Bioinorganic Chemistry

Ilham Maulana

Chemistry Dept. FMIPA Unsyiah

Scope of Bioinorganic Chemistry.

a field that examines the role of metals in biology includes the study of both natural phenomena such as the behavior of metalloproteins as well as artificially introduced metals, including those that are nonessential, in medicine and toxicology also includes the study of inorganic models or mimics that imitate the behaviour of metalloproteins

Chemistry Dept. FMIPA Unsyiah

Major Areas of Bioinorganic Chemistry.

Metal ion transport and storage

Proteins and small molecules whose aim is to carefully control the concentration of metal ions in the cell (sometimes referred to as metallome)

Chemistry Dept. FMIPA Unsyiah

Major Areas of Bioinorganic Chemistry.

Metal ion transport and storage Hydrolase enzymes

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

Chemistry Dept. FMIPA Unsyiah

Major Areas of Bioinorganic Chemistry.

Metal ion transport and storage Hydrolase enzymes Metal-containing electron transfer proteins These electron transport proteins are
complementary to the non-metal electron transporters nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD).

Chemistry Dept. FMIPA Unsyiah

Major Areas of Bioinorganic Chemistry.

Metal ion transport and storage Hydrolase enzymes Metal-containing electron transfer proteins extensive use of metals such as iron, Oxygen transport and copper, and manganese in transporting oxygen (Hemoglobin, activation proteins
Myoglobin). Some metalloproteins are designed to protect a biological system from the potentially harmful effects of oxygen and other reactive oxygencontaining molecules such as hydrogen peroxide

Chemistry Dept. FMIPA Unsyiah

Major Areas of Bioinorganic Chemistry.

Metal ion transport and storage Hydrolase enzymes Metal-containing electron transfer proteins Oxygen transport and activation proteins Bioorganometallic systems
more focused on the utilization of metals by unicellular organisms

Chemistry Dept. FMIPA Unsyiah

Major Areas of Bioinorganic Chemistry.

Metal ion transport and storage Hydrolase enzymes Metal-containing electron transfer proteins Oxygen transport and activation proteins Bioorganometallic systems The nitrogen metabolism Metals that facilitate the metabolism of pathways Nitrogen. Nitrogenase is one of the
more famous metalloproteins associated with nitrogen metabolism

Chemistry Dept. FMIPA Unsyiah

Major Areas of Bioinorganic Chemistry.

Metal ion transport and storage Hydrolase enzymes Metal-containing electron transfer proteins the study of the design and Oxygen transport and mechanism of action of metalcontaining pharmaceuticals, and activation proteins compounds that interact with Bioorganometallic systems The nitrogen metabolism endogenous metal ions in enzyme active sites. This diverse field includes pathways the platinum and ruthenium anti Metals in medicine cancer drugs, chelating agents, gold
drug chaperones, and gadolinium contrast agents.

Chemistry Dept. FMIPA Unsyiah

Metals and Toxicity.

The vast majority of biochemical processes in which a metal plays a role involve a only a relatively small number of metals. Those metals include Na, K, Mg, Ca, Mo, or the fi rst-row transition metals from V to Zn. (Only molybdenum could be considered as a heavy metal) Generally, heavy metals having low charge ( soft ) are toxic (Hg, Pb, Cd, Tl, etc). Some heavy metals bind to groups such as the sulfhydryl (-SH) group in enzymes, destroying the ability of the enzyme to promote the reaction in a normal way Beryllium is an extremely toxic metal that is not soft
Chemistry Dept. FMIPA Unsyiah

Metals and Toxicity.

one way that toxicity of metals rises is by substitution for another metal (Cd for Zn, Be for Mg) When this happens, the enzyme loses its activity numerous nonmetallic substances that are toxic (cyanides, carbon monoxide). The toxicity of these materials is related to their being potential ligands that attach to metals in specific structures,which thereby prevents the metals from serving their normal functions.

Chemistry Dept. FMIPA Unsyiah

Metals and The Action.

One way in which metals function in biochemical structures is in enzyme activity The function of enzymes as catalysts: Absolute specifi city, Group specifi city, Linkage specifi city, Stereochemical specifi city Enzymes may not function well or at all unless some other species known as a cofactor is present The most interesting cofactors are metal ions Mg 2+, Ca2+, K+ , Fe2+ , or Cu2+ The combination of enzyme and cofactor is known as the holoenzyme

Chemistry Dept. FMIPA Unsyiah

Metals and The Action.

One of the most important metals with regard to its role in enzyme chemistry is zinc (carboxypeptidase A and B, alkaline phosphatase, alcohol dehydrogenase, aldolase, and carbonic anhydrase) Carbonic anhydrase, which contains a single zinc atom in its structure, has a molecular weight of about 30,000. In this structure, zinc is surrounded tetrahedrally by three histidine molecules and one water molecule. h3ZnOH2 + H2O H3O+ + h3ZnOH-

h3ZnOH- + CO2 HCO3- + h3Zn

Chemistry Dept. FMIPA Unsyiah

Metals and The Action.

Ribbon diagram showing human carbonic anhydrase II. The grey sphere is the zinc cofactor in the active site.

Chemistry Dept. FMIPA Unsyiah

Photosynthesis.
6 CO2 + 6 H2O C6H12O6 + 6 O2

the reaction requires energy from light, so, it is known as photosynthesis The structures that are responsible for absorption of light in order for its energy to be used are the chlorophylls, which contain porphyrin-type ligands. The porphyrin structure is derived from the basic unit known as porphin The chlorophylls consist of several members of a series, which have structures derived from a molecule known as chlorin
Chemistry Dept. FMIPA Unsyiah

Photosynthesis.

porphin

chlorophyll

Chemistry Dept. FMIPA Unsyiah

Oxygen Transfer.
the transport of oxygen by heme is the basis for respiration Heme is one of several proteins that contain iron When an oxygen molecule is attached to the iron and it changes from high spin to low spin, the size of the Fe2+ changes. The ionic radius of Fe 2+ in the high spin state is approximately 78 pm, but in a low-spin environment it is about 61 pm. This reduction in size is suffi cient to allow the Fe2+ ion to fit between the nitrogen atoms in the porphyrin ring.

Chemistry Dept. FMIPA Unsyiah

Oxygen Transfer.
By the usual standards of coordinate bond strength, the binding of oxygen to iron in hemoglobin is quite weak. On the other hand, groups such as CN-, CO, H 2S, and others bind strongly to Fe2+ . Thus these substances are highly toxic, and they function by preventing the uptake of oxygen.
Chemistry Dept. FMIPA Unsyiah