Hydrogen Sulfide

MICHAEL D. PLUTH, PhD is a Professor at the University of Oregon in the Department of Chemistry and Biochemistry. He is also a member of the Materials Science Institute, Knight Campus for Accelerating Scientific Impact, and Institute of Molecular Biology at the University of Oregon.

• Preface xviiList of Contributors xix1 Fundamental and Biologically Relevant Chemistry of H2S and Related Species 1Jon M. FukutoList of Abbreviations 11.1 Introduction 21.2 The Chemical Biology of H2S 21.2.1 Basic Chemical Properties of H2S 31.2.2 H2S Redox Chemistry 41.2.3 Reactions of H2S with Metals/Metalloproteins 51.2.4 H2S and Sulfheme Formation 61.2.5 H2S and Heavy Metals 71.3 H2S Reactions with Other Sulfur Species 81.3.1 Sulfane Sulfur 81.3.2 Generation of RSSH 81.3.3 RSH Versus RSSH Comparison 91.3.4 RSSH Interactions with Metals/Metalloproteins 141.3.5 The Electrophilicity of RSSH 141.3.6 Higher-Order Polysulfides 151.3.7 RSSH Instability 161.4 The Biochemical Utility of RSSH 171.5 Summary/Conclusion 18References 182 Signaling by Hydrogen Sulfide (H2S) and Polysulfides (H2Sn) and the Interaction with Other Signaling Pathways 27Hideo KimuraList of Abbreviations 272.1 Introduction 282.2 Determination of the Endogenous Concentrations of H2S 292.3 H2S and H2Sn as Signaling Molecules 312.4 Crosstalk Between H2S and NO 322.4.1 The Chemical Interaction of H2S and NO Produces H2Sn 322.4.2 Regulation of NO-Producing Enzymes by H2S and Vice Versa 332.5 Cytoprotective Effect of H2S, H2Sn, and H2SO3 342.6 Energy Formation in Mitochondria with H2S 342.7 S-Sulfurated Proteins and Bound Sulfane Sulfur in Cells 352.8 Regulating the Activity of Target Proteins by H2S and H2Sn 362.8.1 S-Sulfuration by H2S 372.8.2 S-Sulfuration by H2Sn 382.9 Perspectives 38Acknowledgments 40Author Disclosure Statement 41References 413 Persulfides and Their Reactions in Biological Contexts 49Dayana Benchoam, Ernesto Cuevasanta, Matías N. Möller, and Beatriz AlvarezList of Abbreviations 493.1 Persulfides Are Key Intermediates in Sulfur Metabolism and Signaling 493.2 Persulfides Are Formed in Biological Systems through Different Pathways 513.2.1 Disulfides Form Persulfides in the Presence of H2S 513.2.2 Sulfenic Acids Can Also Form Persulfides by Reaction with H2S 533.2.3 Other Persulfide Formation Pathways Involve Oxidation Products of H2S 533.2.4 Some Sulfur Atoms for Persulfides Are Donated by Free Cysteine 543.2.5 Trisulfides Are Also a Source of Persulfides 553.2.6 Persulfides Can Be Prepared in the Lab 563.3 Persulfides Are More Acidic Than Thiols 563.4 Persulfides Are Stronger Nucleophiles Than Thiols 583.5 Persulfidation Protects Against Irreversible Oxidation 603.6 Persulfides Interact with Metals and Metalloproteins 613.7 Persulfides Have Electrophilic Character in Both Sulfur Atoms 623.8 Persulfides Are Efficient One-Electron Reductants 633.9 Concluding Remarks 64References 644 Hydrogen Sulfide, Reactive Nitrogen Species, and “The Joy of the Experimental Play” 77Miriam M. Cortese-Krott4.1 Introduction 774.2 Basic Physicochemical Properties of Nitric Oxide and Its Biological Relevant Metabolites 794.2.1 Nitric Oxide 794.2.2 Nitrite 804.2.3 Nitrosothiols (RSNOs) 814.3 Basic Physicochemical Properties of H2S and Its Biological Relevant Metabolites 824.3.1 H2S/HS− 834.3.2 Polysulfides and Persulfide 854.4 Inorganic Sulfur–Nitrogen