Biocoordination Chemistry: Oxygen Transport
It is a common misconception that there is a mysterious property of organic compounds that made life possible. The pioneering research by Friedrich Wohler on the conversion ammonium cyanate to urea broke this 'vital force dogma'. In the human body, it contains around 1 kg of essential metals per 75 kg adult, from Ca as the most abundant in the body (1050 g) to some transition metals (mainly the first row transition metals). The transition metal ions are bound in proteins to give metalloproteins. Although the molecules may be complex but principles are familiar from basic coordination chemistry. A metallprotein is just a big coordination complex in which the protein acts as a polydentate ligand, controlling environment around, and behaviour of, metal ion. The main focus for this time is on the oxygen transport system in haemoglobin/myoglobin and haemocyanin.
Haemoglobin (Hb) and myoglobin consists of a haeme unit which is a Fe-porphyrin unit which binds O2 at vacant axial site. The main different of haemoglobin and myoglobin is in their role; haemoglobin acts as oxygen transport in blood while myoglobin acts as oxygen storage in muscles. From the picture above, myoglobin (middle) shows a the position of haeme unit at the edge of globin protein. The haeme unit is a 5-coordinate Fe porphyrin unit with the protein wraps around it. With this coordination, the amount of O2 that can be dissolved in blood is significantly higher than in normal water (3 x 10-4 M in water compare to 9 x 10-3 M in blood).
The coordination of O2 at haeme active site is via 'bent' end-on binidng. At its free state (deoxy-Hb), it forms a square pyramidal high spin Fe(II) complex with Fe(II) ion sit below the porphyrin ring. When it binds with O2, Fe(II) moves into prophyrin plane and becomes low spin diamagnetic Fe(III) complex where the radius of Fe(III) is small enough to fit inside the porphyrin ring. The bound O2 is suggested forming a superoxide ion where it is stabilised by distal histidine residue via hydrogen bonding.
Bent coordination of O2 partly because lone pairs are in sp2 hybrid orbitals. As O2 approaches iron centre, there are three possible components to bonding: one sigma donation and two routes for back-bonding interactions.
Another interesting point from this complex is Fe(III) and superoxide are both paramagnetic (1 unpaired electron each) but oxy-Hb is a diamagnetic. This implies that in such a way both unpaired electrons interact with each other to pair up in short distance with the orbital overlap. This phenomenon is called antiferromagnetic coupling.
If we refer back to the bonding mode of oxy-Hb, we see the stabilising effect from distal histidine and this distal histidine also provides an aid to prevent CO poisoning. CO toxicity arises from strong binding to Fe of haemoglobin (240:1 preference over O2) preventing O2 transport. However, distal histidine provides a steric clash with Fe-CO bonding which then bend the the bond angle of Fe-CO from normal. This bending enforces weakening of CO binding to prevent CO from being lethal in tiny quantities.
Another metalloprotein that act as oxygen transport is haemocyanin and it is used for O2 transport in molluscs and crustaceans. Interestingly, this molecule has the same function as haemoglobin but it does not contain haeme unit.
The active site of haemocyanin consists of two Cu(I) ions with three histidine donors each. The cavity between metals accomodates O2 molecule and the exact mode of binding was a mystery for a long time. However, there are 4 important spectroscopic clues to the structure.
The early models of haemocyanin account for all spectroscopic and magnetic properties so structures above are assumed to be correct for many year. Early model complex of haemocyanin shows phenolates bridging between two Cu(II) centres as shown below.
However, there is no direct structural evidence for this extra additional single atom in oxyhaemocyanin.
In 1988, new bridging mode of peroxide was discovered in simple artificial complex which reversibly binds and releases O2 at -80 °C with side on doubly-bridgin coordination of O2.
Tris(pyrazolyl)borate ligand is good mimic of pyramidal tris-histidine donor set around Cu(I) centres in haemocyanin. The binding shows O-O bond is perpendicular to Cu --- Cu line and the structure accounts all spectroscopic and magnetic feactures of oxyhaemocyanin. Furthermore, subsequent crystal structure of oxyhaemocyanin is also shown to have this core structure.
