 131 .6.6 Conclusion 132 .References 132 .7 Photodynamic Therapy in Medicine with Mixed–Metal/Supramolecular Complexes 139Jimmie L. Bullock and Alvin A. Holder .7.1 Introduction 139 .7.2 Platinum and Rhodium Centers as Bioactive Sites 140 .7.2.1 Platinum(II)–Based Chemotherapeutics 140 .7.2.2 Rhodium(III) as a Bioactive Site 141 .7.3 Supramolecular Complexes as DNA Photomodification Agents 142 .7.4 Mixed–Metal Complexes as PhotodynamicTherapeutic Agents 143 .7.4.1 Photosensitizers with a Ru(II)Metal Center Coupled to Pt(II) Bioactive Sites 143 .7.4.1.1 Binuclear Complexes with Ru(II) and Pt(II)Metal Centers with Bidentate Ligands 143 .7.4.1.2 Binuclear and Trinuclear Complexes with Ru, Pt with Tridentate Ligands 146 .7.4.2 Photosensitizers with a Ru(II) Metal Center Coupled to Rh(III) Bioactive Sites 147 .7.4.2.1 Trinuclear Complexes with Ru(II), Rh(III), and Ru(II) Metal Centers 147 .7.4.2.2 Binuclear Complexes with Ru(II) and Rh(III) Metal Centers 149 .7.4.3 Photosensitizers with a Ru(II) Metal Cenetr Coupled to Other Bioactive Sites 150 .7.4.3.1 Binuclear Complexes with Ru(II) and Cu 150 .7.4.3.2 Binuclear Complexes with Ru(II) and Co(III) Metal Centers 151 .7.4.3.3 Binuclear Complexes with Ru (II) and V(IV) Metal Centers 151 .7.4.3.4 Applications of Ru(II) Metal Centers in Nanomedicine 152 .7.5 Summary and Conclusions 155 .Abbreviations 156 .References 157 .8 Ruthenium Anticancer Agents En Route to the Tumor: From Plasma Protein Binding Agents to Targeted Delivery 161Muhammad Hanif and Christian G. Hartinger .8.1 Introduction 161 .8.2 Protein Binding RuIII Anticancer Drug Candidates 163 .8.2.1 RuIII Anticancer Drug Candidates Targeting Primary Tumors 163 .8.2.2 Antimetastatic RuIII Compounds 165 .8.3 Functionalization of Macromolecular Carrier Systems with Ru Anticancer Agents 166 .8.3.1 Proteins as Delivery Vectors for Organometallic Compounds 166 .8.3.2 Polymers and Liposomes as Delivery Systems for Bioactive Ruthenium Complexes 168 .8.3.3 Dendrimers 169 .8.4 Hormones, Vitamins, and Sugars: Ruthenium Complexes Targeting Small Molecule Receptors 169 .8.5 Peptides as Transporters for Ruthenium Complexes into Tumor Cells and Cell Compartments 173 .8.6 Polynuclear Ruthenium Complexes for the Delivery of a Cytotoxic Payload 174 .8.7 Summary and Conclusions 175 .Acknowledgments 175 .References 176 .9 Design Aspects of Ruthenium Complexes as DNA Probes and Therapeutic Agents 181Madeleine De Beer and Shawn Swavey .9.1 Introduction 181 .9.2 Physical Interaction to Disrupt DNA Structure 181 .9.2.1 Irreversible Covalent Binding 182 .9.2.2 Intercalation 184 .9.2.3 Additional Noncovalent Binding Interactions 185 .9.3 Biological Consequences of Ru–Complex/DNA Interactions 186 .9.4 Effects of Ru Complexes on Topoisomerases and Telomerase 191 .9.5 Summary and Conclusions 196 .References 197 .10 Ruthenium–Based Anticancer Compounds: Insights into Their Cellular Targeting andMechanism of Action 201AntónioMatos, FilipaMendes, Andreia Valente, Tânia Morais, Ana Isabel Tomaz, Philippe Zinck, Maria Helena Garcia, Manuel Bicho, and Fernanda Marques .10.1 Introduction 201 .10.2 Cellular Uptake 204 .10.3 DNA and DNA–Related Cellular Targets 205 .10.4 Targeting Signaling Pathways 207 .10.5 Targeting Enzymes of Specific Cell Functions 207 .10.6 Targeting Glycolytic Pathways 209 .10.7 Macromolecular Ruthenium Conjugates: A New Approach to Targeting 211 .10.8 Conclusions 214 .References 215 .11 Targeting cellular DNA with Luminescent Ruthenium(II) Polypyridyl Complexes 221Martin R. Gill and Jim A. Thomas .11.1 Introduction 221 .11.1.1 DNA–Binding Modes of Small Molecules 222 .11.1.2 