The field at the interface between biochemistry and inorganic chemistry; also known as inorganic biochemistry or metallobiochemistry. This field involves the application of the principles of inorganic chemistry to problems of biology and biochemistry. Because most biological components are organic, that is, they involve the chemistry of carbon compounds, the combination of the prefix bio- and inorganic may appear contradictory. However, organisms require a number of other elements to carry out their basic functions. Many of these elements are present as metal ions that are involved in crucial biological processes such as respiration, metabolism, cell division, muscle contraction, nerve impulse transmission, and gene regulation. The characterization of the interactions between such metal centers and biological components is the heart of bioinorganic chemistry.
Metal ions influence biological phenomena by interacting with organic functional groups on biomolecules, forming metal complexes. From this perspective, much of bioinorganic chemistry may be considered as coordination chemistry applied to biological questions. In general, bioinorganic chemists tackle such problems by first focusing on the elucidation of the structure of the metal complex of interest and then correlating structure with function. The attainment of solutions usually requires a combination of physical, chemical, and biological approaches. Biochemistry and molecular biology are often used to provide sufficient amounts of the system for investigation. Physical approaches such as crystallography and spectroscopy are useful in defining structural properties of the metal site. Synthetic methods can be used for the design and assembly of structural, spectroscopic, and functional models of the metal site. All these approaches then converge to elucidate how such a site functions.
Low-molecular-weight compounds. A number of coordination compounds found in organisms have relatively low molecular weights. Ionophores, molecules that are able to carry ions across lipid barriers, are polydentate ligands designed to bind alkali and alkaline-earth metal ions; they span membranes and serve to transport such ions across these biological barriers. Molecular receptors known as siderophores are also polydentate ligands; they have a very high affinity for iron.
Other low-molecular-weight compounds are metal-containing cofactors that interact with macromolecules to promote important biological processes. Perhaps the most widely studied of the metal ligands found in biochemistry are the porphyrins; iron protoporphyrin IX (see illustration) is an example of the all-important complex in biology known as heme. Chlorophyll and vitamin B12 are chemically related to the porphyrins. Magnesium is the central metal ion in chlorophyll, which is the green pigment in plants used to convert light energy into chemical energy. Cobalt is the central metal ion in vitamin B12; it is converted into coenzyme B12 in cells, where it participates in a variety of enzymatic reactions.
. Metalloproteins and metalloenzymes. These are metal complexes of proteins.
In many cases, the metal ion is coordinated directly to functional groups on amino acid residues. In some cases, the protein contains a bound metallo-cofactor such as heme. In metalloproteins with more than one metal-binding site, the metal ions may be found in clusters. Examples include ferredoxins, which contain iron-sulfur clusters (Fe₂S₂ or Fe₄S₄), and nitrogenase, which contains both Fe₄S₄ units and a novel MoFe₇S₈ cluster.
Some metalloproteins are designed for the storage and transport of the metal ions themselves-for example, ferritin and transferrin for iron and metallothionein for zinc. Others, such as the yeast protein Atxl, act as metallochaperones that aid in the insertion of the appropriate metal ion into a metalloenzyme. Still others function as transport agents. Cytochromes and ferredoxins facilitate the transfer of electrons in various metabolic processes.
Many metalloproteins catalyze important cellular reactions and are thus more specifically called metalloenzymes. For example, cytochrome oxidase is the respiratory enzyme in mitochondria responsible for disposing of the electrons generated by mammalian metabolism; it does so by reducing O₂ to water with the help of both heme and copper centers. In contrast, the conversion of water to O₂ is carried out in the photosynthetic apparatus by manganese centers. Other metalloenzymes are involved in the transformation of organic molecules in cells. For example, tyrosine hydroxylase (an iron enzyme) and dopamine .B-hydroxylase (a copper enzyme) carry out oxidation reactions important for the biosynthesis of neurotransmitters. Alternatively, the metal center can serve as a Lewis acidic site to activate substrates for nucleophilic displacement reactions (that is, hydrolysis).
Metals in medicine. Metal complexes have also been found to be useful as therapeutic or diagnostic agents. Prominent among metal-based drugs is cisplatin, which is particularly effective in the treatment of testicular and ovarian cancers. Gold, gallium, and bismuth compounds are used for the treatment of rheumatoid arthritis, hypercalcemia, and peptic ulcers, respectively.
In clinical diagnosis, metal complexes can be used as imaging agents. The convenient half-life and radioemission properties of technetium-99 make its complexes very useful for a number of applications; by varying the ligands bound to the metal ion, diagnostic agents have been developed for imaging the heart, brain, and kidneys. Complexes of paramagnetic metal ions such as gadolinium(III), iron(III), and manganese(II) are also used as contrast agents to enhance images obtained from magnetic resonance imaging (MRI).