Hydrogen sulfide (H2S) is a naturally occurring signaling molecule produced in vivo and plays a pivotal role in regulating a wide array of physiological processes. Additionally, emerging findings have illuminated that many of the biological effects initially attributed to H2S may actually stem from other reactive sulfur species (RSS), including hydropersulfides (RSSH) and various higher-order polysulfur species (RSSnH, RSSnR, and HSnH, where n > 1). These studies have underscored the contributions of these species to essential cellular processes, such as the efficient scavenging of reactive oxygen species and electrophiles, and their influence on mitochondrial function. Nonetheless, the chemistry of RSS remains challenging due to their inherently reactive nature, and their precise measurement within biological systems continues to pose a formidable challenge. This compilation of reprints focuses on recent advancements in the field of H2S/RSS chemical biology. It encompasses original research studies and comprehensive reviews, all geared towards exploring the therapeutic potential of H2S/RSS donors in the treatment of various conditions, including cancer, neurological disorders, and cardiovascular disease. Furthermore, it delves into the molecular mechanisms and physiological roles played by RSS along with the development of methodologies for quantifying and measuring the distribution of RSS within biological systems.

Two decades of research on the signaling capacity of hydrogen sulfide (H2S) in biological systems has led to parallel investigations of other reactive sulfur species (RSS) such as persulfides (RSSH) and polysulfides (RSS[subscript n]R, n>1). The purpose of this dissertation was to develop and assess new investigative tools that selectively detect or effectively deliver RSS under biologically relevant conditions. These chemical tools are of significant interest to the redox and molecular signaling communities and can be used to further define the prevalence, signaling capacity, and therapeutic effects of RSS, representing a significant advancement within the field. In chapter II, we describe the design, synthesis, and examination of an innovative, reaction-based fluorescent probe that exploits the double nucleophilic character of H2S by undergoing an intramolecular cyclization to release a fluorescent reporter. Specifically, we employed a highly unique selenosulfide moiety as a trigger for H2S detection. Given the distinct chemical differences between selenium and sulfur, we reasoned that the selenium half would provide access to chemical probes with high reactivity towards and selectively for H2S. Meanwhile, a suitable handle for improving the physicochemical properties of the probe, including its water solubility, cell permeability, and tissue specificity, could be supplied by the sulfide half. Using this novel design strategy, we successfully produced and assessed two H2S-selective probes: AL1, which displayed good water solubility, cell permeability, and overall biocompatibility, and AL2, which displayed cancer cell specificity. Concomitant to detection, chapter III discusses the synthesis and application of a self-reporting donor (ZL47), sensitive to reactive oxygen species (ROS). To accomplish this, we appended an aryl boronate ester to 7-hydroxycoumarin via an S-alkyl thiocarbonate linker allowing for the simultaneous release of COS, an H2S precursor, and a fluorescent reporter in response to hydrogen peroxide. In addition, we determined that ZL47 was a useful bifunctional tool with an ability to both image and alleviate oxidative stress in live cells, highlighting its potential as a theranostic. Chapter IV describes a novel ROS-activated persulfide donor (RAH393) that operates through a unique mechanistic pathway that avoids the production of a 1,4-quinone methide as a toxic byproduct, a major setback for ZL47 and related donors that employ a 1,6-elimination. In addition to confirming that its lactone byproduct was nontoxic, we were able to demonstrate the impressive cellular protection provided by RAH393 against high concentrations of ROS in live HeLa cells. Because this donor proved to be a valuable tool for generating persulfides in response to ROS, in chapter V, we investigated the therapeutic effects of an analogue that targets mitochondria (Mito-PD), the primary producers of ROS and a known site of RSS oxidation. To accomplish this, the mixed disulfide of RAH393 was modified and equipped with a lipophilic cation to facilitate mitochondrion uptake. Using confocal laser microscopy, we confirmed Mito-PD’s preferential release of persulfides within mitochondria from co-localization studies using AL1 (an H2S-selctive probe) and Mitotracker Red. In addition, we demonstrated that Mito-PD protects cardiomyoblast cells in culture (H9C2) from doxorubicin (DOX)-induced cardiotoxicity. Subsequent studies with JC-1, a fluorescent probe that reports on mitochondrial membrane potential, indicate that Mito-PD effectively preserves the membrane potential of DOX treated cells, increasing their viability. These initial studies highlight the therapeutic benefits of mitochondria-targeting RSS donors and their potential for mitigating DOX-induced cardiotoxicity.