Compounds 864.4.1 HSNO/SNO− 874.4.2 SSNO− 894.4.3 SULFI/NO 904.5 Putative Biological Relevance of the NO/H2S Chemical Interaction 904.5.1 Pharmacological Activity 904.5.2 Putative Sources of SSNO− and SULFI/NO In Vivo 914.5.3 Methods of Detection In Vivo 924.6 Summary and Conclusions 93Acknowledgment 93References 935 H2S and Bioinorganic Metal Complexes 103Zachary J. TonzetichList of Abbreviations 1035.1 Introduction 1045.2 Basic Ligative Properties of H2S/HS− 1055.3 H2S and Heme Iron 1065.4 H2S and Nonheme Iron 1125.5 H2S Chemistry with Other Metals 1225.6 H2S Sensing with Transition Metal Complexes 1265.7 Summary 131Acknowledgments 134References 1346 Measurement of Hydrogen Sulfide Metabolites Using the Monobromobimane Method 143Xinggui Shen, Ellen H. Speers, and Christopher G. KevilList of Abbreviations 1436.1 Introduction 1436.1.1 Hydrogen Sulfide: Biological Significance 1436.1.2 Hydrogen Sulfide Chemistry 1446.1.3 Bioavailable Sulfide 1446.2 Monobromobimane: An Optimal Method of Bioavailable Sulfur Detection 1456.2.1 Monobromobimane Derivatization of Hydrogen Sulfide 1466.2.2 History of the Monobromobimane Method 1476.3 Procedures 1486.3.1 Sulfide-Dibimane Standard Synthesis 1486.3.2 Bioavailable Sulfide Preparation 1496.3.3 Monobromobimane Derivatization 1496.3.4 HPLC with Fluorescence Detection 1506.3.5 Mass Spectrometry Detection 1506.4 Caveats and Considerations 151Acknowledgment 152Disclosures 152References 1527 Fluorescent Probes for H2S Detection: Cyclization-Based Approaches 157Yingying Wang, Yannie Lam, Caitlin McCartney, Brock Brummett, Geat Ramush, and Ming XianList of Abbreviations 1577.1 Introduction 1577.2 General Design of Nucleophilic Reaction-Cyclization Based Fluorescent Probes 1597.2.1 WSP Probes 1597.2.2 2,2′-Dithiosalicylic Ester-Based Probes 1647.2.3 Alkyl Halide-Based Probes 1667.2.4 Diselenide-Based Probes 1677.2.5 Selenenyl Sulfide-Based Probes 1677.2.6 Aldehyde Addition-Based Probes 1697.2.7 Michael Addition-Cyclization Based Probes 1757.3 Conclusions and Perspectives 177Acknowledgments 177References 1778 Fluorescent Probes for H2S Detection: Electrophile-Based Approaches 183Long Yi and Zhen Xi8.1 Introduction 1838.2 Selected Probes Based on Different Reaction Types 1858.2.1 Cleavage of C—O Bond 1858.2.2 Cleavage of C—S Bond 1888.2.3 Cleavage of C—Cl Bond 1908.2.4 Michael Addition 1918.2.5 Cleavage of C—N Bond 1938.2.6 Reduction of Aryl Azide 1938.3 Conclusion and Future Prospects 197References 1999 Fluorescent Probes for H2S Detection: Metal-Based Approaches 203Maria Strianese and Claudio Pellecchia9.1 Introduction 2039.2 Metal Displacement Approach 2059.2.1 Copper-Based Systems 2059.2.2 Zinc-Based Systems 2149.2.3 Different Metal-Based Systems 2169.3 Coordinative-Based Approach 2189.3.1 Metalloporphyrin-Based Systems 2189.3.1.1 Synthetic Systems 2199.3.1.2 Natural Systems 2209.3.2 Salen-Based Systems 2209.3.3 Systems with Different Organic Ligands 2219.4 H2S-Mediated Reduction of the Metal Center 2239.5 Conclusions and Future Outlooks 224References 22510 H2S Release from P=S and Se—S Motifs 235Rynne A. Hankins and John C. Lukesh IIIList of Abbreviations 23510.1 Introduction 23510.2 H2S Release from P=S Motifs 23610.2.1 GYY4137: Synthesis and Characterization of H2S Release 23710.2.2 GYY4137: Biological Studies 23810.2.3 GYY4137: Mechanistic Studies 24010.2.4 GYY4137: