Overview

The fields of molecular biology

Molecular biology

Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

 and inorganic chemistry

Inorganic chemistry

Inorganic chemistry is the branch of chemistry concerned with the properties and behavior of inorganic compounds. This field covers all chemical compounds except the myriad organic compounds , which are the subjects of organic chemistry...

 overlap in the study of metalloenzymes

Metalloprotein

Metalloprotein is a generic term for a protein that contains a metal ion cofactor. Metalloproteins have many different functions in cells, such as enzymes, transport and storage proteins, and signal transduction proteins. Indeed, about one quarter to one third of all proteins require metals to...

 in the form of enzyme mimic

Enzyme mimic

An enzyme mimic is a small molecule complex that models the molecular structure, spectroscopic properties, or reactivity of an enzyme, sometimes called bioinspired complexes.- Overview :...

s among other. The advantage of indirect modeling or enzyme mimic

Enzyme mimic

An enzyme mimic is a small molecule complex that models the molecular structure, spectroscopic properties, or reactivity of an enzyme, sometimes called bioinspired complexes.- Overview :...

ry is high-resolution crystal structures and well-defined spectral data from which comparisons can be made to low-resolution crystal structures and poorly defined spectral data obtained from the native enzymes. Modes of action can be proposed by correlating spectral properties of the hydrogenase mimics with spectral properties of different enzyme states.

Interest in hydrogenase

The Fe-only hydrogenase

Hydrogenase

A hydrogenase is an enzyme that catalyses the reversible oxidation of molecular hydrogen . Hydrogenases play a vital role in anaerobic metabolism....

s are particularly common enzymes for synthetic organometallic chemists to mimic. This interest is motivated by the inclusion of high field ligand

Ligand

In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

s like cyano and CO

Carbon monoxide

Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...

 (metal carbonyl

Metal carbonyl

Metal carbonyls are coordination complexes of transition metals with carbon monoxide ligands. These complexes may be homoleptic, that is containing only CO ligands, such as nickel carbonyl , but more commonly metal carbonyls contain a mix of ligands, such as Re3Cl...

) in the first coordination sphere

Coordination sphere

In coordination chemistry, the coordination sphere refers to a central atom or ion and an array of molecules or anions, the ligands, around.Molecules that are attached noncovalently to the ligands are called the second coordination sphere....

 of the pertinent di-iron cluster. Free cyano and carbonyl ligands are toxic to many biological systems so their inclusion in this system suggests they play pivotal roles. These high field ligands may ensure the iron centers at the active site remain in a low spin state throughout the catalytic cycle. In addition, there is bridging dithiolate between the two iron centers. This dithiolate has a three atom backbone in which the identity of the central atom is still undetermined; it models crystallographically as a CH₂, NH or O group. There is reason to believe that this central atom is an amine

Amine

Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...

 which functions as a Lewis base. This amine combined with Lewis acid

Lewis acid

]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...

ic iron centers makes the enzyme a bifunctional catalyst

Bifunctional catalyst

A bifunctional catalyst is term coined to refer to a specific set of hydrogenation catalyst containing Lewis acid and Lewis base....

 which can split hydrogen between a proton acceptor and a hydride acceptor or produce hydrogen from a proton and hydride.

Since none of the ligands on the iron centers are part of the enzyme's amino acid backbone, they can not be investigated through site-directed mutagenesis

Site-directed mutagenesis

Site-directed mutagenesis, also called site-specific mutagenesis or oligonucleotide-directed mutagenesis, is a molecular biology technique in which a mutation is created at a defined site in a DNA molecule. In general, this form of mutagenesis requires that the wild type gene sequence be known...

, but enzyme mimic

Enzyme mimic

An enzyme mimic is a small molecule complex that models the molecular structure, spectroscopic properties, or reactivity of an enzyme, sometimes called bioinspired complexes.- Overview :...

ry is a feasible approach.

Breadth

Many elegant structural mimics have been synthesized reproducing the atomic content and connectivity of the active site. The work by Pickett

Pickett

Pickett is a surname of English origin, and may refer to:* Albert J. Pickett , American historian* Allistair Pickett , Australian rules footballer* Bill Pickett , American cowboy and rodeo performer...

 is a prime example of this field. The catalytic activity of these mimics do not however compare to the native enzyme. In contrast, functional mimics also known as bioinspired catalysts, aim to reproduce only the functional features of an enzyme often through the use of different atomic content and connectivity than found in the native enzymes. Functional mimics have made advances in the reactive chemistry and have implications on the mechanistic activity of the enzyme as well as acting as catalysts in their own right.