Chemistry Reference
In-Depth Information
6
K
+
5
Cs
+
Ag
+
4
Ba
2+
Ca
2+
3
Sr
2+
2
Na
+
1
Li
+
Mg
2+
0
0
5
10
15
AN (∆IP)
-1
FIGURE 1.2
Ovchinnikov's (1979) estimated stability constants for valinomycin complexes
(in methanol solvent) with a series of class (a) metals and one class (b) metal (Ag
+
) were
plotted against the AN(ΔIP)
−1
metric. The AN(ΔIP)
−1
metric combines the influences of ion
size or inertia and atomic ionization potential (Newman et al. 1998). As is clear in this figure,
valinomycin is very selective for K
+
and bonding with the one class (b) metal ion is more
stable than might have been expected from the class (a) metal ion pattern.
Trends in metal-ligand stability constants for the ionophore, valinomycin,
(Ovchinnikov 1979) illustrate several points about class (a) cation movement across
membranes (Figure 1.2). The AN(ΔIP)
−1
metric (Kaiser 1980) in Figure 1.2 combines
the atomic number (AN) and the difference in ionization potential (ΔIP) between the
ion oxidation number OX and OX-1. Clearly, coordination chemistry trends influence
ionophore binding. Another point illustrated in this figure is that extreme specificity
might be designed into transport processes that fill an essential biological role: the
K
+
stability constant is much higher than expected from the general trend. Favored
transport can be designed into such structures through a combination of features
such as ion size and charge, involved ligand donor atoms, and the configuration of
ligand groups (Fraústo de Silva and Williams 1993). As an illustration of the exact-
ing design associated with selectivity, a mutation changing only two amino acid
clusters in the K
+
channel materially decreases selectivity (Heinemann et al. 1992).
Such features are layered onto the general trends predictable from general metal
coordination chemistry.
Once a metal enters the cell, a wide range of processes occur that, again, are
best understood based on general binding tendencies. By design, the metallothionein
proteins and phytochelatin oligopeptides bind intermediate and class (b), but not
class (a), metals. Because metallothioneins are synthesized and distributed unevenly
among tissues, there will be an associated high accumulation of some metals such
as cadmium in organs like the mammalian kidney. This binding to metal-cysteinyl
thiolate clusters is crucial to essential element (copper and zinc) and nonessential
element (cadmium, mercury, and silver) regulation, sequestration, and elimination
in all phyla. More generally, methylmercury forms stable covalent S-Hg bonds with
diverse proteins in various tissues (Harris et al. 2003) and will become associated
