Metal Ions and Their Complexes in Medication

530 Pages·2004·23.387 MB·English

by  Astrid Sigel

METAL IONS IN
BIOLOGICAL SYSTEMS
Edited by
Astrid Sigel
and Helmut Sigel
Department of Chemistry
Inorganic Chemistry
University of Basel
CH-4056 Basel, Switzerland
VOLUME 41
Metal Ions and
Their Complexes in Medication
MARCEL DEKKER, INC., NEW YORK • BASEL
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Copyright © 2004 by Marcel Dekker, Inc. All Rights Reserved.
ISBN: 0-8247-5351-8
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Preface to the Series
Recently, the importance of metal ions to the vital functions of living
organisms, hence their health and well-being, has become increasingly
apparent. As a result, the long-neglected field of "bioinorganic chemistry"
is now developing at a rapid pace. The research centers on the synthesis,
stability, formation, structure, and reactivity of biological metal ion-
containing compounds of low and high molecular weight. The metabolism
and transport of metal ions and their complexes is being studied, and new
models for complicated natural structures and processes are being devised
and tested. The focal point of our attention is the connection between the
chemistry of metal ions and their role for life.
No doubt, we are only at the brink of this process. Thus, it is with
the intention of linking coordination chemistry and biochemistry in their
widest sense that the Metal Ions in Biological Systems series reflects the
growing field of "bioinorganic chemistry". We hope, also, that this series
will help to break down the barriers between the historically separate
spheres of chemistry, biochemistry, biology, medicine, and physics, with
the expectation that a good deal of future outstanding discoveries will be
made in the interdisciplinary areas of science.
Should this series prove a stimulus for new activities in this fascinating
"field", it would serve its purpose and would be a satisfactory result for the
efforts spent by the authors.
Fall 1973 Helmut Sigel
Department of Chemistry
Inorganic Chemistry
University of Basel
CH-4056 Basel, Switzerland
Copyright © 2004 by Marcel Dekker, Inc. All Rights Reserved.
Preface to Volume 41
This volume on Metal Ions and Their Complexes in Medication opens
with a general chapter on the Speciation Dependent Intake and Uptake
of Essential Elements. When 'life' on this planet began about 3.5 billion
years ago, the primitive cells evolving in oceans used the elements
readily available in the ancient seas and sea-beds. This is still reflected
in the composition of the modern human body, which resembles the
composition of these primitive synthetic arenas, with the lighter elements
of the periodic table (atomic no < 35) being dominant. These elements
and their properties are shortly summarized in this introductory chapter
and the importance of speciation, i.e., the occurrence of an element in
separate, identifiable forms defining the oxidation state, concentration,
and composition of each of the species present, is emphasized. Thus,
speciation provides the explanation why some compounds, e.g., are
'taken up' and easily traverse membranes which others, despite their
'intake', don't. Speciation is clearly an interdisciplinary topic and its
pivotal role in a healthy life and diet reflects the fact that 'the greater the
challenge, the greater the need for metal ions' since 'whenever nature
has a difficult task to perform, a metal ion (or a cluster of such ions) is
invariably employed'.
In accord herewith, in the first part of the volume benign metal
ions, which are hardly toxic but can be deficient, are dealt with; e.g.,
magnesium(II) is an essential nutrient with a variety of pharmacological
effects; it is beneficial inter alia in cardiovascular disorders, allergic
reactions, and acute asthma. Calcium(II) is another example: about 99%
of it are localized in the skeleton as hydroxyapatite, yet the extracellular
Copyright © 2004 by Marcel Dekker, Inc. All Rights Reserved.
ionized fraction is involved in many physiological functions, such as
muscle contraction, neuronal activity, cellular permeability, hormone
secretion, and enzyme activity. Considering that the daily intake may
vary dramatically, even in a given population, calcium status and
supplementation deserve recognition, also in view of the potential
prevention of osteoporosis. This also holds for zinc(II), which was shown
by Raulin in 1869 to be essential for the growth of Aspergillus niger,
but only about 100 years later it became apparent that zinc deficiency in
humans is quite prevalent and that supplementation, not only due to its
positive effects on wound healing, may be desirable in certain instances.
With iron the situation is quite different: both, deficiency and overload
cause serious problems and indeed, disorders of iron metabolism in man
are relatively common. Iron uptake in the presence of dioxygen, due to the
special chemical properties of this element, is not trivial, as is illustrated
by the fact that already Escherichia coli devotes nearly 50 genes to
proteins involved in iron uptake. Since iron excretion in man is almost