This example shows how a simple model complex can provide important insight into structure of biological molecule.
 |
| Left to right: haemoglobin, myoglobin, haemocyanin |
Haemoglobin (Hb) and myoglobin consists of a haeme unit which is a Fe-porphyrin unit which binds O2 at vacant axial site. The main different of haemoglobin and myoglobin is in their role; haemoglobin acts as oxygen transport in blood while myoglobin acts as oxygen storage in muscles. From the picture above, myoglobin (middle) shows a the position of haeme unit at the edge of globin protein. The haeme unit is a 5-coordinate Fe porphyrin unit with the protein wraps around it. With this coordination, the amount of O2 that can be dissolved in blood is significantly higher than in normal water (3 x 10-4 M in water compare to 9 x 10-3 M in blood).
The coordination of O2 at haeme active site is via 'bent' end-on binidng. At its free state (deoxy-Hb), it forms a square pyramidal high spin Fe(II) complex with Fe(II) ion sit below the porphyrin ring. When it binds with O2, Fe(II) moves into prophyrin plane and becomes low spin diamagnetic Fe(III) complex where the radius of Fe(III) is small enough to fit inside the porphyrin ring. The bound O2 is suggested forming a superoxide ion where it is stabilised by distal histidine residue via hydrogen bonding.
Bent coordination of O2 partly because lone pairs are in sp2 hybrid orbitals. As O2 approaches iron centre, there are three possible components to bonding: one sigma donation and two routes for back-bonding interactions.
 |
| sigma donation (left) and back-bonding interactions (middle and right) |
Another interesting point from this complex is Fe(III) and superoxide are both paramagnetic (1 unpaired electron each) but oxy-Hb is a diamagnetic. This implies that in such a way both unpaired electrons interact with each other to pair up in short distance with the orbital overlap. This phenomenon is called antiferromagnetic coupling.
If we refer back to the bonding mode of oxy-Hb, we see the stabilising effect from distal histidine and this distal histidine also provides an aid to prevent CO poisoning. CO toxicity arises from strong binding to Fe of haemoglobin (240:1 preference over O2) preventing O2 transport. However, distal histidine provides a steric clash with Fe-CO bonding which then bend the the bond angle of Fe-CO from normal. This bending enforces weakening of CO binding to prevent CO from being lethal in tiny quantities.
Another metalloprotein that act as oxygen transport is haemocyanin and it is used for O2 transport in molluscs and crustaceans. Interestingly, this molecule has the same function as haemoglobin but it does not contain haeme unit.
 |
| active site of haemocyanin |
The active site of haemocyanin consists of two Cu(I) ions with three histidine donors each. The cavity between metals accomodates O2 molecule and the exact mode of binding was a mystery for a long time. However, there are 4 important spectroscopic clues to the structure.
- O-O stretch in Raman spectroscopy at 750 cm-1 consistent with O-O single bond, suggesting peroxide anion is formed.
- Isotope labelled 16O18O shows one O-O stretch which implies that it doesn't matter which way O-O bond and it must be symmetric for both atoms. This simply rules out non-symmetrical binding modes.
- Strong peak at 580 nm at absorption spectrum shows peroxide-Cu(II) ligand to metal charge transfer. This confirm the presence of peroxide, and means that Cu(I) has been oxidised to Cu(II) when O2 binds. This is a redox reaction in which two Cu(I) oxidised by one electron each, and O2 is reduced by two electrons.
- No magnetic moment at oxygenated Cu(II) implies antiferromagnetic coupling via single atom (Cu-X-Cu bridge). A two-atom Cu-O-O-Cu bridge would not on its own allow electrons on Cu(II) to pair up so extra bridge is needed.
The early models of haemocyanin account for all spectroscopic and magnetic properties so structures above are assumed to be correct for many year. Early model complex of haemocyanin shows phenolates bridging between two Cu(II) centres as shown below.
However, there is no direct structural evidence for this extra additional single atom in oxyhaemocyanin.
In 1988, new bridging mode of peroxide was discovered in simple artificial complex which reversibly binds and releases O2 at -80 °C with side on doubly-bridgin coordination of O2.
Tris(pyrazolyl)borate ligand is good mimic of pyramidal tris-histidine donor set around Cu(I) centres in haemocyanin. The binding shows O-O bond is perpendicular to Cu --- Cu line and the structure accounts all spectroscopic and magnetic feactures of oxyhaemocyanin. Furthermore, subsequent crystal structure of oxyhaemocyanin is also shown to have this core structure.
This example shows how a simple model complex can provide important insight into structure of biological molecule.
Comments
boleh share ga? hahaha,,
kebanyakan yg di sini dari materi kuliah sih, jadi bisa ditemuin di buku referensi kimia kyk Atkins, Housecroft atau nggak Clayden