Biomedical Engineering Reference
In-Depth Information
TABLE 10.4
Chelating Ligands Toward Toxic Metal Ions
Ligand
Commercial or Trivial Name
Preferred Metal Ions
Hg
2+
, As
3+
, Sb
3+
, Ni
2+
(a) 2,3-Dimercapto-1-propanol
Dimercaprol, BAL
Cu
2+
, Hg
2+
d-Penicillamine, PEN
(b) d-β,β-Dimethylcysteine
(c) Ethylenediaminetetraacetic acid
EDTA
Ca
2+
, Pb
2+
Fe
3+
, Al
3+
(d) Desferrioxamine
DFO, desferral
constitutes a fundamental challenge in bioinorganic chemistry, and development of chelating phar-
maceuticals that specii cally sequester the undesired (heavy) metal ions becomes imperative. The
most successful ligands demonstrate selectivity by (1) exclusive i tting to ions of dei nite size and
charge; (2) comprising donor atoms that prefer Lewis acids of certain hardness or softness (Section
10.4.2). Further, the chelates must (3) form thermodynamically stable and kinetically inert coordi-
nation compounds (Sections 10.4.1 through 10.4.3); and i nally (4) be able to excrete the undesired
metal ion rapidly and effectively.
10.5.1 S
ELECTED
C
HELATES
10.5.1.1 BAL
The i rst example of chelate therapy was performed during World War II when BAL (2,3-dimercapto-
1-propanol; British Anti Lewisite [Figure 10.4A]) was applied as antagonist against arsenic containing
poison gas. BAL, being a very soft Lewis base, preferentially coordinates to soft heavy metal ions.
Thus, aside from arsenic, As(III), the chelate will be highly efi cient in treatment of mercury toxication.
Today, however, BAL is exclusively utilized in connection with acute gold poisoning in patients
undergoing treatment with gold containing pharmaceuticals (Section 10.6.5). An advantage of BAL
is its lipophilic character, which facilitates transport into the cells. However, the drug itself is toxic
and must be administered with great care.
10.5.1.2
D
-Penicillamine
The structure of d-penicillamine (d-PEN) is shown in Figure 10.4B where the three different
donor groups should be noticed: Two hard donor atoms (amine-
N
and carboxylate-
O
) together
with a soft thiolate (-SH) group making the chelate a universal drug for both soft and hard Lewis
acids although with limited ion selectivity. d-PEN is water soluble and, in contrast to BAL, not
inherently toxic. But the
L
-isomer is a vitamin-B
6
antagonist and thus harmful to the organism.
d-PEN has found wide application and may in most cases replace BAL, often applied simultane-
ously with EDTA as in the treatment of lead poisoning. It is also effective in sequestering gold
and mercury. The administration of d-PEN to patients suffering from Wilson's disease is of
particular interest (Section 10.6.5).
10.5.1.3 EDTA
Ethylenediaminetetraacetic acid (EDTA) and its analogues are all excellent chelates sequester-
ing most metal ions, but for the same reason they are also not selective. EDTA coordinates
preferentially to hard metal ions (Section 10.4.2) and due to the large chelate effect, quite stable
complexes are formed. Since EDTA is inadequately absorbed only from the gastrointestinal tract,
it is usually administered by intravenous injections. But due to the low degree of selectivity the
hazard of eliminating essential metal ions is high. Adding the drug as Na
2
H
2
EDTA, the serum