non-existent, iron balance is determined primarily by iron absorption
even though a delicate balance, referred to as iron homeostasis, needs
to be achieved. These difficulties including the potential applications
of chelation therapy for the removal of toxic iron are discussed in
Chapter 6.
In the second part of the volume metal-based medications are
considered such as the (potential) use of vanadium compounds in
the treatment of diabetes mellitus, of copper and zinc complexes as
antiinflammatory drugs, of gold complexes in the treatment of rheumatoid
arthritis, and the medical use of lithium salts in the treatment of manic-
depressive patients and beyond, as well as the role of bismuth compounds
in medicine, in particular in gastrointestinal disorders. In fact, the use
of metal complexes as chemotherapeutic agents has gained momentum
in the last decades, mainly as a result of the success of cisplatin as
an antitumor agent; this and related compounds are considered in the
following volume (No 42) entitled Metal Complexes in Tumor Diagnosis
and as Anticancer Agents. Unfortunately the use of metal complexes in
the treatment of tropical parasitic diseases has not advanced to the same
degree, despite the fact that these diseases have been identified among
the most important world health problems. The present knowledge on
Copyright © 2004 by Marcel Dekker, Inc. All Rights Reserved.
metal-based chemotherapeutic agents against malaria, trypanosomiasis,
and leishmaniasis is covered in Chapter 12.
The terminating chapter of Volume 41 is devoted to another most
fascinating topic, namely the use of Metal Complexes as Therapeutic
Agents in Nitrogen Monoxide Modulation. One of the recent most
significant discoveries in biological inorganic chemistry is the role
that the simple diatomic nitrogen monoxide molecule (NO) has as a
cell signalling and regulatory species in the cardiovascular system, and
peripheral and central nervous system, and also as a component of the
immune system. Indeed, disruption of the NO signalling pathway has
been implicated in the pathophysiology of many disease states and this
has led to studies on the potential use of metal complexes as NO donors
as well as NO scavengers; the corresponding state of the art is evaluated
in this chapter.
Astrid Sigel
Helmut Sigel
Copyright © 2004 by Marcel Dekker, Inc. All Rights Reserved.
Contents
PREFACE TO THE SERIES
PREFACE TO VOLUME 41
CONTRIBUTORS
CONTENTS OF PREVIOUS VOLUMES
HANDBOOK NO TOXICITY OF INORGANIC COMPOUNDS
HANDBOOK ON METALS IN CLINICAL AND
ANALYTICAL CHEMISTRY
HANDBOOK ON METALLOPROTEINS
Chapter 1
SPECIATION DEPENDENT INTAKE AND UPTAKE OF
ESSENTIAL ELEMENTS
Janette Davidge and David R. Williams
1. Introduction
2. Elements in Humans
3. Speciation
4. Optimizing Intakes and Uptakes
5. Commercial Element Supplementation
6. Conclusions
Acknowledgments
Abbreviations and Definitions
References
Chapter 2
MAGNESIUM IN HUMAN THERAPY
Hans-Georg Classen, Heimo Franz Schimatschek, andKonrad Wink
1. Early Roots
Copyright © 2004 by Marcel Dekker, Inc. All Rights Reserved.
2. Magnesium Therapy
3. Magnesium in Obstetrics and Gynecology
4. Magnesium in Pediatrics
5. Magnesium in Neurology and Psychiatry
6. Magnesium in Cardiovascular Disorders and Hypertension
7. Renal Magnesium Wasting
8. Magnesium and Allergic Reactions, Acute Asthma
9. Safety Aspects
Abbreviations
References
Chapter 3
CALCIUM STATUS AND SUPPLEMENTATION
Lasse Larsson and Per Magnusson
1. Introduction: General Importance of Calcium
2. Calcium Homeostasis
3. Disturbances in Calcium Absorption
4. Renal Regulation of Calcium
5. Bone and Mineral Metabolism
6. Genetics in Calcium Homeostasis
7. Calcium Intake and Supplementation
3. General Conclusions
Abbreviations
References
Chapter 4
ZINC DEFICIENCY: ITS CHARACTERIZATION
AND TREATMENT
Ananda S. Prasad
1. Brief History of the Discovery of Zinc as an Essential
Element for Human Health
2. Clinical Effects of Zinc Deficiency
3. Major Effects of Zinc Deficiency in Humans
4. Diagnostic Criteria for Zinc Deficiency
5. Therapeutic Uses of Zinc
6. Toxicity of Zinc
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7. Conclusion
Abbreviations
References
Chapter 5
THE USE AND ROLE OF ZINC AND ITS COMPOUNDS
IN WOUND HEALING
Paul W. Jones and David R. Williams
1. Introduction
2. The Anatomy and Functions of the Skin
3. The Physiology of Wound Healing
4. Zinc and Wound Healing
5. Wound Management Products and Treatments Containing Zinc
6. Innovations in Trace Element Based Wound Management
7. Conclusions
Abbreviations
References
Chapter 6
IRON CHELATORS AND THEIR THERAPEUTIC POTENTIAL
Robert R. Crichton and Roberta J. Ward
1. Introduction: The Importance of Iron in Biology and Medicine
2. Iron Metabolism and Its Disorders
3. Classes of Molecules with Potential for Iron Chelation Therapy
4. Potential Chelation Sites
5. Potential Applications of Chelation Therapy
Acknowledgment
Abbreviations
References
Chapter 7
VANADIUM COMPOUNDS IN THE TREATMENT
OF DIABETES
Katherine H. Thompson and Chris Orvig
1. Introduction
2. Insulin Resistance
Copyright © 2004 by Marcel Dekker, Inc. All Rights Reserved.