Download Bioinorganic2

Abstract
Porphyrins and the molecules which coordinate totheir metal centers in terms of ligands
and the Lewis acid-base model. Thepoisonous nature of some small molecules is
investigated by molecular modeling(using both the MacSpartan and CAChe programs).
The first stage involvesmolecular modeling of the HOMO and LUMO orbitals on the
ligands. The
Theory
Ligands
When a metal ion is dissolved in a solution, it almost always has othergroups coordinated
or attached to it. These other groups are called ligands andcan be: molecules like H2O
(water), NH3 (ammonia) or CO (carbon monoxide);monoatomic ions like Cl- (chloride)
or S2- (sulfide); or polyatomic ions likeCN- (cyanide) or NO2- (nitrite). These ligand
examples are shown in Figure 1.The metal ion and ligands together form a complex, and
are an example of Lewisacid-base chemistry. A Lewis base is an electron-pair donor
(think of atraditional base like OH- (hydroxide), which has three electron-pairs
(lonepairs) on the oxygen). A Lewis acid is an electron-pair acceptor (think of
atraditional acid like H+ (hydronium ion) which has no electrons). Metalcations are
positively charged, relatively electron-poor and thus areelectron-pair acceptors and Lewis
acids. Ligands have at least oneelectron-pair to donate to the metal and are Lewis bases.
As we shall seebelow, metal-ligand chemistry is not always as simple as this.
Figure 1. CAChe generated models (showing bonds, lone pairs, and charges) of the
ligands described above.
Ligands can be much larger molecules or ions than those shown above. Anexample of
this is EDTA (ethylenediamminetetraacetic acid), which has six atomsthat can act as a
Lewis base (the two nitrogens and the four singly-bondedoxygens). EDTA coordinates
very well to a variety of metals, generally throughall six atoms. One of its uses is
removing toxic heavy metals from the body.While EDTA is synthetic, many naturally
occurring molecules also can functionas ligands.
Porphyrins
There are many important biomolecules which naturally contain metalswithin the body,
and in biological systems in general. For example, metal ionsare present in many
vitamins (such as Vitamin B12 with cobalt), enzymes (suchas cytochrome p450 with
iron), and molecules important in energy conversion(such as chlorophyll with
magnesium), nitrogen fixation (such as nitrogenasewith molybdenum and iron), and
oxygen transport (such as hemoglobin with iron). Except for nitrogenase,the
biomolecules given as examples all contain similar porphyrin orporphyrin-based ligands.
A porphyrin has four linked pyrrole rings, whose fournitrogens coordinate the metal (see
Figure 2, below).
Figure 2 (left). Structure of the basic
backbone of a porphyrin,known as
porphine
Figure 3 (right). Structure of heme, the iron
containingporphyrin in hemoglobin
Hemoglobin
Figure 3 (above) shows the structure of heme, the ligand-iron porphyrincomplex in
hemoglobin. Each unit of hemoglobin is composed of four subunits,each containing a
heme molecule. The four subunits are nearly identical, withtwo alpha subunits and two
beta subunits in hemoglobin. The heme in both thealpha and beta types of subunit is
surrounded by a long protein chain of about150 amino acid residues. These protein chains
protect the heme and play animportant role in its main function, the transport of oxygen
from the lungs tothe tissue. Iron in heme is also coordinated to nitrogen in a histidine
ligandfrom the protein chain (below the plane of the heme ring).
Cooperativity of oxygen binding
Hemoglobin binds O2 in the lungs and releases it in the tissue. Theoxygen molecule binds
directly to the iron in the heme as the sixth ligand(above the plane of the heme ring).
Because hemoglobin has four heme units,each molecule can transport four oxygen
molecules (and each blood cell hashundreds of thousands of hemoglobins in it). Once an
oxygen molecule binds tothe first subunit's heme, the four subunits in hemoglobin
interactcooperatively in such a way as to increase the ease of coordinating the
secondoxygen molecule. This process continues as the second and third
oxygenscoordinate. In the tissue, the hemoglobin releases the coordinated oxygens(which
are stored by myoglobin, coordinated to an iron in its porphyrin-likeligand).
In tissue, the carbon dioxide present makes the surroundings more acidic,which in turn
lowers the affinity of hemoglobin for the coordinated oxygens(easing their release). The
carbon dioxide is not a ligand though, it isinstead transported back to the lungs
coordinated by some of the amino acidside chains on the protein surrounding the heme
(and not bound to theiron).
Poisons
Many poisons operate in the body by binding as a ligand to a metal betterthan the ligand
the metal is supposed to have. In hemoglobin, cyanide andcarbon monoxide both bind to
the iron as better ligands than oxygen, and thusprevent oxygen from binding to heme
much or at all. A person poisoned by oneof these molecules is literally suffocating
because the oxygen can not betransported from the lungs to the tissues. (Many poisons
also bind to otherenzymatic metal centers, such as the iron in cytochrome p450).
To some extent the protein surrounding the heme helps to prevent CO orCN- poisoning,
because it sterically hinders the binding of these ligands.Oxygen has been found to bind
end-on (through one oxygen atom) and the wholemetal-ligand geometry is bent (Fe-O-O
angle less than 180o). However, CO orCN- bind to the metal in a linear fashion, with a
180o angle (Fe-C-N orFe-C-O). Because the protein subunits surrounding the heme are
very close tothe iron above the plane of the heme, only the bent oxygen ligand can fit
intothis space without distortion. The steric bulk of the protein makes the linearpoisons
bend or tilt, weakening their bond to the iron.