Hydrogen Sulfide: Chemical Biology Basics, Detecti on Methods, Therapeutic Applications, and Case Stu dies: Wiley Series in Drug Discovery and Development

Preface xvii List of Contributors xix 1 Fundamental and Biologically Relevant Chemistry of H2S and Related Species 1 Jon M. Fukuto List of Abbreviations 1 1.1 Introduction 2 1.2 The Chemical Biology of H2S 2 1.2.1 Basic Chemical Properties of H2S 3 1.2.2 H2S Redox Chemistry 4 1.2.3 Reactions of H2S with Metals/Metalloproteins 5 1.2.4 H2S and Sulfheme Formation 6 1.2.5 H2S and Heavy Metals 7 1.3 H2S Reactions with Other Sulfur Species 8 1.3.1 Sulfane Sulfur 8 1.3.2 Generation of RSSH 8 1.3.3 RSH Versus RSSH Comparison 9 1.3.4 RSSH Interactions with Metals/Metalloproteins 14 1.3.5 The Electrophilicity of RSSH 14 1.3.6 Higher-Order Polysulfides 15 1.3.7 RSSH Instability 16 1.4 The Biochemical Utility of RSSH 17 1.5 Summary/Conclusion 18 References 18 2 Signaling by Hydrogen Sulfide (H2S) and Polysulfides (H2Sn) and the Interaction with Other Signaling Pathways 27 Hideo Kimura List of Abbreviations 27 2.1 Introduction 28 2.2 Determination of the Endogenous Concentrations of H2S 29 2.3 H2S and H2Sn as Signaling Molecules 31 2.4 Crosstalk Between H2S and NO 32 2.4.1 The Chemical Interaction of H2S and NO Produces H2Sn 32 2.4.2 Regulation of NO-Producing Enzymes by H2S and Vice Versa 33 2.5 Cytoprotective Effect of H2S, H2Sn, and H2SO3 34 2.6 Energy Formation in Mitochondria with H2S 34 2.7 S-Sulfurated Proteins and Bound Sulfane Sulfur in Cells 35 2.8 Regulating the Activity of Target Proteins by H2S and H2Sn 36 2.8.1 S-Sulfuration by H2S 37 2.8.2 S-Sulfuration by H2Sn 38 2.9 Perspectives 38 Acknowledgments 40 Author Disclosure Statement 41 References 41 3 Persulfides and Their Reactions in Biological Contexts 49 Dayana Benchoam, Ernesto Cuevasanta, Matías N. Möller, and Beatriz Alvarez List of Abbreviations 49 3.1 Persulfides Are Key Intermediates in Sulfur Metabolism and Signaling 49 3.2 Persulfides Are Formed in Biological Systems through Different Pathways 51 3.2.1 Disulfides Form Persulfides in the Presence of H2S 51 3.2.2 Sulfenic Acids Can Also Form Persulfides by Reaction with H2S 53 3.2.3 Other Persulfide Formation Pathways Involve Oxidation Products of H2S 53 3.2.4 Some Sulfur Atoms for Persulfides Are Donated by Free Cysteine 54 3.2.5 Trisulfides Are Also a Source of Persulfides 55 3.2.6 Persulfides Can Be Prepared in the Lab 56 3.3 Persulfides Are More Acidic Than Thiols 56 3.4 Persulfides Are Stronger Nucleophiles Than Thiols 58 3.5 Persulfidation Protects Against Irreversible Oxidation 60 3.6 Persulfides Interact with Metals and Metalloproteins 61 3.7 Persulfides Have Electrophilic Character in Both Sulfur Atoms 62 3.8 Persulfides Are Efficient One-Electron Reductants 63 3.9 Concluding Remarks 64 References 64 4 Hydrogen Sulfide, Reactive Nitrogen Species, and "The Joy of the Experimental Play" 77 Miriam M. Cortese-Krott 4.1 Introduction 77 4.2 Basic Physicochemical Properties of Nitric Oxide and Its Biological Relevant Metabolites 79 4.2.1 Nitric Oxide 79 4.2.2 Nitrite 80 4.2.3 Nitrosothiols (RSNOs) 81 4.3 Basic Physicochemical Properties of H2S and Its Biological Relevant Metabolites 82 4.3.1 H2S/HS. 83 4.3.2 Polysulfides and Persulfide 85 4.4 Inorganic Sulfur-Nitrogen Compounds 86 4.4.1 HSNO/SNO. 87 4.4.2 SSNO. 89 4.4.3 SULFI/NO 90 4.5 Putative Biological Relevance of the NO/H2S Chemical