Metals with biological role

There is an abundant research on the interactions of HIOCs and metals with biological interphases, in which organic chemicals and metals are treated independently. However, few studies have considered the role of combinations of HIOCs with metals. There is a particular lack of mechanistic approaches. With regard to the metals, the FIAM has been very successful, but it remains to be shown under which conditions additional interactions, such as partitioning of hydrophobic complexes and uptake of specific complexes, are important for metal uptake and toxic effects. In particular, the role of hydrophobic complexes with both natural and pollutant compounds in natural waters has not yet been fully elucidated, since neither their abundance nor their behaviour at biological interphases are known in detail. 

In this chapter, we survey the diversity of transition metals, beginning with an overview. Then we describe the stmcture and bonding in transition metal complexes. We describe metallurgy, the processes by which pure metals are extracted from mineral ores. The chapter ends with a presentation of some properties of transition metals and their biological roles. 

In the following section, the role of the various types of complexes mentioned above will be discussed with regard to various mechanisms of interactions at biological interphases. It is clear that metal ions and hydrophilic complexes cannot distribute into the membrane lipid bilayer or cross it. The role of hydrophilic ligands has thus to be discussed in relation to binding of metals by biological ligands. In contrast, hydrophobic complexes may partition into the lipid bilayer of membranes (see below, Section 6). 

Magnesium is perhaps the most versatile metal cation found in living systems. It can and does interact with an extremely wide variety of biomolecules, thus giving rise to multiple biological roles of fundamental importance in life processes. A comprehensive discussion of all biosystems that have an absolute dependency on Mg + as a cofactor would currently have to include hundreds of unrelated examples and more are being discovered all the time. 

Complexes of alkali metals and alkaline-earth metals with carbohydrates have been reviewed in this Series,134 and the interaction of alkaline-earth metals with maltose has been described.135 Standard procedures for the preparation of adducts of D-glucose and maltose with the hydroxides of barium, calcium, and strontium have been established. The medium most suitable for the preparation of the adduct was found to be 80% methanol. It is of interest that the composition of the adducts, from D-glucose, maltose, sucrose, and a,a-trehalose was the same, namely, 1 1, in all cases. The value of such complex-forming reactions in the recovery of metals from industrial wastes has been recognized. Metal hydroxide-sugar complexes may also play an important biological role in the transport of metal hydroxides across cell membranes. 

The sea squirts or tunicates are fascinating marine creatures, their name being derived from the tunic made of cellulosic material that surrounds the body of the animal. In 1911, Henze discovered vanadium in the blood of Phallusia mammillata C.343 He later found the same with other ascidians (a class of tunicates). In vanadium-accumulating species, most vanadium is located in the vacuoles—vanadophores—of certain types of blood cells—the vanadocytes. The concentration in the vanadophore can be as high as 1M and this value must be compared with concentrations of the order of 2 x 10-8 M for vanadium in sea water.344 Kustin et al. have reviewed the work done to understand the efficient accumulation and the possible biological roles of the metal.345... 

In this introductory chapter, some general aspects of bioinorganic chemistry will be dealt with. In Chapter 2 a section of the periodic table of elements is presented, indicating the transition metals that are catalytically active in vivo. Table 1 lists several elements that are essential to life, together with some statistical information and a few comments about their biological role. The compilation is limited and restricted to some of the most important transition elements, the nonmetal Se, and the alkaline earth metals Ca and Mg. 

After the completion of all chapters for the present monograph, a rather extensive study in four volumes has appeared [1] that deals with biological catalysis. Readers with an interest in the general aspects, also dealing with the numerous topics in which metals do not play a key role, are referred to this work. 

Until the late 1960s, whereas there had been considerable interest in the transition metal complexes of natural and synthetic macrocyclic ligands (1—4), relatively few reports described complexes of alkaline earth and more particularly alkali metal cations. Research in this area was stimulated by the recognition of the importance of the biological role of Na+, K, Ca2 , and Mg2 and also the discovery and characterization of the natural antibiotic ionophores (5, 6). These macrocyclic antibiotics, such as valinomycin and nonactin, were shown to complex alkali metal cations with remarkable selectivity (7-9). 

In this chapter, the unique features of transition metals in biological systems are discussed from the point of view of structural roles, spectroscopic properties, electron transfer, hydrolytic and redox catalysis, and metal-responsive gene expression. The following chapters provide more detail on these subjects. Several important examples not discussed elsewhere in this volume will be presented. The goal of this chapter (and this volume) is to acquaint the reader with the wide range of roles played by metal ions in biological systems and thereby to demonstrate why metals are such useful cofactors and why scientists from such broad disciplines are drawn to study their properties. 

Historically, vanadium has received little attention from biochemists. In the past four years, however, the interaction of this element with biological systems has become the focus of intense study in numerous laboratories throughout the world. Many biochemical and physiological effects of this essential metal are now known and new ones are being discovered almost monthly. Despite these recently discovered phenomena, the role of vanadium in vivo remains an open question. The potency of this element at extremely low concentrations, typical of those found in many tissues, is particularly relevant to a possible function. As is the case with most essential metals, vanadium in all probability will be shown to have more than one biological role. 

Only one copper ion has been found in the preparations of both F8a and F5a. It was identified as a type 2 copper (Bihoreau et al., 1994 Mann et al., 1984 Tagliavacca et al., 1997). It is beheved that the single copper ion is not involved in any redox reaction and instead it plays a structural role by stabilizing the association of domain Al with domain A3 in the active trimeric complex. This is a very unusual role for a d redox-active transition metal in biology. Mutant F8 in which the type 2 copper ligand His-195 7 was replaced with Ala displayed secretion, active complex assembly, and activity similar to that of wild-type protein, while a mutant in which the second ligand for the type 2 copper, His-99, was replaced with Ala was partially defective for secretion and had low levels of active complex formation and activity (Tagliavacca et al., 1997). 

---