Biomedical Engineering Reference
In-Depth Information
Copper is a potent poison for any cell and thus proteins of the metallothionein type exist, which
will transport excessive copper ions out of the cells. Due to the delicate balance between excess and
dei ciency of copper, a tight control of uptake and excretion of this metal is needed. Excess copper
leads to copper, accumulation in liver and brain, which untreated leads to severe damage of these
organs and results in early death (Wilson's disease). Therapy with powerful copper chelates like
d-penicillamine (Section 10.5.1.2) can keep the copper concentration on a suitable level. Dei ciency
in copper, is just as serious since it leads to grave mental and physical illnesses (e.g., Menkes' disease)
that involve a hereditary dysfunction in copper metabolism.
Many silver(I) compounds can be used as effective antibacterial drugs, like silver sulfadiazine,
which is used clinically in ointments as an antimicrobial agent in instances of severe burns. Silver
nitrate has also been applied in dilute solutions in cases of eye infections due to its antiseptic
property.
Gold has been applied in certain contexts during history. The ancient Chinese, several thousand
years ago produced an elixir containing colloidal gold, which should ensure eternal life. The benei t
of this treatment, however, has never been fully documented. Nevertheless, gold(I) compounds are
currently the only class of drugs known to halt the progression of rheumatoid arthritis. Initially,
gold compounds like gold suli de and gold thiomalate were painfully administered as intramuscular
injections. Later it was discovered that the triethylphosphinegold(I) tetra-
O
-acetylthioglucose
(auranoi n, Figure 10.15) was equally effective and could be administered orally.
As an extremely soft metal ion Au(I) shows a large afi n ity towa rd soft bases li ke sulf ur (th iolates)
and phosphorous (phosphines) while the afi nity toward oxygen and nitrogen containing ligands is
small. The Au(I) coordination in auranoi n is shown in Figure 10.15. It is interesting to note that the
copper level is directly related to the severity of rheumatoid arthritis, which has led to proposals
that antiarthritic drugs like d-PEN and auranoi n operate by affecting the center of coordination for
copper ions, like the one found in human serum albumin. As demonstrated by NMR studies, aura-
noi n coordinates to cysteine-34 in albumin and induces a conformational change in the protein. This
affects the copper binding center (imidazole from a histidine group) whereby the copper homeostasis
becomes perturbed. It has been suggested that the damage of the joints due to tissue inl ammation
is the result of lipid oxidation caused by free radicals such as O
−
. This notion provides a link from
gold to copper. Yet, in another hypothesis gold(I) complexes are suggested to inhibit formation of
undesired antibodies in the collagen region.
Gold-based pharmaceuticals unfortunately possess unpleasant side effects that include allergic
reactions as well as gastrointestinal and renal problems. These side effects may be linked to the
FIGURE 10.15
Auranoi n. Gold(I) (green) is coordinated linearly to a phosphine group (orange) and a thio-
late sulfur (small green).
