Biomedical Engineering Reference
In-Depth Information
Nitroprusside. The “nitroprusside” anion [Fe(CN)
5
NO]
2−
. N is blue while O is red.
FIGURE 10.9
bacteria produce a siderophore that binds iron(III) with a stability constant of not less than
10
50
M
−1
. Another siderophore, desferrioxamine produced by the
Streptomyces
fungus, is used in
order to prevent iron poisoning in connection with blood transfusion. Pathogenic microorganisms
rely on a constant supply of iron, and therefore the availability of iron to bacteria invading the
organism plays an important role in many diseases, like cholera and tuberculosis where a decrease
in iron content in the blood is invariably observed. Effective iron scavenging chelates will thus act
as potent antibiotics and naturally occurring iron complexing agents are, therefore, of great interest
in medicine both as antibiotics and as drug delivery agents. An example is bleomycin, an antitumor
agent that is isolated from the
Streptomyces
fungus.
“Sodium nitroprusside,” Na
2
[Fe(CN)
5
NO] (Figure 10.9) is an active hypotensive agent used in
the treatment of heart infarct and in the control of blood pressure during heart surgery. The release
of NO causes relaxation of the muscles surrounding the blood vessels, probably by the coordination
of nitric oxide to an iron porphyrin receptor within the guanylate cyclase enzyme, which converts
guanine triphosphate to cyclic guanine monophosphate. NO is also synthesized in the human body
in a process where an iron containing (heme) enzyme catalyzes oxidation of the amino acid, argi-
nine to nitric oxide.
The role of cobalt as essential trace element is coni ned to only one function, namely, as the
redox active metal ion in coenzyme-B
12
(Figure 10.10), which contains a Co−C (adenosyl) bond.
As early as in the 1920s, it was well established that pernicious anemia (a state of anemia due to
vitamin B
12
dei ciency) could be cured with injections of extracts from liver samples, and trace element
analysis demonstrated later that the extracts contained cobalt. One of the axial cobalt ligands can be an
alkyl residue: C
n
H
2
n
+1
. This is the only known example of a naturally occurring benei cial metal-carbon
bond. The rate of alkylation may be accelerated enzymatically up to 10
10
times.
10.6.4 P
LATINUM
AND
R
UTHENIUM
Platinum anticancer agents have been used extensively during the last 35 years in chemotherapy.
The drugs target and interact with DNA in cells and thus prevent cell division. The cytotoxic effect is
most serious on rapidly dividing cells, i.e., in addition to cancer cells there are also the cells of normal
bone marrow, gut, skin epithelium, and mucosa. The lack of high selectivity of the Pt drugs is one
of its main problems and thus constitutes a major challenge in developing new pharmaceuticals.