Structural Modifications and Activity of Analogs 24210.2.5 JK Donors: Cyclization-Assisted H2S Release from P=S Motifs 24810.3 H2S Release from Se—S Motifs 24910.3.1 Acyl Selenylsulfides: Synthesis and Characterization of H2S Release 25110.3.2 Acyl Selenylsulfides: Mechanistic Studies 25110.4 Acyl Selenylsulfides: Structural Modifications and Activity of Analogs 25310.5 Conclusions 253References 25411 Hydrogen Sulfide: The Hidden Player of Isothiocyanates Pharmacology 261Valentina Citi, Eugenia Piragine, Vincenzo Calderone, and Alma Martelli11.1 Organic Isothiocyanates as H2S-Donors 26111.2 Organic ITCs and Cardiovascular System 26611.2.1 Effect of ITCs as H2S Donors in Vascular Inflammation 26611.2.2 Vasorelaxing Effect of ITCs as H2S Donors 26911.2.3 Organic ITCs and Heart 27011.3 Chemopreventive Properties of ITCs 27211.4 Anti-nociceptive Effects of ITCs 27411.5 Anti-inflammatory and Antiviral Effects of ITCs 27711.6 Conclusion 280Acknowledgment 281References 28112 Persulfide Prodrugs 293Bingchen Yu, Zhengnan Yuan, and Binghe WangList of Abbreviations 29312.1 Introduction 29312.2 Persulfide Prodrugs 29512.2.1 Structural Moieties That Have Been Studied for Their Ability to Cage and Release Persulfide Species 29612.2.2 Enzyme-Sensitive Prodrugs 29812.2.3 ROS-Sensitive Persulfide Prodrugs 30312.2.4 pH-Sensitive Persulfide Prodrugs 30612.2.5 Photo-Sensitive Persulfide Prodrugs 30812.2.6 H2S Prodrugs That Release H2S Via Persulfide Intermediate 30912.3 Challenges in Persulfide Prodrug Design and Potential Therapeutic Applications 310References 31313 COS-Based H2S Donors 321Annie K. Gilbert and Michael D. Pluth13.1 Introduction 32113.2 Properties of COS 32213.3 COS-Based H2S Delivery 32313.3.1 Stimuli Responsive COS/H2S Donors 32513.3.2 Bio-orthogonal Donor Activation 32613.3.3 Donors Activated by Nucleophiles 32913.3.4 Enzyme-Activated Donors 33413.3.5 pH-Activated Donors 33713.3.6 Fluorescent Donors 33913.4 Conclusions and Outlook 341Acknowledgments 342References 34214 Light-Activatable H2S Donors 347Petr Klán, Tomáš Slanina, and Peter Štacko14.1 Introduction 34714.2 Photophysical and Photochemical Concepts 34714.3 Phototherapeutic Window 34914.4 Light Sources 34914.5 (Photo)Physical Properties of H2S 35114.6 Mechanisms and Examples of H2S Photorelease 35114.6.1 Photorelease of H2S from Excited State 35214.6.2 Release of H2S from a Reactive Intermediate 35514.6.3 Photorelease of Potential H2S Donors 35714.6.4 Photosensitized H2S Release 36214.6.5 Photothermal Effect 36414.7 Outlook 365Acknowledgment 366References 36615 Macromolecular and Supramolecular Approaches for H2S Delivery 373Sarah N. Swilley-Sanchez, Zhao Li, and John B. MatsonList of Abbreviations 37315.1 Introduction 37515.2 H2S-Donating Linear Polymers 37715.2.1 Pendant H2S Donors 37815.2.2 H2S Donors on Chain Ends 37915.2.3 Depolymerizable Polymers for the Release of H2S via COS 38315.3 H2S Delivery from Branched and Graft Polymer Topologies 38415.3.1 Graft Polymers for the Delivery of H2S 38615.4 Polymer Micelles for H2S Delivery 38815.4.1 H2S Donors Covalently Attached to Polymer Amphiphiles 38915.5 Polymer Networks for Localized H2S Delivery 39415.5.1 Physical Encapsulation of H2S Donors Within Networks 39415.5.2 Covalent Attachment of H2S Donors Within Hydrogels 39615.6 Other Polymeric Systems for the Encapsulation of H2S Donors 39915.6.1 