Related Experiment Video
Updated: May 7, 2026
![Protein Film Infrared Electrochemistry Demonstrated for Study of H2 Oxidation by a [NiFe] Hydrogenase](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F55858.jpg&w=3840&q=50)
10:01
Protein Film Infrared Electrochemistry Demonstrated for Study of H2 Oxidation by a [NiFe] Hydrogenase
Published on: December 4, 2017
Geometric and electronic structure contributions to function in non-heme iron enzymes
Edward I Solomon1, Kenneth M Light, Lei V Liu
1Department of Chemistry, Stanford University , Stanford, California 94305-5080, United States.
Accounts of Chemical Research
|September 28, 2013
Summary
Mononuclear non-heme iron enzymes activate dioxygen for crucial biological reactions. New spectroscopic methods reveal how these enzymes control Fe(II) active sites and O2 activation via intermediates, bridging structure and reactivity.
Area of Science:
- Biochemistry
- Bioinorganic Chemistry
- Enzymology
Background:
- Mononuclear non-heme iron (NHFe) enzymes are vital in DNA repair, antibiotic synthesis, and cancer therapy.
- These enzymes catalyze diverse oxidations but their Fe(II) active sites are difficult to probe spectroscopically.
- Understanding NHFe enzyme mechanisms is key to developing new therapeutics and biotechnologies.
Purpose of the Study:
- To develop and apply novel spectroscopic methodologies for detailed geometric and electronic structure insights into NHFe(II) active sites.
- To elucidate the general mechanistic strategy employed by NHFe enzymes for controlling O2 activation.
- To correlate electronic structure with the diverse reactivity observed in NHFe-catalyzed reactions.
Main Methods:
- Development of a new methodology combining Nuclear Resonance Vibrational Spectroscopy (NRVS) and Magnetic Circular Dichroism (MCD).
- NRVS for determining the geometric structure of key Fe(III)-OOH and Fe(IV)=O intermediates.
- MCD for defining the frontier molecular orbitals (FMOs) and electronic structure governing reactivity.
Main Results:
- A general mechanistic strategy was defined: Fe(II) coordination unsaturation is controlled by cosubstrates to regulate O2 activation.
- Two key intermediates were characterized: a 2e(-) reduced Fe(III)-OOH and a 4e(-) reduced Fe(IV)=O.
- Spectroscopic data provided critical evaluation of electronic structure calculations, establishing a link between structure and reactivity.
Conclusions:
- Experimental spectroscopy is crucial for understanding NHFe enzyme mechanisms and validating computational results.
- The spin state (low-spin vs. high-spin) of Fe(III)-OOH intermediates dictates distinct reaction pathways, including H-atom abstraction or electrophilic aromatic substitution (EAS).
- The electronic structure of Fe(IV)=O intermediates, particularly the presence of π and σ FMOs in high-spin forms, enables enzymatic control over diverse reactions like EAS, H-atom extraction, halogenation, and hydroxylation.
Related Concept Videos
02:51Metal-Ligand Bonds
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
03:02Colors and Magnetism
Color in Coordination Complexes
When atoms or molecules absorb light at the proper frequency, their electrons are excited to higher-energy orbitals. For many main group atoms and molecules, the absorbed photons are in the ultraviolet range of the electromagnetic spectrum, which cannot be detected by the human eye. For coordination compounds, the energy difference between the d orbitals often allows photons in the visible range to be absorbed and emitted, which is seen as colors by the human eye.
When atoms or molecules absorb light at the proper frequency, their electrons are excited to higher-energy orbitals. For many main group atoms and molecules, the absorbed photons are in the ultraviolet range of the electromagnetic spectrum, which cannot be detected by the human eye. For coordination compounds, the energy difference between the d orbitals often allows photons in the visible range to be absorbed and emitted, which is seen as colors by the human eye.
02:34Enzymes
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
02:15Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
01:24Microbes and Other Elemental Cycles
Microbial activity plays a pivotal role in the biogeochemical cycling of iron and manganese, especially at the redox gradients characteristic of stratified aquatic environments. These cycles are driven by microbial transformations between oxidized and reduced forms of the metals, allowing organisms to exploit them for metabolic energy and structural purposes.Iron Cycling Across Redox GradientsIn neutral, oxygen-rich surface waters, iron is predominantly found in its oxidized, insoluble ferric...
01:29Structure and Function of Erythrocytes
There are between 4.2 and 6 million erythrocytes, also known as red blood cells, in every microliter of blood. These cells are small, flattened biconcave discs with centers that are depressed.
The erythrocyte plasma membrane is associated with proteins such as spectrin, which forms a flexible cytoplasmic meshwork. This meshwork allows erythrocytes to twist, turn, become cup-shaped, and regain their biconcave shape as they pass through narrow capillaries. Additionally, erythrocytes can form...
The erythrocyte plasma membrane is associated with proteins such as spectrin, which forms a flexible cytoplasmic meshwork. This meshwork allows erythrocytes to twist, turn, become cup-shaped, and regain their biconcave shape as they pass through narrow capillaries. Additionally, erythrocytes can form...