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INORGANIC CHEMISTRY AND BIOCHEMISTRY ESSENTIALS

1.1 INTRODUCTION

Bioinorganic chemistry involves the study of metal species in biological systems. As an introduction to the basic inorganic chemistry is needed for understanding bioinorganic topics, this chapter will discuss the essential chemical elements, the occurrences and purposes of metal centers in biological species, the geometries of ligand fields surrounding these metal centers and ionic states preferred by the metals. The occurrence of organometallic complexes and clusters in metalloproteins will be discussed briefly and an introduction to electron transfer in coordination complexes will be presented. Since the metal centers under consideration are found in a biochemical milieu, basic biochemical concepts, including a discussion of proteins and nucleic acids, are presented later in this chapter.

1.2 ESSENTIAL CHEMICAL ELEMENTS

Chemical elements essential to life forms can be broken down into four major categories: (i) bulk elements (H/H+, C, N, O2-/O2-·/O22-, P, and S/S2-); (ii) macrominerals and ions (Na/Na+, K/K+, Mg/Mg2+, Ca/Ca2+, Cl-, PO43-, and SO42-); (iii) trace elements (Fe/FeII/FeIII/FeIV, Zn/ZnII, and Cu/CuI/CuIICuIII); and (iv) ultratrace elements, that comprise nonmetals (F/F-, I/I-, Se/Se2-, Si/SiIV, As, and B) and metals (Mn/MnII/MnIII/MnIV, Mo/MoIV/MoV/MoVI, Co/CoII/ CoIII, Cr/CrIII/CrVI, V/VIII/ VIV/ VV/, NiI/ NiII/ NiIII/, Cd/Cd2+, Sn/SnII/SnIV, Pb/Pb2+, and Li/Li+). In the preceding classification, only the common biologically active ion oxidation states are indicated (see references [1, 2d] for more information). If no charge is shown, the element predominately bonds covalently with its partners in biological compounds, although elements such as carbon (C), sulfur (S), phosphorus (P), arsenic (As), boron (B), and selenium (Se) have positive formal oxidation states in ions containing oxygen atoms; i.e. S = +6 in the SO42- ion or P = +5 in the PO43- ion. The identities of essential elements are based on historical work done by Klaus Schwarz in the 1970s [3]. Other essential elements may be present in various biological species. Essentiality has been defined by certain criteria: (i) a physiological deficiency appears when the element is removed from the diet; (ii) the deficiency is relieved by the addition of that element to the diet; and (iii) a specific biological function is associated with the element [4]. Table 1.1 indicates the approximate percentages by weight of selected essential elements for an adult human.

Every essential element follows a dose-response curve, shown in Figure 1.1, as adapted from reference [4]. At lowest dosages, the organism does not survive whereas in deficiency regions the organism exists with less than optimal function. After the concentration plateau of the optimal dosage region, higher dosages cause toxic effects in the organism eventually leading to lethality. Specific daily requirements of essential elements may range from microgram to gram quantities.

Considering the content of earth's contemporary waters and atmospheres, many questions arise as to the choice of essential elements at the time of life's origins 3.5 billion or more years ago. Certainly sufficient quantities of the bulk elements were available in primordial oceans and at shorelines. However, the concentrations of essential trace metals in modern oceans may differ considerably from those found in prebiotic times. Iron's current approximate 10-4 mM concentration in seawater, for instance, may not reflect accurately its prelife-forms availability. If one assumes a mostly reducing atmosphere contemporary with the beginnings of biological life, the availability of the more soluble iron(II) ion in primordial oceans must have been much higher. Thus, the essentiality of iron(II) at a concentration of 0.02?mM in the blood plasma heme (hemoglobin) and muscle tissue heme (myoglobin) may be explained. Beside the availability factor, many chemical and physical properties of elements and their ions are responsible for their inclusion in biological systems. These include ionic charge, ionic radius, ligand preferences, preferred coordination geometries, spin pairings, systemic kinetic control, and the chemical reactivity of the ions in solution. These factors are discussed in detail by daSilva and Williams [1].

TABLE 1.1 Percentage Composition of Selected Elements in the Human Body

Figure 1.1 Dose-response curve for elements.

Source: adapted from Kaim et al. [4].

1.3 INORGANIC CHEMISTRY BASICS

Ligand preference and possible coordination geometries of the metal center are important bioinorganic principles. Metal ligand preference is closely related to the hard-soft acid-base nature of metals and their preferred ligands. These are listed in Table 1.2.

In general, hard metal cations form their most stable compounds with hard ligands and soft metal cations with soft ligands. Hard cations can be thought of as small dense cores of positive charge whereas hard ligands are usually the small highly electronegative elements or ligand atoms within a hard polyatomic ion, i.e. oxygen ligands in (RO)2PO2- or CH3CO2-.

It is possible to modify a hard nitrogen ligand towards an intermediate softness by increasing the polarizability of its substituents or the p electron cloud about it. The imidazole nitrogen of the amino acid histidine, a ubiquitous ligand in biological proteins, is an example. Increasing the softness of phosphate ion substituents can transform the hard oxygen ligand of (RO)2PO2- to a soft state in (RS)2PO2-. Soft cations and anions are those with highly polarizable, large electron clouds - Hg2+, sulfur ligands as sulfides or thiolates, and iodide ions. Also, note that metal ions can overlap into different categories. Lead as Pb2+, for instance, appears in both the intermediate and soft categories. The Fe3+ ion, classified as a hard cation, coordinates to histidine (imidazole) ligands in biological systems and Fe2+, classified as intermediate, can coordinate to sulfur ligands and the carbon atom of CO (see Sections 3.1-3.3, 3.6, and 4.1).

TABLE 1.2 Hard-soft Acid-base Classification of Metal Ions and Ligands

In biological systems, many factors...