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This thesis addresses fundamental scientific questions such as:How are complex natural products synthesized in vivo?Can we replicate these conditions in a laboratory environment?What is the biological function of such secondary metabolites?What are the biological origins of chirality?These issues are explored in an accessible manner using a multidisciplinary approach spanning chemistry, biology and physics to investigate an interesting family of complex natural products isolated from marine molluscs – the tridachiahydropyrones.The work has achieved:Elegant biomimetic syntheses of a number of the tridachiahydropyrone compounds in vitro using organic synthesis techniquesThe characterization of the interactions between these compounds and a range of model membrane systems using a series of fluorescence spectroscopic studiesThe investigation of the antioxidant and photoprotective properties of the compounds by means of biophysical assay techniquesThe synthesis of tridachiahydropyrone utilizing the model membrane systems as biomimetic reaction media.

MILS-15 provides an up-to-date review of the metalloenzymes involved in the activation, production, and conversion of molecular oxygen as well as the functionalization of the chemically inert gases methane and ammonia. Found either in aerobes (humans, animals, plants, microorganisms) or in anaerobes (so-called “impossible bacteria”) these enzymes employ preferentially iron and copper at their active sites, in order to conserve energy by redox-driven proton pumps, to convert methane to methanol, or ammonia to hydroxylamine or other compounds. When it comes to the light-driven production of molecular oxygen, the tetranuclear manganese cluster of photosystem II must be regarded as the key player. However, dioxygen can also be produced in the dark, by heme iron-dependent dismutation of oxyanions. Metalloenzymes Mastering Dioxygen and Other Chewy Gases is a vibrant research area based mainly on structural and microbial biology, inorganic biological chemistry, and environmental biochemistry. All this is covered in an authoritative manner in 7 stimulating chapters, written by 21 internationally recognized experts, and supported by nearly 1100 references, informative tables, and over 140 illustrations (many in color). MILS-15 provides excellent information for teaching; it is also closely related to MILS-14, The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment.Peter M. H. Kroneck is a bioinorganic chemist who is exploring the role of transition metals in biology, with a focus on functional and structural aspects of microbial iron, copper, and molybdenum enzymes and their impact on the biogeochemical cyles of nitrogen and sulfur.Martha E. Sosa Torres is an inorganic chemist, with special interests in magnetic properties of newly synthesized transition metal complexes and their reactivity towards molecular oxygen, applying kinetic, electrochemical, and spectroscopic techniques.

Oxygen free radicals and other reactive oxygen species are being postulated as causal agents in an increasing number of pathological conditions. Indeed, some investigators are suggesting that highly destructive reactive oxygen species are the final common path lead­ ing to tissue damage following a wide variety of insults including trauma, hypoxia, ischemia, hyperoxia, radiation, some toxins, and even strenuous athletic pursuits. But, as Robert Floyd points out,'Proof of the importance of oxygen free radicals and the oxidative damage they initiate depend on unequivocal evidence for the pres­ ence of free radicals and a clear association of their formation with the induction of the dysfunction of pathological conditions.'Since such proof does not come easily, there have been and will continue to be many controversies regarding the role played by reactive oxygen species in tissue damage. There have been many recent reviews of the chemistry and pos­ sible role of reactive oxygen species in many types of organ dys­ functions, tissue damage, degenerative diseases, and aging. This book is not such a review. Rather it presents for a diverse audience of physical-organic chemists, biochemists, medical researchers, and other investigators of pathophysiology, discussions of a variety of is­ sues important for understanding reactive oxygen species and their role in tissue damage.

This book is written for the research biochemist who needs to know more about the particular field of dioxygen metabolism, whether this be for designing lectures for a graduate level course or for his or her own research needs. We hope researchers in a given area of dioxygen metabolism will gain knowledge of related fields of dioxygen metabolism. We have decided to use the term dioxygen to distinguish molecular oxygen from divalent oxygen in water and organic compounds, dioxygen being a simpler term than molecular oxygen. We do not intend to review the metabolism of all compounds that contain oxygen, since this would include all of biochemistry. An understanding of dioxygen chemistry is essential to the discussion of the biochemistry of dioxygen. While this statement could be made about any biochemical constituent, the chemistry of dioxygen is so unusual that interpre­ tations without detailed chemical background are futile. Prediction of dioxygen reaction products by analogy with other oxidants is impossible. The partial reduction products of dioxygen, superoxide ion and peroxides, develop naturally in the chemistry of dioxygen. It would be difficult to discuss dioxygen biochemistry without first discussing these partial reduction products.