Microfibers as H2S Donors 40015.6.2 Membranes as H2S Donors 40015.6.3 Microparticles and Nanoparticles as H2S Donors 40115.7 H2S Release via Supramolecular Systems 40415.7.1 Self-Assembled, Peptide-Based Materials for H2S Delivery 40515.7.2 Self-Assembled Nanoparticles and Proteins for H2S Delivery 41015.8 Conclusions and Future Perspectives 414References 41616 H2S and Hypertension 427Vincenzo Brancaleone, Mariarosaria Bucci, and Giuseppe CirinoList of Abbreviations 42716.1 Hypertension, Vascular Homeostasis and Mediators Controlling Blood Pressure 42816.2 Generation of H2S in the Cardiovascular System 42916.2.1 Biosynthetic Pathways 42916.2.2 Catabolic Pathway for H2S 43016.3 Relevance of H2S in Hypertension 43216.3.1 Preclinical Evidence 43216.3.2 Clinical Evidence 43616.4 Conclusions 437References 43817 H2S Supplementation and Augmentation: Approaches for Healthy Aging 445Christopher Hine, Jie Yang, Aili Zhang, Natalia Llarena, and Christopher LinkList of Abbreviations 44517.1 Introduction and Background 44517.1.1 Global Aging Populations 44517.1.2 Pathophysiological Aspects of Aging 44717.1.3 Alterations in Sulfur Amino Acid Metabolism and Hydrogen Sulfide During Aging 44817.1.4 Geroscience Approaches to Address Longevity and Improved Healthspan, and Their Connection to Hydrogen Sulfide 45117.2 Hydrogen Sulfide Metabolism and Applications in Non-mammalian Aging 45417.2.1 Plants 45417.2.2 Bacteria 45417.2.3 Yeast 45517.2.4 Worms 45817.2.5 Flies 45917.3 Hydrogen Sulfide Metabolism and Applications in Nonhuman Mammalian Aging 46017.3.1 Standard Laboratory Rodents (Mice and Rats) 46017.3.2 Naked Mole-Rats 46417.4 Hydrogen Sulfide Metabolism and Applications in Human Aging and Aging-Related Disorders 46417.4.1 Human Exposure to H2S and Advances in Clinical Biomarker and Interventional H2S Approaches 46417.4.2 Cardiovascular Diseases 46717.4.3 Oncological Diseases 46917.5 Conclusions and Summary 472Acknowledgments 472References 47218 Aberrant Hydrogen Sulfide Signaling in Alzheimer’s Disease 489Bindu D. PaulList of Abbreviations 48918.1 Introduction 49018.1.1 Hydrogen Sulfide 49018.1.2 Protein Sulfhydration/Persulfidation 49218.1.3 Reciprocity of Protein Sulfhydration and Nitrosylation 49218.2 Alzheimer’s Disease 49418.2.1 Neuropathology of AD 49418.2.2 H2S Signaling in Alzheimer’s Disease 49618.2.3 Sulfhydration in Aging and AD 49618.3 Therapeutic Avenues 497Acknowledgments 499References 50019 Multifaceted Actions of Hydrogen Sulfide in the Kidney 507Balakuntalam S. Kasinath and Hak Joo LeeList of Abbreviations 50719.1 Introduction 50819.2 H2S Synthesis in the Kidney 50919.3 H2S and Kidney Physiology 51119.4 H2S and the Aging Kidney 51319.5 H2S and Acute Kidney Injury (AKI) 51719.5.1 H2S in AKI Due to Intrinsic Kidney Injury 51719.5.1.1 Ischemia-Induced AKI 51719.5.1.2 Rhabdomyolysis-Induced AKI 51919.5.1.3 Nephrotoxic AKI 51919.5.1.4 Glomerulonephritis-Associated AKI 52019.5.2 H2S in AKI Due to Obstruction of the Genitourinary Tract 52119.5.3 Injurious Role of H2S in AKI 52119.6 H2S in Chronic Kidney Disease (CKD) 52119.6.1 H2S in Obesity-Related CKD 52419.6.2 H2S in Diabetic Kidney Disease (DKD) 52519.6.3 H2S in Congestive Heart Failure (CHF) Associated CKD 53019.7 H2S and Preeclampsia 53019.8 H2S and Genitourinary Cancers 53119.9 Conclusion and Future Directions 531Acknowledgments 532References 532Index 551