Interaction 90 4.5.1 Pharmacological Activity 90 4.5.2 Putative Sources of SSNO. and SULFI/NO In Vivo 91 4.5.3 Methods of Detection In Vivo 92 4.6 Summary and Conclusions 93 Acknowledgment 93 References 93 5 H2S and Bioinorganic Metal Complexes 103 Zachary J. Tonzetich List of Abbreviations 103 5.1 Introduction 104 5.2 Basic Ligative Properties of H2S/HS. 105 5.3 H2S and Heme Iron 106 5.4 H2S and Nonheme Iron 112 5.5 H2S Chemistry with Other Metals 122 5.6 H2S Sensing with Transition Metal Complexes 126 5.7 Summary 131 Acknowledgments 134 References 134 6 Measurement of Hydrogen Sulfide Metabolites Using the Monobromobimane Method 143 Xinggui Shen, Ellen H. Speers, and Christopher G. Kevil List of Abbreviations 143 6.1 Introduction 143 6.1.1 Hydrogen Sulfide: Biological Significance 143 6.1.2 Hydrogen Sulfide Chemistry 144 6.1.3 Bioavailable Sulfide 144 6.2 Monobromobimane: An Optimal Method of Bioavailable Sulfur Detection 145 6.2.1 Monobromobimane Derivatization of Hydrogen Sulfide 146 6.2.2 History of the Monobromobimane Method 147 6.3 Procedures 148 6.3.1 Sulfide-Dibimane Standard Synthesis 148 6.3.2 Bioavailable Sulfide Preparation 149 6.3.3 Monobromobimane Derivatization 149 6.3.4 HPLC with Fluorescence Detection 150 6.3.5 Mass Spectrometry Detection 150 6.4 Caveats and Considerations 151 Acknowledgment 152 Disclosures 152 References 152 7 Fluorescent Probes for H2S Detection: Cyclization-Based Approaches 157 Yingying Wang, Yannie Lam, Caitlin McCartney, Brock Brummett, Geat Ramush, and Ming Xian List of Abbreviations 157 7.1 Introduction 157 7.2 General Design of Nucleophilic Reaction-Cyclization Based Fluorescent Probes 159 7.2.1 WSP Probes 159 7.2.2 2,2'-Dithiosalicylic Ester-Based Probes 164 7.2.3 Alkyl Halide-Based Probes 166 7.2.4 Diselenide-Based Probes 167 7.2.5 Selenenyl Sulfide-Based Probes 167 7.2.6 Aldehyde Addition-Based Probes 169 7.2.7 Michael Addition-Cyclization Based Probes 175 7.3 Conclusions and Perspectives 177 Acknowledgments 177 References 177 8 Fluorescent Probes for H2S Detection: Electrophile-Based Approaches 183 Long Yi and Zhen Xi 8.1 Introduction 183 8.2 Selected Probes Based on Different Reaction Types 185 8.2.1 Cleavage of C--O Bond 185 8.2.2 Cleavage of C--S Bond 188 8.2.3 Cleavage of C--Cl Bond 190 8.2.4 Michael Addition 191 8.2.5 Cleavage of C--N Bond 193 8.2.6 Reduction of Aryl Azide 193 8.3 Conclusion and Future Prospects 197 References 199 9 Fluorescent Probes for H2S Detection: Metal-Based Approaches 203 Maria Strianese and Claudio Pellecchia 9.1 Introduction 203 9.2 Metal Displacement Approach 205 9.2.1 Copper-Based Systems 205 9.2.2 Zinc-Based Systems 214 9.2.3 Different Metal-Based Systems 216 9.3 Coordinative-Based Approach 218 9.3.1 Metalloporphyrin-Based Systems 218 9.3.1.1 Synthetic Systems 219 9.3.1.2 Natural Systems 220 9.3.2 Salen-Based Systems 220 9.3.3 Systems with Different Organic Ligands 221 9.4 H2S-Mediated Reduction of the Metal Center 223 9.5 Conclusions and Future Outlooks 224 References 225 10 H2S Release from P=S and Se--S Motifs 235 Rynne A. Hankins and John C. Lukesh III List of Abbreviations 235 10.1 Introduction 235 10.2 H2S Release from P=S Motifs 236 10.2.1 GYY4137: Synthesis and Characterization of H2S Release 237 10.2.2 GYY4137: Biological Studies 238 10.2.3 GYY4137: Mechanistic Studies 240 10.2.4 GYY4137: Structural Modifications and Activity of Analogs 242 10.2.5 JK Donors: