Bioinorganic Chemistry -- Inorganic Elements in the Chemistry of Life

An Introduction and Guide

Wolfgang Kaim, Brigitte Schwederski, Axel Klein

• Éditeur: Wiley
• Année: 2013
• ISBN:
  9781118659267
• Édition: 2
• Sujet: Biological Sciences
• Sous-sujet: Biochemistry

The field of Bioinorganic Chemistry has grown significantly in recent years; now one of the major sub-disciplines of Inorganic Chemistry, it has also pervaded other areas of the life sciences due to its highly interdisciplinary nature.

Bioinorganic Chemistry: Inorganic Elements in the Chemistry of Life, Second Edition provides a detailed introduction to the role of inorganic elements in biology, taking a systematic element-by-element approach to the topic. The second edition of this classic text has been fully revised and updated to include new structure information, emerging developments in the field, and an increased focus on medical applications of inorganic compounds. New topics have been added including materials aspects of bioinorganic chemistry, elemental cycles, bioorganometallic chemistry, medical imaging and therapeutic advances.

Topics covered include:

• Metals at the center of photosynthesis
• Uptake, transport, and storage of essential elements
• Catalysis through hemoproteins
• Biological functions of molybdenum, tungsten, vanadium and chromium
• Function and transport of alkaline and alkaline earth metal cations
• Biomineralization
• Biological functions of the non-metallic inorganic elements
• Bioinorganic chemistry of toxic metals
• Biochemical behavior of radionuclides and medical imaging using inorganic compounds
• Chemotherapy involving non-essential elements

This full color text provides a concise and comprehensive review of bioinorganic chemistry for advanced students of chemistry, biochemistry, biology, medicine and environmental science.

1

Historical Background, Current Relevance and Perspectives

The progress of an inorganic chemistry of biological systems has had a curious history.

R. J. P. WILLIAMS, Coord. Chem. Rev. 1990, 100, 573

The description of a rapidly developing field of chemistry as “bioinorganic” seems to involve a contradiction in terms, which, however, simply reflects a misconception going back to the beginning of modern science. In the early 19th century, chemistry was still divided into an “organic” chemistry which included only substances isolated from “organisms”, and an “inorganic” chemistry of “dead matter”.1 This distinction became meaningless after Wöhler's synthesis of “organic” urea from “inorganic” ammonium cyanide in 1828. Nowadays, organic chemistry is defined as the chemistry of hydrocarbons and their derivatives, with the possible inclusion of certain nonmetallic heteroelements such as N, O and S, regardless of the origin of the material.

The increasing need for a collective, not necessarily substance-oriented designation of the chemistry of living organisms then led to the new term “biochemistry”. For a long time, classical biochemistry was concerned mainly with organic compounds; however, the two areas are by no means identical.2 Improved trace analytical methods have demonstrated the importance of quite a number of “inorganic” elements in biochemical processes and have thus revealed a multitude of partially inorganic natural products. A corresponding list would include:

• metalloenzymes (ca. 40% of the known enzymes, especially oxidoreductases (Fe, Cu, Mn, Mo, Ni, V) and hydrolases (e.g. peptidases, phosphatases: Zn, Mg; Ca, Fe);
• nonenzymatic metalloproteins (e.g. hemoglobin: Fe);
• low-molecular-weight natural products (e.g. chlorophyll: Mg);
• coenzymes, vitamins (e.g. vitamin B12: Co);
• nucleic acids: (e.g. DNAn−(M+)n, M = Na, K);
• hormones (e.g. thyroxine, triiodothyronine: I);
• antibiotics (e.g. ionophores: valinomycin/K);
• biominerals (e.g. bones, teeth, shells, coral, pearls: Ca, Si,…).

Some (by today's definition) “inorganic” elements were established quite early as essential components of living systems. Examples include the extractions of potassium carbonate (K2CO3, potash) from plants and of iron-containing complex salts K3,4[Fe(CN)6] from animal blood in the 18th century, and the discoveries of elemental phosphorus (as P4) by dry distillation of urine residues in 1669 and of elemental iodine from the ashes of marine algae in 1811.