Metal Complexes and DNA 223 .11.2 [Ru(bpy)2(dppz)]2+ and the DNA Light–Switch Effect 224 .11.3 Cellular Uptake of RPCs and Application as DNA–Imaging Agents 226 .11.3.1 Mononuclear Complexes 226 .11.3.2 Dinuclear Complexes 228 .11.3.3 Cyclometalated Systems 228 .11.4 Alternative Techniques to Assess Cellular Uptake and Localization 231 .11.5 TowardTheranostics: luminescent RPCs as Anticancer Therapeutics 232 .11.6 Summary and Conclusions 234 .References 235 .12 Biological Activity of Ruthenium ComplexesWith Quinoline Antibacterial and Antimalarial Drugs 239Jakob Kljun and Iztok Turel .12.1 Introduction 239 .12.2 Antibacterial (Fluoro)quinolones 240 .12.2.1 Quinolones and Their Interactions with Metal Ions 241 .12.2.2 Ruthenium and Quinolones 241 .12.2.3 Ruthenium and HIV Integrase Inhibitor Elvitegravir 245 .12.3 Antibacterial 8–Hydroxyquinolines 246 .12.3.1 Mode of Action of 8–Hydroxyquinoline Agents 246 .12.3.2 Ruthenium and 8–Hydroxyquinolines 247 .12.4 Antimalarial 4–Aminoquinolines 248 .12.4.1 Mechanism of Action of Antimalarial Quinoline Agents 248 .12.5 Metallocene Analogues of Chloroquine 249 .12.6 Conclusions 252 .References 252 .13 Ruthenium Complexes as NO Donors: Perspectives and Photobiological Applications 257Loyanne C.B. Ramos, Juliana C. Biazzotto, Juliana A. Uzuelli, Renata G. de Lima, and Roberto S. da Silva .13.1 Introduction 257 .13.2 Photochemical Processes of Some Nitrogen Oxide Derivative Ruthenium Complexes 258 .13.2.1 Metal–Ligand Charge–Transfer Photolysis of {Ru–NO}6 258 .13.2.2 Nitrosyl Ruthenium Complexes: Visible–Light Stimulation 261 .13.3 Photobiological Applications of Nitrogen Oxide Compounds 265 .13.3.1 Photovasorelaxation 265 .References 268 .14 Trends and Perspectives of Ruthenium Anticancer Compounds (Non–PDT) 271Michael A. Jakupec,Wolfgang Kandioller, Beatrix Schoenhacker–Alte, Robert Trondl,Walter Berger, and Bernhard K. Keppler .14.1 Introduction 271 .14.2 Ruthenium(III) Compounds 272 .14.2.1 NAMI–A 273 .14.2.1.1 Biotransformation 273 .14.2.1.2 Antimetastatic Activity 274 .14.2.1.3 Mode of Action 274 .14.2.1.4 Clinical Studies and Perspectives 275 .14.2.2 KP1019/NKP–1339 276 .14.2.2.1 Tumor TargetingMediated by Plasma Proteins 276 .14.2.2.2 Activation by Reduction 277 .14.2.2.3 Mode of Action 278 .14.2.2.4 Clinical Studies and Perspectives 281 .14.3 Organoruthenium(II) Compounds 282 .14.3.1 Ruthenium(II) Arene Compounds in Preclinical Development 282 .14.3.1.1 Organoruthenium Complexes Bearing Bioactive Ligand Scaffolds 284 .14.3.1.2 Cytotoxic Organoruthenium Complexes without Activation by Aquation 285 .References 286 .15 Ruthenium Complexes as Antifungal Agents 293Claudio L. Donnici,Maria H. Araujo, and Maria A. R. Stoianoff .15.1 Introduction 293 .15.2 Antifungal Activity Investigations of Ruthenium Complexes 304 .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, Dinuclearbis– –Diketones and Pentadithiocarbamate Ligands 304 .15.2.2 Aromatic and Heteroaromatic Ligands in Ru Monometallic Centers (Pyridine, Phenantroline, Terpyridine, Quinoline, and Phenazine) 305 .15.2.3 Schiff bases, Thiosemicarbazones, and Chalcones 307 .15.2.3.1 Schiff bases (Tetradentate Salen Like, Tridentate, and bidentate) 307 .15.2.3.2 Thiosemicarbazones 309 .15.2.3.3 Chalcone Derivatives 310 .15.2.4 Other ligands (Dithio–Naphtyl–Benzamide, Arylazo, Catecholamine, Organophosphorated, Hydridotris(pyrazolyl)borate and Bioactive Azole Ligands) 310 .15.3 Conclusion 312 .References 313 .Index 319

• ISBN: 978-3-527-33957-0
• Editorial: Wiley VCH
• Encuadernacion: Cartoné
• Páginas: 344
• Fecha Publicación: 13/12/2017
• Nº Volúmenes: 1
• Idioma: Inglés