Cyclization-Assisted H2S Release from P=S Motifs 248 10.3 H2S Release from Se--S Motifs 249 10.3.1 Acyl Selenylsulfides: Synthesis and Characterization of H2S Release 251 10.3.2 Acyl Selenylsulfides: Mechanistic Studies 251 10.4 Acyl Selenylsulfides: Structural Modifications and Activity of Analogs 253 10.5 Conclusions 253 References 254 11 Hydrogen Sulfide: The Hidden Player of Isothiocyanates Pharmacology 261 Valentina Citi, Eugenia Piragine, Vincenzo Calderone, and Alma Martelli 11.1 Organic Isothiocyanates as H2S-Donors 261 11.2 Organic ITCs and Cardiovascular System 266 11.2.1 Effect of ITCs as H2S Donors in Vascular Inflammation 266 11.2.2 Vasorelaxing Effect of ITCs as H2S Donors 269 11.2.3 Organic ITCs and Heart 270 11.3 Chemopreventive Properties of ITCs 272 11.4 Anti-nociceptive Effects of ITCs 274 11.5 Anti-inflammatory and Antiviral Effects of ITCs 277 11.6 Conclusion 280 Acknowledgment 281 References 281 12 Persulfide Prodrugs 293 Bingchen Yu, Zhengnan Yuan, and Binghe Wang List of Abbreviations 293 12.1 Introduction 293 12.2 Persulfide Prodrugs 295 12.2.1 Structural Moieties That Have Been Studied for Their Ability to Cage and Release Persulfide Species 296 12.2.2 Enzyme-Sensitive Prodrugs 298 12.2.3 ROS-Sensitive Persulfide Prodrugs 303 12.2.4 pH-Sensitive Persulfide Prodrugs 306 12.2.5 Photo-Sensitive Persulfide Prodrugs 308 12.2.6 H2S Prodrugs That Release H2S Via Persulfide Intermediate 309 12.3 Challenges in Persulfide Prodrug Design and Potential Therapeutic Applications 310 References 313 13 COS-Based H2S Donors 321 Annie K. Gilbert and Michael D. Pluth 13.1 Introduction 321 13.2 Properties of COS 322 13.3 COS-Based H2S Delivery 323 13.3.1 Stimuli Responsive COS/H2S Donors 325 13.3.2 Bio-orthogonal Donor Activation 326 13.3.3 Donors Activated by Nucleophiles 329 13.3.4 Enzyme-Activated Donors 334 13.3.5 pH-Activated Donors 337 13.3.6 Fluorescent Donors 339 13.4 Conclusions and Outlook 341 Acknowledgments 342 References 342 14 Light-Activatable H2S Donors 347 Petr Klán, Tomás Slanina, and Peter Stacko 14.1 Introduction 347 14.2 Photophysical and Photochemical Concepts 347 14.3 Phototherapeutic Window 349 14.4 Light Sources 349 14.5 (Photo)Physical Properties of H2S 351 14.6 Mechanisms and Examples of H2S Photorelease 351 14.6.1 Photorelease of H2S from Excited State 352 14.6.2 Release of H2S from a Reactive Intermediate 355 14.6.3 Photorelease of Potential H2S Donors 357 14.6.4 Photosensitized H2S Release 362 14.6.5 Photothermal Effect 364 14.7 Outlook 365 Acknowledgment 366 References 366 15 Macromolecular and Supramolecular Approaches for H2S Delivery 373 Sarah N. Swilley-Sanchez, Zhao Li, and John B. Matson List of Abbreviations 373 15.1 Introduction 375 15.2 H2S-Donating Linear Polymers 377 15.2.1 Pendant H2S Donors 378 15.2.2 H2S Donors on Chain Ends 379 15.2.3 Depolymerizable Polymers for the Release of H2S via COS 383 15.3 H2S Delivery from Branched and Graft Polymer Topologies 384 15.3.1 Graft Polymers for the Delivery of H2S 386 15.4 Polymer Micelles for H2S Delivery 388 15.4.1 H2S Donors Covalently Attached to Polymer Amphiphiles 389 15.5 Polymer Networks for Localized H2S Delivery 394 15.5.1 Physical Encapsulation of H2S Donors Within Networks 394 15.5.2 Covalent Attachment of H2S Donors Within Hydrogels 396 15.6 Other Polymeric Systems for the Encapsulation of H2S Donors 399 15.6.1 Microfibers as H2S Donors 400 15.6.2 