In the middle of the 19th century, Liebig's studies on the metabolism of inorganic nutrients, especially of nitrogen, phosphorus and potassium salts, significantly improved agriculture, so that this particular field of science gained enormous practical importance. However, the theoretical background and the analytical methods of that time were not sufficient to obtain detailed information on the mechanism of action of essential elements, several of which occur only in trace amounts. Some very conspicuous compounds which include inorganic elements like iron-containing hemoglobin and magnesium-containing chlorophyll, the “pigments of life”, were analyzed and characterized later within a special subfield of organic chemistry, the chemistry of natural products. It was only after 1960 that bioinorganic chemistry became an independent and highly interdisciplinary research area.

The following factors have been crucial for this development:

1. Biochemical isolation and purification procedures, such as chromatography, and the new physical methods of trace element analysis, such as atomic absorption or emission spectroscopy, require ever smaller amounts of material. These methodical advances have made it possible not only to detect but also to chemically and functionally characterize trace elements or otherwise inconspicuous metal ions in biological materials. An adult human being, for example, contains about 2 g of zinc in ionic form (Zn2+). Although zinc cannot be regarded as a true trace element, the unambiguous proof of its existence in enzymes was established only in the 1930s. Genuine bioessential trace elements such as nickel (Figures 1.1 and 1.2), (Chapter 9) and selenium (Chapter 16.8) have been known to be present as constitutive components in several important enzymes only since about 1970.

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In a desire “to accomplish something of real importance”, the biochemist James B. Sumner managed to isolate and crystallize in 1926 a pure enzyme for the first time [2], much to the skepticism and disbelief of most experienced scientists. The chosen enzyme, urease (from jack beans), catalyzes the hydrolysis of urea, O=C(NH2)2, to CO2 and 2 NH3. It contains two closely associated nickel ions per subunit (Section 9.2). It was believed by many then that pure enzymes contained no protein, and only after other enzymes were crystallized was Sumner's discovery accepted. He was honored in 1946 with the Nobel Prize in Chemistry. However, Sumner's belief that urea contained only protein was corrected in 1975 when Dixon et al. proved that urease is a nickel metalloenzyme (Section 9.2).

In a very different research area, the biological reduction of carbon dioxide by hydrogen to produce methane has been investigated by studying the relevant archaebacteria, which are found, for example, in sewage plants. Even though the experiments were carried out under strictly anaerobic conditions and all “conventional” trace elements were supplied (Figure 1.2), the results were only partly reproducible. Eventually it was discovered that during sampling with a syringe containing a supposedly inert stainless steel (Fe/Ni) tip, minute quantities of nickel had dissolved. This inadvertent generation of Ni2+ ions led to a distinctive increase in methane production [4], and, in fact, several nickel containing proteins and coenzymes have since been isolated (see Chapter 9). Incidentally, a similar unexpected dissolution effect of an apparently “inert” metal led to the serendipitous discovery of the inorganic anti-tumor agent cis-PtCl2(NH3)2 (“cisplatin”, Section 19.2.1).

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2. Efforts to elucidate the mechanisms of organic, inorganic and biochemical reactions have led to an early understanding of the specific biological functions of some inorganic elements. Nowadays, many attempts are being made to mimic biochemical reactivity through studies of the reactivity of model systems, low-molecular-weight complexes or tailored metalloproteins (Section 2.4).

3. The rapid progress in bioinorganic chemistry, an interdisciplinary field of research (Figure 1.3), has been made possible through contributions from:

• physics (→ techniques for detection and characterization);
• various areas of biology (→ supply of material and specific modifications based on site-directed mutagenesis);
• agricultural and nutritional sciences (→ effects of inorganic elements and their mutual interdependence);
• pharmacology (→ interaction between drugs and endogeneous or exogeneous inorganic substances);
• medicine (→ imaging and other diagnostic aids, chemotherapy);
• toxicology and the environmental scien...