G. W. R a p e r Canham and A. 8. P. Lever
York University Downsview 463, Ontario, Canada
Bioinorganic Chemistry Simple models of iron sites in some biological systems
The complexity of biological systems renders a detailed study of their mechanism very difficult. An increasingly popular method of elucidating structures and mechanisms is the use of a simple model wherein aspects of the structure or properties of the biological system are imitated by a simple chemical compound or system. A major part of the study involves the role of metal ions in biological processes, the field of bio-inorganic chemistry. The realization that metal ion sites in biological systems often bear little resemblance to established structures of simple chemical complexes (1) was instrumental in the sudden rise in interest in this field. Studies have brought to light the function of metal ions in DNA (2) and the importance of complexation for even the alkali and alkaline earth metals (S,4). Some of the most intriguing work centers on the role of iron in the many biological systems in which it is found. I n mammals, for example, it occurs in red blood cells, muscle, spleen, plasma and milk (5). Although the precise function of the iron atom is not established in many systems, its ubiquitous nature appears to be a result of its unique redox properties and its ability to coordinate a wide variety of ligand atoms in many stereochemical environments. In this review it is proposed to discuss some models of the more interesting systems. Hemes
Only very few animal species successfully utilize absorbed oxygen without hemeproteins (6, 7), yet the mode of oxygen uptake of hemes is still speculative (8). I n each of the hemeproteins, the in-plane environment of the single iron atom is a porphyrin ring, and one axial position is filled by an imidazole group. However, whereas hemoglobin and myoglobin have accessible sixth coordination sites (9, lo), that in cytochrome c is blocked by a thioether group (11). The bonding site of the dioxygen moiety in the latter case is believed to be a copper ion in the coenzyme cytochrome e oxidase (a), thus this syst,emwill not be discussed further. An ingenious model of the former type of structure was prepared by embedding imidazole groups in polystyrene and reacting this with a heme ester (12). (The resultant structure is shown schematically in Fig. 1). This species reversibly absorbed molecular oxygen even in the presence of water (I!?), thus it not only mimics the environment, but also the properties of the hemeprotein. Three possible modes of bonding of the dioxygen molecule have found favor (IS), and these may be de656 / Journal o f Chemicol Education
Figure I . Synthetic model of home system using polyswrene motrix (modifled from (1211.
scribed as symmetrical chelating (Fig. Za), asymmetrical chelating (Fig. 2h) and bent monodentate (Fig. 2c) coordination. Recent theoretical discussions favor the bent, monodentate coordination model (Fig. 2c) with an Fe-0-0 angle of approximately 120' (14, 16). Model complexes would clearly be of value in elucidating the bonding, yet of the plethora of simple compounds which coordinate dioxygen, very few contain an iron atom, and none of those has been satisfactorily characterized. The complex Fe(dmg),(im)~ (dmg = dimethylglyoxime, im = imidazole) exhibits similar behavior to the hemeprotein (16), undergoing the following equilibrium in solution (17) (X = 02,CO, CN-)
A second molecule of X may also be absorbed, though no oxygen containing species of either stoichiometry has been isolated in the solid state (17). The similarity to the hemes is explained by the relation in structure between the iron porphyrin system and the planar Fe(dmg), unit (17, 18), which is shown schematically (I). There is a remarkable parallelism in physical CHa
cobalt (cohoglobin) without losing dioxygen absorptive properties (Z5), cobalt dioxygen complexes may be considered for comparative purposes. On the bask of magnetic, electron spin resonance, and electronic spectral data, i t is believed that the 1:1 complexes of this type contain monodentate, bent superoxide groups coordinated to a formally cobalt(II1) ion (26). This supports the proposal of a similar type of bonding in the iron systems (27). The dioxygen adduct of cohalt(I1) phthalocyanin tetrasulfonate would appear to be a monomeric superoxide complex (28), thus further mvestigation of the iron analog would clearly he of interest. With the inability to resolve the dioxygen molecule in X-ray diffraction studies of oxyhemoglobins, potential model systems will be of major value. Rubredoxin and Ferredoxins
N
(c)
Figure 2. Three favored bonding modes of dioxygen to the iron of the heme subunit.
properties of the two species upon addition of the same axial ligands to support this proposal (17, 19). Similar reactions have been observed with 1,2 cyclohexanedione dioxime (nioxime) in place of the dimethylglyoxime (14)
The model which most closely resembles the heme system at least as far as molecular structure is concerned, is that of iron(I1) phthalocyan in tetrasulfonate (20-22), which absorbs dioxygen both in solution and in the solid state. The final product would appear to be a dimer (Fig. 3), however the monomeric 1:1 complex is proposed on scanty evidence as an intermediate (ZO). Considering the dimeric nature of iron(I1) pht,halocyanin tetrasulfonate in solution (Zi), a straightforward insertion of the dioxygen molecule between the two planes would seem possible. Some poorly characterized iron-dioxygen systems have been discussed (24). I t is difficult to know whether the paucity of publications in the field reflects a lack of interest in isolating a solid iron-dioxygen complex or alternatively, difficultyin obtaining positive results. As it is possible to replace the iron in hemoglobin by
Figure 3. Proposed structure of the dimeric dioxygen adduct of iron(ll1 phtholocymin tetrorvlfonote (modifled from (2011.
Rubredoxin contains one iron atom tetrahedrally surrounded by four sulfur atoms (29), though the low resolution of the X-ray studies does not eliminate the possibility of some flattening of the tetrahedron. Many iron sulfideminerals have the sulfur atoms tetrahedrally arranged around the iron atoms, for example MFe& (M = I .,. ,Lm,
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