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Hydrogen Sulfide. Chemical Biology Basics, Detection Methods, Therapeutic Applications, and Case Studies. Edition No. 1. Wiley Series in Drug Discovery and Development

  • Book

  • 560 Pages
  • November 2022
  • John Wiley and Sons Ltd
  • ID: 5839795
HYDROGEN SULFIDE

Covers H2S interactions, methods of detection and delivery in biological environments, and a wide range of applications

Research on hydrogen sulfide (H2S) spans diverse disciplines including chemistry, biology, and physiology. In recent years, new materials and approaches have been developed to deliver H2S and related reactive sulfur species in various clinical contexts. Although many biological pathways involving H2S are complex, all are governed by fundamental chemical interactions between reactive sulfur species and other molecular entities.

Hydrogen Sulfide: Chemical Biology Basics, Detection Methods, Therapeutic Applications, and Case Studies provides the foundation required for understanding the fundamental chemical biology of H2S while highlighting the compound’s therapeutic potential and medicinal applications. This book covers key aspects of H2S chemical biology, including the fundamental chemistry of reactive sulfur species; the measurement, detection, and delivery of H2S in biological environments; and the therapeutic and medicinal uses of exogenous H2S delivery in various pharmacologically relevant systems. Throughout the text, editor Michael Pluth and chapter contributors discuss the opportunities and future of the multidisciplinary field. - Provides approaches for delivering H2S with relevance to biological and therapeutic applications - Describes complex interactions of H2S with bioinorganic complexes and reactive sulfur, nitrogen, and oxygen species - Summarizes advances in available tools to detect, measure, and modulate H2S levels in biological environments, such as real-time methods for H2S fluorescence imaging in live cell and animal systems - Helps readers understand known systems and make connections to new and undiscovered pathways and mechanisms of action - Includes in-depth case studies of different systems in which H2S plays an important role

Hydrogen Sulfide: Chemical Biology Basics, Detection Methods, Therapeutic Applications, and Case Studies is an important source of current knowledge for researchers, academics, graduate students, and industrial scientists in the fields of redox biology, hydrogen sulfide research, and medicinal chemistry of small biological molecules.

Table of Contents

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, Tomáš Slanina, and Peter Štacko

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

Authors

Michael D. Pluth