Dermatology is a complex and puzzling world of itching bumps, pim­ ples, and rashes. The multitude of clinically distinct skin diseases, their frequently unresolved pathogenesis, and the exponentially in­ creasing amount of scientific information add to the confusion about skin diseases. The great prevalence of skin diseases makes them an urgent priority for intensive research effort, and although many scientists and academic clinicians are vigorously trying to uncover we are only at the very brink of understanding the etiol­ their secrets, ogy of most dermatoses. The principle mechanisms of general organ pathology (physical, chemical, microbial, ischemic, degenerative, and neoplastic disturb­ ances) are believed to be relatively well understood. In contrast to skin pathomorphology, however little is known regarding the bio­ chemistry and physiology of dermatoses. The difficulty in under­ standing skin diseases may be overcome partially by finding biome­ dical simplifications, and the concept of'oxidative injury in dermatopathology'is just such a simplification. It should, of course, always be kept in mind that no single mechanism alone can explain the pathogenesis of a disease and that there may be a danger of over­ looking other important biological determinants.

In this volume the policy of review by anonymous referees and minor correction by the editor has been continued, but perhaps should not be extended without an agreed policy statement by the Society. Our choice is minimal revision with rapid publication or proper review with some delay in publication. The editor wishes to express his gratitude to Ann Richardson, Joann Fish, Lance Johnson, and Philip Weinbrecht for their invaluable help in the preparation of this volume. Ian S. Longmuir v BRIEF HISTORY OF ISOTT The Society endured a long gestation period. During the 1960s its formation was discussed at a number of international meetings devoted to oxygen in biological systems. Prominent among a great number of such gatherings were those held at the Institute of Diseases of the Chest, London 1960; Bedford College, London 1963; Queen Elizabeth College, London 1963; and the Seventh Bad Oeynhausen Conference, 1967. At first, reservations were expressed about the desirability of forming a highly specialized society which might not achieve the'critical mass'necessary for its continued existence. However, the 1971 meeting in the Max Planck Institut fur Arbeitsphysiologie, Dortmund, answered these doubts, and Dr. Melvin Knisely commenced planning a very successful inaugural meeting in South Carolina. At this meeting in 1973 in Charleston and Clemson, the Society was formed with the customary remit of the promotion of scientific exchanges.

Following their own brilliant careers in haeme protein research, the outstanding scientists Jonathan and Beatrice Wittenberg continue to provide inspiration to the research community in the study of oxygen-binding proteins. Their research has provided the intellectual stimulus to bring together scientists from all over the world with the common goal of developing fascinating new ideas and performing innovative experiments. This book is dedicated to Jonathan's and Bea's lifetime careers. It further illuminates the facts and ideas which dot the paths they traced in Biochemistry and Physiology, elaborating on how these landmark achievements were made and how the haeme proteins community still refers to them. With the field of haeme protein science such a flourishing area, the contributors to this book predict Jonathan and Bea, having played such a seminal role, will continue to be key figures for quite some time to come.

Despite its crucial importance, scientists interested in the limitations of human physical performance have only just started to give the field of oxygen uptake kinetics the attention it deserves. Understanding the principal determinant of the oxygen uptake kinetics is fundamental to improving human performance or the quality of life. This book provides a detailed overview of the current state of knowledge of this emerging field of study, and features: • an introduction to oxygen uptake kinetics and historical development of the discipline • measurement and analysis of oxygen uptake kinetics• control of and limitations to oxygen uptake kinetics• applications of oxygen uptake kinetics in a range of human populations.Oxygen Uptake Kinetics in Sport, Health and Medicine is richly illustrated and structured to enable easy access of information and represents an invaluable resource for students and researchers in exercise physiology, as well as for respiratory physiologists and pulmonary clinicians.

The ability of cells to sense and respond to changes in oxygenation underlies a multitude of developmental, physiological, and pathological processes. This volume provides a comprehensive compendium of experimental approaches to the study of oxygen sensing in 48 chapters that are written by leaders in their fields.

This concise, well-focused reference addresses the impact of oxygen on evolution and ontogeny-furnishing both animal and cellular models that investigate the use of oxygen in humans for the treatment of various diseases and conditions.