Membranes as H2S Donors 400 15.6.3 Microparticles and Nanoparticles as H2S Donors 401 15.7 H2S Release via Supramolecular Systems 404 15.7.1 Self-Assembled, Peptide-Based Materials for H2S Delivery 405 15.7.2 Self-Assembled Nanoparticles and Proteins for H2S Delivery 410 15.8 Conclusions and Future Perspectives 414 References 416 16 H2S and Hypertension 427 Vincenzo Brancaleone, Mariarosaria Bucci, and Giuseppe Cirino List of Abbreviations 427 16.1 Hypertension, Vascular Homeostasis and Mediators Controlling Blood Pressure 428 16.2 Generation of H2S in the Cardiovascular System 429 16.2.1 Biosynthetic Pathways 429 16.2.2 Catabolic Pathway for H2S 430 16.3 Relevance of H2S in Hypertension 432 16.3.1 Preclinical Evidence 432 16.3.2 Clinical Evidence 436 16.4 Conclusions 437 References 438 17 H2S Supplementation and Augmentation: Approaches for Healthy Aging 445 Christopher Hine, Jie Yang, Aili Zhang, Natalia Llarena, and Christopher Link List of Abbreviations 445 17.1 Introduction and Background 445 17.1.1 Global Aging Populations 445 17.1.2 Pathophysiological Aspects of Aging 447 17.1.3 Alterations in Sulfur Amino Acid Metabolism and Hydrogen Sulfide During Aging 448 17.1.4 Geroscience Approaches to Address Longevity and Improved Healthspan, and Their Connection to Hydrogen Sulfide 451 17.2 Hydrogen Sulfide Metabolism and Applications in Non-mammalian Aging 454 17.2.1 Plants 454 17.2.2 Bacteria 454 17.2.3 Yeast 455 17.2.4 Worms 458 17.2.5 Flies 459 17.3 Hydrogen Sulfide Metabolism and Applications in Nonhuman Mammalian Aging 460 17.3.1 Standard Laboratory Rodents (Mice and Rats) 460 17.3.2 Naked Mole-Rats 464 17.4 Hydrogen Sulfide Metabolism and Applications in Human Aging and Aging-Related Disorders 464 17.4.1 Human Exposure to H2S and Advances in Clinical Biomarker and Interventional H2S Approaches 464 17.4.2 Cardiovascular Diseases 467 17.4.3 Oncological Diseases 469 17.5 Conclusions and Summary 472 Acknowledgments 472 References 472 18 Aberrant Hydrogen Sulfide Signaling in Alzheimer's Disease 489 Bindu D. Paul List of Abbreviations 489 18.1 Introduction 490 18.1.1 Hydrogen Sulfide 490 18.1.2 Protein Sulfhydration/Persulfidation 492 18.1.3 Reciprocity of Protein Sulfhydration and Nitrosylation 492 18.2 Alzheimer's Disease 494 18.2.1 Neuropathology of AD 494 18.2.2 H2S Signaling in Alzheimer's Disease 496 18.2.3 Sulfhydration in Aging and AD 496 18.3 Therapeutic Avenues 497 Acknowledgments 499 References 500 19 Multifaceted Actions of Hydrogen Sulfide in the Kidney 507 Balakuntalam S. Kasinath and Hak Joo Lee List of Abbreviations 507 19.1 Introduction 508 19.2 H2S Synthesis in the Kidney 509 19.3 H2S and Kidney Physiology 511 19.4 H2S and the Aging Kidney 513 19.5 H2S and Acute Kidney Injury (AKI) 517 19.5.1 H2S in AKI Due to Intrinsic Kidney Injury 517 19.5.1.1 Ischemia-Induced AKI 517 19.5.1.2 Rhabdomyolysis-Induced AKI 519 19.5.1.3 Nephrotoxic AKI 519 19.5.1.4 Glomerulonephritis-Associated AKI 520 19.5.2 H2S in AKI Due to Obstruction of the Genitourinary Tract 521 19.5.3 Injurious Role of H2S in AKI 521 19.6 H2S in Chronic Kidney Disease (CKD) 521 19.6.1 H2S in Obesity-Related CKD 524 19.6.2 H2S in Diabetic Kidney Disease (DKD) 525 19.6.3 H2S in Congestive Heart Failure (CHF) Associated CKD 530 19.7 H2S and Preeclampsia 530 19.8 H2S and Genitourinary Cancers 531 19.9 Conclusion and Future Directions 531 Acknowledgments 532 References 532 Index 551