The remarkable development of molecular biology has had its counterpart in an impressive growth of a segment of biology that might be described as atomic biology. The past several decades have witnessed an explosive growth in our knowledge of the many elements that are essential for life and maintenance of plants and animals. These essential elements include the bulk elements (hydro gen, carbon, nitrogen, oxygen, and sulfur), the macrominerals (sodium, potas sium, calcium, magnesium, chloride, and phosphorus), and the trace elements. This last group includes the ultra trace elements and iron, zinc, and copper. Only the ultratrace elements are featured in this book. Iron has attracted so much research that two volumes are devoted to this metal-The Biochemistry of Non-Heme Iron by A. Bezkoravainy, Plenum Press, 1980, and The Biochemistry of Heme Iron (in preparation). Copper and zinc are also represented by a separate volume in this series. The present volume begins with a discussion of essentiality as applied to the elements and a survey of the entire spectrum of possible required elements.

The present book might be regarded as a sequel to my previous work, Bioinorganic Chemistry: An Introduction (Allyn and Bacon, 1977). The latter is essentially a collection of chemical and physical data pertinent to an understanding of the biological functions of the various elements and the proteins dependent on them. The ten years since its publication have seen an enormous increase in research activity in this area, hence of research papers. A number of monographs and review series on specific topics have also appeared, including the volumes in the series of which the present volume is a part. Nevertheless, a gap has developed between the flood of information available at a detailed level (papers and reviews) and a general description of the underlying principles of biofunctions of the elements as presently conceived. It is hoped that this book will help bridge this gap and at the same time provide an overview of the entire Biochemistry of the Elements series. Specifically, the work attempts to focus on "why" questions, especially, "Why has an element been chosen by organisms for a specific biofunction?" and "Why does an element behave the way it does in biological systems?" It therefore complements my 1977 book and, together with Laboratory Introduction to Bio-Inorganic Chemistry (E. -I. Ochiai and D. R. Williams, Macmillan, 1979), completes a trilogy on the topic of bioinorganic chemistry. This book consists of five parts. Two chapters constitute Part I.

There can be few elements with a biochemistry as coherent as that of sulfur. This important element is crucial to myriad aspects of metabo lism, catalysis, and structure. The plurality of functions in which sulfur is involved derives squarely from the numerous oxidation states in which it may exist, some having great stability, some being capable of ready redox interconversions, and yet others having great instability. As a result, the flux of sulfur from the geosphere through the various kingdoms of life leaves few biochemical processes unaffected. Although there are large gaps in the fabric of our basic knowledge of sulfur biochemistry, it is sufficiently framed to allow a unified and organized story, a story which many of the best-known names in bio chemistry have helped to write. It has been both a task and a privilege to try and summarize this story, one that is enormous, complex, fast moving, still developing and, above all, exciting. I suppose that no mo nographer of such a vast subject could be satisfied with his efforts. It is unfortunately probable that in attempting this task I have made as many errors as a Stilton cheese has blue streaks, and as many omissions as a Swiss cheese has holes. Perfection is not to be achieved in a monograph. Inasmuch as I have succeeded, the credit belongs to those whose efforts gave us the knowledge we have. Where I have failed, the fault is only mine.

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.

Biochemistry of Halogenated Organic Compounds has been written as a general reference source for researchers in several related areas, including organic chemists, medicinal chemists, pharmacologists, toxicologists, and medical researchers. The development of halogenated compounds as medicinal agents and pharmacological tools and the fascinating biochemi cal processes that have been discovered and studied using these analogues have generated extremely active areas of research and an enormous volume of literature. Thus, halogenated organic compounds pervade every aspect of biochemistry, a fact made apparent by the numerous reviews and monographs available on individual topics-halogenated nucleosides, halogenated carbohydrates, and so forth. Given the quantity of material already written on these topics, some of which material is quite current, it might be asked whether a one-volume review of these subjects is useful, or possible. Having now completed this work, I feel the answer to both questions is an emphatic yes. There are fascinating stories to be related in each area, and, where appropriate, I have attempted to develop these topics . from a historical perspective. For example, the discovery of the anticancer activity of fluorouracil, the unraveling of the several mechanisms of its action, and the development of a host of later generations of anticancer and antiviral agents based on the parent fluoro-, iodo-, bromo-, and trifluoromethylpyrimidines were, and are, contributions of major magnitude to medical science.

The elements in group 17 (VIlA) of the periodic table of elements-fluorine (F), chlorine (CI), bromine (Br), and iodine (I)-were designated by Berzelius as "halogens" (Greek hals, sea salt; gennao, I beget) because of their propensity to form salts. In this first of the two volumes of Bio chemistry of the Halogens, the biochemistry of the elemental halogens and inorganic halides is reviewed. Discovery, properties, and biochemistry of the elemental halogens are reviewed first (Chapter 1). This is followed by a review of the developments in the various areas of inorganic halide biochemistry (Chapters 2 through 5). The biochemistry of thyroid hor mones is considered in Chapter 6, while biohalogenation, an important link between inorganic and organic halogen biochemistry, is reviewed in Chapter 7. Chapter 8 covers the biochemistry of products produced by human-inspired halogenation, in particular, poly halogenated compounds that present environmental problems. In Chapter 9, the process is reversed and biodehalogenation is reviewed. In each subject, the attempt has been made to find an appropriate balance between depth and breadth of treatment, since a thorough, in depth review of this field would not be possible in a single volume. To provide readers not familiar with subjects with the necessary background to place subsequent discussions in perspective, brief historical develop ments of many of the topics are given.