Structural Biochemistry/Bioorganometallic Chemistry

Bioorganometallic chemistry is a science that describes the research of organometallic compounds in biological systems and organisms. It is an interdisciplinary science in that it involves organometallic chemistry, biochemistry, and medicine. Bioorganometallic compounds that are found in nature include enzymes and sensor proteins. Bioinorganometallic chemistry involves toxicology in that some organometallic compounds are toxic.



Vitamin B12
Vitamin B-12 is a group of very important bioorganometallic compounds. Vitamin B-12 is a class of water-soluble vitamins that are involved with the metabolism of nucleic acids and the development of red blood cells. These molecules all contain a corrin ring structure bonded to cobalt. Vitamin B-12 is not naturally found in humans. The only organism that have the required enzymes to synthesize vitamin B-12 are bacteria. Some sources of vitamin B-12 are meat, eggs, and dairy products. Some diseases that can result from having an abnormal amount of vitamin B-12 (too much or too little) are anemia and some neurological diseases.

Nickel
Some bioorganometallic compounds contain nickel such as the NiFe-hydrogenases. These enzymes also contain iron and sulfur. Another important bioorganometallic compound containing nickel is nickel tetracarbonyl, Ni(CO)4. This compound is not actually a biological molecule but because of its biological effects on humans, it is very important to mention. This compound is very toxic because the metal is toxic and also because it can release carbon monoxide gas. Many other nickel compounds are known to cause allergies and may be carcinogenic.

Cisplatin
Organometallic chemistry is also proving to be very important to medicine. Cisplatin is used in the process of many treatments involving testicular, ovarian, bladder, cervical, head and neck, and small-cell and non–small-cell lung cancers. Cisplatin is a chemotherapy drug that contains a platinum center. Cisplatin works by cross-linking DNA, which leads to apoptosis (programmed cell death). The mechanism in which cisplatin induces apoptosis starts with it binding to mitochondrial DNA, interaction with phospholipids and phosphatidylserine in the membranes, disruption of the cytoskeleton, resulting in inhibition of the polymerization of actin. However, cisplatin has many side effects such as nerve and kidney damage. In addition, some patients can develop cisplatin resistance.

Hydrogenases
Hydrogenases fall in the division of bioorganic metals in that they have active sites that possess Fe-CO functionalities, though the CO ligands only participate as spectator ions. The iron containing hydrogenases have an active site, Fe2(μ-SR)2(μ-CO)(CO)2(CN), that is conntected to an iron sulfide complex through a thiolate bridge. The active site of the nickel-iron hydrogenases is (NC)2(OC)Fe(μ-SR)2Ni(SR)2 (in which SR is cysteinyl).