Page 47 - Academic Press Encyclopedia of Physical Science and Technology 3rd InOrganic Chemistry

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Bioinorganic Chemistry 135

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The inside “diameter” is 75 A and can accommodate up to
4500 iron atoms. The mechanism by which this iron core
is formed is under investigation. One interesting problem
is the introduction of iron atoms into the interior of the
ferritin. There are two channels that might serve as pas-
sageways for the iron: a fourfold and a threefold chan-
nel. Hydrophobic residues line the interior of the fourfold
channel. This channel would serve as a poor entrance for
charged ions such as Fe(II) or Fe(III). However, these hy-
drophobic interactions may play a significant role in the
stabilization of the assembly, helping to satisfy step 1 in
the formation of biominerals—formation of a supramolec-
ular construct. The threefold channel is lined by several
hydrophilic residues and is the more likely candidate for
Fe passage. Recently, dimeric Fe(II)-binding sites in the
protein shell have been investigated as possible sites of
initial introduction of iron into ferritin. At these sites,
Fe(II) is oxidized to Fe(III) by oxygen, forming an oxo-
or hydroxo-bridged Fe(III) that migrates into the interior
of ferritin for storage.
Once the iron is inside the sphere, a site of mineral nu-
cleation is located—step 2 in the biomineralization pro-
cess. Although the site(s) of nucleation are not known,
the walls are lined with carboxylic acids from aspartate
and glutamate residues. These are the probable sites of FIGURE 11 Examples of inorganic pharmaceuticals.
nucleation. After nucleation, the mineral begins to form.
The shape is controlled by the protein shell. Studies of
the resulting mineral are consistent with octahedrally co-
the leading drugs for cancer treatment; (3) photophysi-
ordinated iron(III) ions joined by bridging oxide and/or
cal properties, for maladies ranging from psoriasis to can-
hydroxide ions. A mineral termed ferrihydrite has a sim-
cer; (4) properties of new drugs to treat diabetes with-
ilar postulated structure. Because ferritin is used for iron
out using insulin; (5) radioactivity for use in imaging
storage agents, the supramolecular structures described in
agents; and (6) paramagnetism for magnetic resonance
step 4 of Section III.B are not formed.
imaging (MRI) agents. Examples of each of these proper-
ties is given below and in Fig. 11. Some of the complexes
are already in clinical use, while others are in clinical
IV. MEDICAL USES FOR trials.
INORGANIC COMPOUNDS In addition to the use of inorganic compounds to treat
illnesses, treatments for genetic defects in inorganic ion
A. Overview metabolism and environmental exposure to toxic ions are
also discussed. The majority of these disfunctions are
Inorganic compounds have been used for centuries for
treated with some sort of chelation therapy (for overex-
their pharmacological properties. Recently, however, the
posure) or metal substitutes (for underexposure). These
understanding of how inorganic compounds interact with
therapies are briefly discussed below.
biological molecules has enabled chemists, biologists, and
physicians to synthesize and test the medicinal quali-
ties of these compounds in a more systematic way. The
B. Redox Chemistry in Medicine
unique properties of inorganic compounds enable new
−
mechanisms to be exploited in the treatment of many The free radical superoxide, O , reacts with nitric ox-
2
diseases. ide, NO, to produce damaging peroxinitrite, OONO .
−
Some of the unique properties being explored include This process has been postulated to be a mediator of
the following: (1) physiologically relevant redox poten- ischemia-reperfusion injury as well as inflammatory and
tials for cancer drugs that cleave DNA and drugs that vascular diseases. Superoxide dismutases (SODs), en-
remove harmful oxygen radicals; (2) ligand exchange zymesdiscussedpreviously,areresponsibleforconverting
for many anticancer drugs, including cisplatin, one of superoxide to hydrogen peroxide and oxygen. SODs are