Bioinorganic chemistry

Bioinorganic chemistry is a field that examines the role of metals in biology. Bioinorganic chemistry includes the study of both natural phenomena such as the behavior of metalloproteins as well artificially introduced metals, including those that are non-essential, in medicine and toxicology. Many biological processes such as respiration depend upon molecules that fall within the realm of inorganic chemistry. The discipline also includes the study of inorganic models or mimics that imitate the behaviour of metalloproteins.

As a mix of biochemistry and inorganic chemistry, bioinorganic chemistry is important in elucidating the implications of electron-transfer proteins, substrate bindings and activation, atom and group transfer chemistry as well as metal properties in biological chemistry.

History
Paul Ehrlich used organoarsenic (“arsenicals”) for the treatment of syphilis, demonstrating the relevance of metals, or at least metalloids, to medicine, that blossomed with Rosenberg’s discovery of the anti-cancer activity of cisplatin (cis-PtCl2(NH3)2). The first protein ever crystallized (see James B. Sumner) was urease, later shown to contain nickel at its active site. Vitamin B12, the cure for pernicious anemia was shown crystallographically by Dorothy Crowfoot Hodgkin to consist of a cobalt in a corrin macrocycle. The Watson-Crick structure for DNA demonstrated the key structural role played by phosphate-containing polymers.

Research areas
Several distinct systems are of interest in bioinorganic chemistry. Major areas include:

Metal ion transport and storage covers a diverse collection of ion channels, ion pumps (e.g. NaKATPase), vacuoles, siderophores, and other proteins and small molecules whose aim is to carefully control the concentration of metal ions in the cell (sometimes referred to as metallome).

Hydrolase enzymes include a diverse collection of proteins that interact with water and substrates. Examples of this class of metalloproteins are carbonic anhydrase, metallophosphatases, and metalloproteinases.

Metal-containing electron transfer proteins are organized into three major classes: These electron transport proteins are complementary to the non-metal electron transporters nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD).
 * iron-sulfur proteins such as rubredoxins, ferredoxins, and Rieske proteins
 * blue copper proteins
 * cytochromes

Oxygen transport and activation proteins (see Dioxygen complexes) make extensive use of metals such as iron, copper, and manganese. Heme is utilized by red blood cells in the form of hemoglobin for oxygen transport and is perhaps the most recognized metal system in biology. Other oxygen transport systems include myoglobin, hemocyanin, and hemerythrin. Oxidases and oxygenases are metal systems found throughout nature that take advantage of oxygen to carry out important reactions such as energy generation in cytochrome c oxidase or small molecule oxidation in cytochrome P450 oxidases or methane monooxygenase. Some metalloproteins are designed to protect a biological system from the potentially harmful effects of oxygen and other reactive oxygen-containing molecules such as hydrogen peroxide. These systems include peroxidases, catalases, and superoxide dismutases. A complementary metalloprotein to those that react with oxygen is the oxygen evolving complex present in plants. This system is part of the complex protein machinery that produces oxygen as plants perform photosynthesis.

Bioorganometallic systems such as hydrogenases and methylcobalamin are biological examples of organometallic compounds. This area is more focused on the utilization of metals by unicellular organisms. Bioorganometallic compounds are significant in environmental chemistry.

The nitrogen metabolism pathways make extensive use of metals. Nitrogenase is one of the more famous metalloproteins associated with nitrogen metabolism. More recently, the cardiovascular and neuronal importance of nitric oxide has been examined, including the enzyme nitric oxide synthase. (See also: nitrogen assimilation.)

Metals in medicine is the study of the design and mechanism of action of metal-containing pharmaceuticals, and compounds that interact with endogenous metal ions in enzyme active sites. This diverse field includes the platinum and ruthenium anti-cancer drugs, chelating agents, gold drug chaperones, and gadolinium contrast agents.
 * In mental health inorganic compounds have been found to treat certain disorders. For example, lithium carbonate has been used to treat the manic phase of bipolar disorder.