This text focuses on the biological interactions of sulphur compounds which arise specifically from the presence of the sulphur atom within the molecule. The book opens with introductory chapters on the chemistry and biology of sulphur, before tackling the field by introducing compounds which share a common chemical combination. In general, following a description of the uses and impact upon the biological field, specific chemical group characteristics are discussed together with the biological activity and structure-activity relationships where known. The toxicity of such compounds, their consequences in biochemical and clinical terms, and their mechanisms of biological interaction are then addressed.

Maternal-Fetal and Neonatal Endocrinology: Physiology, Pathophysiology, and Clinical Management systematically examines the normal and abnormal endocrinology of the pregnant and lactating female and of the fetus and neonate. This reference volume expands coverage of specific disorders and diseases beyond the current endocrinology content on the market, which in most cases has a paragraph or no mention at all about pregnancy or aspects of fetal/neonatal development. Formalized source of maternal/fetal endocrine physiology and pathophysiology Key reference for fellows and residents for rarer endocrine pathologies Integrated presentation of new molecular and genetic causes of endocrine disorders Bridges the experience/knowledge gap of endocrinopathies rarely encountered in pregnancy

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.

Presents a multidisciplinary analysis of the integration among reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS). Since plants are the main source of our food, the improvement of their productivity is the most important task for plant biologists. In this book, leading experts accumulate the recent development in the research on oxidative stress and approaches to enhance antioxidant defense system in crop plants. They discuss both the plant responses to oxidative stress and mechanisms of abiotic stress tolerance, and cover all of the recent approaches towards understanding oxidative stress in plants, providing comprehensive information about the topics. It also discusses how reactive nitrogen species and reactive sulfur species regulate plant physiology and plant tolerance to environmental stresses. Reactive Oxygen, Nitrogen and Sulfur Species in Plants: Production, Metabolism, Signaling and Defense Mechanisms covers everything readers need to know in four comprehensive sections. It starts by looking at reactive oxygen species metabolism and antioxidant defense. Next, it covers reactive nitrogen species metabolism and signaling before going on to reactive sulfur species metabolism and signaling. The book finishes with a section that looks at crosstalk among reactive oxygen, nitrogen, and sulfur species based on current research done by experts. Presents the newest method for understanding oxidative stress in plants. Covers both the plant responses to oxidative stress and mechanisms of abiotic stress tolerance Details the integration among reactive oxygen species (ROS), reactive nitrogen species (RNS) and reactive sulfur species (RSS) Written by 140 experts in the field of plant stress physiology, crop improvement, and genetic engineering Providing a comprehensive collection of up-to-date knowledge spanning from biosynthesis and metabolism to signaling pathways implicated in the involvement of RONSS to plant defense mechanisms, Reactive Oxygen, Nitrogen and Sulfur Species in Plants: Production, Metabolism, Signaling and Defense Mechanisms is an excellent book for plant breeders, molecular biologists, and plant physiologists, as well as a guide for students in the field of Plant Science.

This book discusses organoselenium chemistry and biology in the context of its therapeutic potential, taking the reader through synthetic techniques, bioactivity and therapeutic applications

This book is based on the papers presented at the "Fourth International Congress on Oxygen Radicals (4-ICOR)," held June 27 - July 3, 1987, at the University of California, La Jolla. The chapters deal with the phenomena associated with highly reactive oxygen species (hydroxy, peroxy, alkoxy, aroxy, and superoxide radicals, as well as singlet oxygen) and their peroxidation products (hydrogen peroxide, hydroperoxides, peroxides, and epoxides) as they relate to the fields of chemistry, food technology, nutrition, biology, pharmacology, and medicine. The kinetics, energetics, and mechanistic aspects of the reactions of these species and the interrelationship of oxygen radicals (or any other free radicals) and peroxidized products have been emphasized. Special attention is focused on the mechanisms of the generation of free radicals and peroxy products in biosystems and on the adverse effects of these radicals and products in humans. The topics span the continuum from the simple chemistry of model systems to the complex considerations of clinical medicine. The book also explores the mechanisms of agents that protect against free radicals and peroxy products in vitro and in vivo. These agents include antioxidants used in materials, food antioxidants, physiological antioxidants, and antioxienzymes (SOD, glutathione peroxidase, and catalases). The use of these inhibitors to prevent damage to organs being prepared for transplantation, thereby maintaining the quality of transplanted organs and/or extending their "shelf-life